Keratoacanthoma and Cutaneous Squamous Cell Carcinoma With PD-1 and PD-L1 Inhibitor Use.

This cross-sectional study assesses risk of dermatological immune-related adverse events associated with immunotherapy for cancer.

Modulation of Inflammatory Proteins in Serum May Reflect Cutaneous Immune Responses in Cancer Immunotherapy.

Diphencyprone (DPCP), a topical contact sensitizer, has shown efficacy in treating cutaneous melanoma metastases, including at times beyond the directly treated sites, but biomarkers indicative of treatment response have not been characterized. Thus, we performed a proteomic analysis of the skin and serum of five patients with cutaneous melanoma metastases treated with DPCP on days 0, 63, and 112 of the treatment course. In the serum, we found a significant upregulation (P < 0.05) in 13 of 96 assessed immuno-oncology proteins after DPCP treatment. Upregulated proteins included those of the T helper 1 axis (CXCL9, CXCL10), immune checkpoint proteins (PD-1), and various proteins with roles in promoting tumor immunity such as CD80 and TNFRSF4/9. Given the positive clinical response to topical treatment noted in the five patients studied, these proteins may represent prognostic biomarkers in the serum for evaluating the efficacy of DPCP treatment of cutaneous melanoma metastases. Because DPCP does not lead to nonspecific immune-related adverse events seen with immune checkpoint inhibitors, our study provides evidence for potential tumor-specific systemic immune activation and systemic antitumor effectors elicited by topical DPCP.

Phase II Open-Label, Single-Arm Trial to Investigate the Efficacy and Safety of Topical Remetinostat Gel in Patients with Basal Cell Carcinoma.

PURPOSE: The mainstay of treatment for basal cell carcinoma (BCC) is surgical excision, which can result in significant associated morbidity, particularly for patients with recurrent tumors. We previously conducted a drug repositioning screen using molecular data from human BCCs and identified histone deacetylase (HDAC) inhibitors as a potential treatment for BCC. Here we conduct the first proof-of-principle study of a topical pan-HDAC inhibitor, remetinostat, in human BCC. PATIENTS AND METHODS: We conducted a phase II, open-label, single-arm, single-institution trial of a topical HDAC inhibitor. Participants with at least one BCC were recruited. All participants applied 1% remetinostat gel three times daily for 6 weeks, with measurements of tumor diameter conducted at baseline and week 8. Surgical excision of the remaining tumor was conducted at the end of the study and microscopic evaluation was performed. RESULTS: Thirty-three per-protocol tumors from 25 participants were included in the analysis. The overall response rate, defined as the proportion of tumors achieving more than 30% decrease in the longest diameter from baseline to week 8, was 69.7% [90% confidence interval (CI), 54%-82.5%]. On pathologic examination, 54.8% of tumors demonstrated complete resolution. Pharmacodynamic analysis demonstrated similar levels of acetylated histone H3 in skin tissue before and after treatment, however, phosphorylation was increased. No systemic adverse events were reported. CONCLUSIONS: The HDAC inhibitor remetinostat is a well-tolerated and effective topical treatment for reducing BCC disease burden in a clinically significant manner. This provides in-human validation of HDAC inhibitors as a therapy for BCC.

Dermatology Resident Billing and the Impact of 2021 Evaluation and Management Coding Changes.

New billing rules were implemented in 2021 for determining the level of service in outpatient encounters. The purpose of this study was to assess overall dermatology resident billing at our institution and the impact of these rule changes. Billing codes from four months of our resident clinic were extracted from our electronic medical records (EMR) and analyzed. Nationwide Medicare data for dermatologists were used as a comparison. The coding changes were associated with a 13% increase in level 4 codes and a 20% decrease in level 2 codes. Overall, level 3 codes remained the most common codes submitted. Billing patterns were not concordant with nationwide Medicare utilization.

Eosinophils are surprisingly common in biopsy specimens of cutaneous herpes simplex virus and varicella zoster virus infections: Results of a comprehensive histopathologic and clinical appraisal.

BACKGROUND: While usually straightforward, diagnostic features of cutaneous herpes simplex virus and varicella zoster virus infection (HSV/VZV) are not always present in biopsy specimens. Although intuitively the presence of eosinophils may lead the pathologist away from the diagnosis of cutaneous HSV/VZV infection, in our practice we have noted that eosinophils are often encountered in diagnostic specimens. METHODS: To deduce the frequency with which the inflammatory response accompanying cutaneous HSV/VZV infection includes significant numbers of eosinophils, we performed a retrospective review. We included 159 specimens from our database, diagnosed between 2009 and 2017. We determined the number of eosinophils in 10 high-power fields and noted additional histologic factors including presence of follicular involvement, ulceration, and pseudolymphomatous change. RESULTS: Of all included cases, 63% had 0-1 eosinophils, 24% had 2-10 eosinophils, and 13% had more than 10 eosinophils. Statistical analysis did not reveal a significant association between any demographic or histologic features examined and the presence of increased eosinophils. CONCLUSIONS: In this study, more than one-third of biopsy specimens diagnostic of cutaneous HSV/VZV infection had a prominent number of eosinophils. The detection of eosinophils should not be unexpected and should not lessen diagnostic suspicion for cutaneous HSV/VZV infection.

Impact of World War I on brain mapping.

Although much tragedy was experienced during World War I (WWI), the nature of the war and the advancements of weaponry led to a change in the quality and quantity of injuries which were conducive for study. This paper discusses how trauma during WWI led to advances in brain mapping from occipital injuries. Gordon Holmes was a British neurologist who was able to create a retinotopic map of the visual cortex from studying more than 400 cases of occipital injuries; his work has contributed immensely to our understanding of visual processing. There have been many extensions from Holmes' work in regard to how we analyze other sensory modalities and in researching how the brain processes complex stimuli such as faces. Aside from the scholastic benefit, brain mapping also has functional use and can be used for neurosurgical planning to preserve important structures. With the advent of more advanced modalities for analyzing the brain, there have been initiatives in total brain mapping which has added significantly to the body of work started by Holmes during WWI. This paper reviews the history during WWI that led to advances in brain mapping, the lasting scholastic and functional impact from these advancements, and future improvements.

Timing of Decompressive Craniectomy for Ischemic Stroke and Traumatic Brain Injury: A Review.

While studies have demonstrated that decompressive craniectomy after stroke or TBI improves mortality, there is much controversy regarding when decompressive craniectomy is optimally performed. The goal of this paper is to synthesize the data regarding timing of craniectomy for malignant stroke and traumatic brain injury (TBI) based on studied time windows and clinical correlates of herniation. In stroke patients, evidence supports that early decompression performed within 24 h or before clinical signs of herniation may improve overall mortality and functional outcomes. In adult TBI patients, published results demonstrate that early decompressive craniectomy within 24 h of injury may reduce mortality and improve functional outcomes when compared to late decompressive craniectomy. In contrast to the stroke data, preliminary TBI data have demonstrated that decompressive craniectomy after radiographic signs of herniation may still lead to improved functional outcomes compared to medical management. In pediatric TBI patients, there is also evidence for better functional outcomes when treated with decompressive craniectomy, regardless of timing. More high quality data are needed, particularly that which incorporates a broader set of metrics into decision-making surrounding cranial decompression. In particular, advanced neuromonitoring and imaging technologies may be useful adjuncts in determining the optimal time for decompression in appropriate patients.

Preoperative embolization of skull base meningiomas: current indications, techniques, and pearls for complication avoidance.

Skull base meningiomas are technically challenging tumors to treat because of their deep vascular supply that can preclude early devascularization during resection. Preoperative embolization of these arterial feeders is thought to decrease blood loss and facilitate resection; however, given the complex and varied anatomy of these skull base lesions, preoperative embolization is not without risk. It is essential for both endovascular and skull base neurosurgeons to understand these risks in light of the potential benefits. The authors review the vascular anatomy of skull base meningiomas, indications for preoperative devascularization, endovascular techniques, and published results regarding embolization of these lesions.

Diagnosis and treatment options for sequelae following radiation treatment of brain tumors.

Radiation serves an important role in the treatment of metastatic and primary brain tumors. Radiation carries a risk of post radiation treatment effects, such as pseudoprogression and radiation necrosis. The ability to differentiate between radiation necrosis, pseudoprogression, and tumor recurrence remains a diagnostic conundrum with varying treatment options. In this review, we will discuss the pathophysiology, diagnostic imaging modalities, and treatments of these post-radiation treatment effects. We focus on the latest developments in magnetic resonance imaging (MRI) modalities including imaging biomarkers and the newest therapeutics such as VEGF inhibitors, Hyperbaric Oxygen Therapy, sensitized cytotoxic T cells, and Laser Interstitial Thermal Therapy (LITT).

Optogenetic neuronal stimulation of the lateral cerebellar nucleus promotes persistent functional recovery after stroke.

Stroke induces network-wide changes in the brain, affecting the excitability in both nearby and remotely connected regions. Brain stimulation is a promising neurorestorative technique that has been shown to improve stroke recovery by altering neuronal activity of the target area. However, it is unclear whether the beneficial effect of stimulation is a result of neuronal or non-neuronal activation, as existing stimulation techniques nonspecifically activate/inhibit all cell types (neurons, glia, endothelial cells, oligodendrocytes) in the stimulated area. Furthermore, which brain circuit is efficacious for brain stimulation is unknown. Here we use the optogenetics approach to selectively stimulate neurons in the lateral cerebellar nucleus (LCN), a deep cerebellar nucleus that sends major excitatory output to multiple motor and sensory areas in the forebrain. Repeated LCN stimulations resulted in a robust and persistent recovery on the rotating beam test, even after cessation of stimulations for 2 weeks. Furthermore, western blot analysis demonstrated that LCN stimulations significantly increased the axonal growth protein GAP43 in the ipsilesional somatosensory cortex. Our results demonstrate that pan-neuronal stimulations of the LCN is sufficient to promote robust and persistent recovery after stroke, and thus is a promising target for brain stimulation.