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-beta (TGF-beta)-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 de-corin (DCN), a natural TGF-beta inhibitor, resulted in a skin-homing therapeutic molecule (DCN-tCRK). Systemic DCN-tCRK administration in RDEB mice led to inhibition of TGF-beta 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.Peer reviewe

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

The Association of Gender and Mortality in Geriatric Trauma Patients

The association of gender with mortality in trauma remains a subject of debate. Geriatric trauma patients have a higher risk of mortality compared to younger patients. We sought to evaluate the association of gender with mortality in a group of geriatric trauma patients presenting to an academic level 1 trauma center (trauma center designated by New York State capable of handling the most severe injuries and most complex cases). Methods: We performed a retrospective review of geriatric trauma patients who were admitted to our trauma center between January 2018 and December 2020. Data collected included vital signs, demographics, injury, and clinical characteristics, laboratory data and outcome measures. The study controlled for co-morbidities, injury severity score (ISS), and systolic blood pressure (SBP) in the ED. Multivariable logistic regression analysis was performed to evaluate the association of gender and mortality. Results: 4432 geriatric patients were admitted during the study period, there were 1635 (36.9%) men and 3859 (87.2%) were White with an average age of 81 ± 8.5 years. The mean ISS was 6.7 ± 5.4 and average length of stay was 6 ± 6.3 days. There were 165 deaths. Male gender (OR 1.94, 95% CI 1.38 to 2.73), ISS (OR 1.12, 95% CI 1.09 to 1.14), Emergency Department SBP less than 90 mmHg (OR 6.17, 95% CI 3.17 to 12.01), and having more than one co-morbidity (OR 2.28, 95% CI 1.55 to 3.35) were independently predictive of death on multivariable logistic regression analysis. Conclusion: Male gender, Emergency Department systolic blood pressure less than 90 mmHg, having more than one co-morbidity, and injury severity are independent predictors of mortality among geriatric trauma patients