Citations

Background: Eyelid melanoma (EM) is a rare condition that accounts for <1% of all cutaneous melanomas. In this analysis, patients diagnosed with EM in the United States were compared to those with other melanomas in the head and neck. Methods: The National Cancer Database was used to select patients with head and neck melanoma from 2004 to 2015. Results: A total of 137,233 patients met the criteria of the study. Among them, 2694 were diagnosed with EM (2%) and 134,539 in other head and neck locations (98%). Regarding the patients with EM, the mean age was 68.56 years (standard deviation 14.04). A greater number of them were treated in Academic/Research Programs (53.6%), insured by Medicare (55.7%), tumor in situ (52.2%), stage 0 (49%), and without ulceration (75.9%). The mean time to treatment commencement was 18.96 days for EM compared to 14.4 days for other melanoma in the head and neck regions (P < 0.001). There was a greater proportion of EM in female patients (odds ratio [OR] 2.371 [2.191–2.566], P < 0.001), compared to male; age greater than 80 years (OR 1.622 [1.360–1.934], P < 0.001) compared to 0 to 49 years. Moreover, EM was an independent predictor for treatment in Academic/Research Programs (OR 1.258 [1.160–1.365], P < 0.001) and diagnosis at autopsy (OR 1.414 [1.083–1.847], P = 0.011) compared to other melanoma in the head and neck region. Conclusion: These novel findings have the potential to guide clinical decision making in head and neck melanoma management.

Background: While trauma to the upper extremity is known to cause acute compartment syndrome (ACS), nontraumatic causes of ACS of the upper extremity are rare. Nontraumatic ACS of the upper extremity can lead to adverse outcomes if not recognized early. There are limited reports of spontaneous ACS published in the literature. The aim of this comprehensive systematic review is to increase awareness among plastic surgeons and hand surgeons of this acute event and provide an algorithmic approach to management in the acute setting through an illustrative case example. Methods: A comprehensive systematic review of published literature was conducted in the Medline/PubMed database with the search terms, “compartment syndrome,” “extremity,” “spontaneous,” “nontraumatic,” and “atraumatic” without timeframe limitations. Articles were identified and included in this review based on ACS localization in the upper extremity and etiology of nontraumatic, spontaneous origin. Results: Sixteen publications and 19 total cases of nontraumatic ACS of the upper extremity from 1993 to 2016 met our search criteria. A bleeding disorder was the etiology in three cases, systemic anticoagulation in three cases, infection in six cases, and unknown in three cases. The remaining four cases included systemic sclerosis, Ehlers-Danlos syndrome, rhabdomyolysis, and McArdle disease. Conclusions: Nontraumatic causes of ACS of the upper extremity include infection, anticoagulation therapy, and bleeding disorders. Even though trauma is the most common cause of ACS, clinicians should be aware of these other potential causes of ACS in the nontraumatic setting. Appropriate medical and surgical intervention should be done to avoid potential adverse outcomes.

Immunotherapy holds promise for patients with multiple myeloma (MM), but little is known about how MM-induced immunosuppression influences response to therapy. Here, we investigated the impact of disease progression on immunotherapy efficacy in the Vk*MYC mouse model. Treatment with agonistic anti-CD137 (4-1BB) mAbs efficiently protected mice when administered early but failed to contain MM growth when delayed more than 3 weeks after Vk*MYC tumor cell challenge. The quality of the CD8 + T cell response to CD137 stimulation was not altered by the presence of MM, but CD8 + T cell numbers were profoundly reduced at the time of treatment. Our data suggest that an insufficient ratio of CD8 + T cells to MM cells (CD8/MM ratio) accounts for the loss of anti-CD137 mAb efficacy. We established serum M-protein levels prior to therapy as a predictive factor of response. Moreover, we developed an in silico model to capture the dynamic interactions between CD8 + T cells and MM cells. Finally, we explored two methods to improve the CD8/MM ratio: anti-CD137 mAb immunotherapy combined with Treg depletion or administered after chemotherapy treatment with cyclophosphamide or melphalan efficiently reduced MM burden and prolonged survival. Together, our data indicate that consolidation treatment with anti-CD137 mAbs might prevent MM relapse.

Abstract Patients with primary immunodeficiencies undergoing allogeneic hematopoietic cell transplantation (HCT) for difficult-to-control infections can experience immune reconstitution inflammatory syndrome (IRIS) following engraftment. In 3 patients with post-HCT IRIS related to mycobacterial infection, in vitro data demonstrate the emergence of pathogen-specific immune responses and a concomitant rise in plasma inflammatory markers.

Abstract Background: Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences. Methods: Combining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients (299 males and 195 females). Results: Among males, tumor (T1Gd) radius was a predictor of overall survival (HR=1.027, p=0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR=1.011, p<0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p=0.010 t-test), but tumor size was not correlated with female overall survival (p=0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p=0.004, F p=0.001, t-test). Additionally, extent of resection, tumor laterality, and IDH1 mutation status were also found to have sex-specific effects on overall survival. Conclusion: Despite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes.

ABSTRACT Previously, we demonstrated that intratumoral delivery of adenoviral vector encoding single‐chain (sc) IL‐23 (Ad.scIL‐23) was able to induce systemic antitumor immunity. Here, we examined the role of IL‐23 in diabetes in nonobese diabetic mice. Intravenous delivery of Ad.scIL‐23 did not accelerate the onset of hyperglycemia but instead resulted in the development of psoriatic arthritis. Ad.scIL‐23–treated mice developed erythema, scales, and thickening of the skin, as well as intervertebral disc degeneration and extensive synovial hypertrophy and loss of articular cartilage in the knees. Immunological analysis revealed activation of conventional T helper type 17 cells and IL‐17–producing γδ T cells along with a significant depletion and suppression of T cells in the pancreatic lymph nodes. Furthermore, treatment with anti–IL‐17 antibody reduced joint and skin psoriatic arthritis pathologies. Thus, these Ad.scIL‐23–treated mice represent a physiologically relevant model of psoriatic arthritis for understanding disease progression and for testing therapeutic approaches.—Flores, R. R., Carbo, L., Kim, E., Van Meter, M., De Padilla, C. M. L., Zhao, J., Colangelo, D., Yousefzadeh, M. J., Angelini, L. A., Zhang, L., Pola, E., Vo, N., Evans, C. H., Gambotto, A., Niedernhofer, L. J., Robbins, P. D. Adenoviral gene transfer of a single‐chain IL‐23 induces psoriatic arthritis–like symptoms in NOD mice. FASEB J. 33, 9505–9515 (2019). www.fasebj.org