Complexity of Translating Analytics to Recent Cannabis Use and Impairment.

While current analytical methodologies can readily identify cannabis use, definitively establishing recent use within the impairment window has proven to be far more complex, requiring a new approach. Recent studies have shown no direct relationship between impairment and Δ9-tetra-hydrocannabinol (Δ9-THC) concentrations in blood or saliva, making legal "per se" Δ9-THC limits scientifically unjustified. Current methods that focus on Δ9-THC and/or metabolite concentrations in blood, saliva, urine, or exhaled breath can lead to false-positive results for recent use due to the persistence of Δ9-THC well outside of the typical 3-4 h window of potential impairment following cannabis inhalation.

Autologous fat graft injections for the treatment of perianal fistulas in Crohn's disease: a systematic review and single-arm meta-analysis.

Background: Crohn's perianal fistulas are often refractory to standard management. Fat graft injections are hypothesised to improve fistula healing rates. We evaluated the treatment efficacy of fat graft injections for Crohn's perianal fistulas in a systematic review (PRISMA).

Examining impairment and kinetic patterns associated with recent use of hemp-derived Δ-tetrahydrocannabinol: case studies.

Background: As a result of the legalization of U.S. industrial hemp production in late 2018, products containing hemp-derived Δ-tetrahydrocannabinol (Δ-THC) are increasing in popularity.

Indeterminacy of cannabis impairment and ∆-tetrahydrocannabinol (∆-THC) levels in blood and breath.

Previous investigators have found no clear relationship between specific blood concentrations of ∆-tetrahydrocannabinol (∆-THC) and impairment, and thus no scientific justification for use of legal "per se" ∆-THC blood concentration limits. Analyzing blood from 30 subjects showed ∆-THC concentrations that exceeded 5 ng/mL in 16 of the 30 subjects following a 12-h period of abstinence in the absence of any impairment. In blood and exhaled breath samples collected from a group of 34 subjects at baseline prior to smoking, increasing breath ∆-THC levels were correlated with increasing blood levels (P < 0.

Lumbopelvic postural differences in adolescent idiopathic scoliosis: A pilot study.

Background: A primary etiology of adolescent idiopathic scoliosis (AIS) is currently unknown, but poor postural control of the spinal extensor musculature has been identified as an AIS risk factor. Identifiable postural differences would aid in advancing the precise postural behaviors that should be modified during Physiotherapy Scoliosis Specific Exercise (PSSE) to help limit the progression of AIS.

Research Question: Are there any determinable differences in lumbopelvic posture or range of motion between subjects with AIS and controls?

Methods: This prospective cohort pilot study consisted of 53 subjects (27 AIS and 26 control) aged 11-17 years.

A comprehensive breath test that confirms recent use of inhaled cannabis within the impairment window.

Legalization of cannabis for medicinal and/or recreational use is expanding globally. Although cannabis is being regulated country by country, an accurate recent use test with indisputable results correlated with impairment has yet to be discovered. In the present study, a new approach for determining recent cannabis use within the impairment window after smoking was developed by studying 74 subjects with a mean age of 25 years and average use history of 9 years.

Prospective randomised controlled trial of adults with perianal fistulising Crohn's disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol.

Introduction: Perianal fistulising Crohn's disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeutic drug monitoring (TDM) improves outcomes. This randomised controlled trial aimed to assess whether infliximab therapy targeting higher TLIs guided by proactive TDM improves outcomes compared with standard therapy.

Development and Validation of a Liquid Chromatography High-Resolution Mass Spectrometry (LC-HRMS) Bioanalytical Method for Quantifying Cannabinoids in Whole Blood: Application for Determining Recent Cannabis Use.

Background: Cannabis legalization is expanding rapidly throughout the United States, but there is no reliable means of establishing recent use.

Objective: To develop and validate a bioanalytical method for determination of Δ9-tetrahydrocannabinol (Δ9-THC), cannabinol, 11-hydroxy-Δ9-THC, 11-nor-9-carboxy-Δ9-THC, and 8β,11-dihydroxy-Δ9-THC in whole blood microsamples by liquid chromatography high-resolution mass spectrometry (LC-HRMS).

Methods: Cannabinoid extraction from whole blood was performed using a mixture of n-hexane/ethyl acetate (90:10, v/v).

Optimizing the Double-Row Construct: An Untied Medial Row Demonstrates Equivalent Mean Contact Pressures in a Rotator Cuff Model.

Background: The merits of a double-row rotator cuff repair (RCR) construct are well-established for restoration of the footprint and lateral-row security. The theoretical benefit of leaving the medial row untied is to prevent damage to the rotator cuff by tissue strangulation, and the benefit of suture tape is a more even distribution of force across the repair site. These benefits, to our knowledge, have not been evaluated in the laboratory.

Distal Metaphyseal Osteotomy Allows for Greater Ulnar Shortening Compared to Diaphyseal Osteotomy for Ulnar Impaction Syndrome: A Biomechanical Study.

 To compare the biomechanical characteristics between diaphyseal and metaphyseal ulnar-shortening osteotomy with respect to (1) maximal shortening achieved at each osteotomy site and (2) force required to achieve shortening at each site.  Nine fresh frozen cadaveric upper extremities were affixed through the proximal ulna to a wooden surgical board. A metaphyseal 20-mm bone wedge was resected from the distal ulna and sequential shortening was performed.

Biomechanical Evaluation of Interfragmentary Compression of Lag Screw Versus Positional Screw at Different Angles of Fixation.

Objectives: To compare the compressive force achieved and retained with the lag versus positional screw technique at various angles of screw application.

Methods: Sixty humeral sawbones were stratified into 6 groups based on the technique (lag or positional) and fixation angle (30, 60, or 90 degrees relative to the fracture plane). A sensor was placed between fragments to record compressive force.

Quantifying the force transmission through the pelvic joints during total hip arthroplasty: A pilot cadaveric study.

Background: Total hip arthroplasty is one of the most successful and cost effective procedures in orthopedics. The purpose of this study is to investigate force transmission through the sacroiliac joint as a possible source of post-operative pain after total hip arthroplasty through the following three questions: Does the ipsilateral sacroiliac joint, contralateral sacroiliac joint, or pubic symphysis experience more force during placement? Does the larger mallet used to seat the implant generate a higher force? Does the specimen's bone density or BMI alter force transmission?

Methods: A solid design acetabular component was impacted into five human cadaver pelves with intact soft tissues. The pressure at both sacroiliac joints and the pubic symphysis was measured during cup placement.

Metastatic sigmoid colon adenocarcinoma and tumour-related sarcoid reaction.

The association between malignancy and tumour-related sarcoid reaction is well documented, characterised by non-caseating granulomatous disease in haematological and solid malignancies. Its occurrence in colon cancer is rare and of unclear clinical significance. Herein, we present a case report of a 32-year-old woman diagnosed with concurrent metastatic sigmoid colon adenocarcinoma and pulmonary granulomatous disease suggestive of a tumour-related sarcoid reaction.

Repurposing ospemifene for potentiating an antigen-specific immune response.

Objective: Ospemifene, an estrogen receptor agonist/antagonist approved for the treatment of dyspareunia and vaginal dryness in postmenopausal women, has potential new indications as an immune modulator. The overall objective of the present series of preclinical studies was to evaluate the immunomodulatory activity of ospemifene in combination with a peptide cancer vaccine.

Methods: Immune regulating effects, mechanism of action and structure activity relationships of ospemifene and related compounds were evaluated by examining expression of T-cell activating cytokines in vitro, and antigen-specific immune response and cytotoxic T-lymphocyte activity in vivo.

Novel cancer antigens for personalized immunotherapies: latest evidence and clinical potential.

The clinical success of monoclonal antibody immune checkpoint modulators such as ipilimumab, which targets cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and the recently approved agents nivolumab and pembrolizumab, which target programmed cell death receptor 1 (PD-1), has stimulated renewed enthusiasm for anticancer immunotherapy, which was heralded by Science as 'Breakthrough of the Year' in 2013. As the potential of cancer immunotherapy has been recognized since the 1890s when William Coley showed that bacterial products could be beneficial in cancer patients, leveraging the immune system in the treatment of cancer is certainly not a new concept; however, earlier attempts to develop effective therapeutic vaccines and antibodies against solid tumors, for example, melanoma, frequently met with failure due in part to self-tolerance and the development of an immunosuppressive tumor microenvironment. Increased knowledge of the mechanisms through which cancer evades the immune system and the identification of tumor-associated antigens (TAAs) and negative immune checkpoint regulators have led to the development of vaccines and monoclonal antibodies targeting specific tumor antigens and immune checkpoints such as CTLA-4 and PD-1.

Assessing the Effects of Concurrent versus Sequential Cisplatin/Radiotherapy on Immune Status in Lung Tumor-Bearing C57BL/6 Mice.

Concurrent and sequential cisplatin-based chemoradiotherapy regimens are standard therapeutic approaches in cancer treatment. Recent clinical data suggest that these different dosing schedules may adversely affect antigen-specific immunotherapy. The goal of the present preclinical study was to explore the effects of concurrent and sequential cisplatin/radiotherapy on immune status in a lung cancer mouse model.

Tecemotide: an antigen-specific cancer immunotherapy.

The identification of tumor-associated antigens (TAA) has made possible the development of antigen-specific cancer immunotherapies such as tecemotide. One of those is mucin 1 (MUC1), a cell membrane glycoprotein expressed on some epithelial tissues such as breast and lung. In cancer, MUC1 becomes overexpressed and aberrantly glycosylated, exposing the immunogenic tandem repeat units in the extracellular domain of MUC1.

Safety and efficacy of ospemifene for the treatment of dyspareunia associated with vulvar and vaginal atrophy due to menopause.

During the menopausal transition, women experience a number of symptoms due to declining estrogen levels, including vasomotor symptoms and vulvar and vaginal atrophy (VVA). Unlike vasomotor symptoms, vaginal dryness and dyspareunia, the main symptoms of VVA, typically worsen without treatment and can significantly impact the quality of life. Up to 60% of postmenopausal women may be affected by VVA, but many women unfortunately do not seek treatment due to embarrassment or other factors.

Ospemifene: a first-in-class, non-hormonal selective estrogen receptor modulator approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy.

Ospemifene is a selective estrogen receptor modulator (SERM) approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy (VVA) due to menopause. As the first non-hormonal treatment for this indication, the approval of ospemifene represents a significant milestone in postmenopausal women's health. Ospemifene is a triphenylethylene similar in chemical structure to tamoxifen and toremifene.

Antitumor effects of cisplatin combined with tecemotide immunotherapy in a human MUC1 transgenic lung cancer mouse model.

The goals of the present study were to define the effects of simultaneous cisplatin/tecemotide therapy on tumor development in a human mucin 1 (MUC1) transgenic lung cancer mouse model and to examine the effects of radiotherapy (RTX) on splenocytes, serum cytokines, and immune response to tecemotide. Two hundred twenty-six human MUC1 transgenic C57BL/6 mice were used in five studies designed to assess (i) serum cytokine and immune responses following four weekly 10-μg doses of tecemotide; (ii) the effects of simultaneous administration of cisplatin (2.5 mg/kg × 2 doses/cycle × 4 cycles) and tecemotide (2 cycles × 8 weekly 10-μg doses/cycle) therapy on tumor development, serum cytokines, and immune response; (iii) the dose-response effects of RTX on lymphocyte counts 16 hours following doses of 2 to 8 Gy; (iv) the time course of lymphocyte recovery from 16 hours to 20 days following 8-Gy RTX; and (v) the effects of simultaneous administration of RTX (8 Gy) and tecemotide on the immune response to tecemotide (four weekly 10-μg doses).

Activating adaptive cellular mechanisms of resistance following sublethal cytotoxic chemotherapy: implications for diagnostic microdosing.

As Phase 0 studies have proven to be reasonably predictive of therapeutic dose pharmacokinetics, the application of microdosing has expanded into metabolism, drug-drug interactions and now diagnostics. One potentially serious issue with this application of microdosing that has not been previously discussed is the possibility of activating cellular mechanisms of drug resistance. Here, we provide an overview of Phase 0 microdosing and drug resistance, with an emphasis on cisplatin resistance, followed by a discussion of the potential for inducing acquired resistance to platinum-based or other types of chemotherapy in cancer patients participating in Phase 0 diagnostic microdosing studies.