Efficacy and Durability of Intravenous Ertapenem Therapy for Recalcitrant Hidradenitis Suppurativa.

Importance: Hidradenitis suppurativa (HS) is a debilitating follicular skin disorder in which bacterial colonization is typical. Oral antibiotic efficacy can be unreliable; however, selective intravenous antibiotics, specifically ertapenem, may provide favorable clinical outcomes. Objective: To explore optimal course duration, efficacy, and patient satisfaction associated with intravenous ertapenem for HS. Design, Setting, and Participants: This retrospective review of the medical records of 98 patients with HS between 2018 and 2022 measured and evaluated patient outcomes before and after treatment with intravenous ertapenem. Participants were followed up in a telephone survey assessing patient perspectives and satisfaction. All of those included in this study received medical care from the Albert Einstein College of Medicine's Montefiore HS Center. Exposures: Patients were treated with 1 g of ertapenem that was self-administered at home through a peripheral intravenous central catheter using an elastomeric pump for 12 to 16 weeks. Antiandrogens and immunomodulatory biologic therapies initiated prior to ertapenem were maintained throughout the treatment course. Main Outcomes and Measures: The primary outcomes, encompassing clinical severity (evaluated through the HS Physician Global Assessment score [a 6-point scale ranging from clear to very severe] and a numerical rating scale for pain [an 11-point scale in which a score of 0 indicates no pain and a score of 10 indicates the worst possible pain]) and markers of inflammation (such as leukocytes, erythrocyte sedimentation rate, C-reactive protein, and interleukin-6), were measured at baseline, the midcourse of intravenous ertapenem treatment, at the end of the course, and posttherapy. Bacterial abundance was also examined at these 4 points, and patient satisfaction was assessed during follow-up. Results: A total of 98 patients (mean [SD] age, 35.8 [13.0] years; 61 [62.2%] female) with HS were treated with intravenous ertapenem. The self-reported racial distribution included 3 individuals identifying as Asian (3.1%), 59 as Black/African American (60.2%), 13 as White (13.3%), and 23 as either other or unknown (23.5%). Additionally, 24 participants (24.5%) reported Spanish/Hispanic/Latino ethnicity. The mean (SD) treatment duration spanned 13.1 (4.0) weeks, with posttherapy follow-up occurring after 7.8 (3.6) weeks. From baseline to posttherapy follow-up, significant reductions were found in the mean (SD) HS Physician Global Assessment scores (3.9 [1.0] vs 2.7 [1.2]; P < .001) and the numerical rating scale for pain (4.2 [3.3] vs 1.8 [2.7]; P < .001), C-reactive protein (5.4 [11.4] vs 2.4 [2.0] mg/dL; P < .001), interleukin-6 (25.2 [21.1] vs 13.7 [13.9]; P < .001), and leukocytes (11.34 [3.9] vs 10.0 [3.4]; P < .001). At follow-up, 76 patients (78.0%) participated in the telephone survey, where 63 (80.3%) reported medium to high satisfaction; further, 69 (90.8%) would recommend ertapenem to other patients. Conclusions and Relevance: In this retrospective review of medical records and telephone survey, treating HS with intravenous ertapenem, administered for a mean of 13 weeks, was associated with improvement in clinical and inflammatory markers, as well as heightened patient satisfaction. Nonetheless, this approach should be monitored for the emergence of antimicrobial resistance given a longer than standard treatment course.

Therapeutic implications of transcriptomics in head and neck cancer patient-derived xenografts.

There are currently no clinical strategies utilizing tumor gene expression to inform therapeutic selection for patients with head and neck squamous cell carcinoma (HNSCC). One of the challenges in developing predictive biomarkers is the limited characterization of preclinical HNSCC models. Patient-derived xenografts (PDXs) are increasingly recognized as translationally relevant preclinical avatars for human tumors; however, the overall transcriptomic concordance of HNSCC PDXs with primary human HNSCC is understudied, especially in human papillomavirus-associated (HPV+) disease. Here, we characterized 64 HNSCC PDXs (16 HPV+ and 48 HPV-) at the transcriptomic level using RNA-sequencing. The range of human-specific reads per PDX varied from 64.6%-96.5%, with a comparison of the most differentially expressed genes before and after removal of mouse transcripts revealing no significant benefit to filtering out mouse mRNA reads in this cohort. We demonstrate that four previously established HNSCC molecular subtypes found in The Cancer Genome Atlas (TCGA) are also clearly recapitulated in HNSCC PDXs. Unsupervised hierarchical clustering yielded a striking natural division of HNSCC PDXs by HPV status, with C19orf57 (BRME1), a gene previously correlated with positive response to cisplatin in cervical cancer, among the most significantly differentially expressed genes between HPV+ and HPV- PDXs. In vivo experiments demonstrated a possible relationship between increased C19orf57 expression and superior anti-tumor responses of PDXs to cisplatin, which should be investigated further. These findings highlight the value of PDXs as models for HPV+ and HPV- HNSCC, providing a resource for future discovery of predictive biomarkers to guide treatment selection in HNSCC.

Caveolin-1 and Sox-2 are predictive biomarkers of cetuximab response in head and neck cancer.

The epidermal growth factor receptor (EGFR) inhibitor cetuximab is the only FDA-approved oncogene-targeting therapy for head and neck squamous cell carcinoma (HNSCC). Despite variable treatment response, no biomarkers exist to stratify patients for cetuximab therapy in HNSCC. Here, we applied unbiased hierarchical clustering to reverse-phase protein array molecular profiles from patient-derived xenograft (PDX) tumors and revealed 2 PDX clusters defined by protein networks associated with EGFR inhibitor resistance. In vivo validation revealed unbiased clustering to classify PDX tumors according to cetuximab response with 88% accuracy. Next, a support vector machine classifier algorithm identified a minimalist biomarker signature consisting of 8 proteins - caveolin-1, Sox-2, AXL, STING, Brd4, claudin-7, connexin-43, and fibronectin - with expression that strongly predicted cetuximab response in PDXs using either protein or mRNA. A combination of caveolin-1 and Sox-2 protein levels was sufficient to maintain high predictive accuracy, which we validated in tumor samples from patients with HNSCC with known clinical response to cetuximab. These results support further investigation into the combined use of caveolin-1 and Sox-2 as predictive biomarkers for cetuximab response in the clinic.

Mohs Micrographic Surgery for Genital Skin Cancer: A Review of Cases and Reconstructive Techniques.

As the incidence of non-melanoma skin cancer (NMSC) increases in the United States, one area of particular concern is NMSC arising on the genitalia. In the past, most genital skin tumors have been treated by conventional radical surgical approaches such as penectomy, vulvectomy, or wide local excision. In recent years, tissue sparing Mohs micrographic surgery (MMS) has been established as a safe and effective method of achieving cutaneous genital tumor clearance. The aim of this article is to provide an overview of NMSCs arising on genital skin treated with MMS, and describe some of their indications, results, and associated complications. A summary of case reports, case series, and retrospective reviews is made available to guide decision making and surgical planning for tumors of this nature. Pertinent anatomy, site-specific surgical techniques, and reconstruction options of genital skin will be discussed. J Drugs Dermatol. 2021;20(3):311-319. doi:10.36849/JDD.5656.

Understanding the Dizziness Handicap Inventory (DHI): A Cross Sectional Analysis of Symptom Factors That Contribute to DHI Variance.

OBJECTIVE: The Dizziness Handicap Inventory (DHI) is the most commonly used quality of life measure for vestibular disorders. However, there is wide variability in scores, and little is known about which variables contribute to dizziness-related quality of life. Our goal was to investigate the key demographic and symptom-related factors to that account for DHI variance. STUDY DESIGN: Cross-sectional survey. SETTING: Tertiary referral center. PATIENTS: Adult patients presenting to a dizziness clinic. MAIN OUTCOME MEASURE: DHI variance explained by multiple linear regression. RESULTS: Seventy subjects were included in our study. We performed univariate analyses on numerous demographic and dizziness-related factors, and constructed a multivariate model based on explaining the highest variance in the data with the least number of independent variables. Several validated quality of life and mental health survey scores (SF-36-quality of life; PHQ-9-depression; and GAD-7-anxiety) were significantly correlated with higher DHI scores. Additional factors, including the number of dizzy days per month, the number of dizziness descriptors (spinning, lightheadedness, disequilibrium, etc.), and the number of dizziness triggers (loud sounds, stress, riding in a car, etc.), were all significantly associated with higher DHI scores; a multiple linear regression model showed that these three aforementioned factors combined accounted for 56% of the variability in the DHI scores (p < 0.0001). Adding an index of depression, as measured by the PHQ-9, increased the adjusted R to 64% (p < 0.0001). CONCLUSIONS: DHI score variability is explained by mental health and quality-of-life measures in addition to the daily burden of dizziness.

Intraoperative Three-dimensional Virtual Reality and Computed Tomographic Guidance in Temporomandibular Joint Arthroplasty of Syndromic Craniofacial Dysostoses.

Bony ankylosis of the temporomandibular joints (TMJ) occurs in up to 28% of patients with syndromic mandibular dysostoses. Release of complete osseous ankylosis is particularly challenging due to the lack of tissue planes separating the mandible from the skull base and the presence of congenital skeletal abnormalities. One recent advance in surgical imaging technology is three-dimensional virtual reality (3D VR), now in common use in neurosurgical resections. In this study, we describe the usage of 3D VR in TMJ arthroplasty and compare 3D VR to traditional computed tomographic (CT) guidance. Pediatric patients with syndromic mandibular micrognathia including Treacher Collins, Nager, and cerebrocostomandibular syndrome were retrospectively evaluated between 2008 and 2016. Patient characteristics, complications, inpatient times, and operative times were recorded. Of the 29 children with syndromic mandibular micrognathia treated between 2008 and 2016, 7 were diagnosed with TMJ ankyloses. Four consecutive pediatric patients (mean 8.7 years) undergoing interpositional TMJ arthroplasty with Matthews device placement were retrospectively evaluated. Two patients underwent traditional CT-guided versus 3D VR-guided temporomandibular joint arthroplasty (TMJA). No statistically significant differences were found among the age, complications, or inpatient hospitalization times. The average operative time in the traditional CT guidance group was 300 minute versus 134 minutes in the 3D VR group. Three-dimensional VR is a useful preoperative planning and intraoperative guidance tool. The major difference between VR and older technologies is the improved imaging in 3 dimensions for guidance, thereby potentially decreasing operative times.

Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer.

PIK3CA is the most commonly altered oncogene in head and neck squamous cell carcinoma (HNSCC). We evaluated the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on survival in a PIK3CA-characterized cohort of 266 HNSCC patients and explored the mechanism in relevant preclinical models including patient-derived xenografts. Among subjects with PIK3CA mutations or amplification, regular NSAID use (≥6 mo) conferred markedly prolonged disease-specific survival (DSS; hazard ratio 0.23, P = 0.0032, 95% CI 0.09-0.62) and overall survival (OS; hazard ratio 0.31, P = 0.0043, 95% CI 0.14-0.69) compared with nonregular NSAID users. For PIK3CA-altered HNSCC, predicted 5-yr DSS was 72% for NSAID users and 25% for nonusers; predicted 5-yr OS was 78% for regular NSAID users and 45% for nonregular users. PIK3CA mutation predicted sensitivity to NSAIDs in preclinical models in association with increased systemic PGE2 production. These findings uncover a biologically plausible rationale to implement NSAID therapy in PIK3CA-altered HNSCC.