Purpose To i) identify and map the available evidence regarding effectiveness and harms of spinal manipulation and mobilisation for infants, children and adolescents with a broad range of conditions; ii) identify and synthesise policies, regulations, position statements and practice guidelines informing their clinical use. Design Systematic scoping review, utilising four electronic databases (PubMed, Embase, CINHAL and Cochrane) and grey literature from root to 4th February 2021. Participants Infants, children and adolescents (birth to < 18 years) with any childhood disorder/condition. Intervention Spinal manipulation and mobilisation Outcome measures Outcomes relating to common childhood conditions were explored. Method Two reviewers (A.P., L.L.) independently screened and selected studies, extracted key findings and assessed methodological quality of included papers using Joanna Briggs Institute Checklist for Systematic Reviews and Research Synthesis, Joanna Briggs Institute Critical Appraisal Checklist for Text and Opinion Papers, Mixed Methods Appraisal Tool and International Centre for Allied Health Evidence Guideline Quality Checklist. A descriptive synthesis of reported findings was undertaken using a levels of evidence approach. Results Eighty-seven articles were included. Methodological quality of articles varied. Spinal manipulation and mobilisation are being utilised clinically by a variety of health professionals to manage paediatric populations with adolescent idiopathic scoliosis (AIS), asthma, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), back/neck pain, breastfeeding difficulties, cerebral palsy (CP), dysfunctional voiding, excessive crying, headaches, infantile colic, kinetic imbalances due to suboccipital strain (KISS), nocturnal enuresis, otitis media, torticollis and plagiocephaly. The descriptive synthesis revealed: no evidence to explicitly support the effectiveness of spinal manipulation or mobilisation for any condition in paediatric populations. Mild transient symptoms were commonly described in randomised controlled trials and on occasion, moderate-to-severe adverse events were reported in systematic reviews of randomised controlled trials and other lower quality studies. There was strong to very strong evidence for ‘no significant effect’ of spinal manipulation for managing asthma (pulmonary function), headache and nocturnal enuresis, and inconclusive or insufficient evidence for all other conditions explored. There is insufficient evidence to draw conclusions regarding spinal mobilisation to treat paediatric populations with any condition. Conclusion Whilst some individual high-quality studies demonstrate positive results for some conditions, our descriptive synthesis of the collective findings does not provide support for spinal manipulation or mobilisation in paediatric populations for any condition. Increased reporting of adverse events is required to determine true risks. Randomised controlled trials examining effectiveness of spinal manipulation and mobilisation in paediatric populations are warranted.
236 Background: Heterogeneity in the tumor molecular profile based on race is poorly understood. We sought to review the utilization of next generation sequencing (NGS) in patients with advanced gastrointestinal (GI) malignancies treated at a rural academic center and analyze inter racial variations in the molecular tumor profile. Methods: We conducted a retrospective review of patients with advanced GI malignancies that underwent NGS between 2015 to 2018 at East Carolina University.104 patients met eligibility criteria but 8 patients were excluded due to insufficient tissue sampling. Patients with colorectal, gastric, pancreatic, biliary, small intestinal and esophageal cancers were included. Targeted NGS using Caris Life Sciences¨ platform was performed to obtain molecular analysis. We conducted descriptive univariate analysis, cox regression and Kaplan-Meier survival curve analysis. Results: Median age at diagnosis was 64yrs and 64% of patients were black. The study cohort had 41% (n=39) with colon cancer, 18%(17) gastric cancer, 30% (29) pancreatic cancer, 6%(6) biliary cancer, 4%(4) small intestinal cancer and 1%(1) esophageal cancer. 60% (55) had de novo Stage IV disease. Median overall survival (OS) was 25 months (mo), 30 mo in blacks and 32 mo in whites (p value =0.46). Microsatellite stability was seen in 94% (87) and instability in 3% (3). Overall cohort had mutations (mut) in KRAS (50%), TP53 (64%), BRAF (4%), and ERBB amplification (3%). On the cox regression model APC mutation was associated with worse outcome. Black patients had more alterations in KRAS, TP53 (both not significant), and APC (p=0.02). Conclusions: In our analysis we observed inter racial variations in molecular profile of advanced GI malignancies. Black patients had increased rates of APC, KRAS and TP 53 mut. Further studies are required to analyze the impact of these molecular variations on outcomes. Results. [Table: see text]
2626 Background: Early data suggests that co-occurring genetic events define biological heterogeneity in K-RAS mutant NSCLC, with K-RAS/ TP-53 (KP) co-mutated subset having potential therapeutic vulnerabilities to immune checkpoint blockade (ICB). To explore the immunological basis for these findings, we evaluated the immune biomarker profile (TMB/PD-L1) in KP mutant m-NSCLC using a large next-generation sequencing (NGS) dataset. Methods: Caris life sciences NGS dataset consisting of 1317 m-NSCLC tissue samples from 2016-18 was queried. PD-L1pos was defined as ≥ 1% staining using 22c3 Dako assay. TMB was measured by counting all somatic non-synonymous missense mutations using targeted NGS (592 genes). TMB-high (H) was defined as ≥ 10 mutations/Megabase (mut/Mb). P-values were calculated using Chi-square and Mann-Whitney test. Results: K-RAS mutations were identified in 28.7% (378/1317). Within this K-RAS mutant group, KP subset constituted 49.4% (187/378), remaining were K-RAS mutated/ TP-53 wild type (K-Pwt). 72.2 % (135/187) of KP had PD-L1pos with 51.9% (97/187) having PD-L1 ≥ 50%. KP had higher median TMB vs. K-Pwt (14.5 vs. 9.0 mut/Mb, p<0.001) and higher % of TMB-H vs. K-Pwt (79.9 vs. 45.1%, p<0.001; Table). Even in the PD-L1neg group, KP had higher % of TMB-H vs. K-Pwt (86.5 vs. 41.5%, p<0.001). K-RAS or TP-53 exon-subtypes had no difference in median TMB or % of TMB-H. Across metastatic sites, brain tissue had the highest % of KP subset (38.3%, 68/187) followed by bone (28.9%, 54/187). Within KP subset, brain tissue had higher median TMB vs. bone (16 vs. 11 mut/Mb, p<0.01) as well as greater % of TMB-H vs. bone (86.5 vs. 68.5%, p=0.01). Conclusions: This is the largest dataset to date highlighting the unique immune profile of KP mutant m-NSCLC. Our results show that KP subset has a significantly higher TMB than K-Pwt, especially in the PD-L1neg subgroup. Metastatic site-specific variations in TMB were also observed for the KP subset. These findings could have therapeutic implications in guiding patient selection for ICB and merit prospective investigation.[Table: see text]
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