ICF Linking of Patient-Reported Therapy Goals for Children with Acquired Upper Extremity Impairment

BACKGROUND: Patient reported outcome measures are used to evaluate hand therapy outcomes. Yet, limited evidence is available regarding the outcomes children desire from hand therapy. PURPOSE: To determine the desired treatment outcomes of children with acquired upper extremity impairments. STUDY DESIGN: Descriptive case series METHODS: Two raters independently applied International Classification of Function, Disability and Health (ICF) linking rules to the Canadian Occupational Performance goals of 151 children, age 6-18, receiving occupational therapy for acquired upper extremity impairments. Prevalence of the linked ICF codes was examined using frequency distributions. Kappa and the proportion of positive agreement assessed inter-rater agreement of the linked codes. RESULTS: Following consensus, two independent raters linked 894 meaningful concepts to the study population\u27s 501 goals derived from the Canadian Occupational Performance. Ninety-two unique ICF codes were linked to these 894 meaningful concepts. Twenty-three ICF codes account for 77.2% of the most frequently linked codes. For these top 23 codes, the greatest proportion (51.4%) of ICF codes are in the d4 mobility chapter representing specific constructs of hand and arm use. The second largest proportion (14.2%) of linked codes are in the d9 Community, society and civic life chapter aligning with participation in sports, music, performing arts and play. Within the d5 self-care chapter, the study population\u27s top priorities included hair care, fitness and drinking. The primary concerns within the b body functions domain are reduced pain, improved joint mobility and strength. CONCLUSION: The study population\u27s top priorities align with specific dimensions of hand and arm use and participation in sports and fitness, performing arts, and play. Further research may elucidate alignment of these patient-desired outcomes and the item banks of commonly used patient reported outcome measurement scales in this population

The Role of Rehabilitation Following Autologous Chondrocyte Implantation: A Retrospective Chart Review

PURPOSE/BACKGROUND: Clinical outcomes following autologous chondrocyte implantation (ACI) are influenced by multiple factors, including patient demographics, lesion characteristics, quality of the surgical repair, and post-operative rehabilitation. However, it is currently unknown what specific characteristics of rehabilitation have the greatest influence on clinical outcomes following ACI. The purpose of this study was to conduct a retrospective chart review of patients undergoing ACI with the intent to describe this patient population\u27s demographics, clinical outcomes, and rehabilitation practices. This study aimed to assess the consistency of the documentation process relative to post-operative rehabilitation in order to provide information and guide initiatives for improving the quality of rehabilitation practices following ACI. METHODS: The medical records of patients treated for chondral defect(s) of the knee who subsequently underwent the ACI procedure were retrospectively reviewed. A systematic review of medical, surgical, and rehabilitation records was performed. In addition, patient-reported outcome measures (IKDC, WOMAC, Lysholm, SF-36) recorded pre-operatively, and 3, 6, and 12 months post-operatively were extracted from an existing database. RESULTS: 20 medical charts (35.9 ± 6.8 years; 9 male, 11 female) were systematically reviewed. The average IKDC, WOMAC, Lysholm, and SF-36 scores all improved from baseline to 3, 6 and 12 months post-operatively, with the greatest changes occurring at 6 and 12 months. There was inconsistent documentation relative to post-operative rehabilitation, including CPM use, weight-bearing progression, home-exercise compliance, and strength progressions. CONCLUSIONS: Due to variations in the documentation process, the authors were unable to determine what specific components of rehabilitation influence the recovery process. In order to further understand how rehabilitation practices influence outcomes following ACI, specific components of the rehabilitation process must be consistently and systematically documented over time. LEVEL OF EVIDENCE: 2C

A Biologic-Device Combination Product Delivering Tumor-Derived Antigens Elicits Immunogenic Cell Death-Associated Immune Responses Against Glioblastoma

Background IGV-001 is a personalized, autologous cancer cell-based immunotherapy conceived to deliver a tumor-derived antigenic payload in the context of immunostimulatory signals to patients with glioblastoma (GBM). IGV-001 consists of patient-derived GBM cells treated with an antisense oligodeoxynucleotide against insulin-like growth factor 1 receptor (IGF1R) and placed in proprietary biodiffusion chambers (BDCs). The BDCs are then exposed to 5–6 Gy radiation and implanted at abdominal sites for ~48 hours. IGV-001 has previously been shown to be generally safe with promising clinical activity in newly diagnosed GBM patients. Methods Mouse (m) or human (h) variants of IGV-001 were prepared using GL261 mouse GBM cells or human GBM cells, respectively. BDCs containing vehicle or mIGV-001 were implanted in the flanks of C57BL/6 albino female mice in preventative and therapeutic experiments, optionally in combination with a programmed cell death 1 (PD-1) blocker. Bioactivity of the general approach was also measured against hepatocellular carcinoma Hepa 1–6 cells. Mice were followed for the growth of subsequently implanted or pre-existing tumors and survival. Draining lymph nodes from mice receiving mIGV-001 were immunophenotyped. mIGV-001 and hIGV-001 were analyzed for extracellular ATP and high mobility group box 1 (HMGB1) as indicators of immunogenic cell death (ICD), along with flow cytometric analysis of viability, surface calreticulin, and reactive oxygen species. Stress and cell death-related pathways were analyzed by immunoblotting. Results IGV-001 causes oxidative and endoplasmic reticulum stress in GL261 cells, resulting in a cytotoxic response that enables the release of antigenic material and immunostimulatory, ICD-associated molecules including ATP and HMGB1 from BDCs. Immunophenotyping confirmed that IGV-001 increases the percentage of dendritic cells, as well as effector, and effector memory T cells in BDC-draining lymph nodes. Consistent with these observations, preventative IGV-001 limited tumor progression and extended overall survival in mice intracranially challenged with GL261 cells, a benefit that was associated with an increase in tumor-specific T cells with effector features. Similar findings were obtained in the Hepa 1–6 model. Moreover, therapeutically administered IGV-001 combined with PD-1 delayed progression in GBM-bearing mice. Conclusions These results support treatment with IGV-001 to induce clinically relevant ICD-driven anticancer immune responses in patients with GBM

Membrane vesicle-mediated bacterial communication

The classical quorum-sensing (QS) model is based on the assumption that diffusible signaling molecules accumulate in the culture medium until they reach a critical concentration upon which expression of target genes is triggered. Here we demonstrate that the hydrophobic signal N-hexadecanoyl-L-homoserine lactone, which is produced by Paracoccus sp., is released from cells by the aid of membrane vesicles (MVs). Packed into MVs, the signal is not only solubilized in an aqueous environment but is also delivered with varying propensities to different bacteria. We propose a novel MV-based mechanism for binary trafficking of hydrophobic signal molecules, which may be particularly relevant for bacteria that live in open aqueous environments

Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage:a randomised controlled clinical trial

BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone.METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed.FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment.INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups.FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.</p

Microbial Hotspots in Lithic Macrohabitats Inferred from DNA Fractionation and Metagenomics in the Atacama Desert

The existence of microbial activity hotspots in temperate regions of Earth is driven by soil heterogeneities, especially the temporal and spatial availability of nutrients. Here we investigate whether microbial activity hotspots also exist in lithic microhabitats in one of the most arid regions of the world, the Atacama Desert in Chile. While previous studies evaluated the total DNA fraction to elucidate the microbial communities, we here for the first time use a DNA separation approach on lithic microhabitats, together with metagenomics and other analysis methods (i.e., ATP, PLFA, and metabolite analysis) to specifically gain insights on the living and potentially active microbial community. Our results show that hypolith colonized rocks are microbial hotspots in the desert environment. In contrast, our data do not support such a conclusion for gypsum crust and salt rockenvironments, because only limited microbial activity could be observed. The hypolith community is dominated by phototrophs, mostly Cyanobacteria and Chloroflexi, at both study sites. The gypsum crusts are dominated by methylotrophs and heterotrophic phototrophs, mostly Chloroflexi, and the salt rocks (halite nodules) by phototrophic and halotolerant endoliths, mostly Cyanobacteria and Archaea. The major environmental constraints in the organic-poor arid and hyperarid Atacama Desert are water availability and UV irradiation, allowing phototrophs and other extremophiles to play a key role in desert ecology

Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study

Introduction: Consensus criteria for pediatric severe sepsis have standardized enrollment for research studies. However, the extent to which critically ill children identified by consensus criteria reflect physician diagnosis of severe sepsis, which underlies external validity for pediatric sepsis research, is not known. We sought to determine the agreement between physician diagnosis and consensus criteria to identify pediatric patients with severe sepsis across a network of international pediatric intensive care units (PICUs). Methods: We conducted a point prevalence study involving 128 PICUs in 26 countries across 6 continents. Over the course of 5 study days, 6925 PICU patients &lt;18 years of age were screened, and 706 with severe sepsis defined either by physician diagnosis or on the basis of 2005 International Pediatric Sepsis Consensus Conference consensus criteria were enrolled. The primary endpoint was agreement of pediatric severe sepsis between physician diagnosis and consensus criteria as measured using Cohen's ?. Secondary endpoints included characteristics and clinical outcomes for patients identified using physician diagnosis versus consensus criteria. Results: Of the 706 patients, 301 (42.6 %) met both definitions. The inter-rater agreement (? ± SE) between physician diagnosis and consensus criteria was 0.57 ± 0.02. Of the 438 patients with a physician's diagnosis of severe sepsis, only 69 % (301 of 438) would have been eligible to participate in a clinical trial of pediatric severe sepsis that enrolled patients based on consensus criteria. Patients with physician-diagnosed severe sepsis who did not meet consensus criteria were younger and had lower severity of illness and lower PICU mortality than those meeting consensus criteria or both definitions. After controlling for age, severity of illness, number of comorbid conditions, and treatment in developed versus resource-limited regions, patients identified with severe sepsis by physician diagnosis alone or by consensus criteria alone did not have PICU mortality significantly different from that of patients identified by both physician diagnosis and consensus criteria. Conclusions: Physician diagnosis of pediatric severe sepsis achieved only moderate agreement with consensus criteria, with physicians diagnosing severe sepsis more broadly. Consequently, the results of a research study based on consensus criteria may have limited generalizability to nearly one-third of PICU patients diagnosed with severe sepsis

Sustained Isometric Shoulder Contraction on Muscular Strength and Endurance: A Randomized Clinical Trial

BACKGROUND: The Advanced Throwers Ten Exercise Program incorporates sustained isometric contractions in conjunction with dynamic shoulder movements. It has been suggested that incorporating isometric holds may facilitate greater increases in muscular strength and endurance. However, no objective evidence currently exists to support this claim. HYPOTHESIS/PURPOSE: The purpose of this research was to compare the effects of a sustained muscle contraction resistive training program (Advanced Throwers Ten Program) to a more traditional exercise training protocol to determine if increases in shoulder muscular strength and endurance occur in an otherwise healthy population. It was hypothesized that utilizing a sustained isometric hold during a shoulder scaption exercise from the Advanced Throwers Ten would produce greater increases in shoulder strength and endurance as compared to a traditional training program incorporating a isotonic scapular plane abduction (scaption) exercise. STUDY DESIGN: Randomized Clinical Trial. METHOD: Fifty healthy participants were enrolled in this study, of which 25 were randomized into the traditional training group (age: 26 ± 8, height:172 ± 10 cm, weight: 73 ± 13 kg, Marx Activity Scale: 11 ± 4) and 25 were randomized to the Advanced Throwers Ten group (age: 28 ± 9, height: 169 ± 23 cm, weight: 74 ± 16 kg, Marx Activity Scale: 11 ± 5). No pre-intervention differences existed between the groups (P\u3e0.05). Arm endurance and strength data were collected pre and post intervention using a portable load cell (BTE Evaluator, Hanover, MD). Both within and between group analyses were done in order to investigate average torque (strength) and angular impulse (endurance) changes. RESULTS: The traditional and Advanced Throwers Ten groups both significantly improved torque and angular impulse on both the dominant and non-dominant arms by 10-14%. There were no differences in strength or endurance following the interventions between the two training groups (p\u3e0.75). CONCLUSIONS: Both training approaches increased strength and endurance as the muscle loads were consistent between protocols indicating that either approach will have positive effects. LEVEL OF EVIDENCE: Level 2