Defining the role of NRAS in melanoma maintenance

The incidence of melanoma has increased 600 percent over the last four decades; it is the most rapidly increasing malignancy among young people in the United States and is currently the leading cause of cancer death in women aged 25- 29. If detected early, the disease is easily treated; however, once the disease has metastasized it is largely refractory to conventional therapies and is associated with a high mortality rate. The development of cancer from a pre-malignant primary tumor to a metastatic cancer that develops at secondary sites is a multi-step process, thought to require many genetic and epigenetic events that provide a growth advantage to cells. It is still unclear, however, which of the many genetic changes are required late in tumor progression. The increased incidence of melanoma, combined with the poor prognosis of patients with advanced disease, make it imperative that we increase our understanding of the underlying genetic causes of melanoma such that better targeted therapeutic strategies can be developed

Transfemoral amputation and prosthesis provision in Tanzania: Patient and provider perspectives

BackgroundThe burden of disability because of traumatic limb amputation, particularly transfemoral amputation (TFA) is disproportionately carried by low- and middle-income countries. The need for improved access to prosthesis services in these settings is well-documented, but perspectives on the burden imposed by TFA and the challenges associated with subsequent prosthesis provision vary among patients, caregivers and healthcare providers.ObjectivesTo examine the burden of TFA and barriers to prosthesis provision as perceived by patient, caregiver and healthcare professional, at a single tertiary referral hospital in Tanzania.MethodData were collected from five patients with TFA and four caregivers recruited via convenience sampling, in addition to 11 purposively sampled healthcare providers. All participants participated in in-depth interviews regarding their perceptions of amputation, prostheses and underlying barriers to improving care for persons with TFA in Tanzania. A coding schema and thematic framework were established from interviews using inductive thematic analysis.ResultsAll participants noted financial and psychosocial burdens of amputation, and perceived prostheses as an opportunity for return to normality and independence. Patients worried about prosthesis longevity. Healthcare providers noted significant obstacles to prosthesis provision, including infrastructural and environmental barriers, limited access to prosthetic services, mismatched patient expectations and inadequate coordination of care.ConclusionThis qualitative analysis identifies factors influencing prosthesis-related care for patients with TFA in Tanzania which are lacking in the literature. Persons with TFA and their caregivers experience numerous hardships exacerbated by limited financial, social and institutional support.ContributionThis qualitative analysis informs future directions for research into improving prosthesis-related care for patients with TFA in Tanzania

Perceptions of Orthopaedic Volunteers and Their Local Hosts in Low- and Middle-Income Countries: Are We on the Same Page?

ObjectiveOur goal was to compare the perceptions of overseas orthopaedic volunteers and their hosts in low- and middle-income countries (LMICs) regarding the role of international volunteerism. We also sought to determine if differences in perception exist between trainee and fully trained orthoapedic surgeon volunteers.MethodsSurveys with similar multiple-choice and open-ended questions were administered to 163 Health Volunteers Overseas orthopaedic volunteers (response rate 45%) and 53 members of the host orthopaedic staff (response rate 40%). Fifty-four volunteers and 20 hosts also contributed open-ended responses. Quantitative responses were analyzed for significance using Mantel-Haenzel χ tests. Open-ended responses were coded using thematic analysis.ResultsBoth the international volunteers and their LMIC hosts agreed that volunteers learned new skills while volunteering. Both groups believed that international volunteerism had a positive overall impact on the local practice, but hosts viewed these benefits more favorably than volunteers did. LMIC staff believed that, besides altruistic reasons, volunteers were also motivated by professional gains, diverging from volunteer responses. In open-ended responses, hosts desired longer term commitments from volunteers and had some concerns regarding volunteers' qualifications. Between volunteer trainees and fully trained surgeons, trainees were more likely to be motivated by personal benefits.ConclusionEfforts must be made to further align the expectations and goals of volunteers and their hosts in LMICs. Certain measures such as predeparture orientations for volunteers and developing a more longitudinal and bidirectional experience may enhance the impact of orthopaedic volunteerism in LMICs. Further studies are needed to explore the impact of international orthopaedic volunteerism on the host population

Reliability of Modified Radiographic Union Score for Tibia Scores in the Evaluation of Femoral Shaft Fractures in a Low-resource Setting.

IntroductionThe modified Radiographic Union Score for Tibia (RUST) fractures was developed to better describe fracture healing, but its utility in resource-limited settings is poorly understood. This study aimed to determine the validity of mRUST scores in evaluating fracture healing in diaphyseal femur fractures treated operatively at a single tertiary referral hospital in Tanzania.MethodsRadiographs of 297 fractures were evaluated using the mRUST score and compared with outcomes including revision surgery and EuroQol five dimensions questionnaire (EQ-5D) and visual analog scale (VAS) quality-of-life measures. Convergent validity was assessed by correlating mRUST scores with EQ-5D and VAS scores. Divergent validity was assessed by comparing mRUST scores in patients based on revision surgery status.ResultsThe mRUST score had moderate correlation (Spearman correlation coefficient 0.40) with EQ-5D scores and weak correlation (Spearman correlation coefficient 0.320) with VAS scores. Compared with patients who required revision surgery, patients who did not require revision surgery had higher RUST scores at all time points, with statistically significant differences at 3 months (2.02, P < 0.05).DiscussionThese results demonstrate that the mRUST score is a valid method of evaluating the healing of femoral shaft fractures in resource-limited settings, with high interrater reliability, correlation with widely used quality of life measures (EQ-5D and VAS), and expected divergence in the setting of complications requiring revision surgery

Intramedullary Nailing Versus External Fixation in the Treatment of Open Tibial Fractures in Tanzania: Results of a Randomized Clinical Trial

BACKGROUND: Open tibial fractures are common injuries in low and middle-income countries, but there is no consensus regarding treatment with intramedullary nailing versus external fixation. The purpose of the present study was to compare the outcomes of initial treatment with intramedullary nailing or external fixation in adults with open tibial fractures. METHODS: We conducted a randomized clinical trial (RCT) at a tertiary orthopaedic center in Tanzania. Adults with acute diaphyseal open tibial fractures were randomly assigned to statically locked, hand-reamed intramedullary nailing or uniplanar external fixation. The primary outcome was death or reoperation for the treatment of deep infection, nonunion, or malalignment. Secondary outcomes included quality of life as measured with the EuroQol-5 Dimensions (EQ-5D) questionnaire, radiographic alignment, and healing as measured with the modified Radiographic Union Scale for Tibial fractures (mRUST). RESULTS: Of the 240 patients who were enrolled, 221 (92.1%) (including 111 managed with intramedullary nailing and 110 managed with external fixation) completed 1-year follow-up. There were 44 primary outcome events (with rates of 18.0% and 21.9% in the intramedullary nailing and external fixation groups, respectively) (relative risk [RR] = 0.83 [95% confidence interval (CI), 0.49 to 1.41]; p = 0.505). There was no significant difference between the groups in terms of the rate of deep infection. Intramedullary nailing was associated with a lower risk of coronal malalignment (RR = 0.11 [95% CI, 0.01 to 0.85]; p = 0.01) and sagittal malalignment (RR = 0.17 [95% CI, 0.02 to 1.35]; p = 0.065) at 1 year. The EQ-5D index favored intramedullary nailing at 6 weeks (mean difference [MD] = 0.07 [95% CI = 0.03 to 0.11]; p \u3c 0.001), but this difference dissipated by 1 year. Radiographic healing (mRUST) favored intramedullary nailing at 6 weeks (MD = 1.2 [95% CI = 0.4 to 2.0]; p = 0.005), 12 weeks (MD = 1.0 [95% CI = 0.3 to 1.7]; p = 0.005), and 1 year (MD = 0.8 [95% CI = 0.2 to 1.5]; p = 0.013). CONCLUSIONS: To our knowledge, the present study is the first RCT assessing intramedullary nailing versus external fixation for the treatment of open tibial fractures in sub-Saharan Africa. Differences in primary events were not detected, and only coronal alignment significantly favored the use of intramedullary nailing. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence

Impact of prostheses on quality of life and functional status of transfemoral amputees in Tanzania.

BackgroundThe rise of diabetes and traumatic injury has increased limb loss-related morbidity in low- and middle-income countries (LMICs). Despite this, the majority of amputees in LMICs have no access to prosthetic devices, and the magnitude of prosthesis impact on quality of life (QOL ) and function has not been quantified.ObjectivesQuantify the impact of prostheses on QOL and function in Tanzanian transfemoral amputees.MethodA prospective cohort study was conducted. Transfemoral amputees at Muhimbili Orthopaedic Institute were assessed twice before and three times after prosthetic fitting using EuroQol-5D-3L (EQ-5D-3L), Prosthetic Limb Users Survey of Mobility (PLUS-M), 2-minute walk test (2MWT) and Physiologic Cost Index (PCI). Data were analysed for change over time. Subgroup analysis was performed for amputation aetiology (vascular or non-vascular) and prosthesis use.ResultsAmongst 30 patients, EQ-5D, PLUS-M and 2MWT improved after prosthesis provision (p < 0.001). EuroQol-5D increased from 0.48 to 0.85 at 1 year (p < 0.001). EuroQol-5D and 2MWT were higher in non-vascular subgroup (p < 0.030). At 1-year, 84% of non-vascular and 44% of vascular subgroups reported using their prosthesis (p = 0.068).ConclusionProsthesis provision to transfemoral amputees in an LMIC improved QOL and function. This benefit was greater for non-vascular amputation aetiologies. Quality of life and function returned to pre-prosthesis levels with discontinued use of prosthesis