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IntroductionPain, comorbid fatigue and sleep disturbances are common and distressing symptoms for patients with advanced cancer, negatively impacting their quality of life. Clinical guidelines recommend non-pharmacological interventions, including acupuncture and massage, for pain management in adult patients with cancer in adjunct to conventional care. However, high-quality evidence about the comparative effectiveness and long-term durability of these therapies for symptom management is limited.Methods and analysisWe describe the design of a two-arm, parallel group, multicentre randomised controlled trial that investigates the use of acupuncture versus massage for musculoskeletal pain among 300 patients with diverse types of advanced cancer. The primary aim is to evaluate the long-term effectiveness (26 weeks from randomisation) of acupuncture vs massage for pain (primary outcome) and comorbid symptoms (fatigue, sleep disturbance and quality of life). The secondary aim is to identify patient-level demographic characteristics (eg, sex, race, age), clinical factors (eg, insomnia, pain severity) and psychological attributes that are associated with a greater reduction in pain for either acupuncture or massage. Patients will receive weekly acupuncture or massage treatments for 10 weeks, followed by monthly booster sessions up to 26 weeks. The primary endpoint will be the change in worst pain intensity score from baseline to 26 weeks. We will collect validated patient-reported outcomes at multiple time points over 26 weeks.Ethics and disseminationThe Institutional Review Board at Memorial Sloan Kettering Cancer Center in New York approved this protocol. Results will be disseminated via peer-reviewed scientific journals and conference presentations. Our findings will help patients and healthcare providers make informed decisions about incorporating non-pharmacological treatments to manage pain for patients with advanced cancer.Trial registration numberNCT04095234.

Background: High-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT) is associated with a high symptom burden including sleep disturbance. Here we present the results of a secondary analysis of a randomized, sham-controlled trial assessing the effect of acupuncture on sleep quality during HSCT. Methods: Adult multiple myeloma patients undergoing inpatient and outpatient autologous HSCT were randomized and blinded to receive either true or sham acupuncture (by licensed acupuncturists) once daily for 5 days starting the day after chemotherapy. Sleep onset, total sleep time, sleep efficiency percentage and sleep-onset latency time were assessed using an actigraphy-based sleep monitor. A multivariate regression analysis was conducted to compare the average area-under-the-curve of five acupuncture intervention days for each sleep outcome between groups, adjusted by baseline score and inpatient or outpatient chemotherapy stratum. Results: Over 32 months, 63 patients were enrolled. Participants undergoing true acupuncture experienced a significant improvement in sleep efficiency when compared to sham (−6.70, 95% CI −13.15, −0.25, p = 0.042). Subgroup analysis showed that the improvement was more prominent in the inpatient setting (−9.62, 95% CI −18.76, −0.47; p = 0.040). True acupuncture tended to improve wake time after sleep onset (WASO; −10.95, p = 0.054). Between-group differences in other sleep related variables were not statistically significant. Conclusion: Our data suggest that true acupuncture may improve certain aspects of sleep, including sleep efficiency and possibly WASO, in multiple myeloma patients undergoing HSCT. By studying patient reported outcomes in future larger scale studies, acupuncture's role in improving sleep quality during HSCT treatment could be further elucidated. Trial registration number: NCT01811862 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

The integrins and G protein-coupled receptors are both fundamental in cell biology. The cross talk between these two, however, is unclear. Here we show that β3 integrins negatively regulate G protein-coupled signaling by directly inhibiting the Gα13-p115RhoGEF interaction. Furthermore, whereas β3 deficiency or integrin antagonists inhibit integrin-dependent platelet aggregation and exocytosis (granule secretion), they enhance G protein-coupled RhoA activation and integrin-independent secretion. In contrast, a β3-derived Gα13-binding peptide or Gα13 knockout inhibits G protein-coupled RhoA activation and both integrin-independent and dependent platelet secretion without affecting primary platelet aggregation. In a mouse model of myocardial ischemia/reperfusion injury in vivo, the β3-derived Gα13-binding peptide inhibits platelet secretion of granule constituents, which exacerbates inflammation and ischemia/reperfusion injury. These data establish crucial integrin-G protein crosstalk, providing a rationale for therapeutic approaches that inhibit exocytosis in platelets and possibly other cells without adverse effects associated with loss of cell adhesion. Zhang et al. show that the adhesion receptor integrin β3 directly inhibits G protein mediated RhoA activation and granule secretion. A peptide mimicking this effect selectively inhibits platelet secretion but not integrin-mediated platelet adhesion. [ABSTRACT FROM AUTHOR]