Citations

Purpose: Functional septorhinoplasty is an effective treatment for nasal airway obstruction. Little distinction exists between bilaterally and unilaterally obstructed patients in literature. Our study evaluates outcomes in patients with unilateral nasal airway obstruction compared to those with bilateral nasal airway obstruction as measured by nasal obstruction symptom evaluation scores following functional septorhinoplasty. Materials and Methods: A total of 227 patients underwent functional septorhinoplasty for nasal airway obstruction. Patients were grouped into unilateral (n = 64) and bilateral (n = 163) nasal obstruction cohorts based on patient report and physician assessment. Nasal obstruction symptom evaluation (NOSE) scores were obtained pre-operatively and post-operatively at least 3 months following surgery. Results: Patients with unilateral nasal obstruction had slightly less severe symptoms preoperatively than patients with bilateral obstruction. Average preoperative NOSE scores for patients with unilateral obstruction was 64 (SD = 19) and 72 (SD = 18) for patients with bilateral obstruction ( P = .004). Postoperative NOSE scores following septorhinoplasty were significantly reduced for patients with both unilateral and bilateral nasal obstruction (postoperative NOSE scores unilateral: 17, SD = 16 ; bilateral: 23, SD = 21). There was no statistical significance in outcomes between patients with unilateral or bilateral nasal obstruction groups. Conclusions: Symptoms in patients with unilateral obstruction are similar but slightly less severe than patients with bilateral obstruction. Patients with unilateral and bilateral nasal obstruction experienced a similar degree of improvement in symptom following functional septorhinoplasty.

AbstractCellular senescence is an established cause of cell and tissue aging. Senescent cells have been shown to increase in multiple organs during aging, including the skin. Here we hypothesized that senescent cells residing in the skin can spread senescence to distant organs, thereby accelerating systemic aging processes. To explore this hypothesis, we initially observed an increase in several markers of senescence in the skin of aging mice. Subsequently, we conducted experiments wherein senescent fibroblasts were transplanted into the dermis of young mice and assessed various age‐associated parameters. Our findings reveal that the presence of senescent cells in the dermal layer of young mice leads to increased senescence in both proximal and distal host tissues, alongside increased frailty, and impaired musculoskeletal function. Additionally, there was a significant decline in cognitive function, concomitant with increased expression of senescence‐associated markers within the hippocampus brain area. These results support the concept that the accumulation of senescent cells in the skin can exert remote effects on other organs including the brain, potentially explaining links between skin and brain disorders and diseases and, contributing to physical and cognitive decline associated with aging.

Multiligament knee injuries (MLKIs) represent a broad spectrum of pathology with potentially devastating consequences. Currently, disagreement in the terminology, diagnosis and treatment of these injuries limits clinical care and research. This study aimed to develop consensus on the nomenclature, diagnosis, treatment and rehabilitation strategies for patients with MLKI, while identifying important research priorities for further study. An international consensus process was conducted using validated Delphi methodology in line with British Journal of Sports Medicine guidelines. A multidisciplinary panel of 39 members from 14 countries, completed 3 rounds of online surveys exploring aspects of nomenclature, diagnosis, treatment, rehabilitation and future research priorities. Levels of agreement (LoA) with each statement were rated anonymously on a 5-point Likert scale, with experts encouraged to suggest modifications or additional statements. LoA for consensus in the final round were defined ‘a priori’ if >75% of respondents agreed and fewer than 10% disagreed, and dissenting viewpoints were recorded and discussed. After three Delphi rounds, 50 items (92.6%) reached consensus. Key statements that reached consensus within nomenclature included a clear definition for MLKI (LoA 97.4%) and the need for an updated MLKI classification system that classifies injury mechanism, extent of non-ligamentous structures injured and the presence or absence of dislocation. Within diagnosis, consensus was reached that there should be a low threshold for assessment with CT angiography for MLKI within a high-energy context and for certain injury patterns including bicruciate and PLC injuries (LoA 89.7%). The value of stress radiography or intraoperative fluoroscopy also reached consensus (LoA 89.7%). Within treatment, it was generally agreed that existing literature generally favours operative management of MLKI, particularly for young patients (LoA 100%), and that single-stage surgery should be performed whenever possible (LoA 92.3%). This consensus statement will facilitate clinical communication in MLKI, the care of these patients and future research within MLKI.

Abstract Senescent cells secrete proinflammatory factors known as the senescence-associated secretory phenotype (SASP), contributing to tissue dysfunction and aging. Mitochondrial dysfunction is a key feature of senescence, influencing SASP via mitochondrial DNA (mtDNA) release and cGAS/STING pathway activation. Here, we demonstrate that mitochondrial RNA (mtRNA) also accumulates in the cytosol of senescent cells, activating RNA sensors RIG-I and MDA5, leading to MAVS aggregation and SASP induction. Inhibition of these RNA sensors significantly reduces SASP factors. Furthermore, BAX and BAK plays a key role in mtRNA leakage during senescence, and their deletion diminishes SASP expression in vitro and in a mouse model of Metabolic Dysfunction Associated Steatohepatitis (MASH). These findings highlight mtRNA's role in SASP regulation and its potential as a therapeutic target for mitigating age-related inflammation.

Abstract Introduction Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide. Methods This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome‐wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array. Results Around 5,139 differentially methylated CpG‐sites (q < 0.01, lΔβl > 0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors. Multiple representative differentially methylated regions (DMRs), including immune‐related genes, such as CD40 , Galectin3 , OX40L , and STING , were detected in prostate tumors when compared to adjacent normal tissues. Based on an epigenetic clock model, we observed that tumors’ total number of stem cell divisions and the stem cell division rate were significantly higher than adjacent normal tissues. Regarding PCa aggressiveness, 2,061 differentially methylated CpG‐sites (q < 0.05, lΔβl > .05) were identified when the grade group (GG)1 was compared with GG4/5. Among these 2,061 CpG sites, 155 probes were consistently significant in more than one comparison. Among these genes, several immune system genes, such as COL18A1 , S100A2 , ITGA4 , HLA‐C , and ADCYAP1 , have previously been linked to tumor progression in PCa. Conclusion Several differentially methylated genes involved in immune‐oncologic pathways associated with disease risk or aggressiveness were identified. In addition, 261 African American‐specific differentially methylated genes related to the risk of PCa were identified. These results can shedlight on potential mechanisms contributing to PCa disparities in the African American Population.

Women with type 2 diabetes (T2D) have a higher risk of being diagnosed with breast cancer and have worse survival than non-diabetic women if they do develop breast cancer. However, more research is needed to elucidate the biological underpinnings of these relationships. Here, we found that forkhead box A1 (FOXA1), a forkhead family transcription factor, and metformin (1,1-dimethylbiguanide hydrochloride), a medication used to treat T2D, may impact hormone-receptor-positive (HR+) breast cancer (BC) tumor cell growth and metastasis. Indeed, fourteen diabetes-associated genes are highly expressed in only three HR+ breast cancer cell lines but not the other subtypes utilizing a 53,805 gene database obtained from NCBI GEO. Among the diabetes-related genes, FOXA1, MTA3, PAK4, FGFR3, and KIF22 were highly expressed in HR+ breast cancer from 4032 breast cancer patient tissue samples using the Breast Cancer Gene Expression Omnibus. Notably, elevated FOXA1 expression correlated with poorer overall survival in patients with estrogen-receptor-positive/progesterone-receptor-positive (ER+/PR+) breast cancer. Furthermore, experiments demonstrated that loss of the FOXA1 gene inhibited tumor proliferation and invasion in vitro using MCF-7 and T47D HR+ breast cancer cell lines. Metformin, an anti-diabetic medication, significantly suppressed tumor cell growth in MCF-7 cells. Additionally, either metformin treatment or FOXA1 gene deletion enhanced tamoxifen-induced tumor growth inhibition in HR+ breast cancer cell lines within an ex vivo three-dimensional (3D) organoid model. Therefore, the diabetes-related medicine metformin and FOXA1 gene inhibition might be a new treatment for patients with HR+ breast cancer when combined with tamoxifen, an endocrine therapy.

AbstractPurposeTo study implant lead tip heating because of the RF power deposition by developing mathematical models and comparing them with measurements acquired at 1.5 T and 3 T, especially to predict resonant length.Theory and MethodsA simple exponential model and an adapted transmission line model for the electric field transfer function were developed. A set of wavenumbers, including that calculated from insulated antenna theory (King wavenumber) and that of the embedding medium were considered. Experiments on insulated, capped wires of varying lengths were performed to determine maximum temperature rise under RF exposure. The results are compared with model predictions from analytical expressions derived under the assumption of a constant electric field, and with those numerically calculated from spatially varying, simulated electric fields from body coil transmission. Simple expressions for the resonant length bounded between one‐quarter and one‐half wavelength are developed based on the roots of transcendental equations.ResultsThe King wavenumber for both models more closely matched the experimental data with a maximum root mean square error of 9.81°C at 1.5 T and 5.71°C at 3 T compared to other wavenumbers with a maximum root mean square error of 27.52°C at 1.5 T and 22.01°C for 3 T. Resonant length was more accurately predicted compared to values solely based on the embedding medium.ConclusionAnalytical expressions were developed for implanted lead heating and resonant lengths under specific assumptions. The value of the wavenumber has a strong effect on the model predictions. Our work could be used to better manage implanted device lead tip heating.

OBJECTIVE Chordomas are rare tumors of the skull base and spine believed to arise from the vestiges of the embryonic notochord. These tumors are locally aggressive and frequently recur following resection and adjuvant radiotherapy. Proton therapy has been introduced as a tissue-sparing option because of the higher level of precision that proton-beam techniques offer compared with traditional photon radiotherapy. This study aimed to compare recurrence in patients with chordomas receiving proton versus photon radiotherapy following resection by applying tree-based machine learning models. METHODS The clinical records of all patients treated with resection followed by adjuvant proton or photon radiotherapy for chordoma at Mayo Clinic were reviewed. Patient demographics, type of surgery and radiotherapy, tumor recurrence, and other variables were extracted. Decision tree classifiers were trained and tested to predict long-term recurrence based on unseen data using an 80/20 split. RESULTS Fifty-three patients with a mean ± SD age of 55.2 ± 13.4 years receiving surgery and adjuvant proton or photon therapy to treat chordoma were identified; most patients were male. Gross-total resection was achieved in 54.7% of cases. Proton therapy was the most common adjuvant radiotherapy (84.9%), followed by conventional or external-beam radiation therapy (9.4%) and stereotactic radiosurgery (5.7%). Patients receiving proton therapy exhibited a 40% likelihood of having recurrence, significantly lower than the 88% likelihood observed in those treated with nonproton therapy. This was confirmed on logistic regression analysis adjusted for extent of tumor resection and tumor location, which revealed that proton adjuvant radiotherapy was associated with a decreased risk of recurrence (OR 0.1, 95% CI 0.01–0.71; p = 0.047) compared with photon therapy. The decision tree algorithm predicted recurrence with an accuracy of 90% (95% CI 55.5%–99.8%), with the lowest risk of recurrence observed in patients receiving gross-total resection with adjuvant proton therapy (23%). CONCLUSIONS Following resection, adjuvant proton therapy was associated with a lower risk of chordoma recurrence compared with photon therapy. The described machine learning models were able to predict tumor progression based on the extent of tumor resection and adjuvant radiotherapy modality used.

Background: Conventional transthoracic echocardiography (TTE) is currently not recommended as an initial test to diagnose coronary artery disease (CAD) due to its insensitivity. Left ventricular (LV) strain was reported to be more sensitive than regional wall motion abnormality (RWMA). The aim of this study was to evaluate the usefulness of TTE including LV strain analysis in initial assessment of acute chest pain in emergency department (ED). Methods: Patients visiting ED with acute chest pain were included. Patients with ST elevation myocardial infarct (MI), hemodynamic instability, known CAD or cardiomyopathy, high probability of non-cardiac chest pain, and poor echocardiographic window were excluded. All the patients were initially assessed by an ED physician for pretest probability of CAD. TTE was performed including LV strain image and global and regional LV longitudinal stain (S GL and S RL ) was analyzed online. S RL abnormality was defined as decreased S RL in at least 2 adjacent segments. Diagnosis of CAD (based on coronary angiography or CT angiography) and cardiac events (cardiac death, revascularization, MI, or recurrent ED visit due to chest pain) were reviewed at 1 month after ED visit. Results: Overall 104 patients were analyzed. CAD was diagnosed in 24% (n=25) and cardiac event was detected in 25% (n=26) of patients.Diagnostic accuracy for CAD was higher when using S RL with cut-off value of -13% (sensitivity of 89%, specificity of 77%, NPV = 92%, PPV = 70%) than when using RWMA (sensitivity of 62%, specificity of 88%, NPV = 80%, PPV = 76%). S RL showed better diagnostic performance for CAD than S GL , and pretest probability (Figure). Predictive value of S RL for cardiac events was also highest in those of S GL , RWMA, and pretest probability (Figure). Conclusion: LV strain echocardiography can diagnose the CAD and predict future events with high accuracy. TTE including strain analysis can be used as an initial diagnostic tool in evaluation of acute chest pain in ED.

Limb ischaemia is a clinically relevant complication of venoarterial extracorporeal membrane oxygenation (VA ECMO) with femoral artery cannulation. No selective distal perfusion or other advanced techniques were used in the past to maintain adequate distal limb perfusion. A more recent trend is the shift from the reactive or emergency management to the pro-active or prophylactic placement of a distal perfusion cannula to avoid or reduce limb ischaemia-related complications. Multiple alternative cannulation techniques to the distal perfusion cannula have been developed to maintain distal limb perfusion, including end-to-side grafting, external or endovascular femoro-femoral bypass, retrograde limb perfusion (e.g., via the posterior tibial, dorsalis pedis or anterior tibial artery), and, more recently, use of a bidirectional cannula. Venous congestion has also been recognized as a potential contributing factor to limb ischaemia development and specific techniques have been described with facilitated venous drainage or bilateral cannulation being the most recent, to reduce or avoid venous stasis as a contributor to impaired limb perfusion. Advances in monitoring techniques, such as near-infrared spectroscopy and duplex ultrasound analysis, have been applied to improve decision-making regarding both the monitoring and management of limb ischaemia. This narrative review describes the evolution of techniques used for distal limb perfusion during peripheral VA ECMO.