Antagonistic roles of cGAS/STING signaling in colorectal cancer chemotherapy.

FOLFOX, composed of 5-FU, oxaliplatin and leucovorin, is a first line chemotherapy regimen for colorectal cancer (CRC) treatment. In this study, we show that 5-FU and oxaliplatin induce DNA damage and activate cGAS/STING signaling leading to enhanced expression of interferon (IFN) ß, IFN-stimulated genes and inflammatory cytokines in mouse and human colon cancer cells as well as increased intratumoral CD8+ T cells in mice. Crucially, 5-FU and oxaliplatin increase PD-L1 expression at the mRNA and protein levels, which has been shown to inhibit CD8+ T cell function. Depletion of cGAS, STING, IRF3, or IFNα/ß receptor 1 (IFNAR1) abolishes this increase, indicating that 5-FU/oxaliplatin mediated upregulation of PD-L1 expression is dependent on tumor cell intrinsic cGAS/STING signaling. These results imply opposing roles for FOLFOX during cancer treatment. On one hand, 5-FU and oxaliplatin activate the innate immune response to facilitate anti-tumor immunity, and conversely upregulate PD-L1 expression to evade immune surveillance. Analysis of TCGA colon cancer dataset shows a positive correlation between expression of PD-L1 and components of the cGAS/STING pathway, supporting a role for cGAS/STING signaling in upregulating PD-L1 expression in colon cancer patients. Tumor studies in syngeneic immune competent mice demonstrate that the combination of 5-FU/oxaliplatin and anti-PD-1 significantly reduced tumor growth of colon cancer cells compared to 5-FU/oxaliplatin treatment alone. Taken together, our studies have identified a unique pathway leading to chemoresistance and provide a rationale to combine FOLFOX with anti-PD-1/PD-L1 as an effective CRC treatment.

Non-Breast Implantable Medical Devices and Associated Malignancies: A Systematic Review.

Innovation in healthcare has led to the development of numerous implantable medical devices (IMDs). However, advances in our knowledge of breast implant-associated malignancies have raised questions about the prevalence, etiology and management of malignancies associated with non-breast IMDs. The objective of this study was to examine the prevalence and characteristics of malignancies associated with non-breast IMDs. An expert medical librarian developed the search strategy for this review. Databases included MEDLINE (National Library of Medicine, Bethesda, MD; date range of search: 1946 to June 21, 2023), EMBASE (Elsevier, Amsterdam, the Netherlands; date range of search: 1946 to June 21, 2023), and Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane Library, Wiley, Hoboken, NJ; date range of search: 1946 to June 21, 2023). In addition, grey literature sources were searched and relevant references from systematic reviews and meta-analyses were included. The PRISMA guideline was used to guide the review. Risk of bias was evaluated using the JBI Critical Appraisal tools. A total of 12,230 articles were reviewed with a total of 77 meeting inclusion criteria. Risk of bias was highest with case reports (moderate, average of 65.1% with range of 37.5 to 100%) and low for the remaining study types. In total, 616 cases of IMD-associated malignancies were identified. Malignancies associated with IMDs were reported in the head/neck (543, 88.1%), lower extremity (57, 9.6%), thorax (9, 1.4%), abdomen (3, 0.5%), and genitourinary system (2, 0.3%). The most common malignancy type in the lower extremity was sarcoma, in the head and neck was squamous cell carcinoma, and in the thorax was lymphoma. This study is the first comprehensive systematic review of its kind. Overall, the oncologic risk of IMDs is low. The discussion of malignancy is an important part to the overall consent process and malignancy should be considered with any new signs or symptoms in the anatomic area of an implant. More data is needed to better understand how primary malignancies occur around IMDs and how to reduce this risk.

Extrapulmonary hyalinizing granuloma: a rare case with intra-articular and tenosynovial involvement.

Extrapulmonary hyalinizing granuloma (EPHG) is a notably rare condition, representing an exaggerated chronic immune response to antigenic stimuli. This report presents the first documented case of intra-articular and tenosynovial EPHG with radiological evaluation and pathological confirmation in a 60-year-old man presenting with wrist pain and swelling. Imaging findings were relatively symmetric with marked distension of the distal radioulnar joints and extensor tendon sheaths with masses and nodules of various sizes surrounded by synovitis and accompanied by bony erosions. On US, the masses were heterogeneous but mostly hypo- to iso-echoic compared to muscle and relatively hypovascular. On MRI, compared to muscle, the nodules exhibited iso-intense signal on T1-weighted images, iso- to mildly hyper-intense signal on T2-weighted fat-suppressed images, and minimal enhancement on post-contrast images. The diagnosis of EPHG was revealed through biopsy and pathologic examination with glucocorticoids being effective in treatment.

Outcomes in Subfascial Versus Subglandular Planes in Breast Augmentation: A Systematic Review and Meta-analysis.

Breast augmentation is the most commonly performed aesthetic surgery procedure in women worldwide. The use of the subfascial plane has been suggested to decrease the incidence of capsular contracture compared with the subglandular plane, while simultaneously avoiding the complication of animation deformity in the subpectoral plane. The aim of this systematic review and meta-analysis was to compare the adverse outcomes of subfascial vs subglandular planes in breast augmentation. This review was registered a priori on OSF (https://osf.io/pm92e/). A search from inception to June 2023 was performed on MEDLINE, Embase, and CENTRAL. A hand search was also performed. All randomized and comparative cohort studies that assessed the use of the subfascial plane for breast augmentation were included. Outcomes evaluated included the incidences of seroma, hematoma, infection, rippling, capsular contracture, and revision surgery. Ten studies were included in this systematic review. Three randomized controlled trials and 7 comparative cohort studies were used for quantitative synthesis. There was a significant difference favoring subfascial compared with subglandular planes in the incidence of hematoma, rippling, and capsular contracture. All included studies had a high risk of bias. The current evidence suggests that the subfascial plane for breast augmentation decreases the risk of capsular contracture, hematoma, and rippling compared with the subglandular plane. Further randomized evidence with high methodological rigor is still required to validate these findings.

A Millimeter-Scale Soft Robot for Tissue Biopsy Procedures.

While interest in soft robotics as surgical tools has grown due to their inherently safe interactions with the body, their feasibility is limited in the amount of force that can be transmitted during procedures. This is especially apparent in minimally invasive procedures where millimeter-scale devices are necessary for reaching the desired surgical site, such as in interventional bronchoscopy. To leverage the benefits of soft robotics in minimally invasive surgery, a soft robot with integrated tip steering, stabilization, and needle deployment capabilities is proposed for lung tissue biopsy procedures. Design, fabrication, and modeling of the force transmission of this soft robotic platform allows for integration into a system with a diameter of 3.5 mm. Characterizations of the soft robot are performed to analyze bending angle, force transmission, and expansion during needle deployment. In-vitro experiments of both the needle deployment mechanism and fully integrated soft robot validate the proposed workflow and capabilities in a simulated surgical setting.

Aesthetic Refinements in Male Chest Lifting.

The authors describe aesthetic refinements to the approach for male chest lifting in male patients with grade 3 gynecomastia and/or significant chest skin excess. An inferior pedicle is used to transpose the nipple-areolar complex allowing preservation of pigment and sensation, liposuction and direct excision are used to reduce volume and excess skin, and the resulting curvilinear scar along the inferior and lateral border of the chest provide a more masculine appearance. Early experience with this technique has shown it to be safe and effective. Perioperative management and the detailed steps of the procedure are outlined.

18F-FDG PET/CT for the Evaluation of Therapy Response in Hormone Receptor-Positive Bone-Dominant Metastatic Breast Cancer.

Fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT has shown promise for use in assessing treatment response in patients with bone-only or bone-dominant (BD) metastatic breast cancer (mBC). In this single-institution, prospective single-arm study of 23 women (median age, 59 years [range, 38-81 years]) with biopsy-proven estrogen receptor-positive bone-only or BD mBC about to begin new endocrine therapy between October 3, 2013, and August 3, 2018, the value of early 4-week 18F-FDG PET/CT in predicting progression-free survival (PFS) was evaluated. 18F-FDG PET/CT was performed at baseline, 4 weeks, and 12 weeks. Maximum standardized uptake value (SUVmax) and peak SUV (SUVpeak) were measured for up to five index lesions. The primary end point was PFS. Secondary end points were overall survival (OS) and time to skeletal-related events (tSREs). All end points were compared between responders (reduction of 30% or more in the sum of SUVmax for target lesions) and nonresponders at 4 weeks and 12 weeks. Percentage change from baseline in SUVmax at 4- and 12-week 18F-FDG PET/CT were highly correlated (r = 0.81). At the 4-week time point PET responders had numerically longer PFS (14.2 months vs 6.3 months; P = .53), OS (44.0 months vs 29.7 months; P = .47), and tSRE (27.4 months vs 25.2 months; P = .66) compared with nonresponders, suggesting the clinical utility of 4-week 18F-FDG PET/CT as an early predictor of treatment failure. Keywords: Breast Cancer, Metastatic Breast Cancer, Bone-Dominant Metastatic Breast Cancer, FDG PET/CT, Estrogen-Receptor Positive Metastatic Breast Cancer Supplemental material is available for this article. Clinical trial registration no. NCT04316117 © RSNA, 2022.

Vertical Scar Mastopexy With a Centrally Based Auto-Augmentation Flap.

The authors describe their technique for vertical scar mastopexy with a centrally based auto-augmentation flap. Since 2011, the authors have performed this procedure in 212 patients and found that this operative technique has allowed us to achieve reproducible aesthetic outcomes while minimizing complications. Vertical scar mastopexy with a centrally based auto-augmentation flap is an excellent procedure for patients with breast ptosis who desire improved breast shape and superior pole fullness without the use of a breast implant. The perioperative management and detailed steps of the procedure are outlined.

Use of strontium isotope ratios in geolocation of Guatemalan population: Potential role in identification of remains.

Within post-conflict communities, attempts to identify and repatriate unidentified and missing individuals poses a difficult task. As current forensic strategies commonly lack the capacity to provide region of origin assessments, forensic anthropologists/investigators are often unable to identify sources of DNA for kinship analysis. Using Thermal Ionization Mass Spectrometry (TIMS), hair samples from 10 volunteers were used to assess the variation in strontium isotope ratios (87 Sr/86 Sr) between extant people in Guatemala City and Coban; with a leach (external) and digest (dietary) signal analyzed for each sample. A two-way anova demonstrated that the difference between 87 Sr/86 Sr of Guatemala City and Coban was statistically significant (F [1, 16] = 259.839, p < 0.05), with no statistically significant differences observed between leach and digest 87 Sr/86 Sr (F [1,16] = 4.319, p = 0.054). Overall, individuals from Coban demonstrate 87 Sr/86 Sr comparable to previously recorded baseline values, demonstrating a minimal change in diet which is reflected in associated surveys. Volunteers from Guatemala City, however, show a marked shift in 87 Sr/86 Sr away from predicted values highlighting the potential influence of imported goods. The results here highlight the applicability of 87 Sr/86 Sr in hair to serve as a potential tool to support the identification of unknown individuals in Guatemala in a forensic context.

Independent assessment of a deep learning system for lymph node metastasis detection on the Augmented Reality Microscope.

Several machine learning algorithms have demonstrated high predictive capability in the identification of cancer within digitized pathology slides. The Augmented Reality Microscope (ARM) has allowed these algorithms to be seamlessly integrated within the pathology workflow by overlaying their inferences onto its microscopic field of view in real time. We present an independent assessment of the LYmph Node Assistant (LYNA) models, state-of-the-art algorithms for the identification of breast cancer metastases in lymph node biopsies, optimized for usage on the ARM. We assessed the models on 40 whole slide images at the commonly used objective magnifications of 10×, 20×, and 40×. We analyzed their performance across clinically relevant subclasses of tissue, including breast cancer, lymphocytes, histiocytes, blood, and fat. Each model obtained overall AUC values of approximately 0.98, accuracy values of approximately 0.94, and sensitivity values above 0.88 at classifying small regions of a field of view as benign or cancerous. Across tissue subclasses, the models performed most accurately on fat and blood, and least accurately on histiocytes, germinal centers, and sinus. The models also struggled with the identification of isolated tumor cells, especially at lower magnifications. After testing, we reviewed the discrepancies between model predictions and ground truth to understand the causes of error. We introduce a distinction between proper and improper ground truth for analysis in cases of uncertain annotations. Taken together, these methods comprise a novel approach for exploratory model analysis over complex anatomic pathology data in which precise ground truth is difficult to establish.

Evaluating Breast Reconstruction Reviews Using A Measurement Tool to Assess Systematic Reviews (AMSTAR).

BACKGROUND: Breast reconstruction is an important aspect in breast cancer treatment. METHODS: A comprehensive search of MEDLINE, Embase, and the Cochrane Library of Systematic Reviews was performed. Systematic reviews and meta-analyses that focused on breast reconstruction and were published between 2000 and 2020 were included. Quality assessment was performed using A Measurement Tool to Assess Systematic Reviews (AMSTAR). Study characteristics were extracted, including journal and impact factor, year of publication, country affiliation, reporting adherence to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, number of citations, and number of studies included. RESULTS: The average AMSTAR score was moderate (5.32). There was a significant increase in AMSTAR score (P < 0.01) and number of studies (P < 0.01) over time. There were no significant correlations between AMSTAR score and impact factor (P = 0.038), and AMSTAR score and number of citations (P = 0.52), but there was a significant association between AMSTAR score and number of studies (P = 0.013). Studies that adhered to the PRISMA statement had a higher AMSTAR score on average (P < 0.01). CONCLUSIONS: Systematic reviews and meta-analyses about breast reconstruction had, on average, a moderate AMSTAR score. The number of studies and methodological quality have increased over time. Study characteristics including adherence to PRISMA guidelines are associated with improved methodological quality. Further improvements in specific AMSTAR domains would improve the overall methodological quality.

Differential Gene Expression of Brachypodium distachyon Roots Colonized by Gluconacetobacter diazotrophicus and the Role of BdCESA8 in the Colonization.

Alternatives to synthetic nitrogen fertilizer are needed to reduce the costs of crop production and offset environmental damage. Nitrogen-fixing bacterium Gluconacetobacter diazotrophicus has been proposed as a possible biofertilizer for monocot crop production. However, the colonization of G. diazotrophicus in most monocot crops is limited and deep understanding of the response of host plants to G. diazotrophicus colonization is still lacking. In this study, the molecular response of the monocot plant model Brachypodium distachyon was studied during G. diazotrophicus root colonization. The gene expression profiles of B. distachyon root tissues colonized by G. diazotrophicus were generated via next-generation RNA sequencing, and investigated through gene ontology and metabolic pathway analysis. The RNA sequencing results indicated that Brachypodium is actively involved in G. diazotrophicus colonization via cell wall synthesis. Jasmonic acid, ethylene, gibberellin biosynthesis. nitrogen assimilation, and primary and secondary metabolite pathways are also modulated to accommodate and control the extent of G. diazotrophicus colonization. Cellulose synthesis is significantly downregulated during colonization. The loss of function mutant for Brachypodium cellulose synthase 8 (BdCESA8) showed decreased cellulose content in xylem and increased resistance to G. diazotrophicus colonization. This result suggested that the cellulose synthesis of the secondary cell wall is involved in G. diazotrophicus colonization. The results of this study provide insights for future research in regard to gene manipulation for efficient colonization of nitrogen-fixing bacteria in Brachypodium and monocot crops.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Evaluating the Quality of Systematic Reviews and Meta-Analyses About Breast Augmentation Using AMSTAR.

BACKGROUND: Breast augmentation is one of the most commonly performed cosmetic surgeries worldwide. Therefore, it is imperative to have evidence with high methodological quality to guide clinical decision making. OBJECTIVES: To evaluate the methodological quality of the systematic reviews (SRs) focused on breast augmentation. METHODS: A comprehensive search of MEDLINE, Embase, and the Cochrane Library of Systematic Reviews was performed. SRs that have a particular focus on breast augmentation and were published in the top 15 plastic and reconstructive surgery journals were included. Quality assessment was performed using a measurement tool to assess systematic reviews (AMSTAR). Study characteristics were extracted including journal and impact factor, year of publication, country affiliation of the corresponding author, reporting adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, number of citations, and number of studies included. RESULTS: Among the 22 studies included for analysis, the mean AMSTAR score was moderate (5.55), with no SR achieving good quality (AMSTAR score of ≥9). There were no significant associations between AMSTAR score and journal impact factor, number of citations, year of publication, or number of included studies. Studies that reported adherence to PRISMA guidelines on average scored higher on the AMSTAR tool (P = 0.03). CONCLUSIONS: The methodological quality of reviews about breast augmentation was found to be moderate, with no significant increase in studies or quality over time. Adherence to PRISMA guidelines and increased appraisal of SRs about breast augmentation using methodological assessment tools would further strengthen methodological quality and confidence in study findings.

Sine Qua Non: Dentigerous Cyst.

Dentigerous cysts, also known as follicular cysts, are among the most common developmental cysts of the gnathic bones. The majority of cases are clinically asymptomatic and discovered incidentally on panographic radiographs during routine dental care. The cyst appears as a radiolucency, classically unilocular, associated with the crown of an unerupted or impacted tooth. Usually diagnosed in the 2nd-3rd decade, third molars of the mandible are the most commonly affected teeth. Histologically, dentigerous cysts demonstrate a fibrous or fibromyxoid connective tissue wall lined by squamous epithelium, classically lacking rete ridges. Inflammation may introduce histologic changes, however. The differential diagnosis includes hyperplastic dental follicle, periapical or radicular cyst, unicystic ameloblastoma, odontogenic keratocyst, and other odontogenic cysts and tumors. While the findings are generally classic and pose no diagnostic dilemma, the diagnosis is best made in the context of the appropriate clinical and radiographic setting. Submitted tissue with a lack of history, to include a detailed relationship with the affected tooth, may result in misdiagnosis and subsequent confusion for the clinician. So, despite its simple features, dentigerous cysts are not uncommonly mischaracterized. Therefore a review of a classic case of dentigerous cyst is presented.