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1.
Immune Netw ; 24(4): e32, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39246617

RESUMO

Low-dose radiotherapy (LDRT) has been explored as a treatment option for various inflammatory diseases; however, its application in the context of rheumatoid arthritis (RA) is lacking. This study aimed to elucidate the mechanism underlying LDRT-based treatment for RA and standardize it. LDRT reduced the total numbers of immune cells, but increased the apoptotic CD4+ T and B220+ B cells, in the draining lymph nodes of collagen induced arthritis and K/BxN models. In addition, it significantly reduced the severity of various pathological manifestations, including bone destruction, cartilage erosion, and swelling of hind limb ankle. Post-LDRT, the proportion of apoptotic CD4+ T and CD19+ B cells increased significantly in the PBMCs derived from human patients with RA. LDRT showed a similar effect in fibroblast-like synoviocytes as well. In conclusion, we report that LDRT induces apoptosis in immune cells and fibro-blast-like synoviocytes, contributing to attenuation of arthritis.

2.
Korean J Ophthalmol ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39155137

RESUMO

Purpose: To compare changes in the swept-source anterior segment optical coherence tomography (SS AS-OCT) parameters and intraocular pressure (IOP) control after lens extraction in various spectra of primary angle closure disease (PACD). Methods: A total 92 eyes from 92 patients with PACD who underwent lens extraction were included in the study. All patients underwent IOP measurement preoperatively and postoperatively at 1 day, 1 week, 1 month, 3 months, and 6 months. SS AS-OCT was performed in all subjects preoperatively and 1 month postoperatively. All participants were divided into two groups depending on the presence of glaucomatous optic disc or visual field damage (group A: primary angle closure suspect or primary angle closure; group B: primary angle closure glaucoma). The changes in IOP and anterior chamber angle (ACA) parameters of SS AS-OCT of each group were compared. Regression analysis was performed to find factors associated with the degree of IOP reduction after lens extraction. Results: Preoperatively, there was no significant difference in IOP (16.3 ± 2.5 vs 16.9 ± 3.2 mmHg, P=0.297) between the two groups, but the number of glaucoma medications used (0.6 ± 1.0 vs 2.0 ± 0.9, P<0.001) was greater in group B. Postoperatively, IOP was not significantly different, but the number of medications used was greater in group B (0.2 ± 0.7, 0.9 ± 0.8, P<0.001). ACA parameters including angle opening distance and trabecular-iris angle had a greater increase in group B after lens extraction. However, the residual iridotrabecular contact (ITC) index (5.6 ± 7.0 vs 10.7 ± 12.1, P=0.014) was significantly greater in group B. A greater change in the ITC index was related to a greater degree of IOP reduction (beta coefficient = 0.429, P<0.001). Conclusions: Eyes with PACG had a greater residual ITC index after lens extraction compared with eyes of other PACD spectrum, and required a greater number of glaucoma medications to maintain a similar level of IOP.

3.
J Pers Med ; 14(8)2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39202072

RESUMO

Opioids effectively manage perioperative pain but have numerous adverse effects. Opioid-free anesthesia (OFA) eliminates intraoperative opioid use; however, evidence for its use in video-assisted thoracoscopic surgery (VATS) is limited. This study assessed the effect of OFA using ketamine in VATS patients compared to opioid-sparing anesthesia (OSA). A total of 91 patients undergoing VATS lobectomy or segmentectomy were randomized to either the OFA group (ketamine) or the OSA group (remifentanil). The primary outcome was the quality of recovery (QoR) on postoperative day (POD) 1, measured with the QoR-40 questionnaire. Secondary outcomes included postoperative pain scores and adverse events. Both groups had comparable baseline and surgical characteristics. On POD 1, the QoR-40 score was higher in the OFA group than in the OSA group (164.3 ± 10.8 vs. 158.7 ± 10.6; mean difference: 5.6, 95% CI: 1.1, 10.0; p = 0.015), though this did not meet the pre-specified minimal clinically important difference of 6.3. The visual analog scale score was lower in the OFA group as compared to the OSA group at 0-1 h (4.2 ± 2.3 vs. 6.2 ± 2.1; p < 0.001) and 1-4 h after surgery (3.4 ± 1.8 vs. 4.6 ± 1.9; p = 0.003). The OFA group had a lower incidence of PONV (2 [4.4%] vs. 9 [19.6%]; p = 0.049) and postoperative shivering (4 [8.9%] vs. 13 [28.3%]; p = 0.030) than the OSA group at 0-1 h after surgery. Using OFA with ketamine proved feasible, as indicated by the stable intraoperative hemodynamics and absence of intraoperative awareness. Patients undergoing VATS with OFA using ketamine showed a statistically significant, but clinically insignificant, QoR improvement compared to those receiving OSA with remifentanil.

4.
J Clin Med ; 13(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38930019

RESUMO

Background/Objectives: Immediate breast reconstruction surgery (BRS) often leads to significant postoperative pain, necessitating effective analgesia. This study aimed to compare the analgesic efficacy of patient-controlled analgesia (PCA) containing nefopam with that of PCA containing opioids alone in patients undergoing BRS. Methods: A prospective, double-blind, randomized controlled trial was conducted on 120 patients undergoing immediate BRS after mastectomy. Patients were randomly allocated to receive PCA with fentanyl alone (Group F: fentanyl 10 mcg/kg), fentanyl and nefopam (Group FN: fentanyl 5 mcg/kg + nefopam 1 mg/kg), or nefopam alone (Group N: nefopam 2 mg/kg). Pain intensity (expressed in VASr and VASm), opioid consumption, and opioid-related complications were assessed. Results: PCA with nefopam, either alone or in combination with opioids, demonstrated non-inferior analgesic efficacy compared to PCA with fentanyl alone. At 24 h postoperatively, the VASr scores were 2.9 ± 1.0 in Group F, 3.1 ± 1.2 in Group FN, and 2.8 ± 0.9 in Group N (p = 0.501). At the same timepoint, the VASm scores were 4.1 ± 1.2 in Group F, 4.5 ± 1.5 in Group FN, and 3.8 ± 1.4 in Group N (p = 0.129). Significant differences among the three groups were observed at all timepoints except for PACU in terms of the total opioid consumption (p < 0.0001). However, there were no significant differences in opioid-related complications among the three groups. Conclusions: PCA with nefopam, whether alone or in combination with opioids, offers non-inferior analgesic efficacy compared to PCA with fentanyl alone in patients undergoing immediate BRS.

5.
J Clin Med ; 13(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38930122

RESUMO

Background/Objectives: Preoperative fasting guidelines traditionally aim to reduce pulmonary aspiration risk. However, concerns over the adverse effects of prolonged fasting have led to exploring alternatives. This study aimed to investigate the impact of preoperative clear liquid intake on postoperative outcomes in children undergoing minimally invasive repair of pectus excavatum (MIRPE). Methods: A prospective randomized controlled study was conducted on children aged 3-6 years scheduled for elective MIRPE. Patients were randomized into either a routine overnight fasting group (NPO) or a clear liquid group. The incidence and severity of emergence delirium (ED) were assessed using Pediatric Anesthesia Emergence Delirium (PAED) and Watcha scales at recovery room. Postoperative pain scores and opioid requirements were evaluated at intervals of 1-6 h, 6-12 h, and 12-24 h after surgery. Results: Fasting time was 178.6 ± 149.5 min and 608.9 ± 148.4 min in the clear liquid group compared and NPO group, respectively. The incidence of ED, measured by PAED and Watcha scales, was lower in the clear liquid group (PAED score ≥ 12: 55.6% vs. 85.2%, p = 0.037; Watcha score ≥ 3: 51.9% vs. 85.2%, p = 0.019). The highest PAED score recorded in the recovery room was significantly lower in the clear liquid group (11.4 ± 2.8 vs. 14.6 ± 2.8, p < 0.001). Clear liquid group showed significantly lower pain scores at 1-6, 6-12, and 12-24 h postoperatively. Additionally, clear liquid group had lower opioid requirement at 1-6 and 6-12 h postoperatively. Conclusions: Preoperative clear liquid consumption was associated with a lower incidence of ED in pediatric patients undergoing MIRPE.

6.
Sensors (Basel) ; 24(9)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38733019

RESUMO

The burgeoning interest in intelligent transportation systems (ITS) and the widespread adoption of in-vehicle amenities like infotainment have spurred a heightened fascination with vehicular ad-hoc networks (VANETs). Multi-hop routing protocols are pivotal in actualizing these in-vehicle services, such as infotainment, wirelessly. This study presents a novel protocol called multiple junction-based traffic-aware routing (MJTAR) for VANET vehicles operating in urban environments. MJTAR represents an advancement over the improved greedy traffic-aware routing (GyTAR) protocol. MJTAR introduces a distributed mechanism capable of recognizing vehicle traffic and computing curve metric distances based on two-hop junctions. Additionally, it employs a technique to dynamically select the most optimal multiple junctions between source and destination using the ant colony optimization (ACO) algorithm. We implemented the proposed protocol using the network simulator 3 (NS-3) and simulation of urban mobility (SUMO) simulators and conducted performance evaluations by comparing it with GSR and GyTAR. Our evaluation demonstrates that the proposed protocol surpasses GSR and GyTAR by over 20% in terms of packet delivery ratio, with the end-to-end delay reduced to less than 1.3 s on average.

7.
Heliyon ; 10(9): e29780, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38699005

RESUMO

Objective: To evaluate and compare the magnitude of intraocular lens (IOL) decentration and tilt following conventional and femtosecond laser-assisted cataract surgery (FLACS) using swept-source anterior optical coherence tomography (SS-OCT). Methods: In this retrospective observational study, we enrolled patients who underwent conventional cataract surgery or FLACS with the implantation of hydrophobic 1-piece monofocal IOL. The magnitude of IOL decentration and tilt were measured using SS-OCT. Visual acuity, intraocular pressure, spherical equivalent, axial length, contrast sensitivity, and satisfaction questionnaire were evaluated before and one-month post-surgery. Additionally, postoperative internal cylinder measurements were obtained using a wavefront aberrometer. Correlation factors between each parameter and IOL decentration or tilt were analyzed. Results: This study included 100 eyes from 100 patients. Mean IOL decentration and tilt were 0.21 ± 0.13 mm and 5.01 ± 1.49°, respectively. Conventional cataract surgery (versus FLACS, P = 0.001) and male sex (versus female, P = 0.047) were significantly correlated with higher postoperative decentration. Preoperative lens diameter (P < 0.001), preoperative lens tilt (P = 0.007), and preoperative intraocular pressure (P = 0.027) were correlated with higher postoperative tilt. Fifty eyes that underwent FLACS demonstrated mean postoperative decentration of 0.21 ± 0.13 mm and tilt of 4.64 ± 1.48°. Compared with the conventional surgery group, the FLACS group significantly differed in postoperative decentration (0.30 ± 0.12 mm, P < 0.001) but not in tilt (5.03 ± 1.35°, P = 0.173). Postoperative visual acuity did not significantly differ between the two groups. Conclusion: Patients who underwent FLACS demonstrated better IOL decentration and tilt than those who underwent conventional cataract surgery one-month post-surgery. However, differences in IOL decentration and tilt did not affect postoperative visual acuity.

8.
J Cachexia Sarcopenia Muscle ; 15(4): 1298-1308, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38632706

RESUMO

BACKGROUND: The association between the adiponectin-to-leptin ratio (A/L ratio) and the risk of incident chronic kidney disease (CKD) is poorly understood. This study aimed to investigate the association between A/L ratio and the risk of incident CKD and to examine whether such a relationship varied according to sex and body composition. METHODS: In this prospective community-based cohort, participants with normal kidney function were analysed (N = 5192). The association between the A/L ratio at baseline and the risk of incident CKD, defined as two or more occasions with an estimated glomerular filtration rate of <60 mL/min/m2 or proteinuria of ≥1+ on a dipstick test during the follow-up period, was evaluated using multivariable Cox proportional hazards analyses. Subgroup analyses were conducted based on sex, body mass index (BMI) and the presence of sarcopenia. RESULTS: The participants' mean age was 57.2 ± 8.3 years, and 53.2% were women. The A/L ratio was higher in men compared with women (1.5 [0.8-3.2] and 0.5 [0.3-0.9] µg/ng, P < 0.001). During a median follow-up of 9.8 [9.5-10.0] years, 417 incident CKD events occurred (8.7 per 1000 person-years). Men in the highest quartile of A/L ratio had a lower risk of incident CKD (adjusted hazard ratio [aHR], 0.57; 95% confidence interval [CI], 0.33-0.99) than those in the lowest quartile. Additionally, a 1.0 increase in A/L ratio was associated with a 12% decreased risk of incident CKD in men (aHR, 0.88; 95% CI, 0.80-0.97). However, no significant association was observed in women. In subgroup analysis stratified by BMI and the presence of sarcopenia, the association between a high A/L ratio and a reduced risk of incident CKD was consistent in men with a BMI < 23.0 kg/m2 and those with sarcopenia. However, no significant association was observed between men with a BMI ≥ 23.0 kg/m2 and those without sarcopenia. CONCLUSIONS: A high A/L ratio is an independent marker of a reduced risk of incident CKD in men, especially in those with a BMI < 23.0 kg/m2 and sarcopenia.


Assuntos
Adiponectina , Composição Corporal , Leptina , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Insuficiência Renal Crônica/epidemiologia , Pessoa de Meia-Idade , Adiponectina/sangue , Leptina/sangue , Incidência , Estudos Prospectivos , Idoso , Índice de Massa Corporal , Biomarcadores , Fatores de Risco
9.
World J Urol ; 42(1): 261, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38668858

RESUMO

INTRODUCTION: This study investigated the learning curve of retrograde intrarenal surgery (RIRS) in patients with medium-sized stones using cumulative sum analysis (CUSUM) to evaluate the competence and proficiency of three new surgeons during their first RIRS procedures. MATERIALS AND METHODS: We conducted a retrospective review of 227 patients from 2019 to 2022 at a single institution. The patients were divided into four groups based on the operating surgeon: tutor surgeon (85 patients), newbie surgeon A (21 patients), newbie surgeon B (85 patients), and newbie surgeon C (36 patients). Patients had one or multiple stones with the largest stone diameter fell within the range of 10-30 mm. Fragmentation efficacy was calculated as "removed stone volume (mm3) divided by operative time (minutes)." CUSUM analysis monitored changes in fragmentation efficacy and validated surgical outcomes. RESULTS: No statistically significant differences were observed in the total stone volume, maximum stone size, or total operation time between the three newbie surgeons and the tutor surgeon. The mean fragmentation efficacy value was comparable among the newbie surgeons, but significantly different from that of the tutor surgeon. The minimum acceptable fragmentation efficacy level was set at 25.12 mL/min, based on the tutor's average value. The CUSUM curves for the three surgeons initially remained relatively flat until Cases 12-15, after which they increased and eventually plateaued. Stone-free rates and postoperative complications did not differ significantly among the surgeons. CONCLUSION: Learning curve analysis for the three newbie surgeons indicated that approximately 12-15 cases were required to reach a plateau.


Assuntos
Competência Clínica , Cálculos Renais , Curva de Aprendizado , Humanos , Cálculos Renais/cirurgia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Urológicos/educação , Procedimentos Cirúrgicos Urológicos/métodos , Adulto , Idoso
10.
Sci Rep ; 14(1): 5591, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454068

RESUMO

When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.


Assuntos
Asco , Humanos , Julgamento , Princípios Morais , Ira , Emoções
11.
World J Mens Health ; 42(1): 237-244, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38171378

RESUMO

PURPOSE: Patients with cancer have a high risk of depression. However, a few studies have assessed differences in the incidence of depression among patients with prostate cancer (PC) based on whether they received radiotherapy (RTx) or surgical treatment. MATERIALS AND METHODS: We analyzed data from the National Health Insurance Sharing Service database regarding the entire Korean adult population with PC (n=210,924) between 2007 and 2017. The adjusted hazard ratios (HRs) of depression associated with treatment were estimated using propensity score-matched Cox proportional hazards models and Kaplan-Meier survival analyses. RESULTS: Our final cohort comprised 9,456 patients with PC; of which, 8,050 men underwent surgery. During a mean follow-up duration of 7.1 years, 503 (5.3%) patients were newly diagnosed with depression. A significant difference in the incidence of depression was noted between the RTx and surgery groups (RTx vs. surgery: 5.55% vs. 5.28%; p=0.011) in the unmatched cohort. In the matched cohort, older age (≥70 years, HR: 1.596, p<0.001) and poor Charlson comorbidity index scores (HR: 1.232, p=0.039) were correlated with the risk of depression. In addition, the adjusted HR for depression in the surgery group was 0.843 (p=0.221) compared with that in the RTx group. Kaplan-Meier analyses revealed that no significant difference in the cumulative probability of persistent depression was detected between the RTx and surgery groups in matched cohort (p=0.3386). CONCLUSIONS: In this nationwide population-based study, no significant differences in the risk of depression were observed between the surgical and RTx groups.

12.
Int J Med Sci ; 21(3): 492-495, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250604

RESUMO

Purpose: Our aim was to evaluate the effect of prophylactic pilocarpine on acute salivary symptoms after radioactive iodine (RAI) therapy in patients with differentiated thyroid cancer. Methods: We enrolled 88 patients (76 women and 12 men; mean age: 47 years; range: 20-74 years) with differentiated thyroid cancer who received RAI. Patients were divided into pilocarpine (51 patients) and control (37 patients) groups. Pilocarpine was given orally, at a dose of 5 mg three times a day, from 2 days before and 12 days after RAI therapy. Symptoms and signs of acute sialadenitis within 3 months of RAI therapy were recorded. Results: During the 3 months after RAI therapy, 13 of the 88 patients (14.7%) developed acute symptomatic sialadenitis (swelling or pain of salivary glands). Acute salivary symptoms were reported by 4 (7.8%) and 9 (24.3%) patients in the pilocarpine and control groups, respectively. Acute salivary symptoms were less frequent in the pilocarpine than control group (p = 0.04), but did not differ by age, sex, or RAI dose (p = 0.3357, p = 0.428, and p = 0.2792). Conclusions: Pilocarpine reduced the likelihood of acute sialadenitis after RAI therapy in patients with differentiated thyroid cancer.


Assuntos
Adenocarcinoma , Sialadenite , Neoplasias da Glândula Tireoide , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/radioterapia , Radioisótopos do Iodo/efeitos adversos , Pilocarpina/efeitos adversos , Sialadenite/etiologia , Sialadenite/prevenção & controle , Doença Aguda
13.
Anesthesiology ; 140(5): 920-934, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38109657

RESUMO

BACKGROUND: Mechanical power (MP), the rate of mechanical energy (ME) delivery, is a recently introduced unifying ventilator parameter consisting of tidal volume, airway pressures, and respiratory rates, which predicts pulmonary complications in several clinical contexts. However, ME has not been previously studied in the perioperative context, and neither parameter has been studied in the context of thoracic surgery utilizing one-lung ventilation. METHODS: The relationships between ME variables and postoperative pulmonary complications were evaluated in this post hoc analysis of data from a multicenter randomized clinical trial of lung resection surgery conducted between 2020 and 2021 (n = 1,170). Time-weighted average MP and ME (the area under the MP time curve) were obtained for individual patients. The primary analysis was the association of time-weighted average MP and ME with pulmonary complications within 7 postoperative days. Multivariable logistic regression was performed to examine the relationships between energy variables and the primary outcome. RESULTS: In 1,055 patients analyzed, pulmonary complications occurred in 41% (431 of 1,055). The median (interquartile ranges) ME and time-weighted average MP in patients who developed postoperative pulmonary complications versus those who did not were 1,146 (811 to 1,530) J versus 924 (730 to 1,240) J (P < 0.001), and 6.9 (5.5 to 8.7) J/min versus 6.7 (5.2 to 8.5) J/min (P = 0.091), respectively. ME was independently associated with postoperative pulmonary complications (ORadjusted, 1.44 [95% CI, 1.16 to 1.80]; P = 0.001). However, the association between time-weighted average MP and postoperative pulmonary complications was time-dependent, and time-weighted average MP was significantly associated with postoperative pulmonary complications in cases utilizing longer periods of mechanical ventilation (210 min or greater; ORadjusted, 1.46 [95% CI, 1.11 to 1.93]; P = 0.007). Normalization of ME and time-weighted average MP either to predicted body weight or to respiratory system compliance did not alter these associations. CONCLUSIONS: ME and, in cases requiring longer periods of mechanical ventilation, MP were independently associated with postoperative pulmonary complications in thoracic surgery.


Assuntos
Ventilação Monopulmonar , Respiração com Pressão Positiva , Humanos , Respiração com Pressão Positiva/efeitos adversos , Pulmão , Respiração Artificial/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Volume de Ventilação Pulmonar , Ventilação Monopulmonar/efeitos adversos
14.
Artigo em Inglês | MEDLINE | ID: mdl-37919889

RESUMO

Background: This study aimed to develop a machine learning-based 2-year risk prediction model for early identification of patients with rapid progressive immunoglobulin A nephropathy (IgAN). We also assessed the model's performance to predict the long-term kidney-related outcome of patients. Methods: A retrospective cohort of 1,301 patients with biopsy-proven IgAN from two tertiary hospitals was used to derive and externally validate a random forest-based prediction model predicting primary outcome (30% decline in estimated glomerular filtration rate from baseline or end-stage kidney disease requiring renal replacement therapy) and secondary outcome (improvement of proteinuria) within 2 years after kidney biopsy. Results: For the 2-year prediction of primary outcomes, precision, recall, area-under-the-curve, precision-recall-curve, F1, and Brier score were 0.259, 0.875, 0.771, 0.242, 0.400, and 0.309, respectively. The values for the secondary outcome were 0.904, 0.971, 0.694, 0.903, 0.955, and 0.113, respectively. From Shapley Additive exPlanations analysis, the most informative feature identifying both outcomes was baseline proteinuria. When Kaplan-Meier analysis for 10-year kidney outcome risk was performed with three groups by predicting probabilities derived from the 2-year primary outcome prediction model (low, moderate, and high), high (hazard ratio [HR], 13.00; 95% confidence interval [CI], 9.52-17.77) and moderate (HR, 12.90; 95% CI, 9.92-16.76) groups showed higher risks compared with the low group. From the 2-year secondary outcome prediction model, low (HR, 1.66; 95% CI, 1.42-1.95) and moderate (HR, 1.42; 95% CI, 0.99-2.03) groups were at greater risk for 10-year prognosis than the high group. Conclusion: Our machine learning-based 2-year risk prediction models for the progression of IgAN showed reliable performance and effectively predicted long-term kidney outcome.

15.
bioRxiv ; 2023 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-38014289

RESUMO

In triple-negative breast cancer (TNBC) that relies on catabolism of amino acid glutamine, glutaminase (GLS) converts glutamine to glutamate, which facilitates glutathione synthesis by mediating the enrichment of intracellular cystine via xCT antiporter activity. To overcome chemo resistant TNBC, we have tested a strategy of disrupting cellular redox balance by inhibition of GLS and xCT by CB839 and Erastin, respectively. Key findings of our study include: 1. Dual metabolic inhibition (CB839+Erastin) led to significant increases of cellular superoxide level in both parent and chemo resistant TNBC cells, but superoxide level was distinctly lower in resistant cells. 2. Dual metabolic inhibition combined with doxorubicin or cisplatin induced significant apoptosis in TNBC cells and is associated with high degrees of GSH depletion. In vivo , dual metabolic inhibition plus cisplatin led to significant growth delay of chemo resistant human TNBC xenografts. 3. Ferroptosis is induced by doxorubicin (DOX) but not by cisplatin or paclitaxel. Addition of dual metabolic inhibition to DOX chemotherapy significantly enhanced ferroptotic cell death. 4. Significant changes in cellular metabolites concentration preceded transcriptome changes revealed by single cell RNA sequencing, underscoring the potential of capturing early changes in metabolites as pharmacodynamic markers of metabolic inhibitors. Here we demonstrated that 4-(3-[ 18 F]fluoropropyl)-L-glutamic acid ([ 18 F]FSPG) PET detected xCT blockade by Erastin or its analog in mice bearing human TNBC xenografts. In summary, our study provides compelling evidence for the therapeutic benefit and feasibility of non-invasive monitoring of dual metabolic blockade as a translational strategy to sensitize chemo resistant TNBC to cytotoxic chemotherapy.

16.
Radiology ; 309(1): e230006, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37906009

RESUMO

Background Active surveillance (AS) is an accepted strategy for patients with low-risk papillary thyroid microcarcinoma (PTMC). While previous studies have evaluated the prognostic value of US features, results have been inconsistent. Purpose To determine if US features can help predict tumor progression in patients with low-risk PTMC undergoing AS. Materials and Methods This prospective study enrolled 1177 participants with PTMC from three hospitals between June 2016 and January 2021. Participants were self-assigned to either immediate surgery or AS, and those with two or more US examinations in the absence of surgery were included in the analysis. A χ2 test was used to compare estimated tumor progression rate at 4 years between participants stratified according to US features. Multivariable Cox regression analysis was used to assess the association of clinical and US features with overall tumor progression and specific progression criteria. Results Among 699 participants included in the analysis, 68 (mean age, 49 years ± 12 [SD]; 40 female participants) showed tumor progression (median follow-up, 41.4 months ± 16 [SD]). Tumor progression was associated with the US features of diffuse thyroid disease (DTD) (hazard ratio [HR], 2.3 [95% CI: 1.4, 3.7]; P = .001) and intratumoral vascularity (HR, 1.7 [95% CI: 1.0, 3.0]; P = .04) and the participant characteristics of male sex (HR, 2.8 [95% CI: 1.7, 4.6]; P < .001), age less than 30 years (HR, 2.9 [95% CI: 1.2, 6.8]; P = .01), and thyroid-stimulating hormone level of 7 µU/mL or higher (HR, 6.9 [95% CI: 2.7, 17.4]; P < .001). The risk of tumor progression was higher for participants with DTD (14%, P = .001) or intratumoral vascularity (14%, P = .02) than for participants without these features (6%). DTD and intratumoral vascularity were associated with tumor enlargement (HR, 2.7 [95% CI: 1.4, 5.1]; P = .002) and new lymph node metastasis (HR, 5.0 [95% CI: 1.3, 19.4]; P = .02), respectively. Conclusion DTD and intratumoral vascularity were associated with an increased risk of tumor progression in participants with PTMC undergoing AS. Clinical trial registration no. NCT02938702 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Reuter and the review "International Expert Consensus on US Lexicon for Thyroid Nodules" by Durante et al in this issue.


Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Conduta Expectante , Estudos Prospectivos , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Estudos Retrospectivos , Fatores de Risco
17.
Neurobiol Aging ; 132: 175-184, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37837733

RESUMO

The anti-inflammatory efficacy of radiation therapy (RT) with single fractions below 1.0 Gy has been demonstrated in Alzheimer's disease mouse models. As neuroinflammation is also a major pathological feature of Parkinson's disease (PD), RT may also be effective in PD treatment. Therefore, this study aimed to investigate the anti-inflammatory effect of low-moderate dose RT (LMDRT, 0.6 Gy/single dose, for 5 days) exposure in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg, intraperitoneally, for 5 consecutive days)-induced PD mouse model. Importantly, LMDRT reduced the levels of glial fibrillary acidic protein and intercellular adhesion molecule-1 (CD54) in the striatum region, which increased following MPTP administration. LMDRT also modulated inflammatory gene expression patterns in the substantia nigra region of the MPTP-treated mice. However, LMDRT had no direct effects on the severe loss of dopaminergic neurons and impaired motor behavior in the rotarod test. These results indicate that LMDRT has anti-inflammatory effects by modulating neuroinflammatory factors, including glial fibrillary acidic protein and intercellular adhesion molecule-1, but showed no behavioral improvements or neuroprotection in the MPTP-induced mouse model of PD.


Assuntos
Encéfalo , Proteína Glial Fibrilar Ácida , Doença de Parkinson , Animais , Camundongos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/metabolismo , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/uso terapêutico , Encéfalo/metabolismo , Encéfalo/efeitos da radiação , Modelos Animais de Doenças , Neurônios Dopaminérgicos/patologia , Proteína Glial Fibrilar Ácida/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/farmacologia , Molécula 1 de Adesão Intercelular/uso terapêutico , Camundongos Endogâmicos C57BL , Doença de Parkinson/metabolismo , Doença de Parkinson/radioterapia , Substância Negra/metabolismo
18.
J Clin Med ; 12(16)2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37629283

RESUMO

Children with pectus excavatum are treated with surgical repair in a procedure known as minimally invasive repair of pectus excavatum (MIRPE). MIRPE causes considerable postoperative pain, resulting in the administration of a substantial dose of opioids. This study aimed to identify perioperative factors that influence the requirement for opioids in children undergoing MIRPE. Retrospective data from children who underwent MIRPE were analyzed. A multimodal analgesic protocol was implemented with a continuous wound infiltration system and administration of non-opioid analgesics. Intravenous opioid analgesics were administered if the pain score was greater than 4. The cumulative opioid use was assessed by calculating the morphine equivalent dose at 6, 24, and 48 h after surgery. Perioperative factors affecting the postoperative opioid use were identified with multiple linear regression analyses. This study included 527 children aged 3-6 years, with a mean age of 3.9 years. Symmetrically depressed chest walls, a lower Haller index, and a lower revised depression index were found to be associated with decreased postoperative opioids. Boys required higher opioid doses than girls. Longer pectus bars (10 inches versus 9 inches) were associated with increased opioid use. Severity indices, gender, and the length of pectus bars influence postoperative opioid requirement in children undergoing MIRPE surgery with multimodal analgesia.

20.
Investig Clin Urol ; 64(3): 289-295, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37341009

RESUMO

PURPOSE: Recent studies have highlighted increasing infectious complications due to fluoroquinolone (FQ)-resistant organisms in men undergoing transrectal ultrasound-guided prostate biopsy (TRUSPB). This study investigated whether fosfomycin (FM)-based antibiotic prophylaxis reduces infections after TRUSPB and identified risk factors for infective complications. MATERIALS AND METHODS: A multicenter study was conducted in the Republic of Korea from January 2018 to December 2021. Patients undergoing prostate biopsy with FQ or FM-based prophylaxis were included. The primary outcome was the post-biopsy infectious complication rate after FQ (group 1) or FM-based antibiotic prophylaxis with FM alone (group 2) or FQ and FM (group 3). Risk factors for infectious complications after TRUSPB were secondary outcomes. RESULTS: Patients (n=2,595) undergoing prostate biopsy were divided into three groups according to the type of prophylactic antibiotics. Group 1 (n=417) received FQ before TRUSPB. Group 2 (n=795) received FM only and group 3 (n=1,383) received FM and FQ before TRUSPB. The overall post-biopsy infectious complication rate was 1.27%. The infectious complication rates were 2.4%, 1.9%, and 0.5% in groups 1, 2, and 3, respectively (p=0.002). In multivariable analysis, predictors of post-biopsy infectious complications included an association with health care utilization (adjusted odds ratio [OR], 4.66; 95% confidence interval [CI], 1.74-12.4; p=0.002) and combination antibiotic prophylaxis (FQ and FM) (adjusted OR, 0.26; 95% CI, 0.09-0.69; p=0.007). CONCLUSIONS: In comparison with monotherapy with FM or FQ, combination antibiotic prophylaxis (FQ and FM) showed a lower rate of infectious complications after TRUSPB. Utilization of health care was an independent risk factor for infectious complications after TRUSPB.


Assuntos
Anti-Infecciosos , Fosfomicina , Masculino , Humanos , Fosfomicina/efeitos adversos , Próstata/patologia , Antibacterianos/uso terapêutico , Biópsia/efeitos adversos , Anti-Infecciosos/uso terapêutico , Fluoroquinolonas , Antibioticoprofilaxia , Ultrassonografia de Intervenção
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