Exposed CendR Domain in Homing Peptide Yields Skin-Targeted Therapeutic in Epidermolysis Bullosa.

Systemic skin-selective therapeutics would be a major advancement in the treatment of diseases affecting the entire skin, such as recessive dystrophic epidermolysis bullosa (RDEB), which is caused by mutations in the COL7A1 gene and manifests in transforming growth factor-ß (TGF-ß)-driven fibrosis and malignant transformation. Homing peptides containing a C-terminal R/KXXR/K motif (C-end rule [CendR] sequence) activate an extravasation and tissue penetration pathway for tumor-specific drug delivery. We have previously described a homing peptide CRKDKC (CRK) that contains a cryptic CendR motif and homes to angiogenic blood vessels in wounds and tumors, but it cannot penetrate cells or tissues. In this study, we demonstrate that removal of the cysteine from CRK to expose the CendR sequence confers the peptide novel ability to home to normal skin. Fusion of the truncated CRK (tCRK) peptide to the C terminus of an extracellular matrix protein decorin (DCN), a natural TGF-ß inhibitor, resulted in a skin-homing therapeutic molecule (DCN-tCRK). Systemic DCN-tCRK administration in RDEB mice led to inhibition of TGF-ß signaling in the skin and significant improvement in the survival of RDEB mice. These results suggest that DCN-tCRK has the potential to be utilized as a novel therapeutic compound for the treatment of dermatological diseases such as RDEB.

Making Sense: Treating Patients with Opioid Use Disorder through the Lens of Game Theory.

The opioid epidemic continues to influence the field of medicine, creating new challenges and obstacles to quality care. Patients with injection drug use are marginalized individuals who received poor quality of care and often discharged without safe recovery plan. Cooperation between physicians and patients allow the best outcomes for the patient, the physician, and society, however we often see patient-directed discharges and inadequate care. We believe that this result is due to an incentive model in the decision-making process that ultimately makes cooperation difficult. We use different game theory models (assurance model, prisoner's dilemma, centipede model, conflicting interest coordination) in this paper to describe common scenarios within a hospitalization when caring for patient with opioid use disorder, from admission through discharge. When physician and patient are driven away from cooperation, the outcome is the worst and most harmful for society. In today's worsening opioid crisis, game theory can help physician provide high quality care to a complex high-risk population.

Communicating Adolescent and Young Adult Oncology Treatment Guidelines in Practice: The Importance of Documentation for Ensuring Positive Impacts on Oncology Care.

Purpose: Improvements in outcomes for adolescent and young adult (AYA) oncology patients have lagged behind those of other age-specific cancer populations. Research has indicated that low availability of clinical trials, biological differences of this age-group, and several psychosocial factors including higher emotional distress impact outcomes. To improve care and survival rates for these patients, hospitals have implemented AYA oncology programs. The current study evaluated documentation of care in an AYA program housed in an academic medical center based on three areas emphasized in the National Comprehensive Cancer Network's Clinical Practice Guidelines in Oncology for AYAs: clinical trial enrollment, fertility, and psychosocial care. Methods: Retrospective chart reviews were conducted for 45 patients treated before the start of the AYA oncology program and 45 patients treated after program initiation. Patients aged 15-39 years with a diagnosis of a malignant tumor were included. Variables evaluated included documentation of clinical trial enrollment, fertility preservation and sexual health considerations, and behavioral health referrals. Results: Documentation of most clinical trial and fertility variables did not significantly improve from pre- to post-program, although a higher number of patients had these variables documented post-program. Behavioral health referrals increased significantly from 52.8% pre-program to 95.4% post-program. Conclusion: Access to behavioral health care improved the most following implementation of our AYA program, which is likely because of the integration of a dedicated psychologist for AYAs when the program began. The practice of guideline-based care for this population can be better assessed and improved with designated behavioral health providers and more systematic documentation processes.

Applying Game Theory Models to Inpatient Medicine: Opportunities to Improve Care.

Inpatient hospital costs have been increasing exponentially in the United States. Part of this increase is attributed to over and undertreatment, leading to higher costs and potential patient harm. Research improving clinician-patient interactions can help minimize and optimize the costs. Game theory has the ability improve clinician-patient interaction by modeling outcomes. Using variations of game theory, the bad doctor bad patient stigma can reframed to incentives. We believe the use of different models (prisoner dilemma, centipede game, assurance game, and chicken game) can outline the challenges faced during common inpatient scenarios, including end of life conversations and aggressive procedures. Applying game theory to multiple inpatient scenarios may also assist with analysis during morbidity and mortality conferences and quality improvement projects.

A rare triad of appendiceal diverticula, appendiceal carcinoid, and colonic diverticula.

Appendiceal diverticulosis is a rare finding associated with appendiceal neoplasms. Both can masquerade as appendicitis in patients and are overlooked in differentials of right upper quadrant pain. A 37-year-old African American female presented with appendicitis-like symptoms to the emergency room with fever and leukocytosis. Appendectomy was performed with pathological evaluation revealing coexisting appendiceal diverticula and carcinoid of the appendix with lymphovascular invasion and mesoappendiceal involvement. In line with the National Comprehensive Cancer Network guidelines, right hemicolectomy with lymph node dissection was performed which was negative for neoplastic invasion but positive for colonic diverticulosis. While there have been many case reports of appendiceal diverticula with coexisting appendiceal carcinoid, a concurrent colonic diverticulum in the right hemicolectomy specimen during the oncologic resection of the appendiceal carcinoid has not been previously reported. We propose colonic diverticula as another possible feature that may be associated with appendiceal diverticula especially with an underlying appendiceal neoplasm.

Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual.

Osteoblasts, which are the bone-forming cells, operate in a hypoxic environment. The transcription factors hypoxia-inducible factor-1α (HIF1) and HIF2 are key mediators of the cellular response to hypoxia. Both are expressed in osteoblasts. HIF1 is known to be a positive regulator of bone formation. Conversely, the role of HIF2 in the control osteoblast biology is still poorly understood. In this study, we used mouse genetics to demonstrate that HIF2 is an inhibitor of osteoblastogenesis and bone mass accrual. Moreover, we provided evidence that HIF2 impairs osteoblast differentiation at least in part, by upregulating the transcription factor Sox9. Our findings constitute a paradigm shift, as activation of the hypoxia-signaling pathway has traditionally been associated with increased bone formation through HIF1. Inhibiting HIF2 could thus represent a therapeutic approach for the treatment of the low bone mass observed in chronic diseases, osteoporosis, or aging.