A Survey of Patient Experience During Molecular Breast Imaging.

Molecular breast imaging (MBI) is one of several options available to patients seeking supplemental screening due to mammographically dense breasts. Patient experience during MBI may influence willingness to undergo the test but has yet to be formally assessed. We aimed to assess patient comfort level during MBI, to compare MBI comfort with mammography comfort, to identify factors associated with MBI discomfort, and to evaluate patients' willingness to return for future MBI. Methods: A 10-question survey was sent by e-mail to patients undergoing MBI between August and December 2022 to obtain quantitative assessments and qualitative opinions about MBI. Results: Of 561 invited patients, 209 (37%) completed the survey and provided study consent. Their average age was 60.1 y (range, 40-81 y). Of the 209 responders, 202 (97%) were presenting for screening MBI, 195 (94%) had dense breasts, and 46 (22%) had a personal history of breast cancer. The average rating of MBI comfort was 2.9 (SD, 1.5; median, 3.0) on a 7-point scale (1 indicating extremely comfortable and 7 indicating extremely uncomfortable). The rating distribution was as follows: 140 (67%) comfortable (rating, 1-3); 24 (12%) neither comfortable nor uncomfortable (rating, 4); and 45 (22%) uncomfortable (rating, 5 or 6). No responders gave a 7 rating. The most frequently mentioned sources of discomfort included breast compression (n = 16), back or neck discomfort (n = 14), and maintaining position during the examination (n = 14). MBI comfort was associated with responder age (74% ≥55 y old were comfortable, versus 53% <55 y old [P = 0.003]) and history of MBI (71% with prior MBI were comfortable, versus 61% having a first MBI [P = 0.006]). Of 208 responders with a prior mammogram, 148 (71%) said MBI is more comfortable than mammography (a significant majority [P < 0.001]). Of 202 responders to the question of whether they were willing to return for a future MBI, 196 (97%) were willing. A notable factor in positive patient experience was interaction with the MBI nuclear medicine technologist. Conclusion: Most responders thought MBI to be a comfortable examination and more comfortable than mammography. Patient experience during MBI may be improved by ensuring back support and soliciting patient feedback at the time of positioning and throughout the examination. Methods under study to reduce imaging time may be most important for improving patient experience.

Erratum: Influence of structural moieties in squaraine dyes on optoacoustic signal shape and intensity.

[This corrects the article PMC11087056.].

Influence of structural moieties in squaraine dyes on optoacoustic signal shape and intensity.

Optoacoustic imaging has grown in clinical relevance due to inherent advantages in sensitivity, resolution, and imaging depth, but the development of contrast agents is lacking. This study assesses the influence of structural features of squaraine dyes on optoacoustic activity through computational models, in vitro testing, and in vivo experimentation. The squaraine scaffold was decorated with halogens and side-chain extensions. Extension of side chains and heavy halogenation of squaraines both increased optoacoustic signals individually, although they had a more significant effect in tandem. Density functional theory models suggest that the origin of the increased optoacoustic signal is the increase in transition dipole moment and vibrational entropy, which manifested as increased absorbance in near-infrared region (NIR) wavelengths and decreased fluorescence quantum yield. This study provides insight into the structure-function relationships that will lead guiding principles for optimizing optoacoustic contrast agents. Further developments of squaraines and other agents will further increase the relevance of optoacoustic imaging in a clinical setting.

Erratum: Influence of structural moieties in squaraine dyes on optoacoustic signal shape and intensity.

[This corrects the article PMC11087056.].

Correction: Garza-Morales et al. Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro. Cancers 2018, 10, 144.

Error in Figure [...].

The PUG Flap: Conjoined Profunda Artery Perforator and Upper Gracilis Flap for Breast Reconstruction.

Abdominal-based free flaps are the mainstay of autologous breast reconstruction; however, the region may not be ideal for patients with inadequate soft tissue or history of abdominal surgery. This case describes the use of a novel conjoined flap based on the profunda artery perforator and upper gracilis pedicles, named the perforator and upper gracilis (PUG) flap. This flap design aims to maximize medial thigh flap volume while ensuring robust tissue perforation. Here, we present our experience with the PUG flap in a breast cancer patient undergoing autologous reconstruction. The patient was a 41-year-old woman seeking nipple-sparing mastectomy and immediate autologous reconstruction with the PUG flap due to limited abdominal tissue availability. The gracilis and profunda artery perforator flaps were elevated using one boomerang-style skin paddle. Once harvested, the flaps were inset with antegrade and retrograde flow off the internal mammary arteries and both respective internal mammary veins. The donor site was closed in a V-Y pattern resulting in a thigh lift-type lift and concealed scar. In conclusion, the boomerang-style PUG flap maximizes medial thigh free tissue transfer volume, offers internal blood flow redundancy, and maintains good cosmesis of the donor site.

Can You Go the Distance: Collagenase Clostridium histolyticum Manipulation at 1 Month after Injection.

Collagenase Clostridium histolyticum is a popular treatment in Dupuytren contracture. Current guidelines are for manipulation 24 hours to 7 days after injection. We present a case of successful manipulation 28 days after injection.

Meningomyelocele Reconstruction: Comparison of Repair Methods via Systematic Review.

PURPOSE: The purpose of this article was to appraise the various methods of reconstruction for meningomyelocele (MMC) defects. METHODS: A systematic review of the literature was performed to evaluate all reconstructions for MMC. The method of reconstruction was categorized by: primary closure with and without fascial flaps, random pattern flaps, VY advancement flaps (VY), perforator flaps, and myocutaneous flaps. Perforator flaps were subsequently subcategorized based on the type of flap. RESULTS: Upon systematic review, 567 articles were screened with 104 articles assessed for eligibility. Twenty-nine articles were further reviewed and included for qualitative synthesis. Two hundred seventy patients underwent MMC repair. The lowest rates of major wound complications (MWC) were associated with myocutaneous and random pattern flaps. A majority of MWC was in the lumbrosacral/sacral region (87.5% of MWC). In this region, random patterns and perforator flaps demonstrated the lowest rate of MWC (4.5, 8.1%). CONCLUSIONS: Plastic surgery consultation should be strongly considered for MMC with defects in the lumbosacral/sacral region. Perforator flaps are excellent options for the reconstruction of these defects.

Dynamic 2-deoxy-D-glucose-enhanced multispectral optoacoustic tomography for assessing metabolism and vascular hemodynamics of breast cancer.

Clinical tools for measuring tumor vascular hemodynamics, such as dynamic contrast-enhanced MRI, are clinically important to assess tumor properties. Here we explored the use of multispectral optoacoustic tomography (MSOT), which has a high spatial and temporal resolution, to measure the intratumoral pharmacokinetics of a near-infrared-dye-labeled 2-Deoxyglucose, 2-DG-800, in orthotropic 2-LMP breast tumors in mice. As uptake of 2-DG-800 is dependent on both vascular properties, and glucose transporter activity - a widely-used surrogate for metabolism, we evaluate hemodynamics of 2-DG-MP by fitting the dynamic MSOT signal of 2-DG-800 into two-compartment models including the extended Tofts model (ETM) and reference region model (RRM). We showed that dynamic 2-DG-enhanced MSOT (DGE-MSOT) is powerful in acquiring hemodynamic rate constants, including Ktrans and Kep, via systemically injecting a low dose of 2-DG-800 (0.5 µmol/kg b.w.). In our study, both ETM and RRM are efficient in deriving hemodynamic parameters in the tumor. Area-under-curve (AUC) values (which correlate to metabolism), and Ktrans and Kep values, can effectively distinguish tumor from muscle. Hemodynamic parameters also demonstrated correlations to hemoglobin, oxyhemoglobin, and blood oxygen level (SO2) measurements by spectral unmixing of the MSOT data. Together, our study for the first time demonstrated the capability of DGE-MSOT in assessing vascular hemodynamics of tumors.

Intraoperative Imaging in Hepatopancreatobiliary Surgery.

Hepatopancreatobiliary surgery belongs to one of the most complex fields of general surgery. An intricate and vital anatomy is accompanied by difficult distinctions of tumors from fibrosis and inflammation; the identification of precise tumor margins; or small, even disappearing, lesions on currently available imaging. The routine implementation of ultrasound use shifted the possibilities in the operating room, yet more precision is necessary to achieve negative resection margins. Modalities utilizing fluorescent-compatible dyes have proven their role in hepatopancreatobiliary surgery, although this is not yet a routine practice, as there are many limitations. Modalities, such as photoacoustic imaging or 3D holograms, are emerging but are mostly limited to preclinical settings. There is a need to identify and develop an ideal contrast agent capable of differentiating between malignant and benign tissue and to report on the prognostic benefits of implemented intraoperative imaging in order to navigate clinical translation. This review focuses on existing and developing imaging modalities for intraoperative use, tailored to the needs of hepatopancreatobiliary cancers. We will also cover the application of these imaging techniques to theranostics to achieve combined diagnostic and therapeutic potential.

Simultaneous Detection of Multiple Tumor-targeted Gold Nanoparticles in HER2-Positive Breast Tumors Using Optoacoustic Imaging.

Purpose To develop optoacoustic, spectrally distinct, actively targeted gold nanoparticle-based near-infrared probes (trastuzumab [TRA], TRA-Aurelia-1, and TRA-Aurelia-2) that can be individually identifiable at multispectral optoacoustic tomography (MSOT) of human epidermal growth factor receptor 2 (HER2)-positive breast tumors. Materials and Methods Gold nanoparticle-based near-infrared probes (Aurelia-1 and 2) that are optoacoustically active and spectrally distinct for simultaneous MSOT imaging were synthesized and conjugated to TRA to produce TRA-Aurelia-1 and 2. Freshly resected human HER2-positive (n = 6) and HER2-negative (n = 6) triple-negative breast cancer tumors were treated with TRA-Aurelia-1 and TRA-Aurelia-2 for 2 hours and imaged with MSOT. HER2-expressing DY36T2Q cells and HER2-negative MDA-MB-231 cells were implanted orthotopically into mice (n = 5). MSOT imaging was performed 6 hours following the injection, and the Friedman test was used for analysis. Results TRA-Aurelia-1 (absorption peak, 780 nm) and TRA-Aurelia-2 (absorption peak, 720 nm) were spectrally distinct. HER2-positive human breast tumors exhibited a significant increase in optoacoustic signal following TRA-Aurelia-1 (28.8-fold) or 2 (29.5-fold) (P = .002) treatment relative to HER2-negative tumors. Treatment with TRA-Aurelia-1 and 2 increased optoacoustic signals in DY36T2Q tumors relative to those in MDA-MB-231 controls (14.8-fold, P < .001; 20.8-fold, P < .001, respectively). Conclusion The study demonstrates that TRA-Aurelia 1 and 2 nanoparticles operate as a spectrally distinct HER2 breast tumor-targeted in vivo optoacoustic agent. Keywords: Molecular Imaging, Nanoparticles, Photoacoustic Imaging, Breast Cancer Supplemental material is available for this article. © RSNA, 2023.

Susceptibility of Pallid Sturgeon to viral hemorrhagic septicemia virus genotype IVb.

OBJECTIVE: Viral hemorrhagic septicemia virus (VHSV) is an aquatic rhabdovirus causing severe disease in freshwater and saltwater fish species. The susceptibility of endangered Pallid Sturgeon Scaphirhynchus albus to VHSV genotype IVb (VHSV-IVb) infection was investigated. METHODS: An in vitro assessment using two Pallid Sturgeon cell lines derived from skin and spleen tissue and in vivo evaluation of juvenile Pallid Sturgeon after exposure to VHSV-IVb were performed. RESULT: Plaque assay and RT-PCR results confirmed VHSV-IVb replication in Pallid Sturgeon cell lines. Sturgeon were also susceptible to VHSV-IVb infection after immersion and injection exposures during laboratory experiments. However, after widespread mortality occurred in all treatment groups, including negative control fish, it was determined that the Pallid Sturgeon stock fish were infected with Missouri River sturgeon iridovirus (MRSIV) prior to experimental challenge. Nevertheless, mortalities were equal or higher among VHSV-exposed fish than among negative controls (MRSIV infected), and histopathological assessments indicated reduced hematopoietic cells in spleen and kidney tissues and hemorrhage in the gastrointestinal organs only in fish from the VHSV treatment. CONCLUSION: These results indicate that Pallid Sturgeon is a susceptible host for VHSV-IVb, but the degree of pathogenicity was confounded by the underlying MRSIV infection. Research comparing susceptibility of specific pathogen-free and MRSIV-infected fish to VHSV-IVb is needed to accurately assess the vulnerability of Pallid Sturgeon to VHSV-IVb.

Are childhood factors predictive of adult health literacy? A longitudinal birth cohort analysis.

Health literacy (HL), defined as the ability of an individual to understand and appraise health information to make informed decisions on their health, helps maintain and improve one's health and thus reduce the use of healthcare services. There is a recognised global effort to address insufficient HL in early life and understand how HL develops. This study examined the association of a range of factors including educational, speech and language ability, health and healthcare engagement, sleep problems, mental health, demographic, environmental, and maternal factors at different childhood stages (from 5 years to 11 years) with later adult HL at age 25. HL was measured using a HL ordinal score (insufficient, limited, or sufficient) derived from the European Literacy Survey Questionnaire-short version (HLS-EU-Q16) within a large UK based birth cohort (Avon Longitudinal Study of Parents and Children: ALSPAC study). Univariate proportional odds logistic regression models for the probability of having higher levels of HL were developed. Results of analysis of 4248 participants showed that poorer speech and language ability (aged 9 years, OR 0.18 95% CI 0.04 to 0.78), internalising in child (age 11 years, OR 0.62 95% CI 0.5 to 0.78), child depression (age 9 years, OR 0.67 95% CI 0.52 to 0.86), and the presence of maternal depression (child age 5, OR 0.80 95% CI 0.66 to 0.96), reduced the odds of sufficient HL when adult. Our results suggest some useful markers to identify children at potential risk of low HL that could be targeted for research into future interventions within school settings, for example, child's speech and language capability. In addition, this study identified child and maternal mental health as factors associated with later development of limited HL and future research should consider what potential mechanisms might explain this link.

Heterogeneity among Clinical Intestinal Escherichia coli Isolates upon Acquired Streptomycin Resistance.

Escherichia coli isolates from inflammatory bowel disease (IBD) patients are often multidrug resistant, including to streptomycin. Streptomycin resistance (StrR) mutations can alter bacterial behavior, which may influence intestinal disease. We generated a spontaneous StrR strain of the intestinal adherent-invasive E. coli (AIEC) strain NC101. Whole-genome sequencing revealed a single missense mutation in rpsL that commonly confers StrR, rpsL-K43N. StrR NC101 exhibited a striking loss of aggregation and significantly increased motility, behaviors that can impact host-microbe interactions. Behavioral changes were associated with reduced transcription of csgA, encoding the biofilm component curli, and increased transcription of fliC, encoding flagellin. Scanning electron microscopy (SEM) detailed morphologic changes consistent with the observed alterations in multicellular behavior. Because intestinal E. coli isolates exhibit remarkable strain-specific differences, we generated spontaneous StrR mutants of 10 clinical E. coli phylotype B2 strains from patients with IBD, colorectal cancer, and urinary tract infection. Out of these 10 StrR clinical strains, two had altered colony morphology on Congo red agar (suggesting changes in extracellular products), and three had significant changes in motility. These changes were not associated with a particular rpsL mutation nor with the presence of virulence genes encoding the inflammation-associated E. coli metabolites yersiniabactin or colibactin. We conclude that common mutations in rpsL, which confer StrR, can differentially alter disease-associated phenotypes across intestinal E. coli strains. These findings highlight the heterogeneity among seemingly similar intestinal E. coli strains and reveal the need to carefully study the strain-specific effects of antibiotic resistance mutations, particularly when using these mutations during strain selection studies. IMPORTANCE We demonstrate that StrR, commonly acquired through a single point mutation in rpsL (a gene encoding part of the 30S bacterial ribosome), strikingly alters the morphology and behavior of a key intestinal AIEC strain, NC101. These changes include remarkably diminished aggregation and significantly increased motility, traits that are linked to AIEC-defining features and disease development. Phenotypic changes were heterogeneous among other StrR clinical E. coli strains, underscoring the need to evaluate the strain-specific effects of commonly acquired antibiotic resistance mutations. This is important, as the results of studies using mutant StrR Enterobacteriaceae strains (e.g., for cloning or in vivo selection) may be confounded beyond our demonstrated effects. Long term, these findings can help researchers better distinguish the contribution of specific E. coli traits to functional changes in the microbiota. Evaluating these strain-level differences could provide insight into the diversity of IBD symptoms and lead to improved therapies for microbiota-driven intestinal disorders.

Innovative Imaging Techniques Used to Evaluate Borderline-Resectable Pancreatic Adenocarcinoma.

A diagnosis of pancreatic cancer carries a 5-y survival rate of less than 10%. Furthermore, the detection of pancreatic cancer occurs most often in later stages of the disease due to its location in the retroperitoneum and lack of symptoms (in most cases) until tumors become more advanced. Once diagnosed, cross-sectional imaging techniques are heavily utilized to determine the tumor stage and the potential for surgical resection. However, a major determinant of resectability is the extent of local vascular involvement of the mesenteric vessels and critical tributaries; current imaging techniques have limited capacity to accurately determine vascular involvement. Surrounding inflammation and fibrosis can be difficult to discriminate from viable tumor, making determination of the degree of vascular involvement unreliable. New innovations in fluorescence and optoacoustic imaging techniques may overcome these limitations and make determination of resectability more accurate. These imaging modalities are able to more clearly discern between viable tumor tissue and non-neoplastic inflammation or desmoplasia, allowing clinicians to more reliably characterize vascular involvement and develop individualized treatment plans for patients. This review will discuss the current imaging techniques used to diagnose pancreatic cancer, the barriers that current techniques raise to accurate staging, and novel fluorescence and optoacoustic imaging techniques that may provide more accurate clinical staging of pancreatic cancer.

Advances in Imaging of Inflammation, Fibrosis, and Cancer in the Gastrointestinal Tract.

Gastrointestinal disease is prevalent and broad, manifesting itself in a variety of ways, including inflammation, fibrosis, infection, and cancer. However, historically, diagnostic technologies have exhibited limitations, especially with regard to diagnostic uncertainty. Despite development of newly emerging technologies such as optoacoustic imaging, many recent advancements have focused on improving upon pre-existing modalities such as ultrasound, computed tomography, magnetic resonance imaging, and endoscopy. These advancements include utilization of machine learning models, biomarkers, new technological applications such as diffusion weighted imaging, and new techniques such as transrectal ultrasound. This review discusses assessment of disease processes using imaging strategies for the detection and monitoring of inflammation, fibrosis, and cancer in the context of gastrointestinal disease. Specifically, we include ulcerative colitis, Crohn's disease, diverticulitis, celiac disease, graft vs. host disease, intestinal fibrosis, colorectal stricture, gastric cancer, and colorectal cancer. We address some of the most recent and promising advancements for improvement of gastrointestinal imaging, including unique discussions of such advancements with regard to imaging of fibrosis and differentiation between similar disease processes.

Microenvironmental Factors that Shape Bacterial Metabolites in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a significant global health problem that involves chronic intestinal inflammation and can involve severe comorbidities, including intestinal fibrosis and inflammation-associated colorectal cancer (CRC). Disease-associated alterations to the intestinal microbiota often include fecal enrichment of Enterobacteriaceae, which are strongly implicated in IBD development. This dysbiosis of intestinal flora accompanies changes in microbial metabolites, shaping host:microbe interactions and disease risk. While there have been numerous studies linking specific bacterial taxa with IBD development, our understanding of microbial function in the context of IBD is limited. Several classes of microbial metabolites have been directly implicated in IBD disease progression, including bacterial siderophores and genotoxins. Yet, our microbiota still harbors thousands of uncharacterized microbial products. In-depth discovery and characterization of disease-associated microbial metabolites is necessary to target these products in IBD treatment strategies. Towards improving our understanding of microbiota metabolites in IBD, it is important to recognize how host relevant factors influence microbiota function. For example, changes in host inflammation status, metal availability, interbacterial community structure, and xenobiotics all play an important role in shaping gut microbial ecology. In this minireview, we outline how each of these factors influences gut microbial function, with a specific focus on IBD-associated Enterobacteriaceae metabolites. Importantly, we discuss how altering the intestinal microenvironment could improve the treatment of intestinal inflammation and associated disorders, like intestinal fibrosis and CRC.