Evaluation of platelet-rich plasma in combination with anorganic bovine bone in the rabbit cranium: a pilot study

PURPOSE: Platelet-rich plasma (PRP) is potentially useful as an adjunct to allograft and xenograft materials in oral and maxillofacial bone and implant reconstructive surgery. This study compares bone healing and formation in 4 cranial defects in rabbits grafted with autogenous bone, xenograft, and xenograft with PRP (with a no-graft group as a control). MATERIALS AND METHODS: Fifteen New Zealand white rabbits were included in this randomized, blind, prospective pilot study. Four identical 8-mm-diameter defects were created in each rabbit cranium and immediately grafted with the above materials. Five rabbits were evaluated at 1 month, 5 at 2 months, and 5 at 4 months. Radiographs were used to evaluate bone density. RESULTS: Radiographically, sites at which Bio-Oss, autogenous bone, and Bio-Oss + PRP were grafted showed a significant increase in bone density at 1 month (P = .05 for Bio-Oss, P = .02 for autogenous bone, P = .008 for Bio-Oss + PRP) and at 4 months (P = .02 for Bio-Oss, P = .04 for autogenous bone, P = .05 for Bio-Oss + PRP). Autogenous bone sites (P < .001) and Bio-Oss + PRP sites (P < .001) also showed significant increases at 2 months. Histomorphometrically, autogenous bone sites showed a significantly greater increase than control sites (P = .08 at 1 month, P = .03 at 2 months, P = .01 at 4 months), Bio-Oss sites (P < .001 at all 3 evaluation points), or Bio-Oss + PRP sites (P = .009 at 1 month, P = .02 at 2 months, P = .01 at 4 months). Furthermore, Bio-Oss + PRP sites showed a significantly greater increase in bone area at 1, 2, and 4 months than Bio-Oss alone (P = .003 at 1 month, P = .02 at 2 months, P = .006 at 4 months). DISCUSSION: Radiographs showed significantly greater bone density at the Bio-Oss, autogenous bone, and Bio-Oss + PRP sites than at control sites at nearly every point in time evaluated; however, clinical significance is difficult to determine, since all materials appeared dense on the radiograph. Histomorphometry showed that the increase in bone area at autogenous sites was significantly greater than that seen with other grafting materials or at the control sites. CONCLUSION: This study showed a histomorphometric increase in bone formation with the addition of PRP to Bio-Oss in non-critical-sized defects in the rabbit cranium.     

Cardiomyopathies and Genetic Testing in Heart Failure: Role in Defining Phenotype-Targeted Approaches and Management

Cardiomyopathies represent an important cause of heart failure, often affecting young individuals, and have important implications for relatives. Genetic testing for cardiomyopathies is an established care pathway in contemporary cardiology practice. The primary cardiomyopathies where genetic testing is indicated are hypertrophic, dilated, arrhythmogenic, and restrictive cardiomyopathies, with left ventricular noncompaction as a variant phenotype. Early identification and initiation of therapies in patients with inherited cardiomyopathies allow for targeting asymptomatic and presymptomatic patients in stages A and B of the American College of Cardiology/American Heart Association classification of heart failure. The current approach for genetic testing uses gene panel–based testing with the ability to extend to whole-exome and whole-genome sequencing in rare instances. The central components of genetic testing include defining the genetic basis of the diagnosis, providing prognostic information, and the ability to screen and risk-stratify relatives. Genetic testing for cardiomyopathies should be coordinated by a multidisciplinary team including adult and pediatric cardiologists, genetic counsellors, and geneticists, with access to expertise in cardiac imaging and electrophysiology. A pragmatic approach for addressing genetic variants of uncertain significance is important. In this review, we highlight the indications for genetic testing in the various cardiomyopathies, the value of early diagnosis and treatment, family screening, and the care process involved in genetic counselling and testing.     

The efficacy and toxicity of immune checkpoint inhibitors in a real-world older patient population

ImportanceImmunotherapy has emerged as an effective treatment option for the management of advanced cancers. The effects of these immune checkpoint inhibitors in the older patient population has not been adequately assessed.ObjectiveTo understand the impact of aging on CTLA-4 and PDL-1 inhibitors efficacy and immune-related adverse events (irAE) in the context of real-world management of advanced solid cancers.Design, Setting, and ParticipantsThis retrospective study involved all non-study patients with histologically-confirmed metastatic or inoperable solid cancers receiving immunotherapy at Kingston Health Sciences Centre. We defined ‘older patient’ as age ≥ 75. All statistical analyses were conducted under SPSS IBM for Windows version 24.0.Main Outcomes and MeasuresStudy outcomes included immunotherapy treatment response, survival, as well as number, type, and severity of irAEs.ResultsOur study (N = 78) had 29 (37%) patients age <65, 26 (33%) patients age 65–74, and 23 (30%) patients age ≥75. Melanoma, non-small cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the study population, respectively. Distributions of ipilimumab (32%), nivolumab (33%), and pembrolizumab (35%) were similar in the study. The response rates were 28%, 27%, and 39% in the age <65, age 64–74, age ≥75 groups, respectively (P = 0.585). Kaplan-Meier curve showed a median survival of 28 months (12.28–43.9, 95% CI) and 17 months (0–36.9, 95% CI) in the age <65 and age 64–74 groups, respectively; the estimated survival probability did not reach 50% in the age ≥75 group (P = 0.319). There were no statistically significant differences found in terms of irAEs, multiple irAEs, severity of grade 3 or higher, types of irAEs, and irAEs resolution status when comparing between different age groups.Conclusion and RelevanceOur results suggest that patients age ≥75 are able to gain as much benefit from immunotherapy as younger patients, without excess toxicity. Our findings suggest that single agent immunotherapy is generally well-tolerated across different age groups with no significant difference in the type, frequency or severity of irAEs. Future studies evaluating aging and combination immunotherapy are warranted.     

Youth,violence and non-injection drug use: nexus of vulnerabilities among lesbian and bisexual sex workers

Despite increasing evidence of enhanced HIV risk among sexual minority populations, and sex workers (SWs) in particular, there remains a paucity of epidemiological data on the risk environments of SWs who identify as lesbian or bisexual. Therefore, this short report describes a study that examined the individual, interpersonal and structural associations with lesbian or bisexual identity among SWs in Vancouver, Canada. Analysis drew on data from an open prospective cohort of street and hidden off-street SWs in Vancouver. Bivariate and multivariable logistic regressions were used to examine the independent relationships between individual, interpersonal, work environment and structural factors and lesbian or bisexual identity. Of the 510 individuals in our sample, 95 (18.6%) identified as lesbian or bisexual. In multivariable analysis, reporting non-injection drug use in the last six months (adjusted odds ratio [AOR] = 2.89; 95% confidence intervals [CI] = 1.42, 5.75), youth ≤24 years of age (AOR = 2.43; 95% CI = 1.24, 4.73) and experiencing client-perpetrated verbal, physical and/or sexual violence in the last six months (AOR = 1.85; 95% CI = 1.15, 2.98) remained independently associated with lesbian/bisexual identity, after adjusting for potential confounders. The findings demonstrate an urgent need for evidence-based social and structural HIV prevention interventions. In particular, policies and programmes tailored to lesbian and bisexual youth and women working in sex work, including those that prevent violence and address issues of non-injection stimulant use are required.