Successful treatment of PD1-inhibitor induced psoriasiform dermatitis using IL-17 blockade without compromising immunotherapy efficacy.

INTRODUCTION: Pembrolizumab is a monoclonal PD-1 inhibitor used in the treatment of lung cancer in addition to several other malignancies. Psoriasiform dermatitis is a well-documented adverse effect. CASE REPORT: We present a 68 year-old-male with a 50-year smoking history and a 30-year remote history of plaque psoriasis, limited to the knees and elbows, who presented with metastatic non-small cell lung cancer. He was started on a chemotherapy regimen of carboplatin, paclitaxel, and pembrolizumab. One month later, he presented to dermatology with diffuse erythematous scaly papules coalescing into plaques on 80% of body surface area (BSA). MANAGEMENT & OUTCOME: Pembrolizumab treatment was paused. The patient was prescribed triamcinolone 0.1% twice daily, but still had significant BSA at one-month and was started on an Il-17 inhibitor, ixekizumab, clearing the psoriasiform dermatitis. He was rechallenged with pembrolizumab every 3 weeks and repeat PET/CT demonstrated excellent tumor response. DISCUSSION: This case prompted a literature review to further characterize the use of IL-17 inhibitors for psoriasiform dermatitis in the setting of ICI therapy. All six cases demonstrated improvement of psoriasiform dermatitis, with two cases showing partial response and four cases showing complete resolution. In three of the six cases, the patients exhibited clinical response to the primary malignancy after rechallenging with ICI, while remaining on an IL-17 inhibitor. Our case, in conjunction with the other reported cases, seems to suggest that IL-17 blockade can maintain a fine balance in this challenging clinical scenario by treating psoriasiform dermatitis without compromising the efficacy of immunotherapy.

Pembrolizumab induced type 1 diabetes mellitus in a patient with metastatic melanoma and literature review on steroids as a treatment option.

OBJECTIVE: We report a case of a 77-year-old male with metastatic melanoma who developed immune-checkpoint-inhibitor (ICI) induced type 1 diabetes mellitus (T1DM) after seven months of pembrolizumab treatment and required life-long insulin use. This prompted a literature review of best practice guidelines for long-term management of checkpoint-inhibitor induced T1DM including oral steroids as a treatment option similar to other ICI adverse effects. DATA SOURCES AND SUMMARY: A literature search on PubMed was conducted to evaluate the efficacy of steroid treatment ICI-induced T1DM in any cancer type. Search terms consisted of "ipilimumab" OR "nivolumab" OR & "pembrolizumab" OR "immune checkpoint" AND "diabetes" OR "type 1 diabetes" AND "cancer" OR "melanoma" OR "carcinoma OR "sarcoma". Inclusion criteria were case reports published after 2015 in which the patient was diagnosed with ICI-induced T1DM or diabetic ketoacidosis where oral steroids were part of the treatment. Exclusion criteria included oral steroids not used as a treatment modality for T1DM, multiple endocrine comorbidities, no response recorded, and previous history of T1DM. 284 abstracts were found with these search terms of which 33 full-text articles were concluded to be eligible and screened and from which 8 records were included. From these 8 articles, there were 12 cases included. CONCLUSION: This literature search suggests that ICI-induced T1DM cannot be reversed by steroids and that insulin must be used permanently for treatment management.

Impact of tent shade on heat exposures and simulated heat strain for people experiencing homelessness.

Concurrent increases in homelessness and heat intensity, duration, and frequency translate to an urban heat risk trap for the unsheltered population. Homelessness is both a driver and consequence of poor health, co-creating distinct geographies with various risk factors that exacerbate heat vulnerability. We tested the efficacy of different tent shadings over identical tents often observed in the Phoenix area (white bedsheet, mylar, tarp, and aluminum foil) and compared them to a control tent (uncovered) and ambient conditions. We monitored all meteorological variables at all six locations, notably Mean Radiant Temperature (MRT). The in-tent microclimate variability was applied to complete statistical and physiological modeling including substance use on heat strain. Findings indicate that tent shadings resulted in significantly lower in-tent MRT during the day (p < 0.05), but exacerbated in-tent thermal risk during the night compared to the control tent and ambient conditions. Furthermore, we found evidence that the temperature metric matters, and using only either MRT or air temperature (Tair) to assess "heat" could lead to inconsistent conclusions about in-tent microclimate. Interactions between shade types and time significantly amplified in-tent thermal risk. Physiological modeling indicates a higher risk of heat strain (core temperature beyond 40˚C) for people using substances. Decision makers should promote testing different heat intervening strategies toward realizing effective means of protecting human life and preventing heat illnesses. This study illuminates the need for an interdisciplinary approach to studying tents as shelters that considers the total heat load with heat strain modeling.

Bariatric Surgery in the Elderly Is Associated with Similar Surgical Risks and Significant Long-Term Health Benefits.

PURPOSE: Older age (> 60) has been considered a relative contraindication for bariatric surgery due to increased complication risk. This study examined the risks and benefits of bariatric surgery for patients older than 60 years in Canadian population. METHODS: This was a retrospective cohort study of the Ontario Bariatric Registry: a database recording peri-operative and post-operative outcomes of publicly funded bariatric surgeries across the province. Patients who completed 1 year follow-up, who underwent laparoscopic gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) between January 2010 and May 2013, were divided into older (> 60) and younger (> 60) cohorts, and outcomes were compared. RESULTS: Between January 2010 and May 2013, 3166 registry patients underwent LRYGB or LSG and completed 1-year follow-up. Of these, 204 (6.5%) were older than 60 years, with 175 (85.8%) undergoing LRYGB and 29 (14.2%) LSG. Demographics were similar, except for a higher number of males in the older group (59 (28.9%) versus 452 (15.3%) (p < 0.001)). No significant difference in complication rate was noted (15% for younger cohort versus 13.8% (p = 0.889)). The average percentage of excess weight loss was significantly higher in the younger population (60.72% versus 56.25% (p < 0.05)) overall, however not significantly in the LSG group. Reduction in medication use post-surgery for management of co-morbidities was significantly higher in the older patients (- 0.91 versus - 2.03 (p < 0.001)). CONCLUSION: The older cohort who underwent LRYGB or LSG was at no greater risk for intra-operative and post-operative complications and showed greater reduction in medication use post-surgery when compared to the younger cohort.