Immune heterogeneity in small-cell lung cancer and vulnerability to immune checkpoint blockade.

Atezolizumab (anti-PD-L1), combined with carboplatin and etoposide (CE), is now a standard of care for extensive-stage small-cell lung cancer (ES-SCLC). A clearer understanding of therapeutically relevant SCLC subsets could identify rational combination strategies and improve outcomes. We conduct transcriptomic analyses and non-negative matrix factorization on 271 pre-treatment patient tumor samples from IMpower133 and identify four subsets with general concordance to previously reported SCLC subtypes (SCLC-A, -N, -P, and -I). Deeper investigation into the immune heterogeneity uncovers two subsets with differing neuroendocrine (NE) versus non-neuroendocrine (non-NE) phenotypes, demonstrating immune cell infiltration hallmarks. The NE tumors with low tumor-associated macrophage (TAM) but high T-effector signals demonstrate longer overall survival with PD-L1 blockade and CE versus CE alone than non-NE tumors with high TAM and high T-effector signal. Our study offers a clinically relevant approach to discriminate SCLC patients likely benefitting most from immunotherapies and highlights the complex mechanisms underlying immunotherapy responses.

The prevalence and determinants of physical activity promotion by Australian chiropractors: A cross sectional study.

BACKGROUND: Approximately one in four adults do not meet the World Health Organisation physical activity recommendations. While health promotion (i.e., physical activity) is common within chiropractic settings, little is known about chiropractors discussing this public health issue with their patients. The aim of our study is to examine the prevalence and characteristics of Australian chiropractors who frequently discuss patient physical activity. METHODS: A national cross-sectional survey of chiropractors focusing upon practitioner characteristics, practice settings and clinical management characteristics. Regression analyses were conducted on 1924 survey respondents to identify factors associated with practitioners who frequently discuss physical activity with patients. RESULTS: Eighty-five percent of Australian chiropractors reported 'often' discussing physical activity as part of their patient management. The strongest factors associated with chiropractors who frequently discuss physical activity obtained from the multivariate analysis include: often discussing occupational health and safety (odds ratio [OR] = 6.10; 95%CI: 3.88, 9.59), often discussing diet/nutrition (OR = 4.56; 95%CI: 3.12, 6.66), often discussing smoking/drugs/alcohol (OR = 4.41; 95%CI: 2.06, 9.40), often use of specific exercise therapy/rehabilitation/injury taping (OR = 3.76; 95%CI: 2.62, 5.39) and often caring for athletes or sports people (OR = 2.18; 95%CI: 1.56, 3.06) within their practice setting. CONCLUSION: Discussing physical activity is a frequent feature of patient management among most chiropractors in Australia. The association between these practitioners and discussion of other costly public health burdens could suggest chiropractors have a valuable role to play in chronic disease prevention. Given the growing need for practitioner-led promotion of patient physical activity further research examination of the role and contribution of chiropractors in promoting this important public health topic among patients and communities is needed.

Surgery or physical activity in the management of sciatica: a systematic review and meta-analysis.

PURPOSE: Previous reviews have compared surgical to non-surgical management of sciatica, but have overlooked the specific comparison between surgery and physical activity-based interventions. METHODS: Systematic review using MEDLINE, CINAHL, Embase and PEDro databases was conducted. Randomised controlled trials comparing surgery to physical activity, where patients were experiencing the three most common causes of sciatica-disc herniation, spondylolisthesis and spinal stenosis. Two independent reviewers extracted pain and disability data (converted to a common 0-100 scale) and assessed methodological quality using the PEDro scale. The size of the effects was estimated for each outcome at three different time points, with a random effects model adopted and the GRADE approach used in summary conclusions. RESULTS: Twelve trials were included. In the short term, surgery provided better outcomes than physical activity for disc herniation: disability [WMD -9.00 (95 % CI -13.73, -4.27)], leg pain [WMD -16.01 (95 % CI -23.00, -9.02)] and back pain [WMD -12.44 (95 % CI -17.76, -7.09)]; for spondylolisthesis: disability [WMD -14.60 (95 % CI -17.12, -12.08)], leg pain [WMD -35.00 (95 % CI -39.66, -30.34)] and back pain [WMD -20.00 (95 % CI -24.66, -15.34)] and spinal stenosis: disability [WMD -11.39 (95 % CI -17.31, -5.46)], leg pain [WMD, -27.17 (95 % CI -35.87, -18.46)] and back pain [WMD -20.80 (95 % CI -25.15, -16.44)]. Long-term and greater than 2-year post-randomisation results favoured surgery for spondylolisthesis and stenosis, although the size of the effects reduced with time. For disc herniation, no significant effect was shown for leg and back pain comparing surgery to physical activity. CONCLUSION: There are indications that surgery is superior to physical activity-based interventions in reducing pain and disability for disc herniation at short-term follow-up only; but high-quality evidence in this field is lacking (GRADE). For spondylolisthesis and spinal stenosis, surgery is superior to physical activity up to greater than 2 years follow-up. Results should guide clinicians and patients when facing the difficult decision of having surgery or engaging in active care interventions. PROSPERO registration number : CRD42013005746.