Browsing by Author "Chauhan, Ruvi"

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    Age at Diagnosis as a Relative Contraindication for Intervention in Facial Nonmelanoma Skin Cancer
    (American Medical Association, 2018-04-01) Chauhan, Ruvi; Munger, Brook N.; Chu, Michael W.; Munshi, Imtiaz; Cohen, Adam C.; Wooden, William A.; Tholpady, Sunil S.; Surgery, School of Medicine
    Facial nonmelanoma skin cancers (fNMSCs), consisting of basal cell carcinoma and squamous cell carcinoma, are the most common cancers diagnosed worldwide and increase with age. Standard treatment for fNMSCs requires biopsy for pathological confirmation, followed by excision. Excision can lead to a pathological diagnosis of no residual carcinoma (NRC) due to no identifiable carcinoma within the excisional specimen. This situation can occur owing to wound healing in the specimen clearing the carcinoma or to the original biopsy shaving off the entire lesion. This study assesses the utility of excising fNMSCs according to age, with the hypothesis that the indolent nature of fNMSCs and the high NRC rate, coupled with increasing age-related all-cause mortality, should cause the surgeon to counsel patients differently. Such counseling may prevent surgery among elderly patients (>90 years) who may never see a benefit from fNMSC excision.
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    Immunomodulatory Effects of Oxylipin 10-HOME Produced by Biofilm Results in Host-Biofilm Interaction in Breast Implant Illness
    (Wolters Kluwer, 2022) Khan Mohammed, Imran; Minto, Robert; Kelley-Patteson, Christine; Timsina, Lava; Singh, Kanhaiya; Van Natta, Bruce W.; Mohan, Ganesh; Chauhan, Ruvi; Lester, Mary; Hassanein, Al; Gordillo, Gayle M.; Sen, Chandan; Kadin, Marshall; Sinha, Mithun; Surgery, School of Medicine
    PURPOSE: The spread of biofilms on medical implants represents one of the principal triggers of persistent and chronic infections in clinical settings. Nearly 300,000 women annually have breast implant surgery in the United States, for reasons including post-mastectomy breast reconstruction, revision of prior augmentation/ reconstruction, cosmetic augmentation, and gender affirmation. There has been increased identification of patients experiencing a constellation of symptoms related to their implants termed as breast implant illness (BII). In this work, we report that bacterial biofilm associated with breast implant, metabolize fatty acid oleic acid present in the breast tissue milieu to oxylipins, one such oxylipin identified from this study is (E)-10-hydroxy-8-octadecenoic acid (10-HOME). We hypothesize that immunomodulatory effects of oxylipin 10-HOME produced by biofilm present on the implant could be a possible etiology for BII pathogenesis. METHOD: Implants, peri-prosthetic tissues and blood was collected from BII subjects (n=46) and two control groups, group I, (non-BII, n=34) patients with breast implants, no BII symptoms. Group II (normal tissue, n = 20), patients without an implant, whose breast tissue was removed due to surgical procedures. A questionnaire developed based on epidemiological studies on BII screened for the commonly reported symptoms associated with BII. Predictive variables included age, diabetes status, co-morbidities, type (smooth/textured) and duration of implant. Scanning electron microscopy (SEM), 16S rRNA (genomic) next generation sequencing (NGS) were used for bacterial biofilm identification. 10-HOME was quantitated through targeted and untargeted lipidomic analyses using LC-MS-MS. RNA-Seq analysis was performed on peri-prosthetic breast tissues. Flow cytometry and mass cytometry (CyToF) were conducted to investigate the role of immune cells. RESULTS: Bacterial biofilm was detected through SEM and 16SrRNA NGS. Bivariate analysis using cross-tabulation was performed between presence of biofilm and the study groups. Using the two-sample test of proportions with z-tests, Staphylococcus epidermidis colonization was observed to be higher in the BII group (73.33%) compared to non-BII group (16.67%, p=0.018) and the normal group (10%, p=0.036). The BII group was 2.4 times more likely to have S. epidermidis colonization compared to the non-BII group (Odds Ratio=2.4). Similarly, when comparing with normal group, the BII group was 3.4 times more likely to have S. epidermidis. Elevated levels of 10-HOME in BII compared to non-BII samples, (p<0.0001) were observed through mass spectrometry. Positive correlation was observed between bacterial abundance and concentration of 10-HOME in BII subjects (R2=0.88). RNA-Seq analysis on peri-prosthetic tissue and flow/ mass cytometry analyses from peripheral blood derived lymphocytes showed increased abundance of CD4+ Th1 cells. Th1 cells have been reported to be activated in auto-immune diseases. No significant difference was observed in the abundance of other Th subtypes (Th2, Th9 and Th22). Oxylipin 10-HOME polarized CD4+ naïve T cells to Th1 subtype in vitro. CONCLUSION: This study investigated the biofilm hypothesis of BII through a biofilm derived immunogenic metabolite. Through a systematic cause-effect based studies, the work shows activation of Th1 cells in presence of 10-HOME. The study provides the first evidence of a possible etiology of BII mediated via bacterial biofilm derived 10-HOME.
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    Oxylipins in Breast Implant–Associated Systemic Symptoms
    (Oxford University Press, 2024) Khan, Imran; Timsina, Lava; Chauhan, Ruvi; Ingersol, Christopher; Wang, David R.; Rinne, Ethan; Muraru, Rodica; Mohan, Ganesh; Minto, Robert E.; Van Natta, Bruce W.; Hassanein, Aladdin H.; Kelley-Patteson, Christine; Sinha, Mithun; Surgery, School of Medicine
    Background: A subset of females with breast implants have reported a myriad of nonspecific systemic symptoms collectively termed systemic symptoms associated with breast implants (SSBI). SSBI symptoms are similar to manifestations associated with autoimmune and connective tissue disorders. Breast tissue is rich in adipose cells, comprised of lipids. Insertion of an implant creates an oxidative environment leading to lipid oxidation. Oxylipins can influence immune responses and inflammatory processes. Objectives: In this study we explored the abundance of a spectrum of oxylipins in the periprosthetic tissue surrounding the breast implant. Because oxylipins are immunogenic, we sought to determine if they were associated with the SSBI patients. We have also attempted to determine if the common manifestations exhibited by such patients have any association with oxylipin abundance. Methods: The study included 120 patients divided into 3 cohorts. We analyzed 46 patients with breast implants exhibiting manifestations associated with SSBI; 29 patients with breast implants not exhibiting manifestations associated with SSBI (control cohort I, non-SSBI); and 45 patients without implants (control cohort II, no-implant tissue). Lipid extraction and oxylipin quantification were performed with liquid chromatography mass spectrometry (LC-MS/MS). LC-MS/MS targeted analysis of the breast adipose tissue was performed. Results: Of the 15 oxylipins analyzed, 5 exhibited increased abundance in the SSBI cohort when compared to the non-SSBI and no-implant cohorts. Conclusions: The study documents the association of the oxylipins with each manifestation reported by the patient. This study provides an objective assessment of the subjective questionnaire, highlighting which symptoms may be more relevant than the others.