Citations

Abstract Introduction: Stingray envenomation is a relatively common occurrence among water sports enthusiasts, including swimmers, scuba divers, and surfers, as well as fishermen. However, there is a lack of medical literature on the pathophysiology of immediate and delayed hypersensitivity reactions, and more importantly, on the range of infectious bacterial and mycobacterial infections that can result from these envenomation injuries. This paper aims to provide a general overview of the mechanisms, diagnostic challenges, and management of late hypersensitivity reactions and infections that can occur following stingray stings. Case Report: A 63-year-old man with well-controlled hyperlipidemia presented to the Mayo Clinic with a one-week-old injury from accidentally stepping on a stingray barb while walking on a beach in Ventura, California. Immediate pain was relieved with immersion in warm water. He did not take any over-the-counter or prescription medications, and over the following days, he returned to his usual activities of cycling, running, and swimming with minimal discomfort. There was no initial redness or swelling at the puncture site, but he reported intermittent sharp, localized pain with movement leading up to his hospital visit. A biopsy was performed due to concern for a developing necrotic infection, and he was diagnosed with a hypersensitivity reaction. He was initially treated with IV antibiotics, and steroids were added based on biopsy results. After completing his treatment course, his hypersensitivity reaction fully resolved over several weeks. Conclusion: This case underscores the importance of considering both immediate and delayed hypersensitivity reactions that can result from stingray envenomation. These reactions can be managed with conservative measures, such as warming the affected area in a water bath to denature heat-labile venom, as well as with conventional therapies, including topical or systemic antihistamines and steroids. It also highlights the need for early empiric antibiotic coverage and outlines the infectious agents implicated in early- and late-onset infections following stingray envenomation, including Pseudomonas aeruginosa, Vibrio vulnificus , and Mycobacterium fortuitum . Additionally, it emphasizes the need for tetanus vaccine updates, radiography, and a multidisciplinary approach to treating stingray injuries.

Abstract Neoadjuvant therapy (NAT) with HER2-targeted agents is the standard treatment for patients with HER2-positive early breast cancer (HER2 + EBC). Although high levels of tumor-infiltrating lymphocytes (TILs) are associated with higher pathologic complete response (pCR) rates and improved recurrence-free survival (RFS), the specific immune components responsible remain unclear. In this study, pretreatment tumor biopsies from 188 patients receiving HER2-targeted NAT were analyzed. Univariate analysis revealed that enrichment of TIL-B cells in tumors, high HER2 mRNA and low ESR1 mRNA expression were linked to pCR (both p < 0.01). Multivariate analysis confirmed TIL-B-cell enrichment as an independent predictor of pCR. Mature IgD/IgM-high B cells, but not immature RAG1 + B cells, independently predicted pCR. Transcriptomic profiling identified 265 upregulated genes in pCR tumors enriched in MHC class II antigen presentation pathways. Immunofluorescence demonstrated increased spatial interaction of mature B cells with CD4 + T cells in pCR tumors, consistent with active antigen presentation. The antigen presenting B-cell signature, integrated mature B-cell and MHC II profile, was the strongest independent predictor of pCR (OR = 3.008, 95% CI: 1.196–7.544, p = 0.019) and was also significantly associated with improved RFS (HR = 0.109, 95% CI: 0.014–0.872), highlighting B-cell–mediated antigen presentation as a clinically relevant biomarker in HER2 + EBC.

Abstract Background: Early postoperative mortality remains a major clinical challenge in left ventricular assist device implantation. Accurate preoperative identification of high-risk patients could optimize candidate selection and improve perioperative management. Methods: From February 2021 to March 2025, 60 patients who underwent LVAD implantation at Zhongshan Hospital, Fudan University were included in the present study. Early mortality was defined as death within 2 months postoperatively, a threshold derived from survival analysis showing a distinct early hazard phase. Preoperative demographic, echocardiographic, hemodynamic, and laboratory variables were evaluated. Predictor selection used least absolute shrinkage and selection operator (LASSO) logistic regression with 10-fold cross-validation, followed by multivariable Firth logistic regression. Internal validation employed bootstrap resampling (1,000 iterations). Results: The mean age was 55 ± 10 years, and 50 (83%) patients had dilated cardiomyopathy. Kaplan–Meier analysis indicated an early hazard phase, with all deaths occurring by ~ 1.7 months after implantation. LASSO selected age, MELD-XI, passive cardiac index (PasCI), and mixed venous oxygen saturation (SvO₂) for multivariable modeling. In the final Firth model, lower SvO₂ (odds ratio [OR] 0.92; 95% CI 0.83–1.00; p = 0.048) and older age (OR 1.13; 95% CI 1.00–1.35; p = 0.059) were associated with higher early mortality. Internal validation yielded an optimism-adjusted AUC of 0.84. Conclusions: In this exploratory study, lower preoperative SvO₂ and older age were the principal predictors of early mortality after LVAD implantation. Our internally validated risk assessment model supports preoperative risk prediction and stratification; however, confirmation in larger, multicenter cohorts is warranted before broader adoption. (246/250)

Abstract Femoroacetabular impingement with cam morphology that fails nonoperative management can be addressed with hip arthroscopy and cam resection. There exists a wide variation of cam morphology due to various etiologies that can make some cam lesions more challenging to address. A thorough preoperative evaluation and the utilization of a variety of intraoperative techniques can allow for adequate arthroscopic resection of these otherwise challenging cam lesions. In this technique video, we describe a systematic approach for the preoperative assessment of femoroacetabular impingement due to a cam lesion and consideration of different approaches for arthroscopic resection based on cam‐specific morphology.

Color Doppler twinkling improves visibility and ultrasound-guided localization of biopsy markers made of polymethyl methacrylate (PMMA). This study examines the time- and frequency-domain features of twinkling. We performed beamforming on the raw radiofrequency (RF) data collected using a L7-4 transducer, followed by in-phase/quadrature (IQ) demodulation and wall filtering. Frequency content variations were evaluated both within individual Doppler ensembles (pulse-to-pulse) and across multiple frames. Normalized FFT magnitude spectra were computed for both twinkling and non-twinkling (metal) cases using beamformed RF and IQ data. The median of the normalized FFT magnitude (3–10 MHz) was consistently higher for the twinkling case compared to the metal case across RF (–13.75 dB vs –17.29 dB) and the IQ real component (–12.72 dB vs –16.15 dB), indicating broader and more energetic spectral content in twinkling. The frequency spread above the –20 dB threshold was approximately 2.5 times wider (5.38 MHz vs 1.95 MHz) in the twinkling case compared to the metal case. In time domain, the RMS of the standard deviation for the twinkling signal was approximately 28 times higher than that of the metal case across both RF and IQ data. These findings indicate that the ultrasound data from twinkling exhibits a more distributed frequency profile, consistent with observed aperiodic nature.

Elevated intratumoral interstitial fluid pressure (IFP) can negatively impact the efficacy of neoadjuvant chemotherapy (NAC) of breast cancer. This study aims to predict breast cancer pathological complete response (pCR) to NAC based on IFP measures by 3-D subharmonic-aided pressure estimation (SHAPE). SHAPE uses the inverse linear relationship between hydrostatic pressure and subharmonic signal magnitude from intravascular ultrasound contrast agents. Thirty-eight breast cancer patients undergoing NAC from three clinical sites were enrolled for this study. SHAPE data were collected for each subject at 0%, 10%, and 30% of NAC completion using a Logiq E9 system (GE HeathCare) equipped with an RSP6-16D probe. The contrast agent used was Definity (Lantheus Medical Imaging). The subharmonic signal gradients between tumor and adjacent normal tissue were calculated and compared with patient pathological response outcome using t-test and receiver operating characteristic (ROC) curve analysis. Pressure gradients between pCR (15 patients) and non-pCR (23 patients) groups were significantly different at 0 (p = 0.02), 10 (p = 0.03), and 30% (p = 0.0003) completion of NAC. Area under the curve values of 0.69, 0.77, and 0.86 were achieved at 0%, 10%, and 30% of NAC completion, respectively. Overall, SHAPE pressure gradients may aid prediction of NAC pathological response in breast cancer patients.

Color Doppler twinkling is associated with rough-surfaced objects like kidney stones, some clinical breast biopsy markers, and polymethyl methacrylate (PMMA) bone cement. Microbubbles are theorized as the predominant source of twinkling, supported by decreased twinkling under increased pressure. PMMA, metallic breast markers, a low-twinkling PMMA sample, and a non-twinkling metal rod were scanned in a pressure chamber up to 1000 psi using a General Electric Logiq E9 system and C1-6 probe (1.7–3.6 MHz Doppler transmit frequency). Clinical markers maintained distinct twinkling up to 250 psi. PMMA often twinkled at higher pressures, sometimes up to 1000 psi. The controls showed no twinkling. To understand physical structure associations with twinkling, the samples were scanned in a micro-CT system with a pixel resolution of 2 μm. Analysis of PMMA and Cork internal voids showed no correlation with twinkling. However, a correlation between Sa (average difference between the mean surface profile and actual surface profile) values and twinkling was found. This indicates that internal structure is not important for twinkling, and certain surface roughness is critical, possibly providing sites for surface microbubbles to oscillate from incident ultrasound waves.

Ultrasound shear wave elastography is a medical imaging technique where mechanical properties (e.g., shear modulus) of soft tissue are imaged with the goal of diagnosing disease. However, different sources of noise or error often lead to poor images that exacerbate uncertainty of medical diagnosis based on these techniques. Sources of uncertainty include scatterer positions and strengths (e.g., emanating from the cellular structure of tissue), other surrounding tissue not included in the image, and electronic noise, among others. In this work, we are developing Optimal Experimental Design (OED) techniques based on the simulation of the ultrasound imaging process and particle tracking to identify controls that maximize the quality of elastography images. Specifically, we propose a general formulation for OED where the observation error depends on both uncertain quantities and the variables to be inferred (e.g., shear moduli). Furthermore, we pose a nonlinear OED problem where the main design variables are the angles used in plane wave compounding for ultrasound motion tracking of propagating shear waves. The goal of the OED problem is to find the number and values of compounding angles that minimize bias and variance in the estimated shear modulus image. We will demonstrate our approach through various numerical examples.

Background Pancreatic ductal adenocarcinoma (PDAC), the most common malignant type of pancreatic cancer, is characterized by a dense desmoplastic stroma, low neoantigen burden, and a highly immunosuppressive tumor microenvironment (TME). Methods We present a novel strategy harnessing acute transplant rejection mechanisms by employing a recombinant oncolytic rVMG vector engineered to express murine alloantigens H-2Kb (rVMG-H-2Kb) or H-2Kk (rVMG-H-2Kk), thereby inducing tumor-specific antigenic mismatch responses. Results In vitro, rVMG-H-2Kb and rVMG-H-2Kk exhibited strong replication and cytolytic activity while inducing cell surface expression of both H-2Kk and endogenous H-2Kb, in addition to upregulation of antigen presentation genes (β2-microglobulin, Tap1, and Tapbp). In two immunocompetent PDAC models, intratumoral and systemic delivery of rVMG-H-2Kb and rVMG-H-2Kk delayed tumor progression, with rVMG-H-2Kk conferring a survival advantage. Multiplex immunohistochemistry and immunophenotyping revealed substantial TME remodeling, marked by increased effector T-cell infiltration, regulatory T-cell depletion, and reduced fibrosis. Spatial transcriptomics further showed compartment-specific immune activation and epithelial metabolic reprogramming, corroborating with enhanced tumor immunogenicity. Despite these effects, rVMG-H-2Kk also induced compensatory immunosuppressive pathways, including upregulation of antiviral response genes and immune checkpoint receptors such as programmed death-ligand-2. Importantly, combination therapy with rVMG-H-2Kk and murine checkpoint blockade (anti-programmed cell death protein-1 and anti-cytotoxic T-lymphocyte-associated protein 4) drastically improved survival compared to checkpoint blockade alone. Strikingly, surviving mice resisted tumor rechallenge, indicating the establishment of durable antitumor memory. Conclusion These findings establish rVMG-mediated alloantigen delivery as a novel immunotherapeutic platform capable of converting immune-cold tumors into immune-hot, sensitizing tumors to immune checkpoint inhibitors, and establishing durable antitumor immunity in PDAC.

Importance Chronic pain is a leading cause of disability, and many affected patients rely on long-term opioid therapy despite its unfavorable adverse effect profile. Spinal cord stimulation is an established therapy for chronic pain that may secondarily reduce opioid consumption by providing sustained analgesia. Objective To quantify changes in opioid use following spinal cord stimulation implantation for the treatment of chronic pain through a systematic review and meta-analysis. Data sources We conducted a comprehensive search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus from each database’s inception to July 1, 2024. Study selection We included studies describing patients who underwent spinal cord stimulator implantation for the treatment of chronic pain. A total of 2,784 potential studies were identified and screened by multiple independent reviewers, yielding a final total of 43 studies included in the systematic review. Data extraction and synthesis Data extraction was completed by multiple independent reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Meta-analysis Of Observational Studies in Epidemiology guidelines. A random effects model with Hartung-Knapp-Sidik-Jonkman adjustment was used to estimate pooled estimates. Certainty assessment was performed following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Main outcome(s) and measure(s) The primary outcomes were change in continuous opioid use (ie, morphine milligram equivalent (MME)) and categorical opioid use (yes/no) from preimplantation to 12 months following spinal cord stimulator implantation. Results Meta-analysis of 12 month continuous MME use comprising 22 study comparisons (1,666 individuals) revealed a weighted mean difference of −18.06 MME (95% CI −24.41 to −11.70; 95% prediction interval −38.29 to 2.17; p<0.001). Meta-analysis of categorical opioid use at 12 months comprising 24 study comparisons (1,527 individuals) revealed an OR of 0.47 (95% CI 0.30 to 0.75; 95% prediction interval 0.10 to 2.11; p=0.003), signifying lower odds of opioid continuation. Conclusions and relevance Spinal cord stimulation is associated with reduced opioid dose consumption and increased odds of opioid cessation at 12 months postimplantation compared with baseline in patients with chronic pain; however, both of these conclusions are supported by evidence of very low GRADE certainty. PROSPERO registration number CRD42024574921.