A Multicenter Phase II, Double-Blind, Placebo-Controlled Trial of Maintenance Ixazomib After Allogeneic Transplantation for High-Risk Multiple Myeloma: Results of the Blood and Marrow Transplant Clinical Trials Network 1302 Trial.

The role of allogeneic hematopoietic cell transplantation (allo-HCT) followed by maintenance therapy in high-risk multiple myeloma (MM) remains controversial. We evaluated the efficacy of ixazomib maintenance therapy after reduced-intensity conditioning allo-HCT from HLA-matched donors in patients with high-risk MM. The primary study endpoint was progression-free survival (PFS) postrandomization, treated as a time to event. Secondary endpoints were grade II-IV and grade II-IV acute graft-versus-host-disease (GVHD), chronic GVHD, best response, disease progression, nonrelapse mortality (NRM), overall survival (OS), toxicity, infection, and health-related quality of life. In this phase 2, double-blinded, prospective multicenter trial, we randomized patients with high-risk MM (ie, those with poor-risk cytogenetics, plasma cell leukemia, or relapsing within 24 months after autologous HCT) to ixazomib (3 mg on days 1, 8, and 15) or placebo after allo-HCT. The conditioning regimen included fludarabine/melphalan/bortezomib with tacrolimus plus methotrexate for GVHD. Fifty-seven patients were enrolled, of whom 52 (91.2%) underwent allo-HCT and 43 (82.7%) were randomized to ixazomib versus placebo. At 21 months postrandomization, the ixazomib and placebo groups had similar PFS (55.3% versus 59.1%; P = 1.00) and OS (94.7% versus 86.4%; P = .17). The cumulative incidences of grade III-IV acute GVHD at 100 days (9.5% versus 0%) and chronic GVHD at 12 months (68.6% versus 63.6%) also were similar in the 2 groups. The secondary analysis showed that at 24 months post-allo-HCT, PFS and OS were 52% and 82%, respectively, with a corresponding NRM of 11.7%. These results demonstrate the safety and durable disease control with allo-HCT in high-risk MM patients. We could not adequately assess the efficacy of ixazomib maintenance because the trial terminated early owing to enrollment delays, but there was no indication of any impact on outcomes.

Prosthetic femoral interposition arthroplasty with adult humeral implant, for children with cerebral palsy and symptomatic hips.

BACKGROUND: Immobile patients with cerebral palsy can suffer with painful dislocated hips. Decision-making and surgical management can prove challenging in this cohort of patients, with hips that cannot be reconstructed. METHODS: We conduced a retrospective chart review of all patients who underwent prosthetic femoral interposition arthroplasty (PFIA) by two surgeons from 2013 to 2021, for unreconstructable hips. We compared pain and range of motion in preoperative period to the postoperative period. Caregiver reported outcomes were used to assess satisfaction post operatively. During the follow up, radiographs of the PFIA were obtained to assess for proximal migration, heterotopic ossification and loosening of implants. RESULTS: Eleven index surgeries, which met the inclusion criteria, were included in this study. These were performed in eleven patients with an average follow up of 45 months. Regarding pain and range of motion post-operatively an excellent or good result was seen in nine cases. Two patients were classified as having a fair result with none having a poor result. Most caregivers reported being satisfied or very satisfied with the post-operative outcomes. CONCLUSION: A prescriptive operative solution to the painful dislocated hip in children with spastic cerebral palsy remains elusive. In this study, we have demonstrated both clinically and radiologically satisfactory results post proximal femoral interposition arthroplasty, for those patients with unreconstructable hips. Patient caregiver reported outcomes, show that the majority of caregivers were satisfied or very satisfied with the outcome of the surgery.

Ubiquitin E3 ligase Atrogin-1 protein is regulated via the rapamycin-sensitive mTOR-S6K1 signaling pathway in C2C12 muscle cells.

Atrogin-1 and Muscle-specific RING finger protein 1 (MuRF1) are highly expressed in multiple conditions of skeletal muscle atrophy. The phosphoinositide 3-kinase (PI3K)/Akt/forkhead box (FoxO) signaling pathway is well known to regulate Atrogin-1 and MuRF1 gene expressions. However, Akt activation also activates the mechanistic target of rapamycin complex 1 (mTORC1), which induces skeletal muscle hypertrophy. Whether mTORC1-dependent signaling has a role in regulating Atrogin-1 and/or MuRF1 gene and protein expression is currently unclear. In this study, we showed that activation of insulin-mediated Akt signaling suppresses both Atrogin-1 and MuRF1 protein contents and that inhibition of Akt increases both Atrogin-1 and MuRF1 protein contents in C2C12 myotubes. Interestingly, inhibition of mTORC1 with a specific mTORC1 inhibitor, rapamycin, increased Atrogin-1, but not MuRF1, protein content. Furthermore, activation of AMP-activated protein kinase (AMPK), a negative regulator of the mTORC1 signaling pathway, also showed distinct time-dependent changes between Atrogin-1 and MuRF1 protein contents, suggesting differential regulatory mechanisms between Atrogin-1 and MuRF1 protein content. To further explore the downstream of mTORC1 signaling, we employed a specific S6K1 inhibitor, PF-4708671. We found that Atrogin-1 protein content was dose-dependently increased with PF-4708671 treatment, whereas MuRF1 protein content was decreased at 50 µM of PF-4708671 treatment. However, MuRF1 protein content was unexpectedly increased by PF-4708671 treatment for a longer period. Overall, our results indicate that Atrogin-1 and MuRF1 protein contents are regulated by different mechanisms, the downstream of Akt, and that Atrogin-1 protein content can be regulated by the rapamycin-sensitive mTOR-S6K1-dependent signaling pathway.

Impact of Center Experience with Donor Type on Outcomes: A Secondary Analysis, Blood and Marrow Transplant Clinical Trials Network 1101Open for Accrual June 2012Open for Accrual June 2012.

We previously reported the results of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1101, a randomized comparison of hematopoietic cell transplantation (HCT) performed with double umbilical cord blood units (dUCB) or with haploidentical bone marrow (haplo-BMT) with post-transplantation cyclophosphamide (PTCy) in the nonmyeloablative setting. Those results showed similar progression-free survival in the 2 treatment groups but lower nonrelapse mortality and better overall survival in the haplo-BM arm. In this secondary analysis, we sought to investigate whether transplantation center's previous experience with haplo-BM and/or dUCB HCT had an impact on outcomes. All patients randomized in BMT CTN 1101 were included. Center experience was assigned based on the number of transplantations with each platform performed in the year before initiation of the study according to the Center for International Blood and Marrow Transplant Research. Centers were then classified as a dUCB center (>10 dUCB HCTs; n = 117 patients, 10 centers), a haplo-BM center (>10 haplo-BM HCTs and ≤10 dUCB HCTs; n = 110 patients, 2 centers), or other center (≤10 haplo and ≤10 dUCB HCTs; n = 140 patients, 21 centers). After adjusting for age, Karnofsky Performance Status, and Disease Risk Index, we found that haplo-BM centers had lower overall mortality with this donor type compared with dUCB centers (hazard ratio [HR], 2.56; 95% confidence interval [CI], 1.44 to 4.56). In contrast, there were no differences in overall mortality between haplo-BM and dUCB in centers that were experienced with dUCB HCT (HR, 1.02; 95% CI, .59 to 1.79) or had limited to no experience with either dUCB or haplo-BM HCT (HR, 1.36; 95% CI, .83 to 2.21). The higher risk of treatment failure and overall mortality in dUCB HCT in haplo BM-experienced centers was driven by a significantly higher risk of relapse (HR, 1.78; 95% CI, 1.07 to 2.97). With the exception of worse outcomes among dUCB HCT recipients in haplo-BM centers, transplantation center experience in the year before initiation of BMT CTN 1101 had a limited impact on the outcomes of this randomized clinical trial.

Intermediate to Long-Term Follow-up of Distal Femoral Replacements in the Treatment of Neoplastic Disease About the Knee.

BACKGROUND: Limb salvage procedures have become more prevalent in orthopedic oncology. Endoprostheses have been used successfully to reconstruct large skeletal deficits. The aim was to review intermediate to long-term follow-up of distal femoral replacements in the setting of neoplastic disease about the knee. METHODS: This was a single-center retrospective cohort study from 1997 to 2018 in a national referral center for oncology. The secondary objectives were to describe morbidity and mortality in this cohort. We recorded the modes of failure using Henderson classification system, complications, revisions, and all further operations. RESULTS: Seventy-two distal femoral replacements were performed. Osteosarcoma was the most common indication (55 patients). Other indications included chondrosarcoma (7 patients), giant cell tumor (5 patients), Ewing's sarcoma (2 patients), metastatic spread (2 patients), and leiomyosarcoma (1 patient). One-year mortality was 1.38% with an overall mortality of 13.8%, at the end of the study period. The 1-year revision rate was 4.2%, 30.5% for 10 years, and 38.8% for more than 15 years. The overall implant survival rate was 63.8%. The most common reasons for failure included aseptic loosening (16.6%), infection (16.6%), and local recurrence (9.7%) with an amputation rate of 6.9% in the cohort. CONCLUSION: Neoplastic disease of the lower limb is associated with significant morbidity. Aseptic loosening (16.6%) and infection (16.6%) were the most common reasons for failure in this cohort.

Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial.

Results of 2 parallel phase 2 trials of transplantation of unrelated umbilical cord blood (UCB) or bone marrow (BM) from HLA-haploidentical relatives provided equipoise for direct comparison of these donor sources. Between June 2012 and June 2018, 368 patients aged 18 to 70 years with chemotherapy-sensitive lymphoma or acute leukemia in remission were randomly assigned to undergo UCB (n = 186) or haploidentical (n = 182) transplant. Reduced-intensity conditioning comprised total-body irradiation with cyclophosphamide and fludarabine for both donor types. Graft-versus-host disease prophylaxis for UCB transplantation was cyclosporine and mycophenolate mofetil (MMF) and for haploidentical transplantation, posttransplant cyclophosphamide, tacrolimus, and MMF. The primary end point was 2-year progression-free survival (PFS). Treatment groups had similar age, sex, self-reported ethnic origin, performance status, disease, and disease status at randomization. Two-year PFS was 35% (95% confidence interval [CI], 28% to 42%) compared with 41% (95% CI, 34% to 48%) after UCB and haploidentical transplants, respectively (P = .41). Prespecified analysis of secondary end points recorded higher 2-year nonrelapse mortality after UCB, 18% (95% CI, 13% to 24%), compared with haploidentical transplantation, 11% (95% CI, 6% to 16%), P = .04. This led to lower 2-year overall survival (OS) after UCB compared with haploidentical transplantation, 46% (95% CI, 38-53) and 57% (95% CI 49% to 64%), respectively (P = .04). The trial did not demonstrate a statistically significant difference in the primary end point, 2-year PFS, between the donor sources. Although both donor sources extend access to reduced-intensity transplantation, analyses of secondary end points, including OS, favor haploidentical BM donors. This trial was registered at www.clinicaltrials.gov as #NCT01597778.

Hepatitis B seroprevalence in the U.S. military and its impact on potential screening strategies.

INTRODUCTION: Knowledge of the contemporary epidemiology of hepatitis B virus (HBV) infection among military personnel can inform potential Department of Defense (DoD) screening policy and infection and disease control strategies. MATERIALS AND METHODS: HBV infection status at accession and following deployment was determined by evaluating reposed serum from 10,000 service members recently deployed to combat operations in Iraq and Afghanistan in the period from 2007 to 2010. A cost model was developed from the perspective of the Department of Defense for a program to integrate HBV infection screening of applicants for military service into the existing screening program of screening new accessions for vaccine-preventable infections. RESULTS: The prevalence of chronic HBV infection at accession was 2.3/1,000 (95% CI: 1.4, 3.2); most cases (16/21, 76%) identified after deployment were present at accession. There were 110 military service-related HBV infections identified. Screening accessions who are identified as HBV susceptible with HBV surface antigen followed by HBV surface antigen neutralization for confirmation offered no cost advantage over not screening and resulted in a net annual increase in cost of $5.78 million. However, screening would exclude as many as 514 HBV cases each year from accession. CONCLUSIONS: Screening for HBV infection at service entry would potentially reduce chronic HBV infection in the force, decrease the threat of transfusion-transmitted HBV infection in the battlefield blood supply, and lead to earlier diagnosis and linkage to care; however, applicant screening is not cost saving. Service-related incident infections indicate a durable threat, the need for improved laboratory-based surveillance tools, and mandate review of immunization policy and practice.

Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial.

BACKGROUND: The RV144 phase 3 vaccine trial in Thailand demonstrated that ALVAC-HIV (vCP1521) and AIDSVAX B/E administration over 6 months resulted in a 31% efficacy in preventing HIV acquisition. In this trial, we assessed the immunological effect of an additional vaccine boost to the RV144 regimen at varying intervals between the priming vaccine series and the boost. METHODS: RV306 is a double-blind, placebo-controlled, randomised clinical trial done at three clinical sites in Thailand. Eligible volunteers were HIV-uninfected individuals aged 20-40 years who were at low risk for HIV infection and in good health. A randomisation schedule was centrally generated with fixed sized strata for Research Institute for Health Sciences Chiang Mai and combined Bangkok clinics. Participants were randomly assigned to one of five groups and then further randomly assigned to either vaccine or placebo. All participants received the primary RV144 vaccine series at months 0, 1, 3, and 6. Group 1 received no additional boost, group 2 received additional AIDSVAX B/E and ALVAC-HIV (vCP1521) or placebo at month 12, group 3 received AIDSVAX B/E alone or placebo at month 12, group 4a received AIDSVAX B/E and ALVAC-HIV or placebo at month 15, and group 4b received AIDSVAX B/E and ALVAC-HIV or placebo at month 18. Primary outcomes were safety and tolerability of these vaccination regimens and cellular and humoral immune responses compared between the RV144 series alone and regimens with late boosts at different timepoints. Safety and tolerability outcomes were assessed by evaluating local and systemic reactogenicity and adverse events in all participants. This trial is registered at ClinicalTrials.gov (NCT01931358); clinical follow-up is now complete. FINDINGS: Between Oct 28, 2013, and April 29, 2014, 367 participants were enrolled, of whom 27 were assigned active vaccination in group 1, 102 in group 2, 101 in group 3, 52 in group 4a, 51 in group 4b, and 34 combined placebo across all the groups. No vaccine-related serious adverse events were recorded. Occurrence and severity of local and systemic reactogenicity were similar across active groups. Groups with late boosts (groups 2, 3, 4a, and 4b) had increased peak plasma IgG-binding antibody levels against gp70 V1V2 relative to group 1 vaccine recipients with no late boost (gp70 V1V2 92TH023 adjusted p<0·02 for each; gp70 V1V2 CaseA2 adjusted p<0·0001 for each). Boosting at month 12 (groups 2 and 3) did not increase gp120 responses compared with the peak responses after the RV144 priming regimen at month 6; however, boosting at month 15 (group 4a) improved responses to gp120 A244gD- D11 (p=0·0003), and boosting at month 18 (group 4b) improved responses to both gp120 A244gD- D11 (p<0·0001) and gp120 MNgD- D11 (p=0·0016). Plasma IgG responses were significantly lower among vaccine recipients boosted at month 12 (pooled groups 2 + 3) than at month 15 (group 4a; adjusted p<0·0001 for each, except for gp70 V1V2 CaseA2, p=0·0142) and at month 18 (group 4b; all adjusted p<0·001). Boosting at month 18 versus month 15 resulted in a significantly higher plasma IgG response to gp120 antigens (all adjusted p<0·01) but not gp70 V1V2 antigens. CD4 functionality and polyfunctionality scores after stimulation with HIV-1 Env peptides (92TH023) increased with delayed boosting. Groups with late boosts had increased functionality and polyfunctionality scores relative to vaccine recipients with no late boost (all adjusted p<0·05, except for the polyfunctionality score in group 1 vs group 4b, p<0·01). INTERPRETATION: Taken together, these results suggest that additional boosting of the RV144 regimen with longer intervals between the primary vaccination series and late boost improved immune responses and might improve the efficacy of preventing HIV acquisition. FUNDING: US National Institute of Allergy and Infectious Diseases and US Department of the Army.

Randomized multicenter trial of sirolimus vs prednisone as initial therapy for standard-risk acute GVHD: the BMT CTN 1501 trial.

Clinical- and biomarker-based tools may identify a lower-risk acute graft-versus-host disease (GVHD) population amenable to novel, reduced-intensity treatments. Previous data suggest sirolimus may rival standard of care prednisone. We conducted a National Heart, Lung, and Blood Institute/National Cancer Institute-funded Blood and Marrow Transplant Clinical Trials Network multicenter, open-label, randomized phase 2 trial to estimate the difference in day 28 complete response (CR)/partial response (PR) rates for sirolimus vs prednisone as initial treatment of patients with standard risk (SR) acute GVHD as defined by the Minnesota (MN) GVHD Risk Score and Ann Arbor (AA1/2) biomarker status. A total of 127 MN-SR patients were randomized (1:1), and 122 were AA1/2 (sirolimus, n = 58; prednisone, n = 64). Others were AA3 (n = 4), or AA status missing (n = 1). The day 28 CR/PR rates were similar for sirolimus 64.8% (90% confidence interval [CI], 54.1%-75.5%) vs 73% (90% CI, 63.8%-82.2%) for prednisone. The day 28 rate of CR/PR with prednisone ≤0.25 mg/kg/day was significantly higher for sirolimus than prednisone (66.7% vs 31.7%; P < .001). No differences were detected in steroid-refractory acute GVHD, disease-free survival, relapse, nonrelapse mortality, or overall survival. Sirolimus was associated with reduced steroid exposure and hyperglycemia, reduced grade 2 to 3 infections, improvement in immune suppression discontinuation and patient-reported quality of life, and increased risk for thrombotic microangiopathy. For patients with clinical- and biomarker-based SR acute GVHD, sirolimus demonstrates similar overall initial treatment efficacy as prednisone. In addition, sirolimus therapy spares steroid exposure and allied toxicity, does not compromise long-term survival outcomes, and is associated with improved patient-reported quality of life. This trial was registered at www.clinicaltrials.gov as #NCT02806947.

Total hip arthroplasty for the treatment of osteoarthritis secondary to acetabular fractures treated by open reduction and internal fixation.

BACKGROUND: Acetabular fractures are associated with damage to the femoral head, acetabular cartilage and labrum and possible disruption of the femoral head blood supply. Treatment aims to provide the best opportunity for restoration of joint function and to prevent long-term complications. Surgical intervention, in the form of open reduction and internal fixation (ORIF), is often required. Where post-traumatic osteoarthritis develops after ORIF, total hip arthroplasty (THA) is often required. Our aim here has been to identify and highlight our experience with the key technical points associated with successful outcomes for THA in this setting. METHODS: A single-centre retrospective review of patients with acetabular fractures treated with ORIF and subsequent THA over a 4-year period was undertaken. Demographics, mechanism of injury, complications, interval time between surgeries, intra-operative outcomes and post-operative outcomes were recorded. Particular emphasis is made to describe standard pre-operative and intra-operative protocols. RESULTS: Twenty-five patients were identified, with a mean age of 51.1 years at time of first ORIF. 60% presented following RTA. 80% of fractures involved the posterior wall or column. Meantime to eventual THA was 2.3 years. Mean THA duration was 1.52 h, with mean intra-operative blood loss and length of stay of 585 ml and 5 days, respectively. 24% required intra-operative removal of metal, with only one patient suffering a complication post-THA. CONCLUSION: Acceptable post-operative outcomes were demonstrated throughout the case series. In describing the pre-operative work up, intra-operative findings and intra-operative and post-operative complications encountered, common important technical points associated with a successful surgical strategy are described. Furthermore, potential pitfalls that may be encountered can be anticipated.

Informing the Consent Process for Surgeons: A Survey Study of Patient Preferences, Perceptions, and Risk Tolerance.

BACKGROUND: Despite the ethical and statutory requirement to obtain consent for surgical procedures, the actual process itself is less well defined. The degree of disclosure and detail expected may vary greatly. A recent shift toward a more patient-centered approach in both clinical and medico-legal practice has significant implications for ensuring appropriate and legal practice in obtaining informed consent before surgery. METHODS: Two hundred patients undergoing elective surgery across two hospitals returned a survey of attitudes toward consent, perceived important elements in the consent process, and risk tolerance, as well as demographic details. RESULTS: No significant associations between patient demographics and survey responses were found. Patients were least concerned with the environment in which consent was taken and the disclosure of uncommon complications. The most important factors related to communication and rapport between clinician and patients, as opposed to procedure- or complication-specific items. A majority of patients preferred risks to be described using proportional descriptors, rather than percentage or non-numeric descriptors. CONCLUSIONS: Risk tolerance and desired level of disclosure varies for each patient and should not be presumed to be covered by standardized proformas. We suggest an individualized approach, taking into account each patient's background, understanding, and needs, is crucial for consent. Communications skills must be prioritized to ensure patient satisfaction and reduced risk of litigation.

Biomarkers of Inflammation Correlate With Clinical Scoring Indices in Human Immunodeficiency Virus-Infected Kenyans.

Background: In high-income countries, inflammation has been associated with increased morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals despite treatment with antiretroviral therapy (ART). However, these findings may not be generalizable to low-income settings. Methods: In this cross-sectional study, multivariable linear regression was used to compare 28 inflammatory biomarker levels in HIV-infected and -uninfected participants. Correlations between biomarkers and Veterans Aging Cohort Study (VACS) index, Fibrosis-4 (FIB-4) score, and Framingham risk score were assessed. Results: Plasma samples from 304 Kenyans were analyzed. Compared to HIV-uninfected controls, virologically suppressed HIV-infected participants had higher levels of CCL5, CXCL10, fatty acid binding protein (FABP) 2, fas ligand (FASLG), matrix metalloproteinase (MMP) 1, MMP7, soluble CD14 (sCD14), and soluble CD163 (sCD163) and lower MMP9 (P < .01). CD4+/HLA-DR+CD38+ (ρ = 0.32; P < .001), sCD14 (ρ = 0.25; P = .004), and sCD163 (ρ = 0.24; P = .006) were correlated with the VACS index. FABP2 was positively correlated (ρ = 0.29; P = .002), whereas MMP1 (ρ = -.32; P < .001) and MMP2 (ρ = -0.28; P = .002) were inversely correlated with the FIB-4 score. Conclusions: Differences in biomarker levels exist between well-controlled HIV-infected participants on ART and uninfected controls. Some biomarkers are correlated to scoring indices predictive of morbidity and mortality. These biomarkers could serve as prognostic indicators and inform therapeutic development.

Reduced-intensity conditioning for hematopoietic cell transplant for HLH and primary immune deficiencies.

Allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning for disorders associated with excessive inflammation such as hemophagocytic lymphohistiocytosis (HLH) is associated with early mortality. A multicenter prospective phase 2 trial of reduced-intensity conditioning with melphalan, fludarabine, and intermediate-timing alemtuzumab was conducted for HLA matched or single HLA locus mismatched related or unrelated donor HCT in a largely pediatric cohort. Graft-versus-host disease (GVHD) prophylaxis was cyclosporine with methylprednisolone. The primary end point was 1-year overall survival (OS). Thirty-four patients with HLH and 12 with other primary immune deficiencies were transplanted. With a median follow-up of 20 months, the 1-year OS for transplanted patients was 80.4% (90% confidence interval [CI], 68.6%-88.2%). Five additional deaths by 16 months yielded an 18-month OS probability of 66.7% (90% CI, 52.9%-77.3%). Two patients experienced primary graft failure, and 18 patients either experienced a secondary graft failure or required a second intervention (mostly donor lymphocyte infusion [DLI]). At 1 year, the proportion of patients alive with sustained engraftment without DLI or second HCT was 39.1% (95% CI, 25.2%-54.6%), and that of being alive and engrafted (with or without DLI) was 60.9% (95% CI, 45.4 %-74.9%). The day 100 incidence of grade II to IV acute GVHD was 17.4% (95% CI, 8.1%-29.7%), and 1-year incidence of chronic GVHD was 26.7% (95% CI, 14.6%-40.4%). Although the trial demonstrated low early mortality, the majority of surviving patients required DLI or second HCT. These results demonstrate a need for future approaches that maintain low early mortality with improved sustained engraftment. The trial was registered at Clinical Trials.gov (NCT 01998633).

Kite surfing: epidemiology of trauma.

Kite surfing has become an increasingly popular recreational activity worldwide. Thrill seekers can span the water at high speeds and reach great heights risking injury and death. We report the case of a young kite surfer who sustained a fracture dislocation of the right acetabulum that required specialised surgical management. We present this case with a review of the literature outlining the incidence of pelvic and acetabular fractures in the kitesurfing community. Overall, there is a low incidence of pelvic fractures in comparison with other orthopaedic traumas reported among kite surfers, and the most commonly injured sites are the foot and ankle. Emergency departments should be alert to this activity and its associated injury patterns due to its ever-increasing popularity.

Easy-to-Read Informed Consent Form for Hematopoietic Cell Transplantation Clinical Trials: Results from the Blood and Marrow Transplant Clinical Trials Network 1205 Study.

Because of the complexity of hematopoietic cell transplant trial treatments, informed consent forms are often long and difficult to read. We evaluated a 2-column easy-to-read informed consent (ETRIC) form that incorporates elements of health literacy and readability in participants and centers participating in Blood and Marrow Transplant Clinical Trials Network (BMT CTN) clinical trials. In a randomized study 198 adult patients from 25 centers potentially eligible to participate in 4 BMT CTN interventional trials were randomized to the ETRIC form or a standard consent form for that trial. Both forms were written at no more than an eighth-grade reading level. The primary endpoint was objective comprehension score on the Quality of Informed Consent, part A (QuIC-A) instrument. In a parallel evaluation study, 2 moderators conducted semistructured interviews of 49 investigators, research staff, and institutional review board (IRB) members at 9 BMT CTN trial sites. The mean QuIC-A scores were comparable in 152 patients (77%) assessable for the primary endpoint (ETRIC form, 80.5; standard form, 81.8; P = .37). In regression analysis there was no significant association between the consent type and QuIC-A score. In the evaluation study dominant themes identified on qualitative analyses included general comfort and willingness to use the ETRIC template and that its formatting and layout enhancements would offer additional value to research participants, investigators, and IRBs. IRB language preferences and requirements, length, and prior experience with alternative consent formats were perceived as barriers. Among patients considering participation in BMT CTN clinical trials, the formatting enhancements of the ETRIC form did not alter comprehension of the trial. Despite local challenges to implementation, trial sites generally viewed the ETRIC form favorably and expressed willingness to use it over standard consent form.

Administration of growth factors promotes salisphere formation from irradiated parotid salivary glands.

Worldwide, 500,000 cases of head and neck cancer (HNC) are reported each year and the primary treatment for HNC is radiotherapy. Although the goal of radiotherapy is to target the tumor, secondary exposure occurs in surrounding normal tissues, such as the salivary glands. As a result, despite successful treatment of the cancer, patients are left with long-term side effects due to direct damage to the salivary glands. The effect is chronic and currently there is no treatment. Stem cells are an attractive therapeutic option for treatment of radiation-induced glandular dysfunction because of the potential to regenerate damaged cell populations and restore salivary gland function. However, limited knowledge about the endogenous stem cell population post irradiation hinders the development for stem cell-based therapies. In this study, an ex vivo sphere formation cell culture system was utilized to assess the self-renewal capacity of cells derived from parotid salivary glands at a chronic time point following radiation. Salivary glands from irradiated mice generate significantly fewer salispheres, but can be stimulated with fetal bovine serum (FBS) to generate an equivalent number of salispheres as unirradiated salivary glands. Interestingly, the number and size of salispheres formed is dependent on the concentration of FBS supplemented into the media. Salispheres derived from irradiated glands and cultured in FBS media were found to contain cells that proliferate and express progenitor and acinar cell markers such as Keratin 5, Keratin 14, Aquaporin 5, and NKCC1. Utilization of insulin-like growth factor (IGF1) injections following radiation treatment restores salivary gland function and improves salisphere generation. These findings indicate that stimulation of these cellular populations may provide a promising avenue for the development of cell-based therapies for radiation-induced salivary gland damage.