Association of Prophylaxis and Length of Stay With Venous Thromboembolism in Abdominopelvic Surgery.

INTRODUCTION: Extended venous thromboembolism prophylaxis (eVTEp) is recommended for select patients who have undergone major abdominopelvic surgery to prevent postdischarge venous thromboembolism (pdVTE). Criteria for selection of these patients are untested for this purpose and may be ineffective. To address this gap, we investigated the effectiveness of eVTEp on pdVTE rates. METHODS: A retrospective cohort study of patients undergoing abdominopelvic surgery from January 2016 to February 2020 was performed using data from the Michigan Surgical Quality Collaborative. pdVTE was the main outcome. Our exposure variable, eVTEp, was compared dichotomously. Length of stay (LOS) was compared categorically using clinically relevant groups. Age, race, cancer occurrence, inflammatory bowel disease, surgical approach, and surgical time were covariates among other variables. Descriptive statistics, propensity score matching, and multivariable logistic regression were performed to compare pdVTE rates. RESULTS: A total of 45,637 patients underwent abdominopelvic surgery. Of which, 3063 (6.71%) were prescribed eVTEp. Two hundred eighty-five (0.62%) had pdVTE. Of the 285, 59 (21%) patients received eVTEp, while 226 (79%) patients did not. After propensity score matching, multivariable logistic regression analysis showed pdVTE was associated with eVTEp and LOS of 5 d or more (P < 0.001). eVTEp was not associated with LOS. Further analysis showed increased risk of pdVTE with increasing LOS independent of prescription of eVTEp based on known risk factors. CONCLUSIONS: pdVTE was associated with increasing LOS but not with other VTE risk factors after propensity score matching. Current guidelines for eVTEp do not include LOS. Our findings suggest that LOS >5 d should be added to the criteria for eVTEp.

Histologic progression of acne inversa/hidradenitis suppurativa: Implications for future investigations and therapeutic intervention.

Since first recognized in 1839, the pathogenesis of acne inversa (AI) has undergone repeated revisions. Although there is agreement that AI involves occlusion of hair follicles with subsequent inflammation and the formation of tracts, the histologic progression of this disease still requires refinement. The objective of this study was to examine the histologic progression of AI based on the examination of a large cohort of punch biopsies and excisional samples that were examined first by hematoxylin and eosin staining. The most informative of these samples were step-sectioned and stained by immunohistochemistry for epithelial and inflammatory markers. Based on this examination, the following observations were made: 1) AI arises from the epithelium of the infundibulum of terminal and vellus hairs; 2) These form cysts and epithelial tendrils that extend into soft tissue; 3) Immunohistochemical staining demonstrates the epithelium of AI is disordered with infundibular and isthmic differentiation and de novo expression of stem cell markers; 4) The inflammatory response in AI is heterogeneous and largely due to cyst rupture. The conclusions of this investigation were that AI is an epithelial-driven disease caused by infiltrative, cyst forming tendrils and most of the inflammation is due to cyst rupture and release of cornified debris and bacteria. Cyst rupture often occurs below the depths of punch biopsy samples indicating their use for analysis may give an incomplete picture of the disease. Finally, our data suggest that unless therapies inhibit tendril development, it is unlikely they will cause prolonged treatment-induced remission in AI.

Microdermal Implants Show No Effect on Surrounding Tissue During Surgery With Electrocautery.

BACKGROUND: Microdermal implants are an increasingly popular form of body jewelry. The potential for electrical conduction burn at the site of metal jewelry left in situ during electrosurgery has prompted surgical societies to recommend routine removal before surgery. To date, however, there is a lack of evidence to support this practice. We assessed in vivo thermal effect and tissue damage around implants during and after electrocautery. MATERIALS AND METHODS: Stainless steel microdermal anchors were surgically implanted into four swine. After allowing for initial healing, negative controls were excised and evaluated. An electrocautery grounding pad was placed 2 cm caudal to the implant. Continuous electrocautery (coagulation/30 W) for 30 s was applied to the skin 2 cm cranial to the implant. Surface skin temperature was recorded during electrocautery using thermal imaging. Tissue damage was assessed by gross examination and histologic evaluation. The same procedure was then performed to the contralateral nonimplanted side as a sham control. RESULTS: Electrocoagulation raised skin temperature around the electrocautery tip 27.7°C (Tmax 64.8°C). Skin temperature around the dermal implant rose 1.58°C (Tmax 38.6°C) compared with 2.03°C (Tmax 39.2°C) in the nonimplanted control skin (P = 0.627). Skin temperatures at implanted and control sites showed no statistical difference at any recorded time interval. Histologic review of excised tissue samples showed no evidence of thermal injury. CONCLUSIONS: Metallic implants appear to have no effect on skin temperature during the use of electrocautery even when in close proximity to both the electrocautery pen and return pad. Aggressive steps to remove microdermal implants before surgery may be unnecessary.

Incisional Hernia Repair: What the Radiologist Needs to Know.

OBJECTIVE: Incisional hernias are becoming more prevalent with increases in the obesity of the population and the complexity of abdominal surgeries. Radiologists' understanding of these hernias is limited. This article examines abdominal wall anatomy, surgical techniques, the role of imaging (current and emerging), and complications from the surgical perspective, to enhance to the role of the radiologist. CONCLUSION: Knowledge of the relevant anatomy, surgical techniques, and postoperative complications in patients with incisional hernial repair can help the radiologist improve care.

35-Year Experience with Surgical Treatment of Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa is a painful and disfiguring chronic inflammatory condition affecting both men and women. Medical treatments, such as antibiotics and immunosuppressive agents, are often ineffective. Over time, patients can suffer from recurrent abscesses, chronic purulent drainage, scarring, and contractures that can only be corrected by surgical excision. There is no agreement, however, on the best way for the surgeon to manage this condition. The purpose of this review is to describe the results of surgical treatment of this condition in a large cohort of patients managed by local excision of hidradenitis, healing by secondary intention and reoperation as needed. STUDY DESIGN: A retrospective review was conducted of all patients operated on by the author for hidradenitis over a 35-year period. Specific data abstracted included patient age, weight, admission, length of stay, wound size, type of wound care, number of post-op visits, time to heal, and recurrence. Most wounds healed by secondary intention and were managed using simple tap water-moistened plain gauze dressings changed three times a day. RESULTS: From 1979 through 2014, 122 patients (56 men and 66 women), median age 38, underwent 245 operations for hidradenitis suppurativa. Patients underwent from 1 to 10 procedures; 61 patients (50%) underwent two or more procedures; and 26 (21%) underwent three or more. Wound sizes at operation ranged from quite small to over 1500 cm2. Men were older (42 vs 34 years, p < 0.001) and had larger median wound size (98 vs 55 cm2, p < 0.001). A total of 197 wounds healed by secondary intention: 83 of these (median size 159 cm2) were left completely open at the time of surgery; 117 (median size 100 cm2) were partially closed. A total of 30 wounds (median size 38 cm2) were closed primarily; 15 (median size 196 cm2) were closed by skin graft. Patients undergoing 139 procedures were admitted to the hospital for the initial wound care. Their median combined total wound size was 160 cm2; length of stay was 5.5 days; and median time to heal was 60 days. In total, 106 procedures were ambulatory; median wound size was 30 cm2; and median time to heal was 40 days. Recurrent or new disease was common, with some patients requiring multiple procedures over many years to maintain control of symptoms. Although wound healing can take up to several months, patients quickly learned how to care for themselves and were usually pain-free after the first two or three weeks. CONCLUSIONS: Surgical treatment of hidradenitis suppurativa by wide local excision with healing by secondary intention using tap water-moistened plain gauze dressings changed 2-3 times per day is a simple, practical approach that has good results. Recurrence of disease is common and should not be thought of as a failure of surgical treatment, but rather as a feature of the disease that must be anticipated and managed.

Safety and long-term outcomes of percutaneous endoscopic gastrostomy in patients with head and neck cancer.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is used for nutritional support during treatment in patients with head and neck cancer, but long-term nutritional outcomes have not been reported in detail. The purpose of this study was to determine short- and long-term outcomes and success in meeting nutritional goals in patients with head and neck cancer who had PEGs placed over an 18-year period. METHODS: Medical records of all patients who had PEG procedures performed by one of the authors (REB) from 1997 through 2010 were reviewed. Demographic data, patient weights, timing of procedure in relation to cancer treatment, complications, and long-term outcomes were recorded. RESULTS: Five hundred and sixty-five patients with head and neck cancer underwent PEG. Mean age was 59.6 ± 13.6 years; 71% were men. Mean follow-up was 33 ± 38 months. 99% of PEGs were used for nutritional support. Average weight loss prior to PEG was 23 ± 17 lbs (range 0-133 lbs). Average weight loss between PEG and completion of treatment was 2.3 lbs; 44% of patients gained weight or remained stable after PEG. There were no PEG-related deaths. Complications included cellulitis in 27 (4%), pain in 14 (2.5%); leakage in 11 (2%), self-limited gastric bleeding in one patient. PEGs were used an average of 8.1 months. No PEG site tumor implants were observed. Among 366 patients treated with intention to cure, 45% were alive an average of 68 months later. CONCLUSIONS: PEG is both safe and efficacious in arresting weight loss and maintaining nutrition in patients undergoing surgery and/or chemoradiotherapy for head and neck cancer. PEG can be recommended for patients in whom dysphagia and weight loss is anticipated or in whom weight loss occurs as a result of their treatment; 20% of patients will need the PEG for a year or more.

Dexamethasone attenuates the embryotoxic effect of endometriotic peritoneal fluid in a murine model.

PURPOSE: The in vitro fertilization (IVF) pregnancy rate of women with advanced stage endometriosis is nearly half that of the general population, suggesting incomplete targeting of the pathophysiology underlying endometriosis-associated infertility. Compelling evidence highlights inflammation as the etiologic link between endometriosis and infertility and a potential target for adjunctive treatment. The objective of this study was to examine the effect of dexamethasone on murine embryos exposed to human endometriotic peritoneal fluid (PF) using the established murine embryo assay model. METHODS: PF was obtained from women with and without severe endometriosis. Murine embryos were harvested and randomly allocated to five groups of culture media conditions: (1) human tubal fluid (HTF), (2) HTF and 10 % PF from women without endometriosis, (3) HTF and 10 % PF from women with endometriosis (PF-E), (4) HTF with PF-E and 0.01 mcg/mL dexamethasone, and (5) HTF with PF-E and 0.1 mcg/mL dexamethasone. Embryos were cultured in standard conditions and evaluated for blastocyst development. RESULTS: A total of 266 mouse embryos were cultured. Baseline blastulation rates were 63.6 %. The addition of peritoneal fluid from women with endometriosis decreased the blastocyst development rate to 38.9 % (P = 0.008). The addition of 0.1 mcg/mL of dexamethasone to the culture media restored the blastulation rate to near baseline levels (61.2 %; P = 0.019). CONCLUSIONS: The results of our in vitro study demonstrate the capacity of dexamethasone to mitigate the deleterious impact of endometriotic PF on embryo development. If confirmed in vivo, dexamethasone may prove a useful adjunct for the treatment of endometriosis-associated infertility.

Premenstrual spotting of ≥2 days is strongly associated with histologically confirmed endometriosis in women with infertility.

OBJECTIVE: The purpose of this study was to assess the prevalence of endometriosis in women with premenstrual spotting and to determine the predictive value of this symptom in the diagnosis of endometriosis. STUDY DESIGN: We conducted a retrospective cohort study of 80 consecutive women who presented to the infertility clinic for evaluation and who subsequently underwent laparoscopic assessment for infertility with or without pelvic pain. Our main outcome measure was the presence or absence of histologically confirmed endometriosis in women with and without premenstrual spotting. RESULTS: Endometriosis was significantly more prevalent in subfertile women who reported premenstrual spotting for ≥2 days relative to women without this symptom (89% [34/38 women] vs 26% [11/42 women]; P < .0001). Multinomial logistic regression analysis demonstrated the presence of premenstrual spotting for ≥2 days to be associated significantly with the presence of endometriosis (odds ratio, 16; 95% confidence interval, 3.9-65.4; P < .01) and red vesicular lesion type (odds ratio, 52.6; 95% confidence interval, 8.6-323.1; P < .001). CONCLUSION: In this cohort of women with infertility, premenstrual spotting of ≥2 days was associated strongly with histologically confirmed endometriosis and a better predictor than dysmenorrhea or dyspareunia of finding endometriosis at laparoscopy. Premenstrual spotting of at least 2 days was also associated strongly with both higher stage disease and the red vesicular peritoneal endometriosis phenotype.

The uterine secretome initiates growth of gynecologic tissues in ectopic locations.

Endosalpingiosis (ES) and endometriosis (EM) refer to the growth of tubal and endometrial epithelium respectively, outside of their site of origin. We hypothesize that uterine secretome factors drive ectopic growth. To test this, we developed a mouse model of ES and EM using tdTomato (tdT) transgenic fluorescent mice as donors. To block implantation factors, progesterone knockout (PKO) tdT mice were created. Fluorescent lesions were present after oviduct implantation with and without WT endometrium. Implantation was increased (p<0.05) when tdt oviductal tissue was implanted with endometrium compared to oviductal tissue alone. Implantation was reduced (p<0.0005) in animals implanted with minced tdT oviductal tissue with PKO tdT endometrium compared to WT endometrium. Finally, oviductal tissues was incubated with and without a known implantation factor, leukemia inhibitory factor (LIF) prior to and during implantation. LIF promoted lesion implantation. In conclusion, endometrial derived implantation factors, such as LIF, are necessary to initiate ectopic tissue growth. We have developed an animal model of ectopic growth of gynecologic tissues in a WT mouse which will potentially allow for development of new prevention and treatment modalities.

Inhibition of NFAT promotes loss of tissue resident uterine natural killer cells and attendant pregnancy complications in humans.

Uterine natural killer cells (uNKs) are a tissue resident lymphocyte population that are critical for pregnancy success. Although mouse models have demonstrated that NK deficiency results in abnormal placentation and poor pregnancy outcomes, the generalizability of this knowledge to humans remains unclear. Here we identify uterus transplant (UTx) recipients as a human population with reduced endometrial NK cells and altered pregnancy phenotypes. We further show that the NK reduction in UTx is due to impaired transcriptional programming of NK tissue residency due to blockade of the transcription factor nuclear factor of activated T cells (NFAT). NFAT-dependent genes played a role in multiple molecular circuits governing tissue residency in uNKs, including early residency programs involving AP-1 transcription factors as well as TGFß-mediated upregulation of surface integrins. Collectively, our data identify a previously undescribed role for NFAT in uterine NK tissue residency and provide novel mechanistic insights into the biologic basis of pregnancy complications due to alteration of tissue resident NK subsets in humans. One Sentence Summary: Role of NFAT in uterine NK cell tissue residency.

The genetics and biochemistry of endometriosis.

PURPOSE OF REVIEW: Endometriosis is a common gynecologic disorder characterized by the displacement of endometrial tissue to ectopic locations. Although predisposition to endometriosis is likely multifactorial, a genetic component is evident. The biochemistry of the disorder is an area of active investigation with translational potential. This review synopsizes recent developments regarding the molecular underpinnings of endometriosis. RECENT FINDINGS: Significant advancements in understanding the molecular hallmarks of endometriosis have occurred in recent years. Inflammation, attenuated progesterone action, and neuroangiogenesis constitute emerging themes in the pathophysiology of endometriosis. SUMMARY: Delineation of the biochemical processes involved in endometriosis has important implications for clinical care. The discovery of a sufficiently sensitive and specific biomarker for the nonsurgical detection of endometriosis promises earlier diagnosis and prevention of deleterious sequelae. Understanding the inflammatory cause, attenuated progesterone action at the level of the endometrium, and neuronal sensitization of endometriotic lesions has facilitated development of novel therapeutic approaches for associated pain and infertility.

Test-specific funnel plots for healthcare provider profiling leveraging individual- and summary-level information.

In addition to applications in meta-analysis, funnel plots have emerged as an effective graphical tool for visualizing the detection of health care providers with unusual performance. Although there already exist a variety of approaches to producing funnel plots in the literature of provider profiling, limited attention has been paid to elucidating the critical relationship between funnel plots and hypothesis testing. Within the framework of generalized linear models, here we establish methodological guidelines for creating funnel plots specific to the statistical tests of interest. Moreover, we show that the test-specific funnel plots can be created merely leveraging summary statistics instead of individual-level information. This appealing feature inhibits the leak of protected health information and reduces the cost of inter-institutional data transmission. Two data examples, one for surgical patients from Michigan hospitals and the other for Medicare-certified dialysis facilities, demonstrate the applicability to different types of providers and outcomes with either individual- or summary-level information.

Vulvar varicosities mimicking a hernia: case report.

OBJECTIVE: Vulvar varicosities are not uncommon in pregnancy, but there are only a few published reports of symptomatic vulvar varicosities in nonpregnant women. CASE: We report 2 cases of women presenting with symptomatic vulvar masses that were more prominent after exercise or with elevated intra-abdominal pressure. Symptoms included an intermittent vulvar bulge or mass and moderate pain when the masses were present. Imaging studies did not reveal the nature of these masses. On surgical exploration, they were found to be large vulvar varicosities. CONCLUSIONS: Vulvar masses can be caused by hernias, tumors, cysts, or other unusual entities. Differentiating among these etiologies can be a diagnostic challenge. Although most often a positional vulvar mass is a sign of hernia, it is important to be aware that masses that come and go can be caused by other entities, including large varicose veins.

Cellular junction and mesenchymal factors delineate an endometriosis-specific response of endometrial stromal cells to the mesothelium.

Endometriosis is a debilitating gynecologic disorder that affects ∼10% of women of reproductive age. Endometriosis is characterized by growth of endometriosis lesions within the abdominal cavity, generally thought to arise from retrograde menstruation of shed endometrial tissue. While the pathophysiology underlying peritoneal endometriosis lesion formation is still unclear, the interaction between invading endometrial tissue and the peritoneal mesothelial lining is an essential step in lesion formation. In this study, we assessed proteomic differences between eutopic endometrial stromal cells (ESCs) from women with and without endometriosis in response to peritoneal mesothelial cell (PMC) exposure, using single-cell cytometry by time-of-flight (CyTOF). Co-cultured primary eutopic ESCs from women with and without endometriosis with an established PMC line were subjected to immunostaining with a panel of Maxpar CyTOF metal-conjugated antibodies (n = 28) targeting cell junction and mesenchymal markers, which are involved in cell-cell adhesions and epithelial-mesenchymal transition. Exposure of the ESCs to PMCs resulted in a drastic shift in cellular expression profiles in ESCs derived from endometriosis, whereas little effect by PMCs was observed in ESCs from non-endometriosis subjects. The transcription factor SNAI1 was consistently repressed by PMC interactions. ESCs from endometriosis patients are unique in that they respond to PMCs by undergoing changes in adhesive properties and mesenchymal characteristics that would facilitate lesion formation.

D-Day to December 1944: The odyssey of the third auxiliary surgical group in World War II.

ABSTRACT: As a Major in the US Army Medical Corps, Darrell A. Campbell, MD, led Team 13 of the Third Auxiliary Surgical Group in Europe in World War II. The team began work on June 7, 1944, in a clearing station tent near the beach at Normandy. Subsequently, over the next 7 months, it was assigned to mobile hospitals in 15 different locations in France, Belgium, Luxembourg, and Germany. Major Campbell kept the log books used to record all of the operations done by his team during this time and brought them home where three were discovered more than 70 years later. These log books contain descriptions of more than 500 consecutive operations done by Team 13. They provide a unique insight into the activities of the surgeons who worked to save lives on the front lines of battle in the European Theater of Operations between June and December 1944 and form the basis for this historical perspective.This is an article on the history of surgery.

An intrauterine genomic classifier reliably delineates the location of nonviable pregnancies.

OBJECTIVE: To compare the intrauterine gene expression signatures of women with surgically confirmed ectopic pregnancy (ECT) and those of women with miscarriage to inform the development of a genomic classifier for the reliable delineation of pregnancy location in women with clinically nonviable pregnancies of unknown location (NV-PULs). DESIGN: Discovery-based prospective cohort study. SETTING: Academic medical center. PATIENT(S): Women with clinically nonviable early pregnancy to include abnormal intrauterine pregnancy (AIUP), ECT, or NV-PUL. INTERVENTION(S): Endometrial (EM) pipelle sampling of the uterus was conducted at the time of scheduled surgery for clinically nonviable early pregnancy (dilation and curettage, manual vacuum aspiration, or laparoscopy). All pregnancy locations were surgically and/or histologically confirmed as intrauterine or ectopic. MAIN OUTCOME MEASURE(S): Gene expression profiles as determined by array hybridization, quantitative real-time polymerase chain reaction, and nCounter technology. RESULT(S): Intrauterine samples were obtained by EM pipelle from 27 women undergoing surgery for a clinically nonviable early pregnancy. Comparison of array-based global gene expression signatures from women with histologically confirmed ECT versus AIUP revealed 61 differentially expressed genes from which the 5 most informative were included in the pregnancy location classifier. All 5 genes (C20orf85, LRRC46, RSPH4A, WDR49, and ZBBX) were cilia-associated and showed increased expression in pipelle samples from women with ECT relative to expression in samples from women with AIUP. The 5-gene classifier demonstrated an average area under the receiver operator characteristic curve of 0.97 for the detection of ECT. In an external test set composed of publicly available EM pipelle-based gene expression data from a study with similar ECT and AIUP cohorts (n = 19), the classifier revealed an average area under the receiver operator characteristic curve of 0.84. CONCLUSION(S): Consistently increased expression of cilia-associated genes in the uterine cavity of women with ECT provides a reliable molecular signal for the delineation of pregnancy location in women with clinically assessed NV-PUL. A classifier consisting of the 5 most informative cilia-associated genes demonstrated 91% (42/46) accuracy in predicting the pregnancy location.

Endometriosis in the Mouse: Challenges and Progress Toward a 'Best Fit' Murine Model.

Endometriosis is a prevalent gynecologic condition associated with pelvic pain and infertility characterized by the implantation and growth of endometrial tissue displaced into the pelvis via retrograde menstruation. The mouse is a molecularly well-annotated and cost-efficient species for modeling human disease in the therapeutic discovery pipeline. However, as a non-menstrual species with a closed tubo-ovarian junction, the mouse poses inherent challenges as a preclinical model for endometriosis research. Over the past three decades, numerous murine models of endometriosis have been described with varying degrees of fidelity in recapitulating the essential pathophysiologic features of the human disease. We conducted a search of the peer-reviewed literature to identify publications describing preclinical research using a murine model of endometriosis. Each model was reviewed according to a panel of ideal model parameters founded on the current understanding of endometriosis pathophysiology. Evaluated parameters included method of transplantation, cycle phase and type of tissue transplanted, recipient immune/ovarian status, iterative schedule of transplantation, and option for longitudinal lesion assessment. Though challenges remain, more recent models have incorporated innovative technical approaches such as in vivo fluorescence imaging and novel hormonal preparations to overcome the unique challenges posed by murine anatomy and physiology. These models offer significant advantages in lesion development and readout toward a high-fidelity mouse model for translational research in endometriosis.

An international perspective on ultrasound training and use for thyroid and parathyroid disease.

BACKGROUND: Use of ultrasound (USN) by endocrine surgeons has dramatically increased. Presently, optimal training and certification requirements have not been standardized at any level (resident/fellow/attending). We sought to define the types of USN training endocrine surgeons receive and how USN is employed in practice. We hypothesized that in more recent years fellowship-trained endocrine surgeons were more likely to receive formal training in the use of USN during their endocrine surgery fellowship. METHODS: A survey link was sent via email to a large group of endocrine surgeons around the world asking about the settings in which they received USN training, the type of instruction received, current use of USN, and other various questions. chi(2) analysis was performed and P < 0.05 was considered significant. RESULTS: One hundred twenty-one surveys were collected from respondents in 27 countries. Median time from completion of residency to the present was 17 years (range = 2-49). Fifty-nine percent of both fellowship- and nonfellowship-trained endocrine surgeons currently use USN in their practice. Of those currently performing USN, 38% reported no USN training of any kind (47% international vs. 23% United States). USN experience among international and U.S. residents was not different (P = 0.27). Fifty-nine percent of respondents reported completing an endocrine surgery fellowship; of those, 85% reported no formal USN training. Forty-one percent reported not being comfortable performing USN at the completion of their endocrine surgery fellowships, requiring the presence of someone else to assist with the exam. CONCLUSIONS: USN training among endocrine surgeons varies widely around the world. Despite an increase in the number of formal endocrine surgery fellowships offered, it does not appear that the number with formal USN training and certification has increased. Formal USN certification is achieved in only a minority of cases among practicing endocrine surgeons. It is currently unknown whether there is a difference in competency between endocrine surgeons with formal versus informal USN training.

Contribution of plasma cells and B cells to hidradenitis suppurativa pathogenesis.

Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease characterized by chronic abscess formation and development of multiple draining sinus tracts in the groin, axillae, and perineum. Using proteomic and transcriptomic approaches, we characterized the inflammatory responses in HS in depth, revealing immune responses centered on IFN-γ, IL-36, and TNF, with lesser contribution from IL-17A. We further identified B cells and plasma cells, with associated increases in immunoglobulin production and complement activation, as pivotal players in HS pathogenesis, with Bruton's tyrosine kinase (BTK) and spleen tyrosine kinase (SYK) pathway activation as a central signal transduction network in HS. These data provide preclinical evidence to accelerate the path toward clinical trials targeting BTK and SYK signaling in moderate-to-severe HS.