Stress and Inflammatory Bowel Disease: Clear Mind, Happy Colon.

Inflammatory bowel disease (IBD) is a condition whose prevalence in the general population worldwide is increasing at an exponential pace. Many risk factors affect the incidence, progression, and overall outcome of IBD, one of them being psychological stress. This study examined the relationship between psychological stress and inflammatory bowel disease. A search for relevant studies was conducted using PubMed, Google Scholar, ResearchGate, and SCOPUS. A systematic review was conducted on the relevant articles after critical appraisal. This article mainly focused on studies that evaluated the presence of inflammatory markers observed in individuals who have been diagnosed with IBD and have high levels of psychological stress. It also assessed if lowering an individual's psychological stress could help improve the outcomes of IBD. Psychological stress can have a detrimental effect on individuals diagnosed with IBD. There is a need to conduct studies that can further confirm the association between psychological stressors, mental health conditions, and IBD. We should also encourage medical practitioners to educate patients who have been diagnosed with IBD regarding the benefits of stress reduction.

Is Isotretinoin in Acne Patients a Psychological Boon or a Bane: A Systematic Review.

Acne vulgaris is a frequently encountered dermatological condition in clinical practice. Isotretinoin is one of the drugs prescribed for this condition. However, it is unclear whether the use of this drug worsens or improves the psychological effects in an acne patient and whether it is advisable to use this drug commonly. This systematic review aims to assess the relationship between Isotretinoin and psychiatric side effects in acne patients. A literature search was conducted using PubMed, Cochrane, and Google Scholar databases in accordance with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Articles published within the last 10 years were taken into account and a review was conducted on the relevant articles after critical appraisal. Nine studies were finalized for discussion and out of the nine studies, two studies concluded that Isotretinoin could cause psychiatric effects. Five studies showed no association between them. Two studies unexpectedly found that psychiatric symptoms improved because of Isotretinoin use. Lack of adequate sample size and absence of randomized controlled trials are the limitations of this study. To conclude, Isotretinoin can be prescribed as a treatment option for severe acne despite some evidence of link with psychiatric effects. However, bearing the side effects in mind, a detailed evaluation before initiating the drug and a thorough monitoring while using the drug should be done as a standard practice in order to be on the safer side.

Doxycycline Therapy for Abdominal Aortic Aneurysm: Inhibitory Effect on Matrix Metalloproteinases.

Abdominal aortic aneurysm (AAA) is a life-threatening condition associated with smoking, aging, atherosclerosis, and destruction of the connective tissue in the abdominal aortic wall. Disturbances in the synthesis and degradation of matrix metalloproteinase (MMP) have been known to contribute to the development of AAAs. The only available treatment of AAA is surgical repair. Doxycycline, a tetracycline analog, is thought to have an inhibitory effect on MMPs. Knowing the effect of doxycycline, there may be some favorable effects of the drug to reduce the growth of small AAAs and avoid the need for invasive treatment. This article aims to determine the relationship between doxycycline and the MMPs to prevent the growth of small AAAs. We conducted our review using online resources such as PubMed, Google Scholar, The Journal of Vascular Surgery, and ResearchGate. The result of our study supports the effect of doxycycline in preventing the growth of small AAAs. We conclude that therapeutic treatment with doxycycline in patients with small AAAs can prevent the growth of aneurysms, life-threatening aneurysm rupture, and reduce the need for expensive, invasive treatment.

Cancer Immunotherapeutic Potential of NKTT320, a Novel, Invariant, Natural Killer T Cell-Activating, Humanized Monoclonal Antibody.

Invariant natural killer T cells (iNKTs) directly kill tumor cells and trans-activate the anti-tumor functions of dendritic cells (DC), natural killer (NK) cells, and T and B cells. As such, iNKTs serve as a powerful tool for use in cell-based cancer immunotherapy. iNKT cell activation commonly requires engagement of the invariant T cell receptor (iTCR) by CD1d presenting glycolipid antigens. However, transformed cells often down-regulate CD1d expression, which results in a reduction of iNKT cell anti-tumor functions. One approach to circumvent this critical barrier to iNKT cell activation is to develop an agonistic antibody that binds directly to the iTCR without the requirement for CD1d-mediated antigen presentation. To this end, we have characterized the iNKT cell stimulatory properties of NKTT320, a novel, recombinant, humanized, monoclonal antibody that binds selectively and with high affinity to human iTCRs. Strikingly, immobilized NKTT320 mediated robust iNKT cell activation (upregulation of CD25 and CD69) and proliferation (carboxyfluorescein succinimidyl ester (CFSE) dilution), as well as Th1 and Th2 cytokine production. Additionally, iNKTs stimulated by plate-bound NKTT320 exhibited increased intracellular levels of granzyme B and degranulation (exposure of CD107 on the cell surface). Furthermore, both soluble and immobilized NKTT320 induced iNKT cell-mediated activation of bystander immune cells, suggesting that this novel anti-iTCR antibody facilitates both direct and indirect iNKT cell cytotoxicity. These studies are significant, as they provide a framework by which iNKT cell anti-cancer functions could be enhanced for therapeutic purposes.

Enhancing the antitumor functions of invariant natural killer T cells using a soluble CD1d-CD19 fusion protein.

Invariant natural killer T (iNKT) cells comprise a unique lineage of CD1d-restricted lipid-reactive T lymphocytes that potently kill tumor cells and exhibit robust immunostimulatory functions. Optimal tumor-directed iNKT cell responses often require expression of the antigen-presenting molecule CD1d on tumors; however, many tumor cells downregulate CD1d and thus evade iNKT cell recognition. We generated a soluble bispecific fusion protein designed to direct iNKT cells to the site of B-cell cancers in a tumor antigen-specific but CD1d-independent manner. This fusion protein is composed of a human CD1d molecule joined to a single chain antibody FV fragment specific for CD19, an antigen widely expressed on B-cell cancers. The CD1d-CD19 fusion protein binds specifically to CD19-expressing, but not CD19-negative cells. Once loaded with the iNKT cell lipid agonist α-galactosyl ceramide (αGC), the CD1d-CD19 fusion induces robust in vitro activation of and cytokine production by human iNKT cells. iNKT cells stimulated by the αGC-loaded CD1d-CD19 fusion also strongly transactivate T-, B-, and NK-cell responses and promote dendritic cell maturation. Importantly, the αGC-loaded fusion induces robust lysis of CD19+CD1d- Epstein-Barr virus immortalized human B-lymphoblastoid cell lines that are otherwise resistant to iNKT cell killing. Consistent with these findings; administration of the αGC-loaded fusion protein controlled the growth of CD19+CD1d- tumors in vivo, suggesting that it can "link" iNKT cells and CD19+CD1d- targets in a therapeutically beneficial manner. Taken together, these preclinical studies demonstrate that this B cell-directed fusion protein can be used to effectively induce iNKT cell antitumor responses in vitro and in vivo.

Impact of the Mobile HealthPROMISE Platform on the Quality of Care and Quality of Life in Patients With Inflammatory Bowel Disease: Study Protocol of a Pragmatic Randomized Controlled Trial.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic condition of the bowel that affects over 1 million people in the United States. The recurring nature of disease makes IBD patients ideal candidates for patient-engaged care that is centered on enhanced self-management and improved doctor-patient communication. In IBD, optimal approaches to management vary for patients with different phenotypes and extent of disease and past surgical history. Hence, a single quality metric cannot define a heterogeneous disease such as IBD, unlike hypertension and diabetes. A more comprehensive assessment may be provided by complementing traditional quality metrics with measures of the patient's quality of life (QOL) through an application like HealthPROMISE. OBJECTIVE: The objective of this pragmatic randomized controlled trial is to determine the impact of the HealthPROMISE app in improving outcomes (quality of care [QOC], QOL, patient adherence, disease control, and resource utilization) as compared to a patient education app. Our hypothesis is that a patient-centric self-monitoring and collaborative decision support platform will lead to sustainable improvement in overall QOL for IBD patients. METHODS: Participants will be recruited during face-to-face visits and randomized to either an interventional (ie, HealthPROMISE) or control (ie, education app). Patients in the HealthPROMISE arm will be able to update their information and receive disease summary, quality metrics, and a graph showing the trend of QOL (SIBDQ) scores and resource utilization over time. Providers will use the data for collaborative decision making and quality improvement interventions at the point of care. Patients in the control arm will enter data at baseline, during office visits, and at the end of the study but will not receive any decision support (trend of QOL, alert, or dashboard views). RESULTS: Enrollment in the trial will be starting in first quarter of 2015. It is intended that up to 300 patients with IBD will be recruited into the study (with 1:1 allocation ratio). The primary endpoint is number of quality indicators met in HealthPROMISE versus control arm. Secondary endpoints include decrease in number of emergency visits due to IBD, decrease in number of hospitalization due to IBD, change in generic QOL score from baseline, proportion of patients in each group who meet all eligible outpatient quality metrics, and proportion of patients in disease control in each group. In addition, we plan to conduct protocol analysis of intervention patients with adequate HealthPROMISE utilization (more than 6 log-ins with data entry from week 0 through week 52) achieving above mentioned primary and secondary endpoints. CONCLUSIONS: HealthPROMISE is a unique cloud-based patient-reported outcome (PRO) and decision support tool that empowers both patients and providers. Patients track their QOL and symptoms, and providers can use the visual data in real time (integrated with electronic health records [EHRs]) to provide better care to their entire patient population. Using pragmatic trial design, we hope to show that IBD patients who participate in their own care and share in decision making have appreciably improved outcomes when compared to patients who do not. TRIAL REGISTRATION: ClinicalTrials.gov NCT02322307; https://clinicaltrials.gov/ct2/show/NCT02322307 (Archived by WebCite at http://www.webcitation.org/6W8PoYThr).