BackgroundCell therapies are being investigated as potential disease modifying treatment options for osteoarthritis (OA). Progenza (PRG) comprises in vitro expanded mesenchymal stem cells derived from human donor adipose tissue combined with cell culture supernatant. The primary objective of this first-in-human study was to evaluate the safety and tolerability of PRG.MethodsWe conducted a single centre, randomized, double-blind, placebo-controlled, single ascending dose study. Twenty patients aged 40–65 years with symptomatic Kellgren–Lawrence grade 1–3 knee OA were treated in two cohorts and randomized 4:1 to PRG or placebo. Cohort 1: 3.9 million cells (PRG 3.9M, n = 8) or placebo (n = 2) and cohort 2: 6.7 million cells (PRG 6.7M, n = 8) or placebo (n = 2). Each patient received a single intra-articular injection and was followed-up for 12 months.ResultsThe study population comprised 20 patients (placebo, n = 4; PRG 3.9M, n = 8; PRG 6.7M, n = 8). All patients reported at least one treatment-emergent adverse event (TEAE). The majority of events [143/169 (84.6%)] were mild with 34 (20.1%) being considered by the investigator to be treatment related. There were no serious AEs or withdrawals due to AEs during the study. There was a statistically significant within group improvement in VAS pain scores from baseline at all timepoints for the PRG combined group, with highly significant improvements seen at months 3, 6, 9 and 12 (p ≤ 0.005) while VAS pain scores in the placebo group showed marginal improvement. A statistically significant improvement was also seen in WOMAC pain subscale scores from baseline at all timepoints for the PRG combined group while a marginal improvement in the placebo group was not statistically significant. Between screening and month 12, there was no decrease in average lateral tibial cartilage volume in the PRG 3.9M group while the placebo group showed a statistically significant cartilage loss. This difference between the placebo and PRG 3.9M group was statistically significant (LSM difference 106.47 mm3, 95% CI 13.56 mm3, 199.37 mm3, p = 0.028).ConclusionWhen administered as a single intra-articular injection to patients with symptomatic knee OA, PRG was safe and well tolerated. Furthermore, measurable improvements in symptoms and knee structure outcomes warrant further studies on PRG’s potential for disease modification in OA.Trial registration ANZCTR, ACTRN12615000439549. Date registered: 7th May 2015, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368355Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1420-z) contains supplementary material, which is available to authorized users.

Patient perceived needs are similar to those suggested by clinical guideline recommendations. Better aligning patient perceived needs with healthcare requirements may improve OA outcomes and optimise healthcare system utilisation.

Tibio-femoral joint cartilage defects are more prevalent and of greater severity in individuals who had undergone APMM approximately 44 months earlier than in age-matched controls.

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ObjectivesSleep disorders are common in patients with HIV/AIDS, and can lead to poor quality of life. Although many studies have investigated the aetiology of these disorders, it is still unclear whether impaired sleep quality is associated with HIV itself, social problems, or side effects of antiretroviral therapy (ART). Moreover, despite its known neurological associations, little is known about the role of the trans-activator of transcription (Tat) protein in sleep disorders in patients with HIV/AIDS. The purpose of this study was to test the hypothesis that the sleep quality of patients with HIV/AIDS affected by an altered circadian rhythm correlates with cerebrospinal HIV Tat protein concentration.MethodsNinety-six patients with HIV/AIDS between 20 and 69 years old completed the Pittsburgh Sleep Quality Index. Their circadian rhythm parameters of blood pressure, Tat concentration in cerebrospinal fluid, melatonin concentration, CD4 cell count and HIV RNA viral load in serum were measured.ResultsThe circadian amplitude of systolic blood pressure and the score for sleep quality (Pittsburgh Sleep Quality Index) were negatively correlated with HIV Tat protein concentration, while the melatonin value was positively correlated with Tat protein concentration.ConclusionsThe HIV Tat protein affects circadian rhythmicity by interfering with the circadian system in patients with HIV/AIDS and further increases the melatonin excretion value. A Tat protein-related high melatonin value may counteract HIV-related poor sleep quality during the progression of HIV infection. This study provides the first clinical evidence offering an explanation for why sleep quality did not show an association with progression of HIV infection in previous studies.

Purpose: Although obesity is a risk factor for hip osteoarthritis (OA), the role of body composition, if any, is unclear. This study examines whether obesity and body composition are associated with hip cartilage changes using magnetic resonance imaging (MRI) in community-based adults. Methods: 141 community-based participants with no clinical hip disease, including OA, had BMI and body composition (fat mass and fat free mass) measured at baseline (1990 to 1994), and BMI measured and 3.0T MRI performed at follow-up (2009-2010). Femoral head cartilage volume was measured and femoral head cartilage defects were scored in the different hip regions. Results: For females, baseline BMI (b¼-26mm 3 , 95% CI-47 to-6mm 3 , p¼0.01) and fat mass (b¼-11mm 3 , 95% CI-21 to-1mm 3 , p¼0.03) were negatively associated with femoral head cartilage volume. Also, while increased baseline fat mass was associated with an increased risk of cartilage defects in the central superolateral region of the femoral head (OR¼ 1.08, 95% CI 1.00-1.15, p¼0.04), increased baseline fat free mass was associated with a reduced risk of cartilage defects in this region (OR¼0.82, 95% CI 0.67-0.99; p¼0.04). For males, baseline fat free mass was associated with increased femoral head cartilage volume (b¼ 40mm 3 , 95% CI 6 to 74mm 3 , p¼0.02) Conclusions: Increased fat mass was associated with adverse hip cartilage changes for females, while increased fat free mass was associated with beneficial cartilage changes for both genders. Further work is required to determine whether modifying obesity and in particular body composition alters the development of hip OA.

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Purpose: Although obesity is a risk factor for hip osteoarthritis (OA), the role of body composition, if any, is unclear. This study examines whether obesity and body composition are associated with hip cartilage changes using magnetic resonance imaging (MRI) in community-based adults. Methods: 141 community-based participants with no clinical hip disease, including OA, had BMI and body composition (fat mass and fat free mass) measured at baseline (1990 to 1994), and BMI measured and 3.0T MRI performed at follow-up (2009-2010). Femoral head cartilage volume was measured and femoral head cartilage defects were scored in the different hip regions. Results: For females, baseline BMI (b¼-26mm 3 , 95% CI-47 to-6mm 3 , p¼0.01) and fat mass (b¼-11mm 3 , 95% CI-21 to-1mm 3 , p¼0.03) were negatively associated with femoral head cartilage volume. Also, while increased baseline fat mass was associated with an increased risk of cartilage defects in the central superolateral region of the femoral head (OR¼ 1.08, 95% CI 1.00-1.15, p¼0.04), increased baseline fat free mass was associated with a reduced risk of cartilage defects in this region (OR¼0.82, 95% CI 0.67-0.99; p¼0.04). For males, baseline fat free mass was associated with increased femoral head cartilage volume (b¼ 40mm 3 , 95% CI 6 to 74mm 3 , p¼0.02) Conclusions: Increased fat mass was associated with adverse hip cartilage changes for females, while increased fat free mass was associated with beneficial cartilage changes for both genders. Further work is required to determine whether modifying obesity and in particular body composition alters the development of hip OA.