Phase Ib study of combinations of avadomide (CC-122), CC-223, CC-292, and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma.

There is a need for additional treatment options for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who do not benefit from available therapies. We examined combinations of the cereblon E3 ligase modulator (CELMoD) agent avadomide (CC-122), the selective, ATP-competitive mammalian target of rapamycin kinase inhibitor CC-223, and the potent, selective, covalent Bruton tyrosine kinase inhibitor CC-292 in patients with relapsed/refractory (R/R) DLBCL. In the multicenter, phase Ib CC-122-DLBCL-001 study (NCT02031419), the dose-escalation portion explored combinations of CC-122, CC-223, and CC-292 administered as doublets or triplets with rituximab in patients with chemorefractory DLBCL.

Phase Ib study of avadomide (CC-122) in combination with rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma.

The multicenter, phase Ib CC-122-DLBCL-001 dose-expansion study (NCT02031419) explored the cereblon E3 ligase modulator (CELMoD) agent avadomide (CC-122) plus rituximab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Patients received avadomide 3 mg/day 5 days on/2 days off plus rituximab 375 mg/m on day 8 of cycle 1, day 1 of cycles 2 through 6, and day 1 of every third subsequent cycle for 2 years. Primary endpoints were safety and tolerability; preliminary efficacy was a secondary endpoint.

Lumbar Spine Fusion Surgery in Solid Organ Transplant Recipients Is Associated With Increased Medical Complications and Mortality.

Study Design: Retrospective database review.

Objective: To characterize the outcomes of solid organ transplant (SOT) patients after one- or two-level lumbar fusion surgery.

Summary Of Background Data: Over the past decade advances in SOT patients have improved graft survival.

The future of safety science is happening now: The modernization of the benefit-risk paradigm.

The future of safety science is happening now and has the potential to improve patient outcomes through an evolving approach to benefit-risk assessment. Three building blocks for the future of safety science, cognitive and behavioral systems, medical assessment, and data science, individually and collaboratively advance and modernize the benefit-risk paradigm. Incorporating the patient perspective and patient experiences will help identify tools that are useful in real-world practice.

Pigs, Unlike Mice, Have Two Distinct Colonic Stem Cell Populations Similar to Humans That Respond to High-Calorie Diet prior to Insulin Resistance.

Basal colonic crypt stem cells are long lived and play a role in colon homeostasis. Previous evidence has shown that high-calorie diet (HCD) enhances colonic stem cell numbers and expansion of the proliferative zone, an important biomarker for colon cancer. However, it is not clear how HCD drives dysregulation of colon stem cell/colonocyte proliferative kinetics.

The Association of Perioperative Glycemic Control with Deep Postoperative Infection After Anterior Cervical Discectomy and Fusion in Patients with Diabetes.

Objective: To evaluate the association of perioperative hemoglobin A (HbA) level in patients with diabetes with the incidence of infection after anterior cervical discectomy and fusion requiring operative intervention, in addition to determining if a threshold level of HbA above which the risk of infection increases significantly exists.

Methods: A national administrative database was queried for patients who underwent primary anterior cervical discectomy and fusion with diabetes who had a perioperative HbA level recorded within 3 months of surgery. These patients were stratified based on their HbA level in 0.

A food-based approach that targets interleukin-6, a key regulator of chronic intestinal inflammation and colon carcinogenesis.

Studies have shown a causal link between high-calorie diet (HCD) and colon cancer. However, molecular mechanisms are not fully elucidated. To understand etiology of HCD-induced colon carcinogenesis, we screened 10 pathways linked to elevated colonic cell proliferation and chronic inflammation in an HCD-consuming human-relevant pig model.

Does the Timing of Preoperative Epidural Steroid Injection Affect Infection Risk After ACDF or Posterior Cervical Fusion?

Study Design: A retrospective database analysis.

Objective: The aim of this study was to determine whether any association exists between preoperative cervical epidural steroid injections (CESIs) at various time intervals before anterior cervical discectomy and fusion (ACDF) or posterior cervical fusion (PCF) and the incidence of postoperative infection.

Summary Of Background Data: Although infectious complications following CESI are uncommon, the association between preoperative CESI and postoperative infection following ACDF or PCF has yet to be evaluated in the current literature.

Regional efficacy assessment in multiregional clinical development.

It is common in multiregional clinical development that data from a global trial and a local trial (in a target country) together will be used to support local filing in the target country. This approach is considered efficient drug development both globally and in the target country. However, it remains a challenge how to combine global trial data and local trial data toward local filing.

Bioinformatic analysis of microRNA networks following the activation of the constitutive androstane receptor (CAR) in mouse liver.

The constitutive androstane receptor (CAR; NR1I3) is a member of the nuclear receptor superfamily that functions as a xenosensor, serving to regulate xenobiotic detoxification, lipid homeostasis and energy metabolism. CAR activation is also a key contributor to the development of chemical hepatocarcinogenesis in mice. The underlying pathways affected by CAR in these processes are complex and not fully elucidated.

The Effect of Local Intraoperative Steroid Administration on the Rate of Postoperative Dysphagia Following ACDF: A Study of 245,754 Patients.

Study Design: A retrospective database analysis.

Objective: The aim of this study is to compare rates of postoperative dysphagia, length of stay, infection, and wound complications following short and long anterior cervical discectomy and fusion (ACDF) in patients who received local intraoperative steroids and those who did not.

Summary Of Background Data: Only one prior small institutional study has investigated the application of local steroids at the time of ACDF to decrease postoperative dysphagia.

Weighted Youden index and its two-independent-sample comparison based on weighted sensitivity and specificity.

Background: Most indices for evaluating a diagnostic test can be expressed as functions of sensitivity (SEN) and specificity (SPE). Practically, all existing methods suffer from the inability to weight sensitivity and specificity relative to their importance. In this paper, we developed a novel index, the weighted Youden index, that allows Youden index to be a combination of sensitivity and specificity with user-defined weights.

Experience with an online prospective database on adolescent idiopathic scoliosis: development and implementation.

Considerable variability exists in the surgical treatment and outcomes of adolescent idiopathic scoliosis (AIS). This is due to the lack of evidence-based treatment guidelines and outcome measures. Although clinical trials have been extolled as the highest form of evidence for evaluating treatment efficacy, the disadvantage of cost, time, lack of feasibility, and ethical considerations indicate a need for a new paradigm for evidence based research in this spinal deformity.

Innovative approaches for designing and analyzing adaptive dose-ranging trials.

Inadequate selection of the dose to bring forward in confirmatory trials has been identified as one of the key drivers of the decreasing success rates observed in drug development programs across the pharmaceutical industry. In recognition of this problem, the Pharmaceutical Research and Manufacturers of America (PhRMA), formed a working group to evaluate and develop alternative approaches to dose finding, including adaptive dose-ranging designs. This paper summarizes the work of the group, including the results and conclusions of a comprehensive simulation study, and puts forward recommendations on how to improve dose ranging in clinical development, including, but not limited to, the use of adaptive dose-ranging methods.

Thigh pain after cementless total hip arthroplasty: evaluation and management.

Data from short- and long-term follow-up studies indicate that thigh pain is a significant complication after apparently successful cementless total hip arthroplasty. In most cases, reported symptoms are mild to moderate, resolve spontaneously or do not progress, and require little or no therapeutic intervention. However, persistent thigh pain may be a source of dissatisfaction or may present as severe, disabling pain.

Testing non-additivity of biological activity in a combinatorial library.

Combinatorial chemistry offers new opportunities to generate and analyze QSAR data. Traditional QSAR attempts to correlate activity with structure. With combinatorial chemistry, it is possible to correlate activity directly with the reagents used in a combinatorial library.