Comparison of electronic brachytherapy and Mohs micrographic surgery for the treatment of early-stage non-melanoma skin cancer: a matched pair cohort study

Purpose: High-dose-rate electronic brachytherapy (EBT) provides a non-surgical treatment option for non-melanoma skin cancer (NMSC). This matched-pair cohort study compared the outcomes of treatment with EBT to those of Mohs micrographic surgery (MMS) in patients with NMSC. Material and methods : At four treatment centers, patients treated with EBT were case matched to patients treated with MMS based on retrospectively-collected patient age, lesion size, location and type, and year of treatment. Follow-up data were prospectively collected and included local recurrence, toxicities, cosmesis, and patient-reported outcomes. Results: The 369 patients (188 in the EBT treatment group and 181 in the MMS treatment group) had 416 lesions (208 in the EBT group and 208 in the MMS group), including 226 basal cell carcinomas (BCC) and 190 squamous cell carcinomas (SCC). Most patients were Caucasian (98.9% and 99.5%) and male (65.4% and 66.3%) of median age 80.7 (range: 61-98) (EBT) and 76.8 (range: 51-98) years (MMS). Most lesions were size > 1 cm and ≤ 2 cm, and located on the head. At mean 3.4 years post-treatment, 99.5% of EBT, and 100.0% of MMS-treated lesions were free of recurrence (p = ns). One recurrence was noted in the EBT group. Physicians rated cosmesis as “excellent” or “good” in 97.6% of EBT-treated lesions, and 95.7% of MMS-treated lesions. Conclusions : This matched-pair cohort study supports the use of EBT as an effective non-surgical treatment option for NMSC with equivalent recurrence rates and cosmetic outcomes to MMS in appropriately-selected patients with early stage NMSC at extended follow-up

Single cell immunophenotyping of the skin lesion erythema migrans Identifies IgM memory B cells

The skin lesion erythema migrans (EM) is an initial sign of the Ixodes tick–transmitted Borreliella spirochetal infection known as Lyme disease. T cells and innate immune cells have previously been shown to predominate the EM lesion and promote the reaction. Despite the established importance of B cells and antibodies in preventing infection, the role of B cells in the skin immune response to Borreliella is unknown. Here, we used single-cell RNA-Seq in conjunction with B cell receptor (BCR) sequencing to immunophenotype EM lesions and their associated B cells and BCR repertoires. We found that B cells were more abundant in EM in comparison with autologous uninvolved skin; many were clonally expanded and had circulating relatives. EM-associated B cells upregulated the expression of MHC class II genes and exhibited preferential IgM isotype usage. A subset also exhibited low levels of somatic hypermutation despite a gene expression profile consistent with memory B cells. Our study demonstrates that single-cell gene expression with paired BCR sequencing can be used to interrogate the sparse B cell populations in human skin and reveals that B cells in the skin infection site in early Lyme disease expressed a phenotype consistent with local antigen presentation and antibody production

Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells

The skin lesion erythema migrans (EM) is an initial sign of the Ixodes tick-transmitted Borreliella spirochetal infection known as Lyme disease. T cells and innate immune cells have previously been shown to predominate the EM lesion and promote the reaction. Despite the established importance of B cells and antibodies in preventing infection, the role of B cells in the skin immune response to Borreliella is unknown. Here, we used single-cell RNA-Seq in conjunction with B cell receptor (BCR) sequencing to immunophenotype EM lesions and their associated B cells and BCR repertoires. We found that B cells were more abundant in EM in comparison with autologous uninvolved skin; many were clonally expanded and had circulating relatives. EM-associated B cells upregulated the expression of MHC class II genes and exhibited preferential IgM isotype usage. A subset also exhibited low levels of somatic hypermutation despite a gene expression profile consistent with memory B cells. Our study demonstrates that single-cell gene expression with paired BCR sequencing can be used to interrogate the sparse B cell populations in human skin and reveals that B cells in the skin infection site in early Lyme disease expressed a phenotype consistent with local antigen presentation and antibody production

Post-Treatment Lyme Disease Symptoms Score: Developing a New Tool for Research

Some patients have residual non-specific symptoms after therapy for Lyme disease, referred to as post-treatment Lyme disease symptoms or syndrome, depending on whether there is functional impairment. A standardized test battery was used to characterize a diverse group of Lyme disease patients with and without residual symptoms. There was a strong correlation between sleep disturbance and certain other symptoms such as fatigue, pain, anxiety, and cognitive complaints. Results were subjected to a Logistic Regression model using the Neuro-QoL Fatigue t-score together with Short Form-36 Physical Functioning scale and Mental Health component scores; and to a Decision Tree model using only the QoL Fatigue t-score. The Logistic Regression model had an accuracy of 97% and Decision Tree model had an accuracy of 93%, when compared with clinical categorization. The Logistic Regression and Decision Tree models were then applied to a separate cohort. Both models performed with high sensitivity (90%), but moderate specificity (62%). The overall accuracy was 74%. Agreement between 2 time points, separated by a mean of 4 months, was 89% using the Decision Tree model and 87% with the Logistic Regression model. These models are simple and can help to quantitate the level of symptom severity in post-treatment Lyme disease symptoms. More research is needed to increase the specificity of the models, exploring additional approaches that could potentially strengthen an operational definition for post-treatment Lyme disease symptoms. Evaluation of how sleep disturbance, fatigue, pain and cognitive complains interrelate can potentially lead to new interventions that will improve the overall health of these patients

Confirmation of Tick Bite by Detection of Antibody to Ixodes Calreticulin Salivary Protein

Ticks introduce a variety of pharmacologically active molecules into their host during attachment and feeding in order to obtain a blood meal. People who are repeatedly exposed to ticks may develop an immune response to tick salivary proteins. Despite this response, people usually are unaware of having been bitten, especially if they are not repeatedly exposed to ticks. In order to develop a laboratory marker of tick exposure that would be useful in understanding the epidemiology of tick-borne infection and the immune response to tick bite, we developed an enzyme-linked immunosorbent assay (ELISA) to detect antibody to a recombinant form of calreticulin protein found in the salivary glands of Ixodes scapularis, a member of a complex of Ixodes ticks that serve as the vectors for Lyme disease, human babesiosis, and human granulocytic anaplasmosis. Using this assay, we tested sera obtained from C3H/HeN and BALB/c mice before and after experimental deer tick infestation. These mice developed antibody to Ixodes calreticulin antigen after infestation. We then used the same assay to test sera obtained from people before and after they experienced deer tick bite(s). People experiencing deer tick bite(s) developed Ixodes calreticulin-specific antibody responses that persisted for up to 17 months. This Ixodes recombinant calreticulin ELISA provides objective evidence of deer tick exposure in people