Myocardial Bridging-Induced Acute Coronary Syndrome: A Bridge Too Far.

Recent studies suggest a potential association between myocardial bridging (MB) and accelerated atherosclerotic plaque formation. We describe the case report of a 37-year-old South Asian male with no established risk factors for coronary artery disease (CAD) who presented with a non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) with a coincident widowmaker lesion and severe MB. He was successfully managed with comprehensive guideline-directed medical therapy (GDMT) and urgent percutaneous coronary intervention (PCI) of the culprit lesion, sparing the MB segment. The clinician should be cognizant of MB implicating ACS as a major adverse cardiovascular event (MACE) and its key management strategies.

Surgery for Spinal Stenosis in Achondroplasia: Causes of Reoperation and Reduction of Risks.

BACKGROUND: Individuals with achondroplasia are prone to symptomatic spinal stenosis requiring surgery. Revision rates are thought to be high; however, the precise causes and rates of reoperation are unknown. The primary aim of this study is to investigate the causes of reoperation after initial surgical intervention in individuals with achondroplasia and spinal stenosis. In addition, we report on surgical techniques aimed at reducing the risks of these reoperations. METHODS: A retrospective review was conducted over an 8-year period of all patients with achondroplasia at a single institution that serves as a large referral center for patients with skeletal dysplasias. Patients with achondroplasia who underwent spinal surgery for stenosis were identified and the need for revision surgery was studied. Data collected included demographic, surgical, and revision details. Fisher exact test was used to determine if an association existed between construct type and the need for revisions. RESULTS: Thirty-three of the 130 (22%) patients with achondroplasia required spinal stenosis surgery. Twenty-four individuals who met the criteria were selected for analysis. The initial spine surgery was at an average age of 18.7 years (SD: 10.1 y). Nine patients (38%) required revision surgeries, and 3 required multiple revisions. Five of 9 (56%) of the revisions had primary surgery at an outside institution. Revision surgeries were due to caudal pseudarthrosis (the distal instrumented segment) (8), proximal junctional kyphosis (PJK) (7), and new neurological symptoms (7). There was a significant association found between construct type and the need for revision ( P =0.0111). The pairwise comparison found that short fusions were significantly associated with the need for revision compared with the interbody group ( P =0.0180). PJK was associated with short fusions when compared with the long fusion group ( P =0.0294) and the interbody group ( P =0.0300). Caudal pseudarthrosis was associated with short fusions when compared with the interbody group ( P =0.0015). Multivariate logistic regression found long fusion with an interbody was predictive of and protective against the need for revision surgery ( P =0.0246). To date, none of the initial cases that had long fusions with caudal interbody required a revision for distal pseudarthrosis. CONCLUSIONS: In patients with achondroplasia, the rate of surgery for spinal stenosis is 22% and the risk of revision is 38% and is primarily due to pseudarthrosis, PJK, and recurrent neurological symptoms. Surgeons should consider discussing spinal surgery as part of the patient's life plan and should consider wide decompression of the stenotic levels and long fusion with the use of an interbody cage at the caudal level in all patients to reduce risks of revision. LEVEL OF EVIDENCE: Level IV-Retrospective case series.

Peroneal Nerve Decompression in Patients with Multiple Hereditary Exostoses: Indications, Complications, and Recurrence.

BACKGROUND: To our knowledge, there have been no studies examining peroneal nerve decompression and proximal fibular osteochondroma excision exclusively in patients with multiple hereditary exostoses (MHE). The purpose of this study was to evaluate the indications, complications, and recurrence associated with nerve decompression and proximal fibular osteochondroma excision in patients with MHE. METHODS: The records on patients with MHE undergoing peroneal nerve decompression from 2009 to 2023 were retrospectively reviewed. Indications, clinical status, surgical technique, recurrence, and complications were recorded and were analyzed using the Fisher exact test, logistic regression, and the Kaplan-Meier method. RESULTS: There were 126 limbs identified in patients with MHE who underwent peroneal nerve decompression. The most common indications were pain over the proximal fibula, tibialis anterior and/or extensor hallucis longus weakness, and dysesthesias and/or neuropathic pain. Seven cases experienced postoperative foot drop as a complication of the decompression and osteochondroma excision. Logistic regression found significant relationships between complications and excision of anterior osteochondromas (odds ratio [OR], 5.21; p = 0.0062), proximal fibular excision (OR, 14.73; p = 0.0051), and previous decompression (OR, 5.77; p = 0.0124). The recurrence rate was 13.8%, and all recurrences occurred in patients who were skeletally immature at the index procedure. The probability of skeletally immature patients not experiencing recurrence was 88% at 3 years postoperatively and 73% at 6 years postoperatively. CONCLUSIONS: Indications for peroneal nerve decompression included neurologic symptoms and pain. The odds of a complication increased with excision of anterior osteochondromas and previous decompression. Recurrence of symptoms following decompression and osteochondroma excision was found exclusively in skeletally immature patients. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

A Lung Cancer Mouse Model Database.

Lung cancer, the leading cause of cancer mortality, exhibits diverse histological subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. Here we established the Lung Cancer Mouse Model Database (LCMMDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMMs), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors have produced a robust and comprehensive database, enhancing the fidelity of the genetic landscape it depicts. The LCMMDB aligns 859 tumors from GEMMs with human lung cancer mutations, enabling comparative analysis and revealing a pressing need to broaden the diversity of genetic aberrations modeled in GEMMs. Accompanying this resource, we developed a web application that offers researchers intuitive tools for in-depth gene expression analysis. With standardized reprocessing of gene expression data, the LCMMDB serves as a powerful platform for cross-study comparison and lays the groundwork for future research, aiming to bridge the gap between mouse models and human lung cancer for improved translational relevance.

Promises and Perils of Consumer Mobile Technologies in Cardiovascular Care: JACC Scientific Statement.

Direct-to-consumer (D2C) wearables are becoming increasingly popular in cardiovascular health management because of their affordability and capability to capture diverse health data. Wearables may enable continuous health care provider-patient partnerships and reduce the volume of episodic clinic-based care (thereby reducing health care costs). However, challenges arise from the unregulated use of these devices, including questionable data reliability, potential misinterpretation of information, unintended psychological impacts, and an influx of clinically nonactionable data that may overburden the health care system. Further, these technologies could exacerbate, rather than mitigate, health disparities. Experience with wearables in atrial fibrillation underscores these challenges. The prevalent use of D2C wearables necessitates a collaborative approach among stakeholders to ensure effective integration into cardiovascular care. Wearables are heralding innovative disease screening, diagnosis, and management paradigms, expanding therapeutic avenues, and anchoring personalized medicine.

Exploration of field-like torque and field-angle tunability in coupled spin-torque nano oscillators for synchronization.

We investigate the influence of field-like torque and the direction of the external magnetic field on a one-dimensional array of serially connected spin-torque nano oscillators (STNOs), having free layers with perpendicular anisotropy, to achieve complete synchronization between them by analyzing the associated Landau-Lifshitz-Gilbert-Slonczewski equation. The obtained results for synchronization are discussed for the cases of 2, 10, and 100 oscillators separately. The roles of the field-like torque and the direction of the external field on the synchronization of the STNOs are explored through the Kuramoto order parameter. While the field-like torque alone is sufficient to bring out global synchronization in the system made up of a small number of STNOs, the direction of the external field is also needed to be slightly tuned to synchronize the one-dimensional array of a large number of STNOs. The formation of complete synchronization through the construction of clusters within the system is identified for the 100 oscillators. The large amplitude synchronized oscillations are obtained for small to large numbers of oscillators. Moreover, the tunability in frequency for a wide range of currents is shown for the synchronized oscillations up to 100 spin-torque oscillators. In addition to achieving synchronization, the field-like torque increases the frequency of the synchronized oscillations. The transverse Lyapunov exponents are deduced to confirm the stable synchronization in coupled STNOs due to the field-like torque and to validate the results obtained in the numerical simulations. The output power of the array is estimated to be enhanced substantially due to complete synchronization by the combined effect of field-like torque and tunability of the field-angle.

Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel.

The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays.

Well-differentiated liposarcoma of tongue: A case report.

Key Clinical Message: It is important to consider WDLS as a potential cause of tongue lesions and include it in the list of differential diagnoses. When performing surgical intervention, it is crucial to remove enough tissue around the lesion, and regular follow-up is necessary due to the high risk of recurrence, despite its rarity, when margins are positive. Abstract: Liposarcoma (LS) is the most common soft tissue sarcomas (STSs) that arise from embryonic mesenchymal tissue. Though these sarcomas commonly arise at retroperitoneal locations and extremities, the appearance of these tumors in the head and neck region is rare, with the tongue as a preferred site. As per WHO 2020, LS is classified into four subtypes based on morphology, namely, Well-differentiated liposarcoma (WDLS), Dedifferentiated liposarcoma (DDLS), Myxoid liposarcoma (MLS), and Pleomorphic liposarcoma (PLS). WLS is the most common variant among all. Here, we had a case of 55 years old male with the complaint of swelling in the left lateral border of the tongue with the preliminary diagnosis of pleomorphic adenoma. The patient underwent a left partial glossectomy with adequate margins. Further evaluation of the lesion revealed a clear cell tumor that was ultimately confirmed as liposarcoma on immunohistochemistry that showed tumor cells positive for S100, CDK4, and MDM2 with 2% Ki-67. Postsurgical status of the patient was evaluated by F18 FDG PET CTscan, which was normal. Currently, the patient is under regular follow-up.

Transphyseal Humeral Separations: An Often-Missed Fracture.

BACKGROUND: Transphyseal humeral separations (TPHS) are rare injuries often associated with non-accidental trauma, necessitating accurate diagnosis. This study aims to assess the accuracy of diagnosis of TPHS. METHODS: A retrospective review was conducted at five academic pediatric institutions to identify all surgically treated TPHS in patients up to 4 years of age over a 25-year period. Demographics, misdiagnosis rates, and reported misdiagnoses were noted. Comparative analyses were performed to analyze the effects of patient age and injury mechanism on misdiagnosis rates. RESULTS: Seventy-nine patients (average age: 17.4 months) were identified, with injury mechanisms including accidental trauma (n = 49), non-accidental trauma (n = 21), Cesarean-section (n = 6), and vaginal delivery (n = 3). Neither age nor injury mechanism were significantly associated with diagnostic accuracy in the emergency department (ED)/consulting physician group. ED/consulting physicians achieved an accurate diagnosis 46.7% of the time, while radiologists achieved an accurate diagnosis 26.7% of the time. Diagnostic accuracy did not correlate with Child Protective Services (CPS) involvement or with a delay in surgery of more than 24 h. However, a significant correlation (p = 0.03) was observed between injury mechanism and misdiagnosis rates. CONCLUSION: This multicenter analysis is the largest study assessing TPHS misdiagnosis rates, highlighting the need for raising awareness and considering advanced imaging or orthopedic consultation for accurate diagnosis. This also reminds orthopedic surgeons to always have vigilant assessment in treating pediatric elbow injuries. LEVEL OF EVIDENCE: Level III-Retrospective Cohort Study.

Mechano-Activated Cell Therapy for Accelerated Diabetic Wound Healing.

Chronic diabetic wounds are a significant global healthcare challenge. Current strategies, such as biomaterials, cell therapies, and medical devices, however, only target a few pathological features and have limited efficacy. A powerful platform technology combining magneto-responsive hydrogel, cells, and wireless magneto-induced dynamic mechanical stimulation (MDMS) is developed to accelerate diabetic wound healing. The hydrogel encapsulates U.S. Food and Drug Administration (FDA)-approved fibroblasts and keratinocytes to achieve ∼3-fold better wound closure in a diabetic mouse model. MDMS acts as a nongenetic mechano-rheostat to activate fibroblasts, resulting in ∼240% better proliferation, ∼220% more collagen deposition, and improved keratinocyte paracrine profiles via the Ras/MEK/ERK pathway to boost angiogenesis. The magneto-responsive property also enables on-demand insulin release for spatiotemporal glucose regulation through increasing network deformation and interstitial flow. By mining scRNAseq data, a mechanosensitive fibroblast subpopulation is identified that can be mechanically tuned for enhanced proliferation and collagen production, maximizing therapeutic impact. The "all-in-one" system addresses major pathological factors associated with diabetic wounds in a single platform, with potential applications for other challenging wound types.

The Perceptions of Dental Professionals and Laypeople to Facial Aesthetics and Mal-Occlusion in Central India Population.

Introduction: Dental professionals play an important role in an individual's appearance which can affect the perception of others that can vary greatly depending on their educational and socioeconomic background. Aim and Objective: The purpose of this study was to determine an insight of recognizing ability of dental professionals and laypersons toward facial aesthetics with different types of orthodontic malocclusion. Materials and Methods: A questionnaire-based study was conducted on 90 dental professionals and 90 laypersons. The perceptions differences between groups were assessed using visual analogue scale on 11 photographs. Kolmolgorov-Smirnov was used for normality test. Results: The perceptions of facial aesthetics showing various malocclusions were significantly different between dental professionals and laypersons. Conclusion: The dental professionals and layperson perceptions regarding the facial particularly in central Indian population are significantly different for most of the malocclusion types.

Tissue Biology: In Search of a New Paradigm.

Animal tissues are made up of multiple cell types that are increasingly well-characterized, yet our understanding of the core principles that govern tissue organization is still incomplete. This is in part because many observable tissue characteristics, such as cellular composition and spatial patterns, are emergent properties, and as such, they cannot be explained through the knowledge of individual cells alone. Here we propose a complex systems theory perspective to address this fundamental gap in our understanding of tissue biology. We introduce the concept of cell categories, which is based on cell relations rather than cell identity. Based on these notions we then discuss common principles of tissue modularity, introducing compositional, structural, and functional tissue modules. Cell diversity and cell relations provide a basis for a new perspective on the underlying principles of tissue organization in health and disease.

Crystal-Induced Lower GI Necrosis in a Posttransplant Recipient with Diverticular Disease.

We report the case of a 67-year-old male kidney transplant recipient for 12 years with sodium polystyrene sulfonate crystal-induced ileocecal colitis. He had adult polycystic kidney disease with associated colonic diverticular disease. Here, we describe how a potentially fatal complication of colonic perforation was averted with appropriate investigations and management.

Absence of Increased Susceptibility to Acetaminophen-Induced Liver Injury in a Diet-Induced NAFLD Mouse Model.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease and its influence on drug-induced liver injury (DILI) is not fully understood. We investigated whether NAFLD can influence acetaminophen (APAP [N-acetyl-p-aminophenol])-induced hepatotoxicity in a diet-induced obese (DIO) mouse model of NAFLD. The male C57BL/6NTac DIO mice, fed a high-fat diet for more than 12 weeks, developed obesity, hyperinsulinemia, impaired glucose tolerance, and hepatomegaly with hepatic steatosis, similar to human NAFLD. In the acute toxicity study after a single dose of APAP (150 mg/kg), compared with control lean mice, the DIO mice had decreased serum transaminase levels and less severe hepatocellular injury. The DIO mice also had altered expression of genes related to APAP metabolism. Chronic APAP exposure for 26 weeks did not predispose the DIO mice with NAFLD to more severe hepatotoxicity compared with the lean mice. These results suggested that the C57BL/6NTac DIO mouse model appears to be more tolerant to APAP-induced hepatotoxicity than lean mice, potentially related to altered xenobiotic metabolizing capacity in the fatty liver. Further mechanistic studies with APAP and other drugs in NAFLD animal models are necessary to investigate the mechanism of altered susceptibility to intrinsic DILI in some human NAFLD patients.

Chronic Inhalation Exposure to Antimony Trioxide Exacerbates the MAPK Signaling in Alveolar Bronchiolar Carcinomas in B6C3F1/N Mice.

Antimony trioxide (AT) is used as a flame retardant in fabrics and plastics. Occupational exposure in miners and smelters is mainly through inhalation and dermal contact. Chronic inhalation exposure to AT particulates in B6C3F1/N mice and Wistar Han rats resulted in increased incidences and tumor multiplicities of alveolar/bronchiolar carcinomas (ABCs). In this study, we demonstrated Kras (43%) and Egfr (46%) hotspot mutations in mouse lung tumors (n = 80) and only Egfr (50%) mutations in rat lung tumors (n = 26). Interestingly, there were no differences in the incidences of these mutations in ABCs from rats and mice at exposure concentrations that did and did not exceed the pulmonary overload threshold. There was increased expression of p44/42 mitogen-activated protein kinase (MAPK) (Erk1/2) protein in ABCs harboring mutations in Kras and/or Egfr, confirming the activation of MAPK signaling. Transcriptomic analysis indicated significant alterations in MAPK signaling such as ephrin receptor signaling and signaling by Rho-family GTPases in AT-exposed ABCs. In addition, there was significant overlap between transcriptomic data from mouse ABCs due to AT exposure and human pulmonary adenocarcinoma data. Collectively, these data suggest chronic AT exposure exacerbates MAPK signaling in ABCs and, thus, may be translationally relevant to human lung cancers.

Dynamic Stimulations with Bioengineered Extracellular Matrix-Mimicking Hydrogels for Mechano Cell Reprogramming and Therapy.

Cells interact with their surrounding environment through a combination of static and dynamic mechanical signals that vary over stimulus types, intensity, space, and time. Compared to static mechanical signals such as stiffness, porosity, and topography, the current understanding on the effects of dynamic mechanical stimulations on cells remains limited, attributing to a lack of access to devices, the complexity of experimental set-up, and data interpretation. Yet, in the pursuit of emerging translational applications (e.g., cell manufacturing for clinical treatment), it is crucial to understand how cells respond to a variety of dynamic forces that are omnipresent in vivo so that they can be exploited to enhance manufacturing and therapeutic outcomes. With a rising appreciation of the extracellular matrix (ECM) as a key regulator of biofunctions, researchers have bioengineered a suite of ECM-mimicking hydrogels, which can be fine-tuned with spatiotemporal mechanical cues to model complex static and dynamic mechanical profiles. This review first discusses how mechanical stimuli may impact different cellular components and the various mechanobiology pathways involved. Then, how hydrogels can be designed to incorporate static and dynamic mechanical parameters to influence cell behaviors are described. The Scopus database is also used to analyze the relative strength in evidence, ranging from strong to weak, based on number of published literatures, associated citations, and treatment significance. Additionally, the impacts of static and dynamic mechanical stimulations on clinically relevant cell types including mesenchymal stem cells, fibroblasts, and immune cells, are evaluated. The aim is to draw attention to the paucity of studies on the effects of dynamic mechanical stimuli on cells, as well as to highlight the potential of using a cocktail of various types and intensities of mechanical stimulations to influence cell fates (similar to the concept of biochemical cocktail to direct cell fate). It is envisioned that this progress report will inspire more exciting translational development of mechanoresponsive hydrogels for biomedical applications.

Artificial intelligence-enabled mobile electrocardiograms for event prediction in paroxysmal atrial fibrillation.

Background: Paroxysmal atrial fibrillation (AF) often eludes early diagnosis, resulting in significant morbidity and mortality. Artificial intelligence (AI) has been used to predict AF from sinus rhythm electrocardiograms (ECGs), but AF prediction using sinus rhythm mobile electrocardiograms (mECG) remains unexplored. Objective: The purpose of this study was to investigate the utility of AI to predict AF events prospectively and retrospectively using sinus rhythm mECG data. Methods: We trained a neural network to predict AF events from sinus rhythm mECGs obtained from users of the Alivecor KardiaMobile 6L device. We tested our model on sinus rhythm mECGs within ±0-2 days, ±3-7 days, and ±8-30 days from AF events to determine the optimal screening window. Finally, we tested our model on mECGs from before an AF event to determine whether AF can be predicted prospectively. Results: We included 73,861 users with 267,614 mECGs (mean age 58.14 years; 35% women). Users with paroxysmal AF contributed 60.15% of mECGs. Model performance on the test set comprising control and study samples across all windows of interest showed an area under the curve (AUC) score of 0.760 (95% confidence interval [CI] 0.759-0.760), sensitivity of 0.703 (95% CI 0.700-0.705), specificity of 0.684 (95% CI 0.678-0.685), and accuracy of 69.4% (95% CI 0.692-0.700). Model performance was better on ±0-2 day samples (sensitivity 0.711; 95% CI 0.709-0.713) and worse on the ±8-30 day window (sensitivity 0.688; 95% CI 0.685-0.690), with performance on the ±3-7 day window falling in between (sensitivity 0.708; 95% CI 0.704-0.710). Conclusion: Neural networks can predict AF using a widely scalable and cost-effective mobile technology prospectively and retrospectively.

Are Semiquantitative Methods Superior to Deauville Scoring in the Monitoring Therapy Response for Pediatric Hodgkin Lymphoma?

Tailoring treatment in patients with Hodgkin lymphoma (HL) is paramount to maximize outcomes while avoiding unnecessary toxicity. We aimed to compare the performance of SUVmax reduction (ΔSUVmax%) and the PET ratio (rPET) versus the Deauville score (DS) for assessing the chemotherapy response in pediatric HL patients undergoing 18F-FDG PET-CT. Fifty-two patients with biopsy-proven HL (aged 8-16 years) were enrolled at baseline, interim (after the second or third chemotherapy round) and post-therapy (on completion of first-line chemotherapy). Interim and post-therapy DS, ΔSUVmax% and rPET were compared as response predictors. Patients were classified as responders or non-responders based on a 24-month clinical follow-up. Interim DS showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of 100%, 80.4%, 100%, 40% and 82.7%, respectively, in predicting the therapy response. Post-therapy DS showed a sensitivity, specificity, PPV, NPV and accuracy of 66.7%, 97.8%, 95.7%, 80% and 94.2%, repsectively. Interim ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 82.6%, 97.4%, 38.5% and 82.7%, respectively, with a 56.3% cutoff. Post-therapy ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 84.8%, 97.5%, 41.7% and 84.6%, respectively, with a 76.8% cutoff. Compared to ΔSUVmax%, DS showed a significantly higher sensitivity, specificity (p < 0.05) and NPV (p < 0.01). The sensitivity, specificity, PPV, NPV and accuracy of rPET in predicting the therapy response at 24 months were 76.1%, 100%, 100%, 35.3% and 78.8%, respectively, with a cut-off of 1.31. DS and rPET showed comparable predictive performance (p > 0.58). In conclusion, DS is an easier method with better performance than ΔSUVmax% and rPET in predicting the chemotherapy response in pediatric HL patients.