A Phase I Study of Abiraterone Acetate Combined with BEZ235, a Dual PI3K/mTOR Inhibitor, in Metastatic Castration Resistant Prostate Cancer.

Lessons Learned: The combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.Although the clinical development of BEZ235 has been discontinued in prostate cancer, agents that more selectively target PI3K-AKT-mTOR signaling may have a more favorable therapeutic index and should continue to be explored.

Background: Androgen receptor (AR) and phosphatidylinositol-3 kinase (PI3K) signaling are two commonly perturbed pathways in prostate cancer.

Autoimmune limbic encephalitis with anti-contactin-associated protein-like 2 antibody secondary to pembrolizumab therapy.

Immune checkpoint inhibitors such as Pembrolizumab are used to restore antitumour immune response. It is important to be vigilant of immune mediated adverse events related to such therapy. We report a case of autoimmune limbic encephalitis with Contactin-Associated Protein-like 2 (CASPR2) antibody secondary to Pembrolizumab therapy for metastatic melanoma.

Pre-treatment serum lactate dehydrogenase as a biomarker in small cell lung cancer.

Background: Small cell lung cancer is a rapidly progressive disease with high fatality. No sensitive and specific biomarker to assist in managing this disease exists currently.

Aim: Role of pretreatment serum lactate dehydrogenase as a biomarker in small cell lung cancer.

A Biomechanical Comparison of Allograft Tendons for Ligament Reconstruction.

Background: Allograft tendons are frequently used for ligament reconstruction about the knee, but they entail availability and cost challenges. The identification of other tissues that demonstrate equivalent performance to preferred tendons would improve limitations. Hypothesis/Purpose: We compared the biomechanical properties of 4 soft tissue allograft tendons: tibialis anterior (TA), tibialis posterior (TP), peroneus longus (PL), and semitendinosus (ST).

Effects of sex and generation on hepatitis B viral load in families with hepatocellular carcinoma.

Aim: To explore factors associated with persistent hepatitis B virus (HBV) infection in a cohort of hepatocellular carcinoma (HCC)-affected families and then investigate factors that correlate with individual viral load among hepatitis B surface antigen (HBsAg)-positive relatives.

Methods: We evaluated non-genetic factors associated with HBV replication in relatives of patients with HCC. Relatives of 355 HCC cases were interviewed using a structured questionnaire.

When Should We Change Drill Bits? A Mechanical Comparison of New, Reprocessed, and Damaged Bits.

Objectives: We assessed how reprocessed and damaged drill bits perform relative-to-new drill bits in terms of drilling force required, heat generated at near and far cortices, and number of usable passes.

Methods: Nine pairs of nonosteoporotic human cadaveric femora were tested using 3 types of 3.2-mm drill bits (new, reprocessed, and damaged) in 3 investigations (force, temperature, and multiple usable passes).

Risk of cumulative toxicity after complete melanoma response with pembrolizumab.

Pembrolizumab is an approved first-line systemic therapy for unresectable metastatic melanoma. Despite the achievement of complete and durable responses in a small subgroup of patients, it is standard practice that pembrolizumab therapy continues beyond complete response. Nevertheless, the incidence of immune-related toxicities gradually increases with continuing pembrolizumab therapy.

Deformability of Human Mesenchymal Stem Cells Is Dependent on Vimentin Intermediate Filaments.

Mesenchymal stem cells (MSCs) are being studied extensively due to their potential as a therapeutic cell source for many load-bearing tissues. Compression of tissues and the subsequent deformation of cells are just one type physical strain MSCs will need to withstand in vivo. Mechanotransduction by MSCs and their mechanical properties are partially controlled by the cytoskeleton, including vimentin intermediate filaments (IFs).

Biomechanical Comparison of Cadaveric and Commercially Available Synthetic Osteoporotic Bone Analogues in a Locked Plate Fracture Model Under Torsional Loading.

Objectives: Biomechanical studies of osteoporotic bone have used synthetic models rather than cadaveric samples because of decreased variability, increased availability, and overall ease of the use of synthetic models. We compared the torsional mechanical properties of cadaveric osteoporotic bone with those of currently available synthetic osteoporotic bone analogues.

Methods: We tested 12 osteoporotic cadaveric humeri and 6 specimens each of 6 types of synthetic analogues.

Net Budgetary Impact of Ferric Citrate as a First-Line Phosphate Binder for the Treatment of Hyperphosphatemia: A Markov Microsimulation Model.

Ferric citrate (FC) has demonstrated efficacy as a phosphate binder and reduces the requirements for erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron in dialysis patients. We developed a net budgetary impact model to evaluate FC vs. other phosphate binders from the vantage of a large dialysis provider.

A safe and accurate method to perform esthetic mandibular contouring surgery for Far Eastern Asians.

A tapered mandibular contour is popular with Far Eastern Asians. This study describes a safe and accurate method of using preoperative virtual surgical planning (VSP) and an intraoperative ostectomy guide to maximize the esthetic outcomes of mandibular symmetry and tapering while mitigating injury to the inferior alveolar nerve (IAN). Twelve subjects with chief complaints of a wide and square lower face underwent this protocol from January to June 2015.

Preeclampsia and Long-term Risk of Maternal Retinal Disorders.

Objective: To evaluate whether preeclampsia is associated with risk of maternal retinal disease in the decades after pregnancy.

Methods: We carried out a longitudinal cohort study of 1,108,541 women who delivered neonates in any hospital in Quebec, Canada, between 1989 and 2013. We tracked women for later hospitalizations until March 31, 2014.

Preeclampsia and the risk of cataract extraction in life.

Background: Pregnancy-related risk factors for cataract are understudied, including the possibility that preeclampsia increases the risk of cataract later in life.

Objective: We sought to evaluate the long-term risk of cataract extraction following a preeclamptic pregnancy.

Study Design: We carried out a historic cohort study of 1,108,541 women who delivered at least 1 infant in any hospital in the province of Quebec, Canada, from 1989 through 2013, including 64,350 with preeclampsia and 5732 with cataract extractions.

Influence of Transplant Center Procedural Volume on Survival Outcomes of Heart Transplantation for Children Bridged with Mechanical Circulatory Support.

Transplant center expertise improves survival after heart transplant (HTx) but it is unknown whether center expertise ameliorates risk associated with mechanical circulatory support (MCS) bridge to transplantation. This study investigated whether center HTx volume reduced survival disparities among pediatric HTx patients bridged with extracorporeal membrane oxygenation (ECMO), left ventricular assist device (LVAD), or no MCS. Patients ≤18 years of age receiving first-time HTx between 2005 and 2015 were identified in the United Network of Organ Sharing registry.

Relationship Between Age and Trajectories of Rehospitalization Risk in Older Adults.

Objectives: To characterize the magnitude and duration of risk of rehospitalization according to age after hospitalization for heart failure (HF), acute myocardial infarction (AMI), or pneumonia.

Design: Retrospective cohort study.

Setting: U.

Ultrasonic Structural Health Monitoring to Assess the Integrity of Spinal Growing Rods In Vitro.

Background: Rod fracture is a common complication of growing rods and can result in loss of correction, patient discomfort, and unplanned revision surgery. The ability to quantitate rod integrity at each lengthening would be advantageous to avoid this complication. We investigate the feasibility of applying structural health monitoring to evaluate the integrity of growing rods in vitro.

Biomechanical and Cost Comparisons of Near-Far and Pin-Bar Constructs.

Orthopedic dogma states that external fixator stiffness is improved by placing 1 pin close to the fracture and 1 as distant as possible ("near-far"). This fixator construct is thought to be less expensive than placing pins a shorter distance apart and using "pin-bar" clamps that attach pins to outriggers. The authors therefore hypothesized that the near-far construct is stiffer and less expensive.

Trajectories of Risk for Specific Readmission Diagnoses after Hospitalization for Heart Failure, Acute Myocardial Infarction, or Pneumonia.

Background: The risk of rehospitalization is elevated in the immediate post-discharge period and declines over time. It is not known if the extent and timing of risk vary across readmission diagnoses, suggesting that recovery and vulnerability after discharge differ by physiologic system.

Objective: We compared risk trajectories for major readmission diagnoses in the year after discharge among all Medicare fee-for-service beneficiaries hospitalized with heart failure (HF), acute myocardial infarction (AMI), or pneumonia from 2008-2010.

Layered Alginate Constructs: A Platform for Co-culture of Heterogeneous Cell Populations.

Many load bearing tissues possess structurally and functionally distinct regions, typically accompanied by different cell phenotypes with differential mechanosensing characteristics. Engineering and analysis of these tissue types remain a challenge. Layered hydrogel constructs provide an opportunity for investigating the interactions among multiple cell populations within single constructs.

MYC, Metabolic Synthetic Lethality, and Cancer.

The MYC oncogene plays a pivotal role in the development and progression of human cancers. It encodes a transcription factor that has broad reaching effects on many cellular functions, most importantly in driving cell growth through regulation of genes involved in ribosome biogenesis, metabolism, and cell cycle. Upon binding DNA with its partner MAX, MYC recruits factors that release paused RNA polymerases to drive transcription and amplify gene expression.

Vedolizumab: a novel treatment for ipilimumab-induced colitis.

Use of the immune checkpoint inhibitors, ipilimumab and nivolumab, has revolutionised treatment in patients with metastatic melanoma. However, these drugs can cause an autoimmune enterocolitis, with diarrhoea as the presenting symptom. This is conventionally managed by prompt institution of corticosteroid therapy if moderate diarrhoea (3-6 times/day; grade 2) is present for >5 days or if diarrhoea is severe (>6 times/day; grade 3).