Neuropathic pain presenting as dermatologic symptoms can occur when damaged or dysfunctional nerves manifest with symptoms that resemble skin-related conditions. We present a case of a 62-year-old male who presented with burning pain and redness in the perineum and gluteal cleft. Initially, the patient was treated for dermatologic symptoms, resulting in the resolution of erythema. However, the pain persisted, prompting a neurologic workup. Despite the improvement of skin symptoms, the patient's pain persisted, prompting a neurological workup. Diagnostic imaging revealed significant degenerative changes in the lumbar spine, supporting a neuropathic etiology. This case highlights the importance of considering neurologic disorders in dermatologic practice, especially when cutaneous symptoms persist despite appropriate dermatological treatments.
Environments can change in incremental fashions, where a shift from one state to another occurs over multiple organismal generations. The rate of the environmental change is expected to influence how and how well populations adapt to the final environmental state. We used a model system, the lytic RNA bacteriophage Φ6, to investigate this question empirically. We evolved viruses for thermostability by exposing them to heat shocks that increased to a maximum temperature at different rates. We observed increases in the ability of many heat-shocked populations to survive high temperature heat shocks. On their first exposure to the highest temperature, populations that experienced a gradual increase in temperature had higher average survival than populations that experienced a rapid temperature increase. However, at the end of the experiment, neither the survival of populations at the highest temperature nor the number of mutations per population varied significantly according to the rate of thermal change. We also evaluated mutations from the endpoint populations for their effects on viral thermostability and growth. As expected, some mutations did increase viral thermostability. However, other mutations decreased thermostability but increased growth rate, suggesting that benefits of an increased replication rate may have sometimes outweighed the benefits of enhanced thermostability. Our study highlights the importance of considering the effects of multiple selective pressures, even in environments where a single factor changes.
Background/Objectives: Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are non-melanoma skin cancers (NMSCs) and the most prevalent cancers in the United States. Image-guided superficial radiotherapy (IGSRT) is a relatively new treatment option that uses high-resolution dermal ultrasound integrated with superficial radiotherapy to improve tumor visualization. IGSRT is a clinically equivalent non-surgical alternative to Mohs micrographic surgery at 2 years of follow-up in early-stage NMSC, but larger cohort studies with longer follow-up periods that allow for analysis of patient outcomes by demographic and disease characteristics are needed. Methods: This large, retrospective cohort study was conducted to determine the effect of risk factors (tumor location, tumor stage, and sex) on 2-, 4-, and 6-year freedom from recurrence rates in 19,988 NMSC lesions treated with IGSRT, including lesions with complete treatment courses. Results: Overall freedom from recurrence rates were 99.68% at 2 years, 99.54% at 4 years, and 99.54% at 6 years; rates did not differ significantly by tumor location (head/neck versus other locations, p = 0.9) or sex (male versus female, p = 0.4). In contrast, there was a significant difference in freedom from recurrence rates when analyzed by tumor stage (p = 0.004). Conclusions: There was no significant effect of tumor location or sex on freedom from recurrence in IGSRT-treated NMSC. Although there was a significant difference according to tumor stage, freedom from recurrence rates exceeded 99% at all stages.
Summary Advances in the treatment of Ewing’s sarcoma (EWS) are desperately needed, particularly in the case of metastatic disease. A deeper understanding of collateral sensitivity, where the evolution of therapeutic resistance to one drug aligns with sensitivity to another drug, may improve our ability to effectively target this disease. For the first time in a solid tumor, we produced a temporal collateral sensitivity map that demonstrates the evolution of collateral sensitivity and resistance in EWS. We found that the evolution of collateral resistance was predictable with some drugs, but had significant variation in response to other drugs. Using this map of temporal collateral sensitivity in EWS, we can see that the path towards collateral sensitivity is not always repeatable, nor is there always a clear trajectory towards resistance or sensitivity. Identifying transcriptomic changes that accompany these states of transient collateral sensitivity could improve treatment planning for EWS patients.
ABSTRACT Importance This is the first study to quantify the 2-year recurrence rate of non-melanoma skin cancers (NMSCs) treated with image-guided superficial radiation therapy (IGSRT) and compare it to existing data on SRT, which is key to demonstrating the efficacy of IGSRT. Objective To quantify the 2-year recurrence rate for individuals with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and squamous carcinoma in-situ (SCCIS) treated with IGSRT versus SRT without image guidance. Design A retrospective cohort study that collected data from a standardized electronic medical record (Modernizing Medicine – EMA), written radiation treatment records, and record/verify system (Sensus Healthcare – Sentinel) to evaluate the 2-year recurrence rate of NMSCs treated by IGSRT (March 2016 to January 2022) and compare it to existing data on NMSCs treated by SRT via one sample proportion tests. Setting Multi-institution outpatient dermatology practices. Participants Individuals > 18 years old with biopsy-proven SCC, SCCIS, and/or BCC treated with IGSRT. 1602 patients with a total of 2,880 treated lesions were followed until 1/14/2022. As of that date, 22 lesions had recurred, and 2858 lesions were still at risk for recurrence. An 18-month cutoff for recency of assessment was utilized, resulting in 1204 lesions (41.8%) that were lost to follow-up. Exposure Treatment with IGSRT or SRT. Main Outcomes The overall 2-year recurrence probability of 2880 NMSCs treated by IGSRT was 0.7%, which is statistically significantly lower than two previously reported SRT studies (p < 0.001). Results All NMSCs (SCC, SCCIS, BCC) treated by IGSRT in this cohort had an aggregate 2-year freedom from recurrence of 99.23%. When stratified by NMSC histologic type, the recurrence rate for BCC was 1.1%(N=1382), for SCC 0.8% (N=904) and for SCC 0.0% (N=594). These rates of recurrence are significantly improved compared to a pooled study that evaluated NMSCs across histology (Cognetta) and BCCs alone (Silverman) treated without image guidance (standard SRT) (p < 0.001). Conclusions and relevance Image-guided superficial radiation (IGSRT) therapy offers a paradigm-shifting treatment option for patients with NMSCs – offering statistically significantly improved outcomes compared to standard SRT, and a more desirable toxicity profile to surgical options. This study demonstrates that this treatment modality is associated with remarkably low recurrence rates, which are statistically significantly improved from the previous generation of SRT, and in line with modern outcomes for Mohs micrographic surgery, though a head-to-head comparison has yet to be performed. Key Points Question Does treatment by new generation image-guided superficial radiation therapy (IGSRT) improve the rates of recurrence of nonmelanoma skin cancers (NMSCs) compared to non-image-guided SRT? Findings This cohort study evaluated the recurrence rates of 2880 NMSCs treated with IGSRT. In this dataset, the 2-year rate of recurrence for IGSRT-treated NMSCs collectively was 0.7%. This is statistically significantly lower than the recurrence rates of NMSC treated by SRT without image guidance (1.9% Cognetta; 6.3% Silverman). Meaning Recurrence rates in NMSCs when treated with IGSRT are statistically significantly improved from SRT without image guidance, supporting the use of this new technology in clinical practice.
Non-melanoma skin cancers (NMSCs) are the most common cancers in the USA, and their incidence is rising. Mohs micrographic surgery (MMS) is commonly performed to excise NMSCs. MMS replaced superficial radiotherapy (SRT) as a first line treatment, given its superior efficacy. Image-guided superficial radiation therapy (IGSRT) was invented to improve the precision of SRT. This study investigates how the 2-year recurrence probability of IGSRT-treated NMSCs compares to that of MMS-treated lesions.This retrospective cohort study compared the 2-year recurrence probability of early stage NMSCs (squamous and basal cell carcinomas (SCCs and BCCs)) treated by IGSRT (2,286 lesions) to data on NMSCs treated by MMS (5,391 lesions) via one sample proportion tests. Medical Subject Headings were used to search PubMed for reports of 2-year recurrence probability rates of NMSCs treated by MMS. Seventeen studies were screened; 14 studies were excluded for lack of 2-year time to event analysis, or irrelevant patient population (non-BCC/SCC study, advanced disease), leaving 3 studies for comparison.IGSRT-treated NMSCs have a statistically significantly improved 2-year recurrence probability than those treated by MMS, P < 0.001 for pooled data.The 2-year recurrence probability IGSRT-treated NMSCs is superior to MMS-treated and supports IGSRT as an effective treatment option for individuals with early stage NMSCs.
Abstract Environments can change in incremental fashions, where a shift from one state to another occurs over multiple organismal generations. The rate at which the environment changes is expected to influence how and how well populations adapt to the ultimate environment. We used a model system, the lytic RNA bacteriophage Φ6, to investigate this question empirically. We evolved viruses for thermostability by exposing them to heat shocks that increased to a maximum temperature at different rates. We observed increases in the ability of many heat-shocked populations to survive high temperature heat shocks, and on their first exposure to the highest temperature, populations that experienced a gradual increase in temperature had higher average survival than populations that experienced a rapid temperature increase. However, at the end of the experiment, neither the survival of populations at the highest temperature nor the number of mutations per population varied significantly according to the rate of thermal change. We also evaluated mutations from the endpoint populations for their effects on viral thermostability and growth. As expected, some mutations did increase viral thermostability. However, other mutations decreased thermostability but increased growth rate, suggesting that benefits of an increased replication rate may have sometimes outweighed the benefits of enhanced thermostability. Our study highlights the importance of considering the effects of multiple selective pressures, even in environments where a single factor is changing.
This is the first study to quantify the 2-year freedom from recurrence for individuals with nonmelanoma skin cancer (NMSC) such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and squamous carcinoma in situ (SCCIS) treated with image guided superficial radiation therapy (IGSRT) versus SRT without image guidance. This retrospective cohort study evaluates the 2-year freedom recurrence rate of NMSCs treated by IGSRT (March 2016 to January 2022) and compares it to existing data on NMSCs treated by SRT via 1 sample proportion tests. Individuals >18 years old with biopsy-proven SCC, SCCIS, and/or BCC treated with IGSRT were included in the study, and 1602 patients/2880 treated lesions were followed until January 14, 2022. SRT literature was identified through an Ovid Medline search. All NMSCs treated by IGSRT in this cohort had an aggregate 2-year freedom from recurrence of 99.23%. The recurrence rate for BCC (N = 1382) was 1.1%, for SCC (N = 904) 0.8%, and for SCCIS (N = 594) 0.0%. These recurrence rates are significantly improved compared with a pooled study that evaluated NMSCs across histology and BCCs alone treated without image guidance (standard SRT) ( IGSRT offers a paradigm-shifting treatment option for patients with NMSCs - offering statistically significantly improved outcomes compared with standard SRT and a more desirable toxicity profile to surgical options. This study demonstrates that IGSRT is associated with remarkably low recurrence rates, which are statistically significantly improved from the previous generation of SRT and in line with modern outcomes for Mohs micrographic surgery.
A morbidostat is a bioreactor that uses antibiotics to control the growth of bacteria, making it well-suited for studying the evolution of antibiotic resistance. However, morbidostats are often too expensive to be used in educational settings. Here we present a low-cost morbidostat called the EVolutionary biorEactor (EVE) that can be built by students with minimal engineering and programming experience. We describe how we validated EVE in a real classroom setting by evolving replicate Escherichia coli populations under chloramphenicol challenge, thereby enabling students to learn about bacterial growth and antibiotic resistance.
Abstract The morbidostat automatically adjusts antibiotic concentration as a bacterial population evolves resistance. Although this device has advanced our understanding of the evolutionary and ecological processes that drive antibiotic resistance, no low-cost and open-source systems are available for educators. Here, we present the EVolutionary biorEactor (EVE), an accessible alternative to other morbidostats for use in low-resource classrooms that requires minimal engineering and programming experience. We first compare our system to others, emphasizing how it differs in design and cost. We then describe how we validated the EVE by evolving replicate Escherichia coli populations under chloramphenicol challenge and comparing our results to those in the published literature. Lastly, we detail how high school students used the EVE to learn about bacterial growth and antibiotic resistance.
