Multiple Anatomical Locations Research Articles

Individuals lack the ability to accurately detect emotional piloerection.

Piloerection (e.g., goosebumps) is an essential thermoregulatory and social signaling mechanism in non-human animals. Although humans also experience piloerection-often being perceived as an indicator of profound emotional experiences-its comparatively less effective role in thermoregulation and communication might influence our capacity to monitor its occurrence. We present three studies (total N = 617) demonstrating participants' general inability to detect their own piloerection events and their lack of awareness that piloerection occurs with a similar frequency on multiple anatomical locations. Self-reported goosebumps were more frequent than observed piloerection. However, only 31.8% of self-reports coincided with observable piloerection, a bias unrelated to piloerection intensity, anatomical location, heart-rate variability, or interoceptive awareness. We also discovered a self-report bias for the forearm, contradicting the observation that piloerection occurs with equal frequency on multiple anatomical locations. Finally, there was low correspondence between self-reports of being "emotionally moved" and observed piloerection. These counterintuitive findings not only highlight a disconnect between an obvious physiological response and our capacity for self-monitoring, but they underscore a fascinating divergence between human and non-human species. Although piloerection is vital in non-human organisms, the connection between piloerection and psychological experience in humans may be less significant than previously assumed, possibly due to its diminished evolutionary relevance.

Erythema nodosum in northern Finland between 1996 and 2019: A register-based study.

Erythema nodosum (EN) is seen at any age with varying and often unidentified etiology. We studied the etiology and characteristics of EN in Northern Finland. Medical records of all patients with a diagnosis code for EN between 1996 and 2019 from Oulu University Hospital were retrieved and analyzed. There were in total 142 EN cases with a female predominance (n = 112, 72.9%). The mean age of the patients was 35.9 years. There were five cases diagnosed with EN in those younger than 2 years of age. Almost one third had EN nodules in multiple anatomical locations. In addition to skin findings, systemic symptoms were common (81.0%), and seen more often in men (p < 0.05). In children and adolescents, the most common etiological factors were gastroenteritis caused by 'Yersinia, Salmonella or Campylobacter', followed by inflammatory bowel diseases and hormonal contraception. Bacterial infections were the most common etiological factor among adults. In 28.2% of the cases there was no identified causative factor. In this study, EN was seen surprisingly often in small children. Etiological factors varied markedly among different age groups and symptoms differed between the sexes in adults. These aspects should be taken into account when diagnosing EN patients.

An artificial intelligence approach for investigating multifactorial pain-related features of endometriosis.

Endometriosis is a debilitating, chronic disease that is estimated to affect 11% of reproductive-age women. Diagnosis of endometriosis is difficult with diagnostic delays of up to 12 years reported. These delays can negatively impact health and quality of life. Vague, nonspecific symptoms, like pain, with multiple differential diagnoses contribute to the difficulty of diagnosis. By investigating previously imprecise symptoms of pain, we sought to clarify distinct pain symptoms indicative of endometriosis, using an artificial intelligence-based approach. We used data from 473 women undergoing laparoscopy or laparotomy for a variety of surgical indications. Multiple anatomical pain locations were clustered based on the associations across samples to increase the power in the probability calculations. A Bayesian network was developed using pain-related features, subfertility, and diagnoses. Univariable and multivariable analyses were performed by querying the network for the relative risk of a postoperative diagnosis, given the presence of different symptoms. Performance and sensitivity analyses demonstrated the advantages of Bayesian network analysis over traditional statistical techniques. Clustering grouped the 155 anatomical sites of pain into 15 pain locations. After pruning, the final Bayesian network included 18 nodes. The presence of any pain-related feature increased the relative risk of endometriosis (p-value < 0.001). The constellation of chronic pelvic pain, subfertility, and dyspareunia resulted in the greatest increase in the relative risk of endometriosis. The performance and sensitivity analyses demonstrated that the Bayesian network could identify and analyze more significant associations with endometriosis than traditional statistical techniques. Pelvic pain, frequently associated with endometriosis, is a common and vague symptom. Our Bayesian network for the study of pain-related features of endometriosis revealed specific pain locations and pain types that potentially forecast the diagnosis of endometriosis.

Efficacy and safety of dendrimer-enhanced (DEP) cabazitaxel (CTX-SPL9111) in advanced esophagogastric cancers in a phase 1/2 trial.

374 Background: There is a significant unmet need in esophagogastric cancers (EGC) due to limited effective treatments (Tx) and poor prognosis. Dendrimers are highly branched nanoparticles that enable sustained delivery of cytotoxic drugs and achieve selective tumor targeting via an enhanced permeability and retention effect. DEP cabazitaxel is a highly optimised dendrimer formulation of cabazitaxel. Unlike standard cabazitaxel, DEP cabazitaxel is highly water soluble, does not contain toxic excipients such as polysorbate-80 associated with anaphylaxis, and avoids the need for steroid/antihistamine pre-medication. The objective of this Phase 1/2 trial was to assess preliminary efficacy and safety of DEP cabazitaxel in patients (pts) with advanced solid tumors including EGC, for which standard cabazitaxel is not approved. Methods: In the P2 part of the trial, advanced EGC pts with measurable disease were treated with DEP cabazitaxel 20 mg/m2 cabazitaxel, the recommended Phase 2 dose, IV 3-weekly. Anti-tumour activity was assessed by RECIST v1.1, safety by CTCAE v4.03. (EudraCT 2017-003424-76). Results: Fifteen pts with advanced EGC were enrolled; 9 adenocarcinoma (ADENOCA) (3 gastric, 2 esophageal and 4 EG junction) and 6 esophageal squamous cell carcinoma (ESCC); median age 62 yrs (26–73 yrs), with all pts having ≤3 prior anticancer Tx, and the majority (9) having progressed on or immediately after 1st line Tx (1L). All had ≥1 prior platinum-based regimen and 4 pts had received prior taxanes. Pts received a median of 4.5 DEP cabazitaxel cycles without the need for routine steroid/antihistamine or primary G-CSF prophylaxis. In all evaluable pts, disease control rate (DCR) was 80%. Disease control was observed in both histological subtypes and was durable, including stable disease (SD) for up to 27 weeks and partial responses (PR) for up to 17 weeks, with objective response rate (ORR) of 30%. In EG ADENOCA pts, DCR was 100%, ORR was 33%, and median progression free survival (mPFS) was 4.0 months. In ESCC pts, DCR was 50% and ORR was 25%, with mPFS of 1.9 months. DEP cabazitaxel was well-tolerated with mostly mild (62.9%, Grade (G) 1)/moderate (20.2%, G2) treatment-related adverse events (TRAEs), including nausea, vomiting, fatigue, neuropathy, neutropenia (only 1 pt had G-CSF Tx, 1 pt had secondary G-CSF prophylaxis) and anemia, that were like those observed with standard cabazitaxel Tx. Of severe TRAEs (G3/4; 16.9%) most (80%) were observed in 2 pts, including neutropenia, anemia, thrombocytopenia, fistula, elevated liver enzymes. Conclusions: DEP cabazitaxel exhibited highly encouraging anti-tumor activity in &gt;1L, advanced EGC in multiple anatomic locations and of different histological sub-types. The preliminary efficacy and safety results compare favorably to available treatment options and highlight the promising clinical potential of DEP cabazitaxel in advanced EGC. Clinical trial information: EudraCT 2017-003424-76 .

Initial Experience with 68Ga-FAP-2286 PET Imaging in Patients with Urothelial Cancer.

Improved imaging modalities are needed to accurately stage patients with muscle-invasive bladder cancer (MIBC) and metastatic urothelial carcinoma. Imaging with small-molecule ligands or inhibitors of fibroblast activation protein (FAP) is a promising modality that has demonstrated initial efficacy across a broad range of tumors. We present our experience with the novel FAP-peptide binder 68Ga-FAP-2286 in patients with MIBC. Methods: Patients with histopathologically confirmed bladder cancer who had either localized disease at diagnosis (localized cohort, n = 13) or known metastatic disease (metastatic cohort, n = 8) were imaged with 68Ga-FAP-2286 PET as part of a clinical trial (NCT04621435). The SUVmax of 68Ga-FAP-2286 PET-positive lesions and lesion size were documented. In patients who had available 18F-FDG PET performed within 45 d of 68Ga-FAP-2286 PET (n = 5), uptake on the 2 scans was compared. When there was a discrepancy between imaging modalities on retrospective review, biopsy of suggestive lesions was performed as the standard of care. Results: In the metastatic and localized cohorts, 36 and 18 68Ga-FAP-2286-avid lesions, respectively, were identified across multiple anatomic locations, including lymph nodes, visceral metastases, and bones. Fourteen of 36 lesions in the metastatic cohort and 14 of 18 lesions in the localized cohort were lymph nodes measuring less than 1 cm. Among lesions measuring less than 0.5 cm, 0.5-1 cm, and more than 1 cm, average SUVmax was 5.2 ± 2.6, 9.6 ± 3.7, and 13.0 ± 4.3, respectively, in the metastatic cohort and 10.5 ± 5.1, 10.8 ± 5.7, and 9.9 ± 5.4, respectively, in the localized cohort. Five patients had 18F-FDG PET available for comparison. The average SUVmax for lesions avid on 68Ga-FAP-2286 PET and 18F-FDG PET was 9.9 ± 3.4 versus 4.2 ± 1.9, respectively (n = 16 lesions). For 3 patients in the localized cohort, 68Ga-FAP-2286 PET informed clinical management, including identification of both false-positive findings on 18F-FDG PET and false-negative findings on conventional CT. Conclusion: 68Ga-FAP-2286 imaging is highly sensitive in patients with urothelial cancer and is effective in identifying metastatic lesions across a variety of anatomic sites, including subcentimeter lymph nodes that would not have raised suspicion on conventional scans. This novel imaging modality may inform clinical decision-making in patients with MIBC both by refining local nodal staging and by defining metastatic disease that would otherwise be undetectable on conventional imaging.

Deletion of the Artery Specific Enhancer Promotes B Cell and Impairs T Cell Development from the Hemogenic Endothelium

HSCs and HSC-independent lymphoid progenitors in the embryo arise from hemogenic endothelium (HE) at multiple anatomical locations. Although activation of arterial program in HE has been shown to play an important role in HSC development, the impact of the arterial program on specification of HSC-independent lymphoid cell remains unclear. During vascular development, arterial fate is specified following induction of DLL4 expression by VEGF by signaling through a highly conserved VEGF-responsive artery-specific enhancer located within the third intron of DLL4 ( DLL4-i3) which is controlled by ETS, SOXF and RBPJ factors. To investigate how the arterial program affects T and B cell lymphoid development, we generated DLL4-i3:Venus reporter and knockout ( DLL4 Di3/Di3) human pluripotent stem cells (hPSCs). Using a 3-dimensional, serum- and feeder-free spheroid differentiation system, we demonstrated that DLL4: i3 enhancer activity recapitulates endogenous DLL4 expression and arterial endothelial cell specification in human hPSC cultures. Moreover, DLL4-i3: Venus + HE and hematopoietic progenitors produced more myeloid CFCs and T cells as compared DLL4-i3: Venus - hemogenic cells. Deletion of DLL4i3 enhancer impaired arterial specification from hPSCs including formation of arterial DLL4 +CXCR4 +/- HE. In contrast to wild type (WT), hematopoietic progenitors (HPs) generated from DLL4 Di3/Di3hPSCs showed impaired CFC potential with significantly reduced G-CFCs and markedly diminished T cell potential. However, DLL4 Di3/Di3hPSCs showed efficient and highly reproducible B cell potential as compared to WT. To define the impact of artery-specific enhancer deletion on transcriptional program during endothelial-to-hematopoietic transition (EHT) and HP formation, we performed scRNAseq of all endothelial and hematopoietic cells from D5 and D8 differentiation cultures of DLL4-i3:Venus and DLL4 Di3/Di3 hPSCs. Through unsupervised clustering, 10 cell clusters (C0-C9) were distinguished and visualized using UMAP. Based on the expression panel of known pan-, arterial and hemogenic endothelial and hematopoietic markers we defined three clusters of HE with arterial features (AHE; high EFNB2, CDH5 and RUNX1 positive and SPN negative), two non-arterial HE clusters (low EFNB2, CDH5 and RUNX1 positive and SPN negative), two EHT clusters (CDH5 and SPN positive, high RUNX1, and GFI1b), and three HP clusters (SPN positive, high RUNX1 and CDH5 negative). GSEA of DLL4i3: Venus+ cells with active enhancer vs DLL4 Di3/Di3 cells revealed enrichment in ribosomes and oxidative phosphorylation pathways across all clusters and focal adhesion and tight junction pathways in HE and EHT clusters. DEG analysis demonstrated upregulation of EFNB2, MECOM HES4 in DLL4-i3: Venus+ cells within HE and EHT clusters, while DLL4 Di3/Di3 cells demonstrated upregulation of NRP2 and CDH13 genes. Interestingly, in EHT and HP clusters, we noticed that DLL4-i3 knockout significantly upregulates the expression of GAS5 lncRNAs known to be involved in growth arrest of human peripheral blood T cells. Using siRNA, we demonstrated that knockdown of GAS5 in D5 cultures of DLL4 Di3/Di3 cells rescued the T cell potential of the hematopoietic progenitors suggesting that NOTCH-mediated GAS5 suppression is essential for the T cell specification and expansion following EHT. In contrast to T cells, GAS5 downregulation had no effect on B cell specification of DLL4 Di3/Di3 HE. Overall, we established that DLL4-i3 enhancer is required for arterial programming of HE with T cell potential while deletion of this enhancers promotes B cell development. In addition, we demonstrated an important role of GAS5 lncRNA in the regulation of T cell development from HE.

Ductal Carcinoma Arising in a Squamous Epithelial Inclusion Cyst within an Axillary Lymph Node: A Challenging Nodal Metastasis

Introduction. Assessment of axillary lymph nodes in breast carcinoma is an important part of staging to guide appropriate clinical management. Lymph node inclusions of different types, including nevoid, squamous, and glandular, are rare but have been reported in multiple different anatomic locations including the axilla. These can result in diagnostic challenges and pose risks of misdiagnoses. Rarely, malignancies may arise intrinsic to otherwise incidental benign nodal inclusions. Case Presentation. We report a case of ductal carcinoma diagnosed within a squamous epithelial inclusion cyst within an axillary lymph node in a patient with pure ductal carcinoma in situ (DCIS) of the ipsilateral right breast. To our knowledge, this is the fifth report in the literature of breast carcinoma confirmed within an axillary inclusion in a patient with pure DCIS. Evaluation of the primary DCIS and lymph node inclusions, by routine and immunohistochemical stains, was performed for assessment. Discussion. The presence of lymph node inclusions can pose a challenge in assessment of benignity and malignancy, on frozen and permanent histologic sections. Pathologists should carefully evaluate lymph node inclusions to ensure that intrinsic malignancies are not missed within rare otherwise benign appearing incidental epithelial rests.

Morphological variations of two cases of maxillary myofibromas

The aim of this case report is to depict the varied spectrum of clinical presentation of two cases of solitary myofibromas, one of which was intra-osseous whilst the other presented as a soft tissue lesion. This highlights the spectrum of the clinical presentation of the same pathology. In the most recent World Health Organisation (WHO) 2022 classification of soft tissue tumours, myofibroma is included under the category of myopericytomas. Myopericytoma is a distinctive perivascular myoid neoplasm that forms a morphological spectrum with myofibroma. Molecular evidence has revealed PDGFRB (platelet-derived growth factor receptor beta) mutations in myopericytoma and myofibroma as well as SRF-RELA gene fusions in both lesions confirming a common pathogenesis for both.1 Myofibromas are benign soft tissue neoplasms derived from myofibroblastic cells.2 The term myofibroma refers to a solitary lesion. Myofibromatosis refers to cases in which multiple lesions are present which may affect either one or multiple anatomical locations. Myofibromatosis is almost exclusively seen in young children under the age of 2-years. Myofibromas exhibit a wide age range of clinical presentation and may be present at birth or arise within the first two years of age, but may also present in adults with a significant male predominance. Solitary myofibromas have a predilection to occur in the oral cavity, skin or subcutis of the head, neck and trunk.

SINGLE CELL RNA SEQUENCING OF ULCERATIVE COLITIS AND CROHN'S DISEASE TISSUE SAMPLES INFORMS THE SELECTION OF TREM1 AS A TARGET FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASES

Abstract Ulcerative colitis (UC) and Crohn’s disease (CD) are complex and heterogenous diseases characterized by chronic and progressive inflammation of the digestive tract. Single cell RNA sequencing combined with computational biology provides unprecedented insights into disease biology, informing novel therapeutic targets and precision medicine approaches. To identify potential mediators of persistent inflammation in inflammatory bowel disease (IBD), we performed single cell RNA sequencing on tissue samples collected from UC and CD patients before and after beginning adalimumab. In this study, 41 participants, including 21 UC patients, 17 CD patients and 3 healthy individuals, were enrolled at the University of Oxford’s Translational Gastroenterology Unit and Kennedy Institute of Rheumatology. Patients had moderate-to-severe disease based on symptoms and endoscopy, were biologic naïve, and planned to initiate adalimumab. Mucosal biopsies for single cell RNA sequencing were collected from multiple anatomic locations for each subject before beginning and after a minimum of 3 months of adalimumab, at which time treatment response was assessed. During the study, clinical response as defined by composite measures was observed in 8 UC and 9 CD patients. Differential cell composition and gene expression analysis of the single cell data revealed inflammatory monocyte subtypes as highly enriched in inflamed relative to uninflamed samples, and this cellular subset remained highly elevated in inflamed samples from adalimumab non-responders. These cells were characterized by expression of multiple cell-surface receptors with potential to drive pathology, including TREM1 (Triggering Receptor Expressed on Myeloid Cells 1), a transmembrane receptor that amplifies anti-bacterial neutrophil and monocyte mediated responses. TREM1+ inflammatory monocytes were highly enriched in UC and CD inflamed samples (Fig 1), both prior to adalimumab and in adalimumab non-responders. The enrichment of TREM1+ cells was specific to inflamed IBD tissue and was not observed in non-inflamed tissue from IBD patients or healthy subjects; enrichment of TREM1+ cells was also not observed in circulating peripheral blood mononuclear cells. TREM1+ neutrophils and monocytes in the gut mucosa amplify innate immune responses to bacteria in the context of epithelial barrier dysfunction and bacterial dysbiosis in IBD. When activated, TREM1 signaling induces multiple soluble mediators relevant for IBD pathology. Our single cell RNA sequencing data provide further evidence that TREM1 is an exciting therapeutic target for UC and CD, with inhibition of TREM1 signaling expected to address pathology while maintaining an anti-bacterial response. We therefore developed a highly potent and selective monoclonal antibody inhibitor of TREM-1, CEL383, with the Phase 1 clinical trial expected to start in 2023. Figure 1. tSNE plot of myeloid cells from inflamed IBD tissue samples demonstrating high TREM1 expression across inflammatory monocytes

Are the thickness and ADC values reliable to evaluate pancreas in children? A retrospective MRI study.

To define the pancreatic thickness on the transverse plane and apparent diffusion coefficient (ADC) values at multiple anatomical locations in the normal pancreas of children and to evaluate inter-rater and intra-rater reliability. Two reviewers measured the thickness and ADC values of the pancreas at four locations obtained from two different 1,5 Tesla MRI scanners [MAGNETOM Symphony (Siemens Medical Systems, Erlangen, Germany) and Signa HDxt(GE Healthcare, Milwaukee, WI, USA)]. Measurements were made based on 190 retrospective MRI examinations. Patients were distributed among ten age groups for thickness measurements and three age groups for ADC measurements between 0 and 18years. The thickness measurements from each segment of the pancreas were significantly correlated with patient age, height and weight (p < 0.01). Inter-rater agreement was excellent for pancreatic head (intraclass correlation coefficient (ICC): 0.837) and good for pancreatic neck, body and tail (ICC: 0.646, 0.632 and 0.678, respectively). We also defined the mean ADC values for three age groups. There was significant difference in the mean ADC value of the head and body by both the vendor and age group (p < 0.05). The mean ADC values and mean ranks of the Signa HDxt were significantly higher and the frequencies were lower than those of the MAGNETOM Symphony at all locations (p < 0.001). The thickness of the pancreatic head is more reliable than that at other locations. Pancreatic body and tail measurements are not as reliable as head or neck measurements due to discrepancies between published studies and low interobserver agreement. ADC values of the normal pancreas can be significantly different among vendors; therefore, ADC comparison on follow-up should be performed using same MRI machine.

Intrapulmonary solitary fibrous tumor coexisting with lung adenocarcinomas

BackgroundSolitary fibrous tumor (SFT) is a rare tumor of mesenchymal origin and accounts for < 2% of all soft tissue masses. Although SFT has been identified in multiple anatomic locations and can grow anywhere in the body, intrapulmonary SFT are rare.Case presentationIn this report, we presented a rare case of intrapulmonary solitary fibrous tumor (SFT) coexisting with lung adenocarcinoma in a 74-year-old man. Chest computed tomography showed a well-defined nodule with punctate calcification and measuring 2.3 × 2.1 cm and two ground-grass nodules with solid component. To obtain a definitive diagnosis and achieve complete resection, surgery was performed. The postoperative diagnosis was intrapulmonary SFT coexisting with lung adenocarcinoma. After surgery, he survived for 6 months without any signs of recurrence.ConclusionComplete resection may be the best treatment for intrapulmonary SFT. Careful follow-up of the postoperative course is important, because differentiating between benignity and malignancy is difficult by histologic findings alone.

Epidemiology of Emergency Medical Services Activations for Sport-Related Injuries in the United States

BackgroundLiterature examining emergency medical services (EMS) activations for sport-related injuries is limited to the pediatric, high school, and collegiate student-athlete populations, excluding older individuals and recreational athletes. The purpose of this study was to examine EMS activations for sport-related injuries using the National EMS Information System Database from 2017-2018.MethodsData were obtained using the National EMS Information System Database from 2017-2018. EMS activations were limited to 9-1-1 responses for individuals aged 3-99 who sustained a sports-related injury. Independent variables included patient age group: pediatric (<18 years old) vs. adult (≥18 years old). Dependent variables were patient age, gender, and chief complaint anatomic location. Frequencies and proportions were calculated for each variable. Injury proportion ratios (IPRs) with 95% confidence intervals were calculated to compare chief complaint anatomic location by age group.ResultsThere were 71,322 sport-related injuries. Patients were 36.6±22.9 years and most (58.1%, n=41,132) were male. Adults had higher proportions of injuries affecting the abdomen (IPR: 2.05, 95%CI: 1.83, 2.31), chest (IPR: 1.90, 95%CI: 1.75, 2.05), general/global (IPR: 1.54, 95%CI: 1.50, 1.58), and genitalia (IPR: 2.40, 95%CI: 1.39, 4.15), and lower proportions of injuries affecting the back (IPR: 0.55, 95%CI: 0.50, 0.60), lower extremity (IPR: 0.63, 95%CI: 0.60, 0.65), upper extremity (IPR: 0.50, 95%CI: 0.47, 0.53), head (IPR: 0.73, 95%CI: 0.70, 0.77), and neck (IPR: 0.18, 95%CI: 0.16, 0.20) compared to pediatric patients.ConclusionInjuries sustained differed between adult and pediatric patients, indicating sport-related emergencies may change across the lifespan. General/global chief complaints likely indicate sport-related injuries affecting multiple anatomic locations and organ systems. Stakeholders planning large or high-risk athletic events should consider arranging standby or dedicated advanced life support units for their events.

N-Tools-Browser: Web-Based Visualization of Electrocorticography Data for Epilepsy Surgery.

Epilepsy affects more than three million people in the United States. In approximately one-third of this population, anti-seizure medications do not control seizures. Many patients pursue surgical treatment that can include a procedure involving the implantation of electrodes for intracranial monitoring of seizure activity. For these cases, accurate mapping of the implanted electrodes on a patient’s brain is crucial in planning the ultimate surgical treatment. Traditionally, electrode mapping results are presented in static figures that do not allow for dynamic interactions and visualizations. In collaboration with a clinical research team at a Level 4 Epilepsy Center, we developed N-Tools-Browser, a web-based software using WebGL and the X-Toolkit (XTK), to help clinicians interactively visualize the location and functional properties of implanted intracranial electrodes in 3D. Our software allows the user to visualize the seizure focus location accurately and simultaneously display functional characteristics (e.g., results from electrical stimulation mapping). Different visualization modes enable the analysis of multiple electrode groups or individual anatomical locations. We deployed a prototype of N-Tools-Browser for our collaborators at the New York University Grossman School of Medicine Comprehensive Epilepsy Center. Then, we evaluated its usefulness with domain experts on clinical cases.

Revisiting the East-West advancement flap: great for multiple anatomic locations.

The east-west advancement flap is a simple flap traditionally used to repair Mohs surgery defects on the nose. We aim to demonstrate this flap can be used with good cosmetic outcome and minimal complications on a variety of anatomical sites. This study was a case series of four patients taking place between March 2021 and September 2021 with 4- to 6-week postoperative follow-up. Four male patients were included in the study. Repair sites included the helix, chin, wrist, and scalp. All patients and the Mohs surgeon reported satisfaction with the cosmetic outcome at 4- to 6-week postoperative follow-up with no complications. The east-west advancement flap is a viable repair option for Mohs surgery defects on a variety of anatomical sites.

Prevalence of Co-infection by Human Papillomavirus, Epstein- Barr Virus and Merkel Cell Polyomavirus in Iranian Oral Cavity Cancer and Pre-malignant Lesions.

Human papillomavirus (HPV) is recognized as the most important risk factor in oral cavity cancer and pre-malignant lesions; however, the etiological association of concomitant infection with other oncogenic viruses as a co-factor has not been definitively proven. The present study aimed to determine the prevalence of co-infection with HPV, Epstein-Barr virus (EBV) and Merkel Cell PolyomaVirus (MCPyV) in oral cavity lesions in Iranian patients. One hundred and fourteen oral cavity samples, including 33 oral squamous cell carcinoma, 28 oral lichen planus, 16 oral epithelial dysplasia and 37 oral irritation fibromas were analyzed for the HPV, EBV and MCPyV infection by quantitative real-time PCR. According to histological features 32.5% and 28.9% of cases were oral irritation fibroma and oral squamous cell carcinoma, respectively. Infection with at least two viruses was detected in 21.1% of patients. In this group, co-infection with HPV/EBV was identified in 37.5% of cases, HPV/MCPyV in 29.2%, EBV/MCPyV in 12.5%, and HPV/EBV/MCPyV in 20.8%. There was no statistically significant difference between multiple infections and anatomical locations of cancer. The prevalence of triple viral infection (HPV/EBV/MCPyV) in well differentiated tumors was higher than EBV or MCPyV single infection. This study revealed that co-infection of HPV, EBV and MCPyV can be detected in both malignant and non-malignant oral cavity tissues, and co-infection with all three viruses in well differentiated tumors can be shown as a synergistic hypothesis of the pathogenic role of these viruses in oral malignant transformation.

Syndesmosis screw breakage: An analysis of multiple breakage locations

Introduction/purposeConcerns have been raised about screw breakage within the tibia or fibula, referred to as intraosseous breakage. The purpose of this investigation is to analyze the technical aspects of syndesmotic screw placement in multiple anatomic breakage locations. MaterialsA retrospective analysis of over 1056 patients who underwent syndesmosis fixation was completed. Demographics, screw length, width, number, height above the tibial plafond, angle, breakage location, and breakage location on the screw were collected and analyzed. ResultsIntraosseous (IO) screw breakage (91 screws, 68 patients) was more common than clear space (CS) breakage (28 screws, 18 patients) (P = < 0.001). Within the IO group, screw breakage within the tibia (60 screws, 52 patients) was more common compared to fibula breakage (29 screws, 24 patients) (P = < 0.001).Increased BMI and the use of multiple screws were associated with IO breakage (P = .007) and CS breakage (P = .012), respectively. Increased screw angle and age were associated with fibular IO breakage (P = .021, P = .036) when compared to other IO breakage locations. Screw angle and placement showed no significant differences between compared groups (P = .629, P = .570). ConclusionSyndesmosis screw breakage, overall, occurred more commonly in an IO location. When compared to IO breakage, the use of multiple syndesmosis screws is most associated with CS breakage. Increased BMI is associated with increased IO breakage when compared to CS breakage. Patients with IO screw breakage within the fibula had increased age and placed at a higher angle when compared to other IO breakage locations. No other factors related to screw placement, including the height of placement, were found to be significantly associated with location of screw breakage.

Integrated molecular analysis identifies a conserved pericyte gene signature in zebrafish

ABSTRACT Pericytes reside in capillary beds where they share a basement membrane with endothelial cells and regulate their function. However, little is known about embryonic pericyte development, in part, due to lack of specific molecular markers and genetic tools. Here, we applied single cell RNA-sequencing (scRNA-seq) of platelet derived growth factor beta (pdgfrb)-positive cells to molecularly characterize pericytes in zebrafish larvae. scRNA-seq revealed zebrafish cells expressing mouse pericyte gene orthologs, and comparison with bulk RNA-seq from wild-type and pdgfrb mutant larvae further refined a pericyte gene set. Subsequent integration with mouse pericyte scRNA-seq profiles revealed a core set of conserved pericyte genes. Using transgenic reporter lines, we validated pericyte expression of two genes identified in our analysis: NDUFA4 mitochondrial complex associated like 2a (ndufa4l2a), and potassium voltage-gated channel, Isk-related family, member 4 (kcne4). Both reporter lines exhibited pericyte expression in multiple anatomical locations, and kcne4 was also detected in a subset of vascular smooth muscle cells. Thus, our integrated molecular analysis revealed a molecular profile for zebrafish pericytes and allowed us to develop new tools to observe these cells in vivo.

Glucocorticoid-induced osteonecrosis in systemic lupus erythematosus patients.

Osteonecrosis (ON) is a complex and multifactorial complication of systemic lupus erythematosus (SLE). ON is a devastating condition that causes severe pain and compromises the quality of life. The prevalence of ON in SLE patients is variable, ranging from 1.7% to 52%. However, the pathophysiology and risk factors for ON in patients with SLE have not yet been fully determined. Several mechanisms for SLE patients’ propensity to develop ON have been proposed. Glucocorticoid is a widely used therapeutic option for SLE patients and high‐dose glucocorticoid therapy in SLE patients is strongly associated with the development of ON. Although the hips and knees are the most commonly affected areas, it may be present at multiple anatomical locations. Clinically, ON often remains undetected until patients feel discomfort and pain at specific sites at which point the process of bone death is already advanced. However, strategies for prevention and options for treatment are limited. Here, we review the epidemiology, risk factors, diagnosis, and treatment options for glucocorticoid‐induced ON, with a specific focus on patients with SLE.

MP24-08 RELATIONSHIPS OF SITES AND BURDEN OF METASTASES WITH LONG-TERM OUTCOMES AND MOLECULAR SUBTYPES IN TITAN

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) II (MP24)1 Sep 2021MP24-08 RELATIONSHIPS OF SITES AND BURDEN OF METASTASES WITH LONG-TERM OUTCOMES AND MOLECULAR SUBTYPES IN TITAN Anders Bjartell, Neeraj Agarwal, Lawrence Karsh, Axel S. Merseburger, Andrea J. Pereira de Santana Gomes, Álvaro Juárez Soto, Robert Given, Amitabha Bhaumik, Sabine Brookman-May, Florence Lefresne, Suneel D. Mundle, Sharon A. McCarthy, Shibu Thomas, Justin Lucas, Clemente Aguilar-Bonavides, Hirotsugu Uemura, Simon Chowdhury, and Kim N. Chi Anders BjartellAnders Bjartell More articles by this author , Neeraj AgarwalNeeraj Agarwal More articles by this author , Lawrence KarshLawrence Karsh More articles by this author , Axel S. MerseburgerAxel S. Merseburger More articles by this author , Andrea J. Pereira de Santana GomesAndrea J. Pereira de Santana Gomes More articles by this author , Álvaro Juárez SotoÁlvaro Juárez Soto More articles by this author , Robert GivenRobert Given More articles by this author , Amitabha BhaumikAmitabha Bhaumik More articles by this author , Sabine Brookman-MaySabine Brookman-May More articles by this author , Florence LefresneFlorence Lefresne More articles by this author , Suneel D. MundleSuneel D. Mundle More articles by this author , Sharon A. McCarthySharon A. McCarthy More articles by this author , Shibu ThomasShibu Thomas More articles by this author , Justin LucasJustin Lucas More articles by this author , Clemente Aguilar-BonavidesClemente Aguilar-Bonavides More articles by this author , Hirotsugu UemuraHirotsugu Uemura More articles by this author , Simon ChowdhurySimon Chowdhury More articles by this author , and Kim N. ChiKim N. Chi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002015.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The final analysis of TITAN confirmed improvement in long-term outcomes in metastatic castration-sensitive prostate cancer (mCSPC) with apalutamide (APA) + androgen deprivation therapy (ADT) (Chi ASCO GU 2021). We assessed relationships between the number and location of metastases, signatures associated with poor prognosis and ADT insensitivity and outcome measures. METHODS: 1052 mCSPC pts with ≥1 bone lesion were randomized 1:1 to APA (240 mg QD) or placebo (PBO)+ADT, and were stratified by sites of metastases. Outcomes in APA-treated pts (n=525) (Table) were analyzed by Kaplan-Meier and Cox proportional hazards methods. Molecular subtypes from 222 primary tumors (biomarker population; APA=110, PBO=112) were defined using biologically distinct signatures categorized by expression levels: androgen receptor activity (AR-A) high to average vs low, genomic classifier (GC) score high vs low to average, basal vs luminal (A + B), hypoxia high vs low, and adenocarcinoma vs neuroendocrine-like small-cell 3 score. The association between categorical expression and sites of metastases was assessed with Fisher’s exact test. RESULTS: In 1052 TITAN pts, metastases at baseline (BL) were: 53.0% in bone only, 37.9% in bone +1 other location, 9.0% in bone +2 or 3 other locations; 38.3% of pts had >10 bone lesions. The risk of worse outcomes in APA-treated pts increased with an increased number of metastatic locations and with >10 bone lesions (Table). Multiple metastatic locations at BL were significantly associated with higher risk of worse outcomes vs bone-only metastases (Table 1). In the biomarker population, 43.2% had AR-A low, 74.8% GC high, 50.5% basal, 50.0% hypoxia low, and 83.8% adenocarcinoma subtypes. Primary tumors from pts with i) bone-only metastases or ii) concomitant bone and visceral metastases were significantly enriched for low levels of hypoxia or adenocarcinoma (i), or for basal, AR-A low, or neuroendocrine-like features, respectively (ii) (p<0.05 for all). CONCLUSIONS: In APA-treated TITAN pts, multiple anatomic locations and >10 bone metastases were significantly associated with worse oncologic outcomes in mCSPC. Association of poor-prognosis and ADT-insensitivity signatures with metastatic locations needs further investigation. Source of Funding: Janssen Research & Development © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e414-e415 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anders Bjartell More articles by this author Neeraj Agarwal More articles by this author Lawrence Karsh More articles by this author Axel S. Merseburger More articles by this author Andrea J. Pereira de Santana Gomes More articles by this author Álvaro Juárez Soto More articles by this author Robert Given More articles by this author Amitabha Bhaumik More articles by this author Sabine Brookman-May More articles by this author Florence Lefresne More articles by this author Suneel D. Mundle More articles by this author Sharon A. McCarthy More articles by this author Shibu Thomas More articles by this author Justin Lucas More articles by this author Clemente Aguilar-Bonavides More articles by this author Hirotsugu Uemura More articles by this author Simon Chowdhury More articles by this author Kim N. Chi More articles by this author Expand All Advertisement Loading ...

Impact of residual disease at interval debulking surgery on platinum resistance and patterns of recurrence for advanced-stage ovarian cancer

ObjectiveTo evaluate the impact of size and distribution of residual disease after interval debulking surgery on the timing and patterns of recurrence for patients with advanced-stage epithelial ovarian cancer.MethodsPatient demographics...