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1.
Arch Gerontol Geriatr ; 127: 105548, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38964053

RESUMEN

PURPOSE: Despite the ongoing rise in hip fractures and the adverse effects of hearing impairment (HI) on increased mortality and morbidity, research addressing the influence of HI on mortality risk or complications in patients with hip fractures remains absent. This study aimed to analyze the effects of HI on mortality and treatment outcomes among patients with hip fracture. METHODS: We retrospectively collected data from consecutive patients diagnosed with hip fractures between January 2007 and March 2022 who had auditory examination records. From the initially enrolled 265 patients, data for 58 with HI and 58 without HI (control group) were extracted using a 1:1 propensity score matching. The primary outcome included comparison of mortality rates, and the secondary outcome encompassed the comparison of postoperative medical and surgical complications. RESULTS: The 1-year cumulative mortality rate was not significantly different between the HI and control groups, but the overall cumulative mortality rate was significantly higher in the HI than in the control group (63.0 % and 48.6, respectively; P = 0.046) in a follow-up period of up to 16 years. The HI group had a significantly higher incidence of "second hip fractures due to falls" than the control group (P = 0.016), although no differences in other medical and surgical complications were revealed. CONCLUSIONS: Awareness of the long-term risk of higher mortality when managing patients with hip fracture and HI is important. To reduce the risk of second hip fractures, paying more attention to fall prevention education and taking a more proactive approach, especially for those with HI.

2.
FASEB J ; 38(13): e23759, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38949635

RESUMEN

The epidermal growth factor receptor (EGFR) is an important target for cancer therapies. Many head and neck cancer (HNC) cells have been reported to overexpress EGFR; therefore, anti-EGFR therapies have been attempted in patients with HNC. However, its clinical efficacy is limited owing to the development of drug resistance. In this study, we developed an EGFR-targeting immunotoxin consisting of a clinically proven anti-EGFR IgG (cetuximab; CTX) and a toxin fragment (LR-LO10) derived from Pseudomonas exotoxin A (PE) using a novel site-specific conjugation technology (peptide-directed photo-crosslinking reaction), as an alternative option. The immunotoxin (CTX-LR-LO10) showed specific binding to EGFR and properties of a typical IgG, such as stability, interactions with receptors of immune cells, and pharmacokinetics, and inhibited protein synthesis via modification of elongation factor-2. Treatment of EGFR-positive HNC cells with the immunotoxin resulted in apoptotic cell death and the inhibition of cell migration and invasion. The efficacy of CTX-LR-LO10 was evaluated in xenograft mouse models, and the immunotoxin exhibited much stronger tumor suppression than CTX or LR-LO10. Transcriptome analyses revealed that the immunotoxins elicited immune responses and altered the expression of genes related to its mechanisms of action. These results support the notion that CTX-LR-LO10 may serve as a new therapeutic agent targeting EGFR-positive cancers.


Asunto(s)
ADP Ribosa Transferasas , Receptores ErbB , Exotoxinas , Neoplasias de Cabeza y Cuello , Inmunoglobulina G , Inmunotoxinas , Exotoxina A de Pseudomonas aeruginosa , Factores de Virulencia , Humanos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Receptores ErbB/inmunología , Animales , Inmunotoxinas/farmacología , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/metabolismo , Ratones , Inmunoglobulina G/farmacología , Línea Celular Tumoral , Exotoxinas/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Cetuximab/farmacología , Ratones Desnudos , Toxinas Bacterianas , Apoptosis/efectos de los fármacos , Ratones Endogámicos BALB C , Femenino , Movimiento Celular/efectos de los fármacos , Antineoplásicos/farmacología
3.
Clin Orthop Surg ; 16(3): 363-373, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38827761

RESUMEN

Background: Operative management with intramedullary nail fixation remains the definitive treatment of choice for osteoporotic subtrochanteric (ST) fractures; however, there remains no consensus regarding the proper nail length. We aimed to use 3-dimensional finite element (FE) analysis to determine the optimal nail length for the safe fixation of osteoporotic ST fractures. Methods: Nine modes of FE models were constructed using 9 different lengths of cephalomedullary nails (short nails: 170, 180, and 200 mm; long nails: 280, 300, 320, 340, 360, and 380 mm) from the same company. The interfragmentary motion was analyzed. Additionally, the peak von Mises stress (PVMS) in the cortical bone, cancellous bone of the femoral head, and the nail were measured, and the yielding risk for each subject was investigated. Results: Long nails were associated with less interfragmentary motion. In the cortical bone, the PVMS of short nails was observed at the distal locking screw holes of the femoral medial cortex; however, in long nails, the PVMS was observed at the lag screw holes on the lateral cortex. The mean yielding risk of long nails was 40.1% lower than that of short nails. For the cancellous bone of the femoral head, the PVMS in all 9 FE models was in the same area: at the apex of the femoral head. There was no difference in the yielding risk between short and long nails. For implants, the PVMS was at the distal locking screw hole of the nail body in the short nails and the nail body at the fracture level in the long nails. The mean yielding risk was 74.9% lower for long nails than that for short nails. Conclusions: Compared to short nails, long nails with a length of 320 mm or more showed less interfragmentary motion and lower yielding risk in low-level osteoporotic ST fractures. The FE analysis supports long nails as a safer option than short nails, especially for treating transverse-type low-level osteoporotic ST fractures.


Asunto(s)
Clavos Ortopédicos , Análisis de Elementos Finitos , Fijación Intramedular de Fracturas , Fracturas de Cadera , Fracturas Osteoporóticas , Humanos , Fracturas Osteoporóticas/cirugía , Fijación Intramedular de Fracturas/métodos , Fijación Intramedular de Fracturas/instrumentación , Fracturas de Cadera/cirugía , Femenino , Anciano
5.
Clin Orthop Surg ; 16(3): 430-440, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38827763

RESUMEN

Background: Computer-assisted navigation surgery (CAS) during primary total knee arthroplasty (TKA) may help improve outcomes for patients with extra-articular deformity (EAD); however, this has not been extensively studied. Therefore, we aimed to investigate the clinical and radiological outcomes following primary TKA using CAS in patients with EAD. Methods: We searched Medline, Embase, and the Cochrane Library up to March 3, 2023 for studies investigating surgical outcomes of using the navigation system for TKA to treat patients with EAD. From 14 studies, 539 knees with EAD that underwent navigation TKA were enrolled. We investigated the knee range of motion (ROM), outcome scores at final follow-up (Knee Society Score [KSS] and Knee Functional Score [KFS]), and pre- and postoperative mechanical hip-knee-ankle (mHKA) angle using lower extremity scanogram. The meta-analysis was based on the single-arm method, and all data were pooled using a random-effects model. Results: Following our meta-analyses, the mean knee ROM changed from 87.0° (95% confidence interval [CI], 75.9°-98.1°) preoperatively to 109.4° (95% CI, 97.9°-120.8°) postoperatively. The adjusted KSS was 93.45 points (95% CI, 88.36-98.54 points), and the adjusted KFS was 91.57 points (95% CI, 86.80-96.33 points) in knees with EAD that underwent CAS-TKA. As a radiological outcome, the mHKA angle changed from 169.53° (95% CI, 166.90°-172.16°) preoperatively to 178.81° (95% CI, 178.31°-179.30°) postoperatively. Conclusions: CAS-TKA yielded positive clinical results and demonstrated a satisfactory alignment of the lower limb's mechanical axis. CAS-TKA showed promise for primary TKA procedures, demonstrating favorable clinical and radiological outcomes even in complex cases involving EAD.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Rango del Movimiento Articular , Cirugía Asistida por Computador , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Cirugía Asistida por Computador/métodos , Articulación de la Rodilla/cirugía , Articulación de la Rodilla/diagnóstico por imagen
6.
BMJ Open ; 14(5): e079417, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38777592

RESUMEN

OBJECTIVES: We aimed to develop an automated method for measuring the volume of the psoas muscle using CT to aid sarcopenia research efficiently. METHODS: We used a data set comprising the CT scans of 520 participants who underwent health check-ups at a health promotion centre. We developed a psoas muscle segmentation model using deep learning in a three-step process based on the nnU-Net method. The automated segmentation method was evaluated for accuracy, reliability, and time required for the measurement. RESULTS: The Dice similarity coefficient was used to compare the manual segmentation with automated segmentation; an average Dice score of 0.927 ± 0.019 was obtained, with no critical outliers. Our automated segmentation system had an average measurement time of 2 min 20 s ± 20 s, which was 48 times shorter than that of the manual measurement method (111 min 6 s ± 25 min 25 s). CONCLUSION: We have successfully developed an automated segmentation method to measure the psoas muscle volume that ensures consistent and unbiased estimates across a wide range of CT images.


Asunto(s)
Aprendizaje Profundo , Músculos Psoas , Sarcopenia , Tomografía Computarizada por Rayos X , Humanos , Músculos Psoas/diagnóstico por imagen , Músculos Psoas/anatomía & histología , Tomografía Computarizada por Rayos X/métodos , Estudios Transversales , Femenino , Masculino , Sarcopenia/diagnóstico por imagen , Reproducibilidad de los Resultados , Persona de Mediana Edad , Anciano , Adulto , Tamaño de los Órganos
7.
ESC Heart Fail ; 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637996

RESUMEN

This case study investigated the impact of SCS on alterations in blood pressure during constant-load exercise in a female patient with heart failure. Three different SCS frequencies [No SCS (~0 Hz), Low SCS (~100 Hz), and High SCS (~1000 Hz)] with and without ischaemic stimulation of the legs (cuffs) were randomly applied during constant-load exercise. To determine cardiovascular and ventilatory responses to exercise following SCS frequencies, BP, heart rate (HR), and respiratory gas exchange were measured. This experiment was duplicated in visit 1 and visit 2 with a random application of SCS frequency order and the data were averaged. There were no significant differences among three frequencies with no leg ischaemia. However, High SCS demonstrated lower BP, HR, and respiratory gas exchange relative to No SCS and Low SCS. SCS may be effective in improving cardiovascular and ventilatory responses in HF and high-frequency stimulation provides more clinical benefit; however, further studies are needed.

8.
Pharmaceutics ; 16(4)2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38675118

RESUMEN

Enzalutamide (ENZ), marketed under the brand name Xtandi® as a soft capsule, is an androgen receptor signaling inhibitor drug actively used in clinical settings for treating prostate cancer. However, ENZ's low solubility and bioavailability significantly hinder the achievement of optimal therapeutic outcomes. In previous studies, a liquid self-nanoemulsifying drug delivery system (L-SNEDDS) containing ENZ was developed among various solubilization technologies. However, powder formulations that included colloidal silica rapidly formed crystal nuclei in aqueous solutions, leading to a significant decrease in dissolution. Consequently, this study evaluated the efficacy of adding a polymer as a recrystallization inhibitor to a solid SNEDDS (S-SNEDDS) to maintain the drug in a stable, amorphous state in aqueous environments. Polymers were selected based on solubility tests, and the S-SNEDDS formulation was successfully produced via spray drying. The optimized S-SNEDDS formulation demonstrated through X-ray diffraction and differential scanning calorimetry data that it significantly reduced drug crystallinity and enhanced its dissolution rate in simulated gastric and intestinal fluid conditions. In an in vivo study, the bioavailability of orally administered formulations was increased compared to the free drug. Our results highlight the effectiveness of solid-SNEDDS formulations in enhancing the bioavailability of ENZ and outline the potential translational directions for oral drug development.

9.
Mol Oncol ; 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38511232

RESUMEN

Immune checkpoint blockers (ICBs) targeting programmed cell death protein 1 (PD-1) have been proven to be an effective first-line therapy against programmed cell death 1 ligand 1 (PD-L1; also known as CD274 molecule)-expressing head and neck squamous cell carcinoma (HNSCC) in recent KEYNOTE-048 trial. However, associated changes in the tumor microenvironment (TME) and underlying mechanisms remain elusive. Oral tumors in C57/BL6 mice were induced by administering 7,12-dimethylbenzanthracene into the buccal mucosa. Single-cell suspension was isolated from tumor tissue; proliferating cells were injected subcutaneously into the left flank of mice to establish Ajou oral cancer (AOC) cell lines. Subsequently, a syngeneic PD-L1-expressing HNSCC model was developed by injecting AOC cells into the buccal or tongue area. The model recapitulated human HNSCC molecular features and showed reliable in vivo tumorigenicity with significant PD-L1 expression. ICB monotherapy induced global changes in the TME, including vascular normalization. Furthermore, the antitumor effect of ICB monotherapy was superior to those of other therapeutic agents, including cisplatin and inhibitors of vascular endothelial growth factor receptor 2 (VEGFR2). The ICB-induced antitumorigenicity and TME normalization were alleviated by blocking the type I interferon pathway. In summary, ICB monotherapy is sufficient to induce TME normalization in the syngeneic model; the type I interferon pathway is indispensable in realizing the effects of ICBs. Furthermore, these results explain the underlying mechanism of the efficacy of ICB monotherapy against PD-L1-expressing HNSCC in the KEYNOTE-048 trial.

10.
Sci Rep ; 14(1): 5406, 2024 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443446

RESUMEN

Research on the treatment outcomes and mortality of patients with cancer and hip fractures remains limited. We aimed to assess the treatment outcomes and mortality in older patients with cancer and hip fractures. We retrospectively reviewed the data of 1264 patients aged ≥ 60 years treated for hip fractures between January 2005 and April 2022. The operation time, blood transfusion-related indicators, postoperative complications, reoperation rate, length of hospital stay, admission to the intensive care unit, mortality rate, and clinical scores were compared. We also performed survival analysis. Subsequently, 1:1 propensity-score matching was performed. In the unmatched cohort, we compared 273 patients with cancer and 991 controls. The cancer group exhibited a higher incidence of pneumonia (P = 0.025) and higher in-hospital and 1-year follow-up mortality rates (P = 0.044 and P < 0.001, respectively). In the matched cohort, the 1-year mortality rate remained higher in the cancer group (P < 0.001). The control group showed a higher survival rate in both unmatched and matched cohorts (P < 0.001 for both). The surgical outcomes for hip fractures were comparable between patients with and without cancer. We recommend surgical treatment for hip fractures in patients with cancer.


Asunto(s)
Fracturas de Cadera , Neoplasias , Humanos , Anciano , Puntaje de Propensión , Estudios Retrospectivos , Fracturas de Cadera/cirugía , Reoperación
11.
Acute Crit Care ; 39(1): 162-168, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38476069

RESUMEN

BACKGROUND: Using peripheral arteries to infer central hemodynamics is common among hemodynamic monitors. Doppler ultrasound of the common carotid artery has been used in this manner with conflicting results. We investigated the relationship between changing common carotid artery Doppler measures and stroke volume (SV), hypothesizing that more consecutively-averaged cardiac cycles would improve SV-carotid Doppler correlation. METHODS: Twenty-seven healthy volunteers were recruited and studied in a physiology laboratory. Carotid artery Doppler pulse was measured with a wearable, wireless ultrasound during central hypovolemia and resuscitation induced by a stepped lower body negative pressure protocol. The change in maximum velocity time integral (VTI) and corrected flow time of the carotid artery (ccFT) were compared with changing SV using repeated measures correlation. RESULTS: In total, 73,431 cardiac cycles were compared across 27 subjects. There was a strong linear correlation between changing SV and carotid Doppler measures during simulated hemorrhage (repeated-measures linear correlation [Rrm ]=0.91 for VTI; 0.88 for ccFT). This relationship improved with larger numbers of consecutively-averaged cardiac cycles. For ccFT, beyond four consecutively-averaged cardiac cycles the correlation coefficient remained strong (i.e., Rrm of at least 0.80). For VTI, the correlation coefficient with SV was strong for any number of averaged cardiac cycles. For both ccFT and VTI, Rrm remained stable around 25 consecutively-averaged cardiac cycles. CONCLUSIONS: There was a strong linear correlation between changing SV and carotid Doppler measures during central blood volume loss. The strength of this relationship was dependent upon the number of consecutively-averaged cardiac cycles.

12.
Orthop Surg ; 16(5): 1153-1159, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38556482

RESUMEN

OBJECTIVES: Arthroscopic treatment is indicated for external snapping hip (ESH) syndrome in patients refractory to conservative treatment, but snapping does not disappear completely in some case. No previous studies have described the clinical course of ESH syndrome in patients who presented with persistent snapping after an arthroscopic procedure. We demonstrated the clinical outcomes following an incomplete arthroscopic iliotibial band (ITB) release for ESH syndrome. METHODS: This retrospective observational study was performed at two teaching hospitals between October 2015 and December 2021. We reviewed the data of 33 patients (34 hips) aged ≥18 years, diagnosed with ESH syndrome, who were treated with arthroscopic ITB release. Patients who presented with persistent snapping despite sufficient arthroscopic ITB release following systematic order were defined as having an incomplete release. We collected the data for recurrent symptomatic snapping hip as the primary outcome after a minimum 2-year follow-up. The visual analogue scale (VAS) and modified Harris hip (mHHS) scores were measured as secondary outcome. RESULTS: "Incomplete release" was identified in three of the 34 hips (8.9%). Cases of recurrent symptomatic snapping or conversion to open surgery were not observed. The symptoms of residual snapping spontaneously disappeared in all cases following routine postoperative rehabilitation within a 3-month follow-up period. The VAS (4 ± 1) and mHHS (17 ± 6) scores of all the patients improved. CONCLUSION: When refractory ESH syndrome is identified during arthroscopic surgery, appropriate ITB release and removal of the major lesion causing snapping are expected to lead to resolution of residual symptoms without conversion to open surgery.


Asunto(s)
Artroscopía , Síndrome de la Banda Iliotibial , Humanos , Artroscopía/métodos , Estudios Retrospectivos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Síndrome de la Banda Iliotibial/cirugía , Adulto Joven , Resultado del Tratamiento , Adolescente , Articulación de la Cadera/cirugía , Articulación de la Cadera/fisiopatología , Dimensión del Dolor
13.
J Pers Med ; 14(3)2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38541045

RESUMEN

Benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder characterized by episodic vertigo. BPPV primarily affects older adults. Thus, understanding the potential relationship between BPPV and osteoporosis is clinically important. We performed a systematic search of MEDLINE (PubMed), Embase, and Cochrane Library databases for studies on the risk of osteoporosis between BPPV (+) and BPPV (-) groups up until 17 April 2023. We compared osteoporosis prevalence between groups and performed subgroup analyses for male, female, and older patients (aged ≥ 55 years). The 12 studies included 32,460 patients with BPPV and 476,304 controls. Pooled analysis showed that the BPPV (+) group had a significantly higher osteoporosis risk than the control group (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.45-2.06; p < 0.01). Subgroup analyses also presented similar trends as male (OR, 2.41; 95% CI, 1.18-4.90; p = 0.02), female (OR, 2.14; 95% CI, 1.57-2.92; p < 0.001), and older patient subgroups (OR, 1.91; 95% CI, 1.47-2.49; p < 0.01) showed a higher osteoporosis risk in the BPPV (+) group than in the control group. This meta-analysis supports the hypothesis that patients with BPPV have a higher osteoporosis prevalence than those without.

14.
Cell Commun Signal ; 22(1): 138, 2024 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-38374138

RESUMEN

BACKGROUND: Applications of nonthermal plasma have expanded beyond the biomedical field to include antibacterial, anti-inflammatory, wound healing, and tissue regeneration. Plasma enhances epithelial cell repair; however, the potential damage to deep tissues and vascular structures remains under investigation. RESULT: This study assessed whether liquid plasma (LP) increased nitric oxide (NO) production in human umbilical vein endothelial cells by modulating endothelial NO synthase (eNOS) phosphorylation and potential signaling pathways. First, we developed a liquid plasma product and confirmed the angiogenic effect of LP using the Matrigel plug assay. We found that the NO content increased in plasma-treated water. NO in plasma-treated water promoted cell migration and angiogenesis in scratch and tube formation assays via vascular endothelial growth factor mRNA expression. In addition to endothelial cell proliferation and migration, LP influenced extracellular matrix metabolism and matrix metalloproteinase activity. These effects were abolished by treatment with NG-L-monomethyl arginine, a specific inhibitor of NO synthase. Furthermore, we investigated the signaling pathways mediating the phosphorylation and activation of eNOS in LP-treated cells and the role of LKB1-adenosine monophosphate-activated protein kinase in signaling. Downregulation of adenosine monophosphate-activated protein kinase by siRNA partially inhibited LP-induced eNOS phosphorylation, angiogenesis, and migration. CONCLUSION: The present study suggests that LP treatment may be a novel strategy for promoting angiogenesis in vascular damage. Video Abstract.


Asunto(s)
Matriz Extracelular , Óxido Nítrico Sintasa de Tipo III , Plasma , Lesiones del Sistema Vascular , Humanos , Adenosina Monofosfato/metabolismo , Adenosina Monofosfato/farmacología , Angiogénesis , Matriz Extracelular/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Neovascularización Fisiológica , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacología , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa/farmacología , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fosforilación , Proteínas Quinasas/metabolismo , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismo , Lesiones del Sistema Vascular/metabolismo , Lesiones del Sistema Vascular/terapia , Plasma/metabolismo
15.
Cell Mol Immunol ; 21(5): 466-478, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38409251

RESUMEN

Inflammasomes are multiprotein complexes involved in the host immune response to pathogen infections. Thus, inflammasomes participate in many conditions, such as acne. Recently, it was shown that NETosis, a type of neutrophil cell death, is induced by bacterial infection and is involved in inflammatory diseases such as delayed wound healing in patients with diabetes. However, the relationship between inflammasomes and NETosis in the pathogenesis of inflammatory diseases has not been well studied. In this study, we determined whether NETosis is induced in P. acnes-induced skin inflammation and whether activation of the nucleotide-binding domain, leucine-rich family, and pyrin domain-containing-3 (NLRP3) inflammasome is one of the key factors involved in NETosis induction in a mouse model of acne skin inflammation. We found that NETosis was induced in P. acnes-induced skin inflammation in mice and that inhibition of NETosis ameliorated P. acnes-induced skin inflammation. In addition, our results demonstrated that inhibiting inflammasome activation could suppress NETosis induction in mouse skin. These results indicate that inflammasomes and NETosis can interact with each other to induce P. acnes-induced skin inflammation and suggest that targeting NETosis could be a potential treatment for inflammasome-mediated diseases as well as NETosis-related diseases.


Asunto(s)
Acné Vulgar , Trampas Extracelulares , Inflamasomas , Inflamación , Proteína con Dominio Pirina 3 de la Familia NLR , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Animales , Inflamasomas/metabolismo , Trampas Extracelulares/metabolismo , Trampas Extracelulares/inmunología , Acné Vulgar/inmunología , Ratones , Inflamación/inmunología , Inflamación/patología , Piel/patología , Piel/inmunología , Neutrófilos/inmunología , Neutrófilos/metabolismo , Ratones Endogámicos C57BL , Humanos , Modelos Animales de Enfermedad
16.
J Med Virol ; 96(1): e29386, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38235919

RESUMEN

Human papillomavirus (HPV) is a major causative factor of head and neck squamous cell carcinoma (HNSCC), and the incidence of HPV- associated HNSCC is increasing. The role of tumor microenvironment in viral infection and metastasis needs to be explored further. We studied the molecular characteristics of primary tumors (PTs) and lymph node metastatic tumors (LNMTs) by stratifying them based on their HPV status. Eight samples for single-cell RNA profiling and six samples for spatial transcriptomics (ST), composed of matched primary tumors (PT) and lymph node metastases (LNMT), were collected from both HPV- negative (HPV- ) and HPV-positive (HPV+ ) patients. Using the 10x Genomics Visium platform, integrative analyses with single-cell RNA sequencing were performed. Intracellular and intercellular alterations were analyzed, and the findings were confirmed using experimental validation and publicly available data set. The HPV+ tissues were composed of a substantial amount of lymphoid cells regardless of the presence or absence of metastasis, whereas the HPV- tissue exhibited remarkable changes in the number of macrophages and plasma cells, particularly in the LNMT. From both single-cell RNA and ST data set, we discovered a central gene, pyruvate kinase muscle isoform 1/2 (PKM2), which is closely associated with the stemness of cancer stem cell-like populations in LNMT of HPV- tissue. The consistent expression was observed in HPV- HNSCC cell line and the knockdown of PKM2 weakened spheroid formation ability. Furthermore, we found an ectopic lymphoid structure morphology and clinical effects of the structure in ST slide of the HPV+ patients and verified their presence in tumor tissue using immunohistochemistry. Finally, the ephrin-A (EPHA2) pathway was detected as important signals in angiogenesis for HPV- patients from single-cell RNA and ST profiles, and knockdown of EPHA2 declined the cell migration. Our study described the distinct cellular composition and molecular alterations in primary and metastatic sites in HNSCC patients based on their HPV status. These results provide insights into HNSCC biology in the context of HPV infection and its potential clinical implications.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Infecciones por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas/patología , Virus del Papiloma Humano , Papillomaviridae/genética , Neoplasias de Cabeza y Cuello/genética , Perfilación de la Expresión Génica/métodos , ARN , Microambiente Tumoral/genética
17.
Sci Rep ; 14(1): 267, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38167450

RESUMEN

This study aimed to assess the impact of varying monopolar diathermy power settings on postoperative pain, hemorrhage, and wound healing following tonsillectomy. A single-center, prospective, randomized, double-blinded, controlled clinical study was conducted. During bilateral tonsillectomy procedures, one tonsil received low-power settings (15 W, cutting/blend) while the other tonsil received high-power settings (35 W, cutting/blend). Postoperative pain scores (0-10) and wound healing scores (0-3) were evaluated immediately after surgery and at 1, 2, and 4 weeks postoperatively using the visual analog scale. Additionally, histological analysis was performed on electrically resected tonsil tissues to assess tissue damage in the tonsil bed. The allocation of high and low power settings to each side was randomized. Results showed that 1 week after the surgery, the high-power group experienced significantly higher pain scores (mean ± standard deviation: 4.84 ± 2.21) compared to the low-power group (3.56 ± 2.24, p = 0.049). Moreover, the high-power side exhibited slower wound healing during the initial 1-2 weeks postoperatively, as indicated by lower wound scores at 2 weeks (high-power: 1.96 ± 0.64; low-power: 2.43 ± 0.59, p = 0.008). Furthermore, histological analysis revealed significantly deeper tissue degradation on the high-power side compared to the low-power side (p < 0.001), with mean depths of 565.2 ± 291.0 µm and 156.0 ± 36.8 µm, respectively. In conclusion, these findings suggest that when employing monopolar diathermy in tonsillectomy, lower power settings can lead to improved outcomes in terms of postoperative pain, wound healing, and tissue damage.Trial registration: CRIS identifier: KCT0005670 (cris.nih.go.kr, registration date: 11/12/2020).


Asunto(s)
Diatermia , Tonsilectomía , Humanos , Tonsilectomía/efectos adversos , Tonsilectomía/métodos , Estudios Prospectivos , Diatermia/efectos adversos , Dolor Postoperatorio/etiología , Cicatrización de Heridas , Hemorragia Posoperatoria
18.
Sci Rep ; 14(1): 922, 2024 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-38195717

RESUMEN

This study focused on a novel strategy that combines deep learning and radiomics to predict epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC) using computed tomography (CT). A total of 1280 patients with NSCLC who underwent contrast-enhanced CT scans and EGFR mutation testing before treatment were selected for the final study. Regions of interest were segmented from the CT images to extract radiomics features and obtain tumor images. These tumor images were input into a convolutional neural network model to extract 512 image features, which were combined with radiographic features and clinical data to predict the EGFR mutation. The generalization performance of the model was evaluated using external institutional data. The internal and external datasets contained 324 and 130 EGFR mutants, respectively. Sex, height, weight, smoking history, and clinical stage were significantly different between the EGFR-mutant patient groups. The EGFR mutations were predicted by combining the radiomics and clinical features, and an external validation dataset yielded an area under the curve (AUC) value of 0.7038. The model utilized 1280 tumor images, radiomics features, and clinical characteristics as input data and exhibited an AUC of approximately 0.81 and 0.78 during the primary cohort and external validation, respectively. These results indicate the feasibility of integrating radiomics analysis with deep learning for predicting EGFR mutations. CT-image-based genetic testing is a simple EGFR mutation prediction method, which can improve the prognosis of NSCLC patients and help establish personalized treatment strategies.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Aprendizaje Profundo , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Mutación , Radiómica
19.
Respir Physiol Neurobiol ; 320: 104200, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38036081

RESUMEN

BACKGROUND: The forced oscillation technique (FOT) enables non-invasive measurement of respiratory system impedance. Limited data exists on how changes in operating lung volume (OLV) impact FOT-derived measures of airway resistance (Rrs) and reactance (Xrs). OBJECTIVES: This study examined the reproducibility and responsiveness of FOT-derived measures of Rrs and Xrs during simulated changes in OLV. METHODS: Participants simulated breathing at six OLVs: total lung capacity (TLC), ∼50% of inspiratory reserve volume (IRV50), ∼two-times tidal volume (VT2), tidal volume (VT), ∼50% of expiratory reserve volume (ERV50), and residual volume (RV), on a commercially available FOT device. Each simulated OLV manuever was performed in triplicate and in random order. Total Rrs and Xrs were recorded at 5, 11, and 19 Hz. RESULTS: Twelve healthy participants (2 female) completed the study (weight: 76.5 ± 13.6 kg, height: 178.6 ± 9.7 cm, body mass index: 23.9 ± 3.1 kg/m2). Reproducibility of Rrs and Xrs at VT, VT2 and IRV50 was good to excellent (Range: ICC: 0.89-0.98, 95% confidence interval (CI): 0.70-0.98), while reproducibility at TLC, RV, and ERV50 was poor to excellent (Range: ICC: 0.60-0.98, 95% CI: 0.36-0.97). Rrs and Xrs were not different between VT and VT2 at any frequency (P > .05). With lung hyperinflation from VT to TLC, Rrs and Xrs decreased at all three frequencies (e.g., At 5 Hz Rrs: mean difference (MD): - 0.89, 95%CI: - 0.03 to - 1.75, P = .04; Xrs: MD: - 0.56, 95%CI: - 0.25 to - 0.86, P < .01). With lung hypoinflated from VT to RV, Rrs increased, and Xrs decreased for all frequencies (e.g., MD at 5 Hz, Rrs: MD: 2.31, 95%CI: 0.94-3.67, P < .01; Xrs: MD: -2.53, 95%CI: -4.02 to -1.04, P < .01). CONCLUSION: FOT-derived measures of airway Rrs and Xrs are reproducible across a range of OLV's, and are responsive to hyper- and hypo-inflation of the lung. To further understand the impact of lung hyper- and hypo-inflation on FOT-derived airway impedance additional study is required in individuals with pathological variations in operating lung volume.


Asunto(s)
Resistencia de las Vías Respiratorias , Pulmón , Humanos , Femenino , Reproducibilidad de los Resultados , Impedancia Eléctrica , Pruebas de Función Respiratoria/métodos , Mediciones del Volumen Pulmonar
20.
Cardiology ; 149(2): 183-188, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37827127

RESUMEN

BACKGROUND: Although assessment of cardiovascular hemodynamics during exercise can provide clinical insights, it is challenging to acquire it in clinical settings. OBJECTIVES: Accordingly, this preliminary study was to determine whether a novel elaboration on systolic time interval measures (eSTICO) method of quantifying cardiac output and stroke volume was comparable to those obtained using a validated soluble gas (open circuit CO measure [OpCircCO]) method or calculation based on oxygen consumption (oxygen consumption-based CO [VO2CO]) during exercise. METHODS: For the present study, 14 healthy subjects (male: n = 12, female: n = 2) performed incremental exercise on a recumbent cycle ergometer. At rest and during exercise, cardiac output (CO) was obtained via the eSTICO method, while the OpenCircCO and VO2CO measures were obtained at the last minute of each workload. RESULTS: At peak, there was no difference between eSTICO and OpCircCO (12.39 ± 3.06 vs. 13.96 ± 2.47 L/min, p > 0.05), while there was a slight difference between eSTICO and VO2CO (12.39 ± 3.06 vs. 14.28 ± 2.55 L/min, p < 0.05). When we performed correlation analysis with all subjects and all measures of CO at all WL, between eSTICO and OpenCircCO, there was a good relationship (r = 0.707, p < 0.001) with a Bland and Altman agreement analysis demonstrating a -1.6 difference (95% LoA: -6.3-3.5). Between eSTICO and VO2CO, we observed an r = 0.865 (p < 0.001) and a Bland and Altman agreement analysis with a -1.2 difference (95% LoA: -4.8-2.4). CONCLUSION: A novel exploitation of cardiac hemodynamics using systolic timing intervals may allow a relatively good assessment of CO during exercise in healthy adults.


Asunto(s)
Prueba de Esfuerzo , Adulto , Humanos , Masculino , Femenino , Sístole , Estudios de Factibilidad , Gasto Cardíaco , Volumen Sistólico
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