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1.
Int Arch Otorhinolaryngol ; 28(3): e509-e516, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38974644

RESUMEN

Introduction Facial trauma can cause damage to the facial nerve, which can have negative effects on function, aesthetics, and quality of life if left untreated. Objective To evaluate the effectiveness of peripheral facial nerve direct end-to-end anastomosis and/or nerve grafting surgery for patients with facial nerve injury after facial trauma. Methods Fifty-nine patients with peripheral facial nerve paralysis after facial injuries underwent facial nerve rehabilitation surgery from November 2017 to December 2021 at Ho Chi Minh City National Hospital of Odontology. Results All 59 cases of facial trauma with damage to the peripheral facial nerve underwent facial nerve reconstruction surgery within 8 weeks of the injury. Of these cases, 25/59 (42.3%) had end-to-end anastomosis, 22/59 (37.3%) had nerve grafting, and 12/59 (20.4%) had a combination of nerve grafting and end-to-end anastomosis. After surgery, the rates of moderate and good recovery were 78.4% and 11.8%, respectively. All facial paralysis measurements showed statistically significant improvement after surgery, including the Facial Nerve Grading Scale 2.0 (FNGS 2.0) score, the Facial Clinimetric Evaluation (FaCE) scale, and electroneurography. The rate of synkinesis after surgery was 34%. Patient follow-up postoperatively ranged from 6 to > 36 months; 51 out of 59 patients (86.4%) were followed-up for at least 12 months or longer. Conclusion Nerve rehabilitation surgery including direct end-to-end anastomosis and nerve grafting is effective in cases of peripheral facial nerve injury following facial trauma. The surgery helps restore nerve conduction and improve facial paralysis.

2.
Stroke ; 55(7): 1808-1817, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38913799

RESUMEN

BACKGROUND: Tandem lesions consist of cervical internal carotid artery (ICA) stenosis or occlusion, most commonly of atherosclerosis or dissection etiology, plus a large vessel occlusion. In this study, we compare outcomes in patients with atherosclerosis versus dissection of the cervical ICA. METHODS: This multicenter retrospective cohort study includes data from tandem lesion patients who underwent endovascular treatment from 2015 to 2020. Atherosclerosis was defined as ICA stenosis/occlusion associated with a calcified lesion and dissection by the presence of a tapered or flame-shaped lesion and intramural hematoma. Primary outcome: 90-day functional independence (modified Rankin Scale score, 0-2); secondary outcomes: 90-day favorable shift in the modified Rankin Scale score, modified Thrombolysis in Cerebral Infarction score 2b-3, modified Thrombolysis in Cerebral Infarction score 2c-3, symptomatic intracranial hemorrhage, parenchymal hematoma type 2, petechial hemorrhage, distal embolization, early neurological improvement, and mortality. Analysis was performed with matching by inverse probability of treatment weighting. RESULTS: We included 526 patients (68 [59-76] years; 31% females); 11.2% presented dissection and 88.8%, atherosclerosis. Patients with dissection were younger, had lower rates of hypertension, hyperlipidemia, diabetes, and smoking history. They also exhibited higher rates of ICA occlusion, multiple stents (>1), and lower rates of carotid self-expanding stents. After matching and adjusting for covariates, there were no differences in 90-day functional independence. The rate of successful recanalization was significantly lower in the dissection group (adjusted odds ratio, 0.38 [95% CI, 0.16-0.91]; P=0.031), which also had significantly higher rates of distal emboli (adjusted odds ratio, 2.53 [95% CI, 1.15-5.55]; P=0.021). There were no differences in other outcomes. Acute ICA stenting seemed to increase the effect of atherosclerosis in successful recanalization. CONCLUSIONS: This study reveals that among patients with acute stroke with tandem lesions, cervical ICA dissection is associated with higher rates of distal embolism and lower rates of successful recanalization than atherosclerotic lesions. Using techniques to minimize the risk of distal embolism may mitigate this contrast. Further prospective randomized trials are warranted to fully understand these associations.


Asunto(s)
Procedimientos Endovasculares , Humanos , Femenino , Persona de Mediana Edad , Masculino , Anciano , Estudios Retrospectivos , Procedimientos Endovasculares/métodos , Disección de la Arteria Carótida Interna/diagnóstico por imagen , Disección de la Arteria Carótida Interna/cirugía , Disección de la Arteria Carótida Interna/terapia , Estenosis Carotídea/cirugía , Estenosis Carotídea/complicaciones , Resultado del Tratamiento , Embolia
3.
Seizure ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38918105

RESUMEN

The aim of the present study was to review the current knowledge on the neuropathological spectrum of late onset epilepsies. Several terms including 'neuropathology*' AND 'late onset epilepsy' (LOE) combined with distinct neuropathological diagnostic terms were used to search PubMed until November 15, 2023. We report on the relevance of definitional aspects of LOE with implications for the diagnostic spectrum of epilepsies. The neuropathological spectrum in patients with LOE is described and includes vascular lesions, low-grade neuroepithelial neoplasms and focal cortical dysplasias (FCD). Among the latter, the frequency of the FCD subtypes appears to differ between LOE patients and those with seizure onset at a younger age. Neurodegenerative neuropathological changes in the seizure foci of LOE patients require careful interdisciplinary interpretation with respect to the differential diagnosis of primary neurodegenerative changes or epilepsy-related changes. Innate and adaptive neuroinflammation represents an important cause of LOE with intriguing therapeutic options.

4.
Mol Oncol ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38899375

RESUMEN

Low-grade neuroepithelial tumors (LGNTs), particularly those with glioneuronal histology, are highly associated with pharmacoresistant epilepsy. Increasing research focused on these neoplastic lesions did not translate into drug discovery; and anticonvulsant or antitumor therapies are not available yet. During the last years, animal modeling has improved, thereby leading to the possibility of generating brain tumors in mice mimicking crucial genetic, molecular and immunohistological features. Among them, intraventricular in utero electroporation (IUE) has been proven to be a valuable tool for the generation of animal models for LGNTs allowing endogenous tumor growth within the mouse brain parenchyma. Epileptogenicity is mostly determined by the slow-growing patterns of these tumors, thus mirroring intrinsic interactions between tumor cells and surrounding neurons is crucial to investigate the mechanisms underlying convulsive activity. In this review, we provide an updated classification of the human LGNT and summarize the most recent data from human and animal models, with a focus on the crosstalk between brain tumors and neuronal function.

5.
Epilepsia ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38837755

RESUMEN

OBJECTIVE: Short-term outcomes of deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) were reported for people with drug-resistant focal epilepsy (PwE). Because long-term data are still scarce, the Medtronic Registry for Epilepsy (MORE) evaluated clinical routine application of ANT-DBS. METHODS: In this multicenter registry, PwE with ANT-DBS were followed up for safety, efficacy, and battery longevity. Follow-up ended after 5 years or upon study closure. Clinical characteristics and stimulation settings were compared between PwE with no benefit, improvers, and responders, that is, PwE with average monthly seizure frequency reduction rates of ≥50%. RESULTS: Of 170 eligible PwE, 104, 62, and 49 completed the 3-, 4-, and 5-year follow-up, respectively. Most discontinuations (68%) were due to planned study closure as follow-up beyond 2 years was optional. The 5-year follow-up cohort had a median seizure frequency reduction from 16 per month at baseline to 7.9 per month at 5-year follow-up (p < .001), with most-pronounced effects on focal-to-bilateral tonic-clonic seizures (n = 15, 77% reduction, p = .008). At last follow-up (median 3.5 years), 41% (69/170) of PwE were responders. Unifocal epilepsy (p = .035) and a negative history of epilepsy surgery (p = .002) were associated with larger average monthly seizure frequency reductions. Stimulation settings did not differ between response groups. In 179 implanted PwE, DBS-related adverse events (AEs, n = 225) and serious AEs (n = 75) included deterioration in epilepsy or seizure frequency/severity/type (33; 14 serious), memory/cognitive impairment (29; 3 serious), and depression (13; 4 serious). Five deaths occurred (none were ANT-DBS related). Most AEs (76.3%) manifested within the first 2 years after implantation. Activa PC depletion (n = 37) occurred on average after 45 months. SIGNIFICANCE: MORE provides further evidence for the long-term application of ANT-DBS in clinical routine practice. Although clinical benefits increased over time, side effects occurred mainly during the first 2 years. Identified outcome modifiers can help inform PwE selection and management.

6.
Cell Rep ; 43(6): 114325, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38870014

RESUMEN

The sensitivity of malignant tissues to T cell-based immunotherapies depends on the presence of targetable human leukocyte antigen (HLA) class I ligands. Peptide-intrinsic factors, such as HLA class I affinity and proteasomal processing, have been established as determinants of HLA ligand presentation. However, the role of gene and protein sequence features as determinants of epitope presentation has not been systematically evaluated. We perform HLA ligandome mass spectrometry to evaluate the contribution of 7,135 gene and protein sequence features to HLA sampling. This analysis reveals that a number of predicted modifiers of mRNA and protein abundance and turnover, including predicted mRNA methylation and protein ubiquitination sites, inform on the presence of HLA ligands. Importantly, integration of such "hard-coded" sequence features into a machine learning approach augments HLA ligand predictions to a comparable degree as experimental measures of gene expression. Our study highlights the value of gene and protein features for HLA ligand predictions.


Asunto(s)
Antígenos de Histocompatibilidad Clase I , Humanos , Ligandos , Antígenos de Histocompatibilidad Clase I/metabolismo , Antígenos de Histocompatibilidad Clase I/genética , ARN Mensajero/metabolismo , ARN Mensajero/genética , Secuencia de Aminoácidos , Aprendizaje Automático , Péptidos/metabolismo , Péptidos/química
7.
Breast Cancer Res ; 26(1): 76, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745208

RESUMEN

BACKGROUND: Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women globally. Despite advances, there is considerable variation in clinical outcomes for patients with non-luminal A tumors, classified as difficult-to-treat breast cancers (DTBC). This study aims to delineate the proteogenomic landscape of DTBC tumors compared to luminal A (LumA) tumors. METHODS: We retrospectively collected a total of 117 untreated primary breast tumor specimens, focusing on DTBC subtypes. Breast tumors were processed by laser microdissection (LMD) to enrich tumor cells. DNA, RNA, and protein were simultaneously extracted from each tumor preparation, followed by whole genome sequencing, paired-end RNA sequencing, global proteomics and phosphoproteomics. Differential feature analysis, pathway analysis and survival analysis were performed to better understand DTBC and investigate biomarkers. RESULTS: We observed distinct variations in gene mutations, structural variations, and chromosomal alterations between DTBC and LumA breast tumors. DTBC tumors predominantly had more mutations in TP53, PLXNB3, Zinc finger genes, and fewer mutations in SDC2, CDH1, PIK3CA, SVIL, and PTEN. Notably, Cytoband 1q21, which contains numerous cell proliferation-related genes, was significantly amplified in the DTBC tumors. LMD successfully minimized stromal components and increased RNA-protein concordance, as evidenced by stromal score comparisons and proteomic analysis. Distinct DTBC and LumA-enriched clusters were observed by proteomic and phosphoproteomic clustering analysis, some with survival differences. Phosphoproteomics identified two distinct phosphoproteomic profiles for high relapse-risk and low relapse-risk basal-like tumors, involving several genes known to be associated with breast cancer oncogenesis and progression, including KIAA1522, DCK, FOXO3, MYO9B, ARID1A, EPRS, ZC3HAV1, and RBM14. Lastly, an integrated pathway analysis of multi-omics data highlighted a robust enrichment of proliferation pathways in DTBC tumors. CONCLUSIONS: This study provides an integrated proteogenomic characterization of DTBC vs LumA with tumor cells enriched through laser microdissection. We identified many common features of DTBC tumors and the phosphopeptides that could serve as potential biomarkers for high/low relapse-risk basal-like BC and possibly guide treatment selections.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , Proteogenómica , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Biomarcadores de Tumor/genética , Proteogenómica/métodos , Mutación , Captura por Microdisección con Láser , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Adulto , Proteómica/métodos , Pronóstico
8.
J Orthop Surg Res ; 19(1): 295, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750567

RESUMEN

INTRODUCTION: Hip arthroplasty is a common orthopaedic procedure worldwide. There is an ongoing debate related to the fixation and anaesthesia impact on the 30-day mortality, particularly in the aging population with higher American Society of Anaesthesiology (ASA) Physical-Status. AIM: To study the 30-day all-cause mortality in patients undergoing primary hip arthroplasty, with regards to the impact of age, ASA-class, anaesthesia techniques, indication for surgery and fixation techniques. MATERIALS AND METHODS: Perioperative data for primary hip arthroplasty procedures for osteoarthritis and hip fractures registered in the Swedish Perioperative Registry (SPOR) between 2013 and June 2022 were collected. Binary logistic regressions were performed to assess the impact of age, ASA-class, anaesthetic technique, indication for surgery and fixation on odds ratio for 30-day mortality in Sweden. RESULTS: In total, 79,114 patients, 49,565 with osteoarthritis and 29,549 with hip fractures were included in the main study cohort. Mortality was significantly higher among hip fracture patients compared with osteoarthritis, cumulative 8.2% versus 0.1% at 30-days respectively (p < 0.001). Age above 80 years (OR3.7), ASA 3-5 (OR3.3) and surgery for hip fracture (OR 21.5) were associated with significantly higher odds ratio, while hybrid fixation was associated with a significantly lower odds ratio (OR0.4) of 30-day mortality. In the same model, for the subgroups of osteoarthritis and hip fracture, only age (OR 3.7) and ASA-class (OR 3.3) had significant impact, increasing the odds ratio for 30-day mortality. Hemi arthroplasty was commonly used among the hip fracture patients 20.453 (69.2%), and associated with a significantly higher odds ratio for all-cause 30-day mortality as compared to total hip arthroplasty when adjusting for age and ASA-class and fixation 2.3 (95%CI 1.9-2.3, p < 0.001). CONCLUSIONS: All-cause 30-day mortality associated with arthroplasty differed significantly between the two cohorts, hip fracture, and osteoarthritis (8.2% and 0.1% respectively) and mortality expectedly increased with age and higher ASA-class. Anaesthetic method and cement-fixation did not impact the odds ratio for all-cause 30-day mortality after adjustment for age and ASA-class.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Fracturas de Cadera , Osteoartritis de la Cadera , Sistema de Registros , Humanos , Artroplastia de Reemplazo de Cadera/mortalidad , Suecia/epidemiología , Anciano , Femenino , Masculino , Anciano de 80 o más Años , Fracturas de Cadera/cirugía , Fracturas de Cadera/mortalidad , Osteoartritis de la Cadera/cirugía , Osteoartritis de la Cadera/mortalidad , Persona de Mediana Edad , Factores de Edad , Estudios de Cohortes , Factores de Tiempo
9.
PLoS One ; 19(5): e0300883, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38758927

RESUMEN

Development of novel biodosimetry assays and medical countermeasures is needed to obtain a level of radiation preparedness in the event of malicious or accidental mass exposures to ionizing radiation (IR). For biodosimetry, metabolic profiling with mass spectrometry (MS) platforms has identified several small molecules in easily accessible biofluids that are promising for dose reconstruction. As our microbiome has profound effects on biofluid metabolite composition, it is of interest how variation in the host microbiome may affect metabolomics based biodosimetry. Here, we 'knocked out' the microbiome of male and female C57BL/6 mice (Abx mice) using antibiotics and then irradiated (0, 3, or 8 Gy) them to determine the role of the host microbiome on biofluid radiation signatures (1 and 3 d urine, 3 d serum). Biofluid metabolite levels were compared to a sham and irradiated group of mice with a normal microbiome (Abx-con mice). To compare post-irradiation effects in urine, we calculated the Spearman's correlation coefficients of metabolite levels with radiation dose. For selected metabolites of interest, we performed more detailed analyses using linear mixed effect models to determine the effects of radiation dose, time, and microbiome depletion. Serum metabolite levels were compared using an ANOVA. Several metabolites were affected after antibiotic administration in the tryptophan and amino acid pathways, sterol hormone, xenobiotic and bile acid pathways (urine) and lipid metabolism (serum), with a post-irradiation attenuative effect observed for Abx mice. In urine, dose×time interactions were supported for a defined radiation metabolite panel (carnitine, hexosamine-valine-isoleucine [Hex-V-I], creatine, citric acid, and Nε,Nε,Nε-trimethyllysine [TML]) and dose for N1-acetylspermidine, which also provided excellent (AUROC ≥ 0.90) to good (AUROC ≥ 0.80) sensitivity and specificity according to the area under the receiver operator characteristic curve (AUROC) analysis. In serum, a panel consisting of carnitine, citric acid, lysophosphatidylcholine (LysoPC) (14:0), LysoPC (20:3), and LysoPC (22:5) also gave excellent to good sensitivity and specificity for identifying post-irradiated individuals at 3 d. Although the microbiome affected the basal levels and/or post-irradiation levels of these metabolites, their utility in dose reconstruction irrespective of microbiome status is encouraging for the use of metabolomics as a novel biodosimetry assay.


Asunto(s)
Ratones Endogámicos C57BL , Animales , Ratones , Femenino , Masculino , Exposición a la Radiación , Microbiota/efectos de la radiación , Metabolómica/métodos , Metaboloma/efectos de la radiación , Radiación Ionizante
10.
J Contemp Brachytherapy ; 16(2): 150-155, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38808204

RESUMEN

Patients with primary tumor progression after stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC) have a second chance at complete tumor eradication with salvage local therapies, including lung resection, repeat course of SBRT, and percutaneous ablative therapies. In this paper, we presented our institution's initial experience with percutaneous high-dose-rate (HDR) brachyablation for a relapsed stage I NSCLC that had been treated with SBRT 4.3 years earlier. Lung tumor measuring approximately 5 cm in maximum tumor dimension at the time of relapse was histopathologically confirmed to be persistent squamous cell carcinoma, and successfully treated with a single fraction of 24 Gy with HDR brachyablation. Treatment was delivered via two percutaneous catheters inserted under CT-guidance, and treated in less than 20 minutes. The patient was discharged home later the same day without the need for a chest tube, and has been monitored with serial surveillance scans every 3 to 6 months without evidence of further lung cancer progression or complications at 2.8 years post-HDR brachyablation procedure and 7.8 years after initial SBRT.

11.
Sci Rep ; 14(1): 10637, 2024 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724569

RESUMEN

Hadron therapy is an advanced radiation modality for treating cancer, which currently uses protons and carbon ions. Hadrons allow for a highly conformal dose distribution to the tumour, minimising the detrimental side-effects due to radiation received by healthy tissues. Treatment with hadrons requires sub-millimetre spatial resolution and high dosimetric accuracy. This paper discusses the design, fabrication and performance tests of a detector based on Gas Electron Multipliers (GEM) coupled to a matrix of thin-film transistors (TFT), with an active area of 60 × 80 mm2 and 200 ppi resolution. The experimental results show that this novel detector is able to detect low-energy (40 kVp X-rays), high-energy (6 MeV) photons used in conventional radiation therapy and protons and carbon ions of clinical energies used in hadron therapy. The GEM-TFT is a compact, fully scalable, radiation-hard detector that measures secondary electrons produced by the GEMs with sub-millimetre spatial resolution and a linear response for proton currents from 18 pA to 0.7 nA. Correcting known detector defects may aid in future studies on dose uniformity, LET dependence, and different gas mixture evaluation, improving the accuracy of QA in radiotherapy.

12.
Am J Surg Pathol ; 48(7): 777-789, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38597260

RESUMEN

Since their original description as a distinctive neoplastic entity, ~50 TFE3 -rearranged perivascular epithelioid cell tumors (PEComas) have been reported. We herein report 25 new TFE3 -rearranged PEComas and review the published literature to further investigate their clinicopathologic spectrum. Notably, 5 of the 25 cases were associated with a prior history of chemotherapy treatment for cancer. This is in keeping with prior reports, based mainly on small case series, with overall 11% of TFE3 -rearranged PEComas being diagnosed postchemotherapy. The median age of our cohort was 38 years. Most neoplasms demonstrated characteristic features such as nested architecture, epithelioid cytology, HMB45 positive, and muscle marker negative immunophenotype. SFPQ was the most common TFE3 fusion partner present in half of the cases, followed by ASPSCR1 and NONO genes. Four of 7 cases in our cohort with meaningful follow-up presented with or developed systemic metastasis, while over half of the reported cases either recurred locally, metastasized, or caused patient death. Follow-up for the remaining cases was limited (median 18.5 months), suggesting that the prognosis may be worse. Size, mitotic activity, and necrosis were correlated with aggressive behavior. There is little evidence that treatment with MTOR inhibitors, which are beneficial against TSC -mutated PEComas, is effective against TFE3 -rearranged PEComas: only one of 6 reported cases demonstrated disease stabilization. As co-expression of melanocytic and muscle markers, a hallmark of conventional TSC -mutated PEComa is uncommon in the spectrum of TFE3 -rearranged PEComa, an alternative terminology may be more appropriate, such as " TFE3 -rearranged PEComa-like neoplasms," highlighting their distinctive morphologic features and therapeutic implications.


Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Biomarcadores de Tumor , Reordenamiento Génico , Neoplasias de Células Epitelioides Perivasculares , Humanos , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Neoplasias de Células Epitelioides Perivasculares/genética , Neoplasias de Células Epitelioides Perivasculares/patología , Neoplasias de Células Epitelioides Perivasculares/tratamiento farmacológico , Femenino , Masculino , Adulto , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Adulto Joven , Anciano , Adolescente , Predisposición Genética a la Enfermedad , Inmunohistoquímica , Resultado del Tratamiento , Fenotipo , Antineoplásicos/uso terapéutico
13.
Med Image Anal ; 94: 103157, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38574544

RESUMEN

Computer-aided detection and diagnosis systems (CADe/CADx) in endoscopy are commonly trained using high-quality imagery, which is not representative for the heterogeneous input typically encountered in clinical practice. In endoscopy, the image quality heavily relies on both the skills and experience of the endoscopist and the specifications of the system used for screening. Factors such as poor illumination, motion blur, and specific post-processing settings can significantly alter the quality and general appearance of these images. This so-called domain gap between the data used for developing the system and the data it encounters after deployment, and the impact it has on the performance of deep neural networks (DNNs) supportive endoscopic CAD systems remains largely unexplored. As many of such systems, for e.g. polyp detection, are already being rolled out in clinical practice, this poses severe patient risks in particularly community hospitals, where both the imaging equipment and experience are subject to considerable variation. Therefore, this study aims to evaluate the impact of this domain gap on the clinical performance of CADe/CADx for various endoscopic applications. For this, we leverage two publicly available data sets (KVASIR-SEG and GIANA) and two in-house data sets. We investigate the performance of commonly-used DNN architectures under synthetic, clinically calibrated image degradations and on a prospectively collected dataset including 342 endoscopic images of lower subjective quality. Additionally, we assess the influence of DNN architecture and complexity, data augmentation, and pretraining techniques for improved robustness. The results reveal a considerable decline in performance of 11.6% (±1.5) as compared to the reference, within the clinically calibrated boundaries of image degradations. Nevertheless, employing more advanced DNN architectures and self-supervised in-domain pre-training effectively mitigate this drop to 7.7% (±2.03). Additionally, these enhancements yield the highest performance on the manually collected test set including images with lower subjective quality. By comprehensively assessing the robustness of popular DNN architectures and training strategies across multiple datasets, this study provides valuable insights into their performance and limitations for endoscopic applications. The findings highlight the importance of including robustness evaluation when developing DNNs for endoscopy applications and propose strategies to mitigate performance loss.


Asunto(s)
Diagnóstico por Computador , Redes Neurales de la Computación , Humanos , Diagnóstico por Computador/métodos , Endoscopía Gastrointestinal , Procesamiento de Imagen Asistido por Computador/métodos
14.
Artículo en Inglés | MEDLINE | ID: mdl-38653897

RESUMEN

BACKGROUND: Discrimination is associated with worse mental and physical health outcomes. However, the associations among cancer survivors are limited. OBJECTIVE: We examined whether discrimination is associated with HRQoL and whether adjusting for it reduces racial/ethnic disparities in HRQoL among cancer survivors. METHODS: Cross-sectional data from adult cancer survivors who completed surveys on discrimination in the medical settings (DMS), everyday perceived discrimination (PD), and HRQoL in the "All of Us" Program from 2018 to 2022 were assessed. We created a binary indicator for fair-to-poor vs. good-to-excellent physical health and mental health. PD and DMS scores were a continuous measure with higher scores reflecting more discrimination. Multivariable logistic regression models tested whether DMS and PD are associated with HRQoL and whether they differently affect the association between race/ethnicity and HRQoL. RESULTS: The sample (N = 16,664) of cancer survivors was predominantly White (86%) and female (59%), with a median age of 69. Every 5-unit increase in DMS and PD scores was associated with greater odds of fair-to-poor physical health (DMS: OR [95%CI] = 1.66 [1.55, 1.77], PD: 1.33 [1.27, 1.40]) and mental health (DMS: 1.57 [1.47, 1.69], PD: 1.33 [1.27, 1.39]). After adjusting for DMS or PD, Black and Hispanic survivors had a decreased likelihood of fair-to-poor physical health and mental health (decrease estimate range: - 6 to - 30%) compared to White survivors. This effect was greater for Black survivors when adjusting for PD, as the odds of fair-to-poor mental health compared to White survivors were no longer statistically significant (1.78 [1.32, 2.34] vs 1.22 [0.90, 1.64]). CONCLUSION: Experiences of discrimination are associated with lower HRQoL and reducing it may mitigate racial/ethnic disparities in HRQoL.

15.
Radiat Res ; 201(6): 617-627, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38573158

RESUMEN

This review focuses on early discoveries that contributed to our understanding and the scope of transcriptional responses after radiation damage. Before the development of modern approaches to assess overall global transcriptomic responses, the idea that mammalian cells could respond to DNA-damaging agents in a manner analogous to bacteria was not generally accepted. To investigate this possibility, the development of technology to identify differentially expressed low-abundance transcripts substantially facilitated our appreciation that DNA damaging agents like UV radiation and subsequently ionizing radiation did in fact produce robust transcriptional responses. Here we focus on our identification and characterization of radiation-inducible genes, and how even early studies on stress gene signaling highlighted the broad scope of transcriptional responses to radiation damage. Since then, the central role of transcriptional responses to radiation injury in maintaining genome integrity has been highlighted in many processes, including cell cycle checkpoint control, resistance to cancer by p53 and other key factors, cell senescence, and metabolism.


Asunto(s)
Daño del ADN , Humanos , Animales , Transcripción Genética/efectos de la radiación , Rayos Ultravioleta
16.
Neurogastroenterol Motil ; 36(6): e14794, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38587128

RESUMEN

BACKGROUND: Peroral endoscopic myotomy (POEM) is an effective and safe treatment for achalasia, but often leads to posttreatment gastroesophageal reflux disease. The aim of this study was to examine the incidence and severity of reflux esophagitis after POEM and to identify associated predictive factors. METHODS: Patients who underwent POEM between August 2011 and December 2022 were included. Multivariate logistic regression was used to assess predictive factors for reflux esophagitis after POEM. KEY RESULTS: In total, 252 patients were included; of which, 46% were female and age ranged between 18 and 87 years. Reflux esophagitis within 1 year after POEM was observed in 131 patients (52%), which was severe in 29 patients (LA grade C/D, 12%). Length of full-thickness myotomy (cm; OR 1.11, 95% CI 1.02-1.21), Eckardt scores before POEM (OR 0.84, 95% CI 0.74-0.96), previous pneumatic dilation (OR 0.51, 95% CI 0.29-0.91), and previous laparoscopic Heller myotomy (LHM; OR 0.44, 95% CI 0.23-0.86) were associated with reflux esophagitis after POEM. Alcohol use (none vs > 7 units per week; OR 3.51, 95% CI 1.35-9.11) and overweight (BMI ≥25 kg/m2; OR 2.67, 95% CI 1.17-6.09) were positive predictive factors and previous LHM (OR 0.13, 95% CI 0.02-0.95) was a negative predictive factor for severe reflux esophagitis after POEM (LA grade C/D). CONCLUSION: About half of the patients develop reflux esophagitis after POEM and 12% is graded as severe. Recognizing predictive factors of reflux esophagitis after POEM treatment leads to better patient selection before POEM and provides an opportunity to take preventive measures or start preemptive treatment.


Asunto(s)
Acalasia del Esófago , Esofagitis Péptica , Complicaciones Posoperatorias , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Factores de Riesgo , Incidencia , Acalasia del Esófago/cirugía , Acalasia del Esófago/epidemiología , Esofagitis Péptica/epidemiología , Esofagitis Péptica/etiología , Adulto Joven , Adolescente , Anciano de 80 o más Años , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Miotomía/efectos adversos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Estudios Retrospectivos
17.
J Neurointerv Surg ; 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38429099

RESUMEN

BACKGROUND: Endovascular therapy (EVT) stands as an established and effective intervention for acute ischemic stroke in patients harboring tandem lesions (TLs). However, the optimal anesthetic strategy for EVT in TL patients remains unclear. This study aims to evaluate the impact of distinct anesthetic techniques on outcomes in acute ischemic stroke patients presenting with TLs. METHODS: Patient-level data, encompassing cases from 16 diverse centers, were aggregated for individuals with anterior circulation TLs treated between January 2015 and December 2020. A stratification based on anesthetic technique was conducted to distinguish between general anesthesia (GA) and procedural sedation (PS). Multivariable logistic regression models were built to discern the association between anesthetic approach and outcomes, including the favorable functional outcome defined as 90-day modified Rankin Score (mRS) of 0-2, ordinal shift in mRS, symptomatic intracranial hemorrhage (sICH), any hemorrhage, successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) score ≥2b), excellent recanalization (mTICI 3), first pass effect (FPE), early neurological improvement (ENI), door-to-groin and recanalization times, intrahospital mortality, and 90-day mortality. RESULTS: Among 691 patients from 16 centers, 595 patients (GA 38.7%, PS 61.3%) were included in the final analysis. There were no significant differences noted in the door-to-groin time (80 (46-117.5) mins vs 54 (21-100), P=0.607) and groin to recanalization time (59 (39.5-85.5) mins vs 54 (38-81), P=0.836) among the groups. The odds of a favorable functional outcome (36.6% vs 52.6%; adjusted OR (aOR) 0.56, 95% CI 0.38 to 0.84, P=0.005) and a favorable shift in the 90-day mRS (aOR 0.71, 95% CI 0.51 to 0.99, P=0.041) were lower in the GA group. No differences were noted for sICH (3.9% vs 4.7%, P=0.38), successful recanalization (89.1% vs 86.5%, P=0.13), excellent recanalization (48.5% vs 50.3%, P=0.462), FPE (53.6% vs 63.4%, P=0.05), ENI (38.9% vs 38.8%, P=0.138), and 90-day mortality (20.3% vs 16.3%, P=0.525). An interaction was noted for favorable functional outcome between the type of anesthesia and the baseline Alberta Stroke Program Early CT Score (ASPECTS) (P=0.033), degree of internal carotid artery (ICA) stenosis (P<0.001), and ICA stenting (P<0.001), and intraparenchymal hematoma between the type of anesthesia and intravenous thrombolysis (P=0.019). In a subgroup analysis, PS showed better functional outcomes in patients with age ≤70 years, National Institutes of Health Stroke Scale (NIHSS) score <15, and acute ICA stenting. CONCLUSIONS: Our findings suggest that the preference for PS not only aligns with comparable procedural safety but is also associated with superior functional outcomes. These results prompt a re-evaluation of current anesthesia practices in EVT, urging clinicians to consider patient-specific characteristics when determining the optimal anesthetic strategy for this patient population.

18.
Artículo en Inglés | MEDLINE | ID: mdl-38521482

RESUMEN

BACKGROUND: The decision to treat shoulder osteoarthritis (OA) definitively with shoulder arthroplasty (SA) is multifactorial, considering objective findings, subjective information, and patient goals. The first goal of this study was to determine if Patient Reported Outcome Measurement Information System (PROMIS) measures correlated with patients with shoulder OA who underwent SA within 1 year. The second goal of this study was to determine if score cut-offs in PROMIS domains could further discriminate which shoulder OA patients underwent SA within 1 year. METHODS: This retrospective case-control study examined patients with a diagnosis of shoulder OA who consulted an orthopedic provider from November 1, 2020 to May 23, 2022, and recorded PROMIS measures in the domains of Physical Function, Depression, and/or Pain Interference. A surgical group was defined as patients who underwent SA within 1 year of the most recent PROMIS measures and the nonsurgical patients were defined as the control group. Mean PROMIS scores were compared between the surgical and control groups. Separate logistic regression models controlling for age, race, ethnicity, and comorbidity count were performed for each PROMIS domain as a 1) continuous variable, and then as 2) binary variable defined by PROMIS score cut-off points to determine which scores correlated with undergoing SA to further characterize the potential clinical utility of PROMIS score cut-offs in relating to undergoing SA. RESULTS: The surgical group of 478 patients was older (68.2 vs. 63.8 years), more often of White race (82.6% vs. 70.9%), and less often of Hispanic Ethnicity (1.5% vs. 2.9%) than the control group of 3343 patients. Using optimal cut-offs in PROMIS scores, Pain Interference ≥63 (odds ratio [OR] = 2.97 (2.41-3.64), P < .001), Physical Function ≤39 (OR = 1.81 (95% confidence interval, 1.48-2.22), P < .001), and depression ≥49 (OR = 1.82 (95% confidence interval, 1.50-2.22), P < .001) were all found to correlate with undergoing SA within 1 year in multivariable logistic regressions. CONCLUSION: The results of this study demonstrate that cut-off scores for PROMIS measures differentiated patients undergoing SA within 1 year. These cut-off scores may have clinical utility in aiding in decision-making regarding surgical candidates for SA. Further research is needed to validate these cut-off scores and determine how they relate to patient outcomes after SA.

19.
HLA ; 103(2): e15401, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38414174

RESUMEN

Two novel alleles, HLA-G*01:04:09 and HLA-DPB1*04:01:01:136, were identified in a single healthy individual.


Asunto(s)
Genes MHC Clase I , Antígenos HLA-G , Humanos , Alelos , Cadenas beta de HLA-DP/genética
20.
BMC Womens Health ; 24(1): 89, 2024 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-38311740

RESUMEN

PURPOSE: Women diagnosed with ductal carcinoma in situ (DCIS) face confusion and uncertainty about treatment options. The objective of this study was to determine whether there are differences in decisional conflict about treatment by age and race/ethnicity. METHODS: A cross-sectional survey was conducted of women (age ≥ 18) diagnosed with DCIS enrolled at Kaiser Permanente of Southern California. The Decisional Conflict Scale (DCS) measured personal perceptions of decision uncertainty, values clarity, and effective decision-making. We used a multivariable regression to study whether age, race, and ethnicity were associated with patient-reported DCS. RESULTS: 45% (N = 1395) of women who received the online survey, participated. The mean age was 56 (± 9.6) years, the majority were white. Compared to women younger than 50, women aged 60-69 reported lower overall DCS scores (-5.4; 95% CI -1.5 to -9.3). Women > 70 had lower values clarity scores (-9.0; 95% CI -2.8 to -15.2) about their treatment compared to women aged 50-59 and 60-69 (-7.1; 95% CI -2.9 to -11.3 and - 7.2; 95% CI -2.9 to -11.5) and likewise, lower effective decision-making scores (-5.4; 95% CI -1.7 to -9.2 and - 5.2; 95% CI -1.4 to -9.0) compared to women < 50. Compared to whites, blacks reported lower decision conflict (-4.4; 95% CI 0.04 to -8.8) and lower informed decision (-5.2; 95% CI -0.18 to -10.3) about DCIS treatment. CONCLUSION: Younger women reported higher decisional conflict about DCIS treatment, compared to older women (> 70). Age based tailored discussions about treatment options, health education, and supportive decision-making interventions/tools may reduce decision conflict in future DCIS patients. TRADE REGISTRATION: The IRB number is 10678.


Asunto(s)
Carcinoma Intraductal no Infiltrante , Toma de Decisiones , Humanos , Femenino , Anciano , Persona de Mediana Edad , Carcinoma Intraductal no Infiltrante/terapia , Etnicidad , Estudios Transversales , Encuestas y Cuestionarios
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