ABSTRACTThe objective of this study was to describe the functional status of US service members after combat-related amputation. This was a cross-sectional analysis of data from a subsample of the ...Wounded Warrior Recovery Project, an ongoing, web-based, longitudinal examination of patient-reported outcomes of injured service members. The study sample included 82 Wounded Warrior Recovery Project participants with a combat-related lower extremity amputation who reported using a prosthetic device and completed the Orthotics and Prosthetics Usersʼ Survey Lower Extremity Functional Status, which measures self-reported functional status in participants with a prosthetic device. Basic activities, such as walking indoors, getting on and off the toilet, and getting up from a chair, were reported by the majority of participants as “very easy/easy,” whereas higher-level activities, such as climbing stairs, walking long distances, or running, were more often reported as “slightly difficult/very difficult” or “cannot do this activity.” Functional status varied significantly by amputation site (unilateral below knee, unilateral above knee, or bilateral; P = 0.004), with significantly better function reported in those with unilateral below knee than bilateral amputation (P < 0.05). These findings highlight deficits in the functional status of US service members with combat-related amputation. Self-reported functional status of daily activities may help target important activities for patient-centered goals.
Purpose Little is known about the long-term, health-related quality of life (HRQOL) of those wounded in combat during Operations Enduring Freedom, Iraqi Freedom, and New Dawn. The present study ...described the overall HRQOL for a large group of US service members experiencing mild-to-severe combat-related injuries, and assessed the unique contribution of demographics, service- and injury-related characteristics, and mental health factors on long-term HRQOL. Method The Wounded Warrior Recovery Project examines patient-reported outcomes in a cohort of US military personnel wounded in combat. Participants were identified from the Expeditionary Medical Encounter Database, a US Navy-maintained deployment health database, and invited to complete a web-based survey. At the time of this study, 3245 service members consented and completed the survey. Hierarchical linear regression analyses were conducted to assess the unique contribution of each set of antecedents on HRQOL scores. Results HRQOL was uniquely associated with a number of demographics, and service- and injury-related characteristics. Nevertheless, screening positive for posttraumatic stress disorder (B=-.09; P<.001), depression (B=-.10; P<.001), or both as a set (B=-.19; P<.001) were the strongest predictors of lower long-term HRQOL. Conclusions Postinjury HRQOL among service members wounded in combat was associated with service and injury experience, and demographic factors, but was most strongly linked with current mental health status. These findings underscore the significance of mental health issues long after injury. Further, findings reinforce that long-term mental health screening, services, and treatment are needed for those injured in combat.
Only 10-30% of oesophageal and rectal adenocarcinoma patients treated with neoadjuvant chemoradiotherapy have a complete pathological response. Inflammatory and angiogenic mediators in the tumour ...microenvironment (TME) may enable evasion of anti-tumour immune responses.
The TME influence on infiltrating dendritic cells (DCs) was modelled by treating immature monocyte-derived DCs with Tumour Conditioned Media (TCM) from distinct gastrointestinal sites, prior to LPS-induced maturation.
Cell line conditioned media from gastrointestinal cell lines inhibited LPS-induced DC markers and TNF-α secretion. TCM generated from human tumour biopsies from oesophageal, rectal and colonic adenocarcinoma induced different effects on LPS-induced DC markers - CD54, CD80, HLA-DR, CD86 and CD83 were enhanced by oesophageal cancer; CD80, CD86 and CD83 were enhanced by rectal cancer, whereas CD54, HLA-DR, CD86, CD83 and PD-L1 were inhibited by colonic cancer. Notably, TCM from all GI cancer types inhibited TNF-α secretion. Additionally, TCM from irradiated biopsies inhibited DC markers. Profiling the TCM showed that IL-2 levels positively correlated with maturation marker CD54, while Ang-2 and bFGF levels negatively correlated with CD54.
This study identifies that there are differences in DC maturational capacity induced by the TME of distinct gastrointestinal cancers. This could potentially have implications for anti-tumour immunity and response to radiotherapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Many cancer survivors experience physical and/or psychosocial side effects, which can be severe, debilitating, and sometimes permanent. These NCCN Guidelines for Survivorship provide screening, ...evaluation, and treatment recommendations for common consequences of cancer and cancer treatment for health care professionals who work with survivors of adult-onset cancer in the posttreatment period. These introductory sections of the guidelines include the panel's definition of cancer survivors, a discussion of the effects of cancer and its treatment, general principles and standards for survivorship care, and guidance regarding screening for problems that require further assessment.
Extremity injuries have comprised the majority of battlefield injuries in modern U.S. conflicts since World War II. Most reports have focused on serious injuries only and, to date, no reports have ...described the full extent of combat extremity injuries, from mild to severe, resulting from post-9/11 conflicts. This study aims to identify and characterize the full spectrum of non-amputation combat-related extremity injury and extend the findings of previous reports.
The Expeditionary Medical Encounter Database was queried for all extremity injured service members (SMs) deployed in support of post-9/11 conflicts through July 2018. Only injuries incurred during combat operations were included in this report. Major amputations were excluded as well as SMs killed in action or who died of wounds. Extremity injuries were categorized by body region, nature of injury, and severity. Demographics and injury event characteristics are also presented.
A total of 17,629 SMs sustained 42,740 extremity injuries during 18,004 separate injury events. The highest number of SMs were injured in 2004 (n = 3,553), 2007 (n = 2,244), and 2011 (n = 2,023). Injured SMs were mostly young (78% under 30 years), male (97%), junior- to mid-level enlisted (89%), in the Army (69%) or Marine Corps (28%), active duty (84%), serving as infantry and gun crew (59%), and injured in support of Operation Iraqi Freedom (60%). Blast weaponry was responsible for 75% of extremity injuries. Injuries were similarly distributed between the lower (52%) and upper (48%) extremities. The most common sites of lower extremity injury were the lower leg/ankle complex (40%) and thigh (26%). The most common upper extremities sites were the shoulder and upper arms (37%), and the hand, wrist, and fingers (33%). Nearly half (48%) of all extremity injuries were open wounds (48%), followed by fractures (20%) and contusions/superficial injuries (16%). SMs sustained an average of 2.4 extremity injuries per event and 56% of injuries were considered mild, with a median Injury Severity Score (ISS) of 3.
This study is the first publication to capture, review, and characterize the full range, from mild to severe, of non-amputation combat-related extremity injuries resulting from post-9/11 conflicts. The high prevalence of extremity injury, particularly in such a young population, and associated short- and long-term health outcomes, will impact military health care systems for decades to come.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Preliminary in vitro and in vivo studies with valproic acid (VPA) in cell lines and patients with spinal muscular atrophy (SMA) demonstrate increased expression of SMN, supporting the possibility of ...therapeutic benefit. We performed an open label trial of VPA in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future controlled clinical trials. Subjects included 2 SMA type I ages 2-3 years, 29 SMA type II ages 2-14 years and 11 type III ages 2-31 years, recruited from a natural history study. VPA was well-tolerated and without evident hepatotoxicity. Carnitine depletion was frequent and temporally associated with increased weakness in two subjects. Exploratory outcome measures included assessment of gross motor function via the modified Hammersmith Functional Motor Scale (MHFMS), electrophysiologic measures of innervation including maximum ulnar compound muscle action potential (CMAP) amplitudes and motor unit number estimation (MUNE), body composition and bone density via dual-energy X-ray absorptiometry (DEXA), and quantitative blood SMN mRNA levels. Clear decline in motor function occurred in several subjects in association with weight gain; mean fat mass increased without a corresponding increase in lean mass. We observed an increased mean score on the MHFMS scale in 27 subjects with SMA type II (p<or=0.001); however, significant improvement was almost entirely restricted to participants <5 years of age. Full length SMN levels were unchanged and Delta7SMN levels were significantly reduced for 2 of 3 treatment visits. In contrast, bone mineral density (p<or=0.0036) and maximum ulnar CMAP scores (p<or=0.0001) increased significantly.
While VPA appears safe and well-tolerated in this initial pilot trial, these data suggest that weight gain and carnitine depletion are likely to be significant confounding factors in clinical trials. This study highlights potential strengths and limitations of various candidate outcome measures and underscores the need for additional controlled clinical trials with VPA targeting more restricted cohorts of subjects.
ClinicalTrials.gov.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUNDGuidelines endorse educating patients to self-manage atrial fibrillation (AF) to mitigate AF-related adverse events contributing to personal and societal burden. Published interventions to ...improve patientsʼ knowledge about AF and self-management are emerging, but evaluations of interventions are limited by lack of a psychometrically sound instrument to measure learning outcomes.
OBJECTIVEWe report results of initial psychometric testing of the Knowledge about Atrial Fibrillation and Self-Management (KAFSM) survey.
METHODSParticipants (N = 383), from midwest and southeast medical centers, completed the KAFSM survey. Content validity was evaluated by expert review. Construct validity was evaluated using the Pearson correlation procedure for convergent validity with the Knowledge about Atrial Fibrillation test and independent t test for known groups. Factor analysis using principal axis factoring was performed with a tetrachoric matrix. The Kuder-Richardson procedure was used to determine internal consistency reliability.
RESULTSA content validity index of 0.86 resulted from expert review. A positive (r = 0.60) correlation between the KAFSM survey and Knowledge about Atrial Fibrillation test demonstrated convergent validity. Higher KAFSM scores (difference, 3.28; t = 6.44, P < .001) observed in participants who underwent AF ablation compared with those with an AF diagnosis of less than or equal to 6 months supported known groups validity. Factor analysis revealed a single-factor structure explaining 35% of the variance. The Kuder-Richardson coefficient was 0.86.
CONCLUSIONSThe KAFSM survey demonstrates content and construct validity and internal consistency reliability. Implementation of the KAFSM in the clinical setting will permit evaluation of the feasibility of its use and value to assess learning outcomes of AF education.
Survivorship: cognitive function, version 1.2014 Denlinger, Crystal S; Ligibel, Jennifer A; Are, Madhuri ...
Journal of the National Comprehensive Cancer Network
12, Številka:
7
Journal Article
Recenzirano
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Cognitive impairment is a common complaint among cancer survivors and may be a consequence of the tumors themselves or direct effects of cancer-related treatment (eg, chemotherapy, endocrine therapy, ...radiation). For some survivors, symptoms persist over the long term and, when more severe, can impact quality of life and function. This section of the NCCN Guidelines for Survivorship provides assessment, evaluation, and management recommendations for cognitive dysfunction in survivors. Nonpharmacologic interventions (eg, instruction in coping strategies; management of distress, pain, sleep disturbances, and fatigue; occupational therapy) are recommended, with pharmacologic interventions as a last line of therapy in survivors for whom other interventions have been insufficient.
Preclinical data suggest that radiotherapy (RT) is beneficial in combination with immune checkpoint blockade. Clinical trials have explored RT with single-agent immune checkpoint blockade, but no ...trials have reported RT with the combination of nivolumab and ipilimumab.
We conducted a phase 1 study of patients with stage IV melanoma receiving nivolumab and ipilimumab with two different dose-fractionation schemes of RT. Patients had at least one melanoma metastasis that would benefit from palliative RT and one metastasis that would not be irradiated. Nivolumab 1 mg/kg + ipilimumab 3 mg/kg and extracranial RT with a dose of 30 Gy in 10 fractions was administered in Cohort A, and then 27 Gy in 3 fractions was administered in Cohort B. The primary outcome was safety.
Twenty patients were treated (10 in each cohort). The rates of treatment-related grade 3-4 adverse events in Cohort A and B were 40% and 30%, respectively. There were no grade ≥3 adverse events attributed to RT. Patients responded to treatment outside of the irradiated volume (Cohort A 5/10; Cohort B 1/9). No evaluable patients had progression of irradiated metastases. Immunologic changes were seen in the peripheral blood with increases in T-cell receptor diversity in some responding patients.
RT with nivolumab and ipilimumab was safe compared with historical data of nivolumab and ipilimumab alone. Immunologic effects were observed in the peripheral blood. Randomized studies are ongoing to assess whether RT increases the efficacy of nivolumab and ipilimumab.
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