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1.
SLAS Technol ; : 100142, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38723895

RESUMO

The classification of motor imagery (MI) using Electroencephalography (EEG) plays a pivotal role in facilitating communication for individuals with physical limitations through Brain-Computer Interface (BCI) systems. Recent strides in Attention-Based Networks (ATN) have showcased remarkable performance in EEG signal classification, presenting a promising alternative to conventional Convolutional Neural Networks (CNNs). However, while CNNs have been extensively analyzed for their resilience against adversarial attacks, the susceptibility of ATNs in comparable scenarios remains largely unexplored. This paper aims to fill this gap by investigating the robustness of ATNs in adversarial contexts. We propose a high-performing attention-based deep learning model specifically designed for classifying Motor Imagery (MI) brain signals extracted from EEG data. Subsequently, we conduct a thorough series of experiments to assess various attack strategies targeting ATNs employed in EEG-based BCI tasks. Our analysis utilizes the widely recognized BCI Competition 2a dataset to demonstrate the effectiveness of attention mechanisms in BCI endeavors. Despite achieving commendable classification results in terms of accuracy (87.15%) and kappa score (0.8287), our findings reveal the vulnerability of attention-based models to adversarial manipulations (accuracy: 9.07%, kappa score: -0.21), highlighting the imperative for bolstering the robustness of attention architectures for EEG classification tasks.

2.
NPJ Breast Cancer ; 10(1): 26, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575691

RESUMO

To evaluate the role of chemotherapy in stage IA triple-negative breast cancer, we conducted a retrospective population-based study including 8601 patients. The use of chemotherapy significantly increased from 2010 to 2019 in patients with T1b and T1c tumors (p = 0.001 and p < 0.001, respectively). Receipt of chemotherapy was associated with improved breast cancer-specific survival (BCSS, adjusted hazard ratio = 0.70; p = 0.006), particularly in patients with T1c tumors (5-year BCSS 94.5% vs. 91.2%).

3.
J Biol Chem ; 300(4): 107128, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38432635

RESUMO

Both POLG and MGME1 are needed for mitochondrial DNA (mtDNA) maintenance in animal cells. POLG, the primary replicative polymerase of the mitochondria, has an exonuclease activity (3'→5') that corrects for the misincorporation of bases. MGME1 serves as an exonuclease (5'→3'), producing ligatable DNA ends. Although both have a critical role in mtDNA replication and elimination of linear fragments, these mechanisms are still not fully understood. Using digital PCR to evaluate and compare mtDNA integrity, we show that Mgme1 knock out (Mgme1 KK) tissue mtDNA is more fragmented than POLG exonuclease-deficient "Mutator" (Polg MM) or WT tissue. In addition, next generation sequencing of mutant hearts showed abundant duplications in/nearby the D-loop region and unique 100 bp duplications evenly spaced throughout the genome only in Mgme1 KK hearts. However, despite these unique mtDNA features at steady-state, we observed a similar delay in the degradation of mtDNA after an induced double strand DNA break in both Mgme1 KK and Polg MM models. Lastly, we characterized double mutant (Polg MM/Mgme1 KK) cells and show that mtDNA cannot be maintained without at least one of these enzymatic activities. We propose a model for the generation of these genomic abnormalities which suggests a role for MGME1 outside of nascent mtDNA end ligation. Our results highlight the role of MGME1 in and outside of the D-loop region during replication, support the involvement of MGME1 in dsDNA degradation, and demonstrate that POLG EXO and MGME1 can partially compensate for each other in maintaining mtDNA.


Assuntos
DNA Polimerase gama , DNA Mitocondrial , Animais , Camundongos , DNA Polimerase gama/metabolismo , DNA Polimerase gama/genética , Replicação do DNA , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , DNA Polimerase Dirigida por DNA/metabolismo , DNA Polimerase Dirigida por DNA/genética , Camundongos Knockout
4.
Breast Cancer Res Treat ; 205(3): 579-587, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38453783

RESUMO

PURPOSE: There have been significant advances in the treatment of metastatic breast cancer (BC) over the past years, and long-term outcomes after a diagnosis of brain metastases are lacking. We aimed to identify predictors of brain metastases at initial breast cancer diagnosis, describe overall survival (OS) in the past decade, and identify factors associated with OS after brain metastases diagnosis. METHODS: We evaluated patients with de novo stage IV BC using the Surveillance, Epidemiology and End Results database from 2010 to 2019. Multivariate logistic regression was conducted to assess predictors of brain metastases at initial breast cancer diagnosis. OS was estimated using the Kaplan-Meier method and log rank test was used to compare differences between groups. Cox regression was used to assess associations between several variables and OS. RESULTS: 1,939 patients with brain metastases at initial breast cancer diagnosis were included. Factors associated with this presentation were grade III/IV tumors, ductal histology, hormone receptor (HR)-negative/human epidermal growth factor receptor 2 (HER2)-positive subtype, and extracranial metastases. Patients with HR-positive/HER2-positive disease had the longest OS (median 18 months) and 12.2% were alive at 8 years. Factors associated with shorter OS included older age, lower income, triple-negative subtype, higher grade, and visceral metastases. CONCLUSION: Over the last decade, the median OS of patients with brain metastases at initial breast cancer diagnosis remained poor; however, a substantial minority survive 5 or more years, with rates higher in patients with HER2-positive tumors. In addition to tumor subtype, OS varied according to age, extracranial metastases, and sociodemographic factors.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Programa de SEER , Humanos , Feminino , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Neoplasias da Mama/epidemiologia , Pessoa de Meia-Idade , Idoso , Adulto , Receptor ErbB-2/metabolismo , Prognóstico , Análise de Sobrevida , Estadiamento de Neoplasias , Estimativa de Kaplan-Meier
5.
Med Sci (Basel) ; 12(1)2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38535156

RESUMO

Breast cancer in men represents approximately 1% of all breast cancer diagnoses. Among all patients with breast cancer, approximately 30% will develop brain metastases. Over the past decade, there have been multiple advances in the treatment of metastatic breast cancer; however, long-term outcomes of this presentation in male patients are lacking. We evaluated male patients with de novo stage IV breast cancer using the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2019. Overall survival (OS) was estimated using the Kaplan-Meier method and differences between groups were compared using log rank tests. In total, 22 male patients with brain metastases at initial breast cancer diagnosis were included. Patients with HR-positive/HER2-negative tumors had the longest OS (median 13 months). Factors associated with shorter overall survival were advanced age, unmarried marital status, lower household income, and grade III disease, among others. Brain metastases remains an unmet medical need for patients with breast cancer; the development of new drugs may provide an improvement in overall survival for male patients in the future.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Humanos , Masculino , Mama , Análise de Sobrevida , Bases de Dados Factuais
6.
Nucleic Acids Res ; 52(6): 3088-3105, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38300793

RESUMO

Mitochondrial DNA (mtDNA) recombination in animals has remained enigmatic due to its uniparental inheritance and subsequent homoplasmic state, which excludes the biological need for genetic recombination, as well as limits tools to study it. However, molecular recombination is an important genome maintenance mechanism for all organisms, most notably being required for double-strand break repair. To demonstrate the existence of mtDNA recombination, we took advantage of a cell model with two different types of mitochondrial genomes and impaired its ability to degrade broken mtDNA. The resulting excess of linear DNA fragments caused increased formation of cruciform mtDNA, appearance of heterodimeric mtDNA complexes and recombinant mtDNA genomes, detectable by Southern blot and by long range PacBio® HiFi sequencing approach. Besides utilizing different electrophoretic methods, we also directly observed molecular complexes between different mtDNA haplotypes and recombination intermediates using transmission electron microscopy. We propose that the known copy-choice recombination by mitochondrial replisome could be sufficient for the needs of the small genome, thus removing the requirement for a specialized mitochondrial recombinase. The error-proneness of this system is likely to contribute to the formation of pathological mtDNA rearrangements.


Assuntos
Mitocôndrias , Recombinação Genética , Animais , Mitocôndrias/genética , Mitocôndrias/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Reparo do DNA , Replicação do DNA/genética , Mamíferos/genética
7.
J Pediatr Surg ; 59(5): 889-892, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38383176

RESUMO

PURPOSE: Motor vehicle collisions (MVC) are the second leading cause of death in children and adolescents, but appropriate restraint use remains inadequate. Our previous work shows that about half of pediatric MVC victims presenting to our trauma center were unrestrained. This study evaluates restraint use among children and adolescents who did not survive after MVC. We hypothesize that restraint use is even lower in this population than in pediatric MVC patients who reached our trauma center. METHODS: We reviewed the local Medical Examiner's public records for fatal MVCs involving decedents <19 years old from 2010 to 2021. When restraint use was not documented, local Fire Rescue public records were cross-referenced. Patients were excluded if restraint use was still unknown. Age, demographics, and restraint use were compared using standard statistical methods. RESULTS: Of 199 reviewed cases, 92 met selection criteria. Improper restraint use was documented in 72 patients (78%). Most decedents were White (72% versus 28% Black) and male (74%), with a median age of 17 years [15-18]. Improper restraint use was more common among Black (92% vs 73% White, p = 0.040) and male occupants (85% vs 58% female, p = 0.006). Improper restraint use was lower in the Hispanic population (73%) compared to non-Hispanic individuals (89%), but this difference was not statistically significant (p = 0.090). CONCLUSION: Most pediatric patients who die from MVCs in our county are improperly restrained. While male and Black patients are especially high-risk, the overall dismal rates of restraint use in our pediatric population present an opportunity to improve injury prevention measures. TYPE OF STUDY: Retrospective Comparative Study. LEVEL OF EVIDENCE: Level III.


Assuntos
Sistemas de Proteção para Crianças , Ferimentos e Lesões , Adolescente , Feminino , Humanos , Masculino , Acidentes de Trânsito , Veículos Automotores , Estudos Retrospectivos , Centros de Traumatologia
8.
Obes Surg ; 34(4): 1152-1158, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38351199

RESUMO

INTRODUCTION: Marginal ulcers are the most prevalent endoscopic abnormality after RYGB. The etiology is still poorly understood; however, an increase in acid secretion has been strongly implicated as a causal agent. Although gastrin is the greatest stimulant of acid secretion, to date, the presence of gastrin producing G cells retained in the gastric pouch, related to the occurrence of marginal ulcers, has not been evaluated. OBJECTIVE: Evaluate the density of G cells and parietal cells in the gastric pouch of RYGB patients with a diagnosis of marginal ulcer on the post-op EGD. METHOD: We retrospectively evaluated 1104 gastric bypasses performed between 2010 and 2020. Patients with marginal ulcer who met the inclusion criteria and controls were selected from this same population. Endoscopic gastric pouch biopsies were evaluated using immunohistochemical study and HE staining to assess G cell and parietal cell density. RESULTS: In total, 572 (51.8%) of the patients performed endoscopic follow-up after RYGB. The incidence of marginal ulcer was 23/572 (4%), and 3 patients required revision surgery due to a recalcitrant ulcer. The mean time for ulcer identification was 24.3 months (2-62). G cell count per high-power field (× 400) was statistically higher in the ulcer group (p < 0.05). There was no statistical difference in parietal cell density between groups (p 0.251). CONCLUSION: Patients with a marginal ulcer after gastric bypass present a higher density of gastrin-producing G cells retained in the gastric pouch.


Assuntos
Derivação Gástrica , Obesidade Mórbida , Úlcera Péptica , Humanos , Derivação Gástrica/efeitos adversos , Células Secretoras de Gastrina , Úlcera/complicações , Obesidade Mórbida/cirurgia , Gastrinas , Estudos Retrospectivos , Incidência , Úlcera Péptica/etiologia
9.
JAMA Oncol ; 10(4): 508-515, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38421673

RESUMO

Importance: In women with hormone receptor-positive (HR+) breast cancer, the risk of distant recurrence and death persists for at least 20 years from diagnosis. The risk of late mortality in men with HR+ breast cancer has not been reported. Objective: To report 20-year risks of breast cancer-specific mortality (BCSM) and non-BCSM in men with stage I to III HR+ breast cancer and identify factors associated with late BCSM. Design, Setting, and Participants: An observational cohort study was conducted of men diagnosed with HR+ breast cancer from 1990 to 2008, using population-based data from the Surveillance, Epidemiology, and End Results program. Men diagnosed with stage I to III HR+ breast cancer were included in the analysis. Cumulative incidence function was used to estimate the outcomes of baseline clinicopathologic variables regarding cumulative risk of BCSM and non-BCSM since diagnosis. Smoothed hazard estimates over time were plotted for BCSM. Fine and Gray multivariable regression evaluated the association of preselected variables with BCSM, conditional on having survived 5 years. Main Outcome Measure: BCSM. Results: A total of 2836 men with stage I to III HR+ breast cancer were included, with a median follow-up of 15.41 (IQR, 12.08-18.67) years. Median age at diagnosis was 67 (IQR, 57-76) years. The cumulative 20-year risk of BCSM was 12.4% for stage I, 26.2% for stage II, and 46.0% for stage III. Smoothed annual hazard estimates for BCSM revealed an increase in late hazard rates with each incremental node category, reaching a bimodal distribution in N3 and stage III, with each having peaks in hazard rates at 4 and 11 years. Among patients who survived 5 years from diagnosis, the adjusted BCSM risk was higher for those younger than 50 years vs older than 64 years, those with grade II or III/IV vs grade I tumors, and stage II or III vs stage I disease. Conclusions and Relevance: The findings of this study suggest that, in men with stage I to III HR+ breast cancer, the risk of BCSM persists for at least 20 years and depends on traditional clinicopathologic factors, such as age, tumor stage, and tumor grade. Among men with higher stages of disease, the kinetics of the BCSM risk appear different from the risk that has been reported in women.


Assuntos
Neoplasias da Mama Masculina , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Coortes , Estadiamento de Neoplasias , Neoplasias da Mama Masculina/epidemiologia , Neoplasias da Mama Masculina/genética , Neoplasias da Mama Masculina/mortalidade , Neoplasias da Mama Masculina/patologia , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Medição de Risco , Fatores de Tempo , Programa de SEER
10.
Mol Ther Nucleic Acids ; 35(1): 102132, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38404505

RESUMO

Mutations within mtDNA frequently give rise to severe encephalopathies. Given that a majority of these mtDNA defects exist in a heteroplasmic state, we harnessed the precision of mitochondrial-targeted TALEN (mitoTALEN) to selectively eliminate mutant mtDNA within the CNS of a murine model harboring a heteroplasmic mutation in the mitochondrial tRNA alanine gene (m.5024C>T). This targeted approach was accomplished by the use of AAV-PHP.eB and a neuron-specific synapsin promoter for effective neuronal delivery and expression of mitoTALEN. We found that most CNS regions were effectively transduced and showed a significant reduction in mutant mtDNA. This reduction was accompanied by an increase in mitochondrial tRNA alanine levels, which are drastically reduced by the m.5024C>T mutation. These results showed that mitochondrial-targeted gene editing can be effective in reducing CNS-mutant mtDNA in vivo, paving the way for clinical trials in patients with mitochondrial encephalopathies.

11.
Sci Total Environ ; 919: 170714, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38331276

RESUMO

Duckweeds are widely recognized for their efficiency in the phytoremediation of agricultural and industrial effluents. This study had two main objectives: 1) Implement a Nature-based Solutions (NBS) utilizing the environmental services of duckweeds to improve water quality through phytoremediation in small fish farms; 2) Analysis of duckweeds biomass produced in these fish farms to develop coproducts from a circular economy perspective in family agrisystem in Brazilian Atlantic Forest. The effectiveness of the phytoremediation system was assessed by the reduction of the Trophic State Index (TSI). Phytoremediation in small fish farming NBS was implemented using Clarias gariepinus, employing two different managements approaches: (i) System I - L. minor cultured every 15 days, with biomass harvest and effluent analysis conducted in each cycle over 60 days; (ii) System II - L. minor cultured every 30 days, following a similar cycle and analysis. Additionally, effluent from fish production underwent testing for phytoremediation in a batch system within a climate-controlled laboratory. L. minor demonstrated efficiency in System II, leading to a reduction of the TSI. The dry biomass of the plants emerged as a viable source of amino acid for application in functional foods and feed or nutraceuticals. The findings underscore the potential integration of L. minor into the NBS system and the generation of new co-products from circular production. In addition to its effective phyto- remediation properties, L. minor's dry biomass exhibited appealing characteristics, with elevated levels of crude protein, minerals, fatty acids, and carotenoids. This positions L. minor as a promising candidate for developing bioproducts tailored for functional foods and nutraceuticals. This underscores the potential of duckweeds to produce valuable nutritional compounds beyond their remediation capabilities.


Assuntos
Araceae , Águas Residuárias , Biodegradação Ambiental , Biomassa , Araceae/metabolismo , Agricultura
12.
J Cardiovasc Electrophysiol ; 35(4): 641-650, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38240356

RESUMO

BACKGROUND: Cardioneuroablation (CNA) is a novel therapeutic approach for functional bradyarrhythmias, specifically neurocardiogenic syncope or atrial fibrillation, achieved through endocardial radiofrequency catheter ablation of vagal innervation, obviating the need for pacemaker implantation. Originating in the nineties, the first series of CNA procedures was published in 2005. Extra-cardiac vagal stimulation (ECVS) is employed as a direct method for stepwise denervation control during CNA. OBJECTIVE: This study aimed to compare the long-term follow-up outcomes of patients with severe cardioinhibitory syncope undergoing CNA with and without denervation confirmation via ECVS. METHOD: A cohort of 48 patients, predominantly female (56.3%), suffering from recurrent syncope (5.1 ± 2.5 episodes annually) that remained unresponsive to clinical and pharmacological interventions, underwent CNA, divided into two groups: ECVS and NoECVS, consisting of 34 and 14 cases, respectively. ECVS procedures were conducted with and without atrial pacing. RESULTS: Demographic characteristics, left atrial size, and ejection fraction displayed no statistically significant differences between the groups. Follow-up duration was comparable, with 29.1 ± 15 months for the ECVS group and 31.9 ± 20 months for the NoECVS group (p = .24). Notably, syncope recurrence was significantly lower in the ECVS group (two cases vs. four cases, Log Rank p = .04). Moreover, the Hazard ratio revealed a fivefold higher risk of syncope recurrence in the NoECVS group. CONCLUSION: This study demonstrates that concluding CNA with denervation confirmation via ECVS yields a higher success rate and a substantially reduced risk of syncope recurrence compared to procedures without ECVS confirmation.


Assuntos
Síncope Vasovagal , Humanos , Feminino , Masculino , Síncope Vasovagal/diagnóstico , Síncope Vasovagal/cirurgia , Síncope , Átrios do Coração , Bradicardia/cirurgia , Nervo Vago/cirurgia
13.
RSC Adv ; 14(2): 855-862, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38174271

RESUMO

Copper deficiency can trigger various diseases such as Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease (PD) and even compromise the development of living beings, as manifested in Menkes disease (MS). Thus, the regulated administration (controlled release) of copper represents an alternative to reduce neuronal deterioration and prevent disease progression. Therefore, we present, to the best of our knowledge, the first experimental in vitro investigation for the kinetics of copper release from MOF-74(Cu) and its distribution in vivo after oral administration in male Wistar rats. Taking advantage of the abundance and high periodicity of copper within the crystalline-nanostructured metal-organic framework material (MOF-74(Cu)), it was possible to control the release of copper due to the partial degradation of the material. Thus, we simultaneously corroborated a low accumulation of copper in the liver (the main detoxification organ) and a slight increase of copper in the brain (striatum and midbrain), demonstrating that MOF-74(Cu) is a promising pharmacological alternative (controlled copper source) to these diseases.

14.
Am Surg ; 90(4): 510-517, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38061913

RESUMO

BACKGROUND: Melanoma causes most skin cancer-related deaths, and disparities in mortality persist. Rural communities, compared to urban, face higher levels of poverty and more barriers to care, leading to higher stage at presentation and shorter survival in melanoma. To further evaluate these disparities, we sought to assess the association between rurality and melanoma cause-specific mortality and receipt of recommended surgery in a national cohort. METHODS: Patients with primary non-ocular, cutaneous melanoma from the SEER database, 2000-2017, were included. Outcomes included melanoma-specific survival and receipt of recommended surgery. Rurality was based on Rural-Urban Continuum Codes. Variables included age, sex, race, ethnicity, income, and stage. Multivariate regression models assessed the effect of rurality on survival and receipt of recommended surgery. RESULTS: 103,606 patients diagnosed with non-ocular cutaneous primary melanoma met criteria during this period. 93.3% (n = 96620) were in urban areas and 6.7% (n = 6986) were in rural areas. On multivariate regression controlling for age, sex, race, ethnicity, and stage patients living in a rural area were less likely to receive recommended surgery (aOR .52, 95% CI: .29-.90, P = .02) and had increased hazard of melanoma-specific mortality (aHR 1.19, 95% CI: 1.02-1.40, P = .03) even after additionally controlling for surgery receipt. CONCLUSION: Using a large national cohort, our study found that rural patients were less likely to receive recommended surgery and had shorter melanoma cause-specific survival. Our findings highlight the importance of access to cancer care in rural areas and how this ultimately effects survival for these patients.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/cirurgia , População Rural , Neoplasias Cutâneas/cirurgia , Bases de Dados Factuais , Etnicidade
15.
Am Surg ; 90(4): 866-874, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37972411

RESUMO

BACKGROUND: The role of neoadjuvant chemotherapy (NAC) in advanced sigmoid colon carcinoma remains to be further characterized. Rationale for NAC includes downstaging on final pathology and optimization of microscopically negative margins (R0 resection). We investigated rates of neoadjuvant chemotherapy use in advanced sigmoid colon cancer at academic cancer centers and assessed factors associated with likelihood of NAC administration. METHODS: The National Cancer Database was queried from 2004 to 2017 for patients with clinical T3 or T4, N0-2, M0 sigmoid colon cancer who underwent surgical resection. Those with neoadjuvant radiation or metastatic disease were excluded. The outcomes of patients who did and did not receive neoadjuvant chemotherapy were evaluated for this retrospective cohort study. RESULTS: There were 23,597 patients of whom 364 (1.5%) received NAC. More patients received NAC at academic (41%, P < .001) and high-volume centers (27%, P < .001). Patients with Medicare/Medicaid (39%) and private insurance (52%) were more likely to receive NAC (P < .001). There was a significantly higher rate of N2 to N1 downstaging in the NAC group. Propensity-score matching demonstrated comprehensive community cancer programs (CCCP) were less likely to provide NAC (OR 0.4; 95% CI 0.23, 0.70, P < .001). There was no difference in survival (P = .20), R0 resection (P = .090), or 30-day readmission rates (P = .30) in the NAC cohort compared to the non-NAC cohort. CONCLUSIONS: Access to centers offering multi-disciplinary care with NAC prior to surgical resection is important. This care was associated with academic and high-volume centers and private or government-sponsored insurance. There was no difference in survival between NAC and non-NAC cohort.


Assuntos
Terapia Neoadjuvante , Neoplasias do Colo Sigmoide , Humanos , Idoso , Estados Unidos/epidemiologia , Colo Sigmoide/cirurgia , Pontuação de Propensão , Neoplasias do Colo Sigmoide/tratamento farmacológico , Neoplasias do Colo Sigmoide/cirurgia , Estudos Retrospectivos , Estadiamento de Neoplasias , Medicare
16.
Macromol Biosci ; 24(2): e2300289, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37717210

RESUMO

The treatment of burn wounds remains a clinical challenge due to the need for repeated dressings changes. Therefore, the development of a dressing system that can be atraumatically removed from the wound bed can be considered a breakthrough and improve treatment times. In this work, the development of an injectable, fast-gelling hydrogel is proposed that can change its mechanical properties when exposed to visible light. The hydrogels are prepared by a "click" amino-yne reaction between poly(ethylene glycol) (PEG) functionalized with propiolic acid and the amino groups of poly(ethyleneimine) (PEI). The hydrogels exhibit a fast gelation time, which can be adjusted by changing the weight percentage and molecular weight of the precursors. They also exhibit good swelling ability and adhesion to living tissues. More importantly, their mechanical properties changed upon irradiation with green light. This loss of properties is achieved by a 1 O2 -mediated mechanism, as confirmed by the degradation of the ß-aminoacrylate linker. Moreover, the in vitro cell compatibility results of the hydrogels and their degradation products show good cytocompatibility. Therefore, it is believed that these hydrogels can be considered as materials with great potential for an innovative strategy for the treatment of burn wounds.


Assuntos
Queimaduras , Polietilenoimina , Humanos , Materiais Biocompatíveis , Hidrogéis/farmacologia , Polietilenoglicóis , Luz , Queimaduras/terapia
17.
Am Surg ; 90(4): 739-747, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37902098

RESUMO

BACKGROUND: Crohn's patients' nutritional status can be suboptimal given disease pathophysiology; the effect of a malnourished state prior to elective surgery on post-operative outcomes remains to be more clearly elucidated. This study aims to characterize the effect of malnutrition on post-operative outcomes and readmission patterns for Crohn's patients undergoing elective ileocecectomy using a nationally representative cohort. METHODS: The colectomy-targeted National Surgical Quality Improvement Program Database (2016-2020) was used to identify patients with Crohn's disease without systemic complications who underwent elective ileocecectomy; emergency surgeries were excluded. Malnourished status was defined as pre-operative hypoalbuminemia <3.5 g/dL, weight loss >10% in 6 months, or body mass index <18.5 kg/m2 prior to surgery. RESULTS: Of 1464 patients (56% female) who met inclusion criteria, 1137 (78%) were well-nourished and 327 (22%) were malnourished. Post-operatively, malnourished patients had more organ space surgical site infections (SSI) (9% vs 4% nourished groups, P < .001) and more bleeding events requiring transfusion (9% vs 3% nourished, P < .001). 30-day unplanned readmission was higher in the malnourished group (14% vs 9% nourished, P = .032). Index admission length of stay was significantly longer in the malnourished group (4 days [3-7 days] vs the nourished cohort: 4 days [3-5 days], P < .001). DISCUSSION: Poor nutritional status is associated with organ space infections and bleeding as well as longer hospitalizations and more readmissions in Crohn's patients undergoing elective ileocecectomy. A detailed nutritional risk profile and nutritional optimization is important prior to elective surgery.


Assuntos
Doença de Crohn , Desnutrição , Humanos , Feminino , Masculino , Doença de Crohn/complicações , Doença de Crohn/cirurgia , Ceco/cirurgia , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Desnutrição/complicações , Desnutrição/epidemiologia , Redução de Peso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
18.
Neurobiol Dis ; 190: 106370, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38049013

RESUMO

After spinal cord injury (SCI), infiltrating macrophages undergo excessive phagocytosis of myelin and cellular debris, forming lipid-laden foamy macrophages. To understand their role in the cellular pathology of SCI, investigation of the foamy macrophage phenotype in vitro revealed a pro-inflammatory profile, increased reactive oxygen species (ROS) production, and mitochondrial dysfunction. Bioinformatic analysis identified PI3K as a regulator of inflammation in foamy macrophages, and inhibition of this pathway decreased their lipid content, inflammatory cytokines, and ROS production. Macrophage-specific inhibition of PI3K using liposomes significantly decreased foamy macrophages at the injury site after a mid-thoracic contusive SCI in mice. RNA sequencing and in vitro analysis of foamy macrophages revealed increased autophagy and decreased phagocytosis after PI3K inhibition as potential mechanisms for reduced lipid accumulation. Together, our data suggest that the formation of pro-inflammatory foamy macrophages after SCI is due to the activation of PI3K signaling, which increases phagocytosis and decreases autophagy.


Assuntos
Fosfatidilinositol 3-Quinases , Traumatismos da Medula Espinal , Camundongos , Animais , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Macrófagos/metabolismo , Traumatismos da Medula Espinal/metabolismo , Lipídeos , Medula Espinal/patologia
19.
J Pediatr Surg ; 59(3): 488-493, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37993397

RESUMO

BACKGROUND: Previous studies have shown improved survival for severely injured adult patients treated at American College of Surgeons verified level I/II trauma centers compared to level III and undesignated centers. However, this relationship has not been well established in pediatric trauma centers (PTCs). We hypothesize that severely injured children will have lower mortality at verified level I/II PTCs compared to centers without PTC verification. METHODS: All patients 1-15 years of age with ISS >15 in the 2017-2019 American College of Surgeons Trauma Quality Programs (ACS TQP) dataset were reviewed. Patients with pre-hospital cardiac arrest, burns, and those transferred out for ongoing inpatient care were excluded. Logistic regression models were used to assess the effects of pediatric trauma center verification on mortality. RESULTS: 16,301 patients were identified (64 % male, median ISS 21 [17-27]), and 60 % were admitted to verified PTCs. Overall mortality was 6.0 %. Mortality at centers with PTC verification was 5.1 % versus 7.3 % at centers without PTC verification (p < 0.001). After controlling for injury mechanism, sex, age, pediatric-adjusted shock index (SIPA), ISS, arrival via interhospital transfer, and adult trauma center verification, pediatric level I/II trauma center designation was independently associated with decreased mortality (OR 0.72, 95 % CI 0.61-0.85). CONCLUSIONS: Treatment at ACS-verified pediatric trauma centers is associated with improved survival in critically injured children. These findings highlight the importance of PTC verification in optimizing outcomes for severely injured pediatric patients and should influence trauma center apportionment and prehospital triage. LEVEL OF EVIDENCE: Level IV - Retrospective review of national database.


Assuntos
Centros de Traumatologia , Ferimentos e Lesões , Adulto , Criança , Humanos , Masculino , Feminino , Hospitalização , Mortalidade Hospitalar , Estudos Retrospectivos , Modelos Logísticos , Escala de Gravidade do Ferimento , Ferimentos e Lesões/terapia
20.
J Pediatr Surg ; 59(1): 134-137, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37858390

RESUMO

INTRODUCTION: Cryptorchidism is commonly treated with orchiopexy at 6-12 months of age, often allowing time for undescended testicle(s) (UT) to descend spontaneously. However, when an inguinal hernia (IH) is also present, some surgeons perform orchiopexy and inguinal hernia repair (IHR) immediately rather than delaying surgery. We hypothesize that early surgical intervention provides no benefit for newborns with both IH and UT. METHODS: The Nationwide Readmissions Database was used to identify newborns with diagnoses of both IH and UT from 2010 to 2014. Patients were stratified by management: IHR performed on initial admission (Repair) or not (Deferral). Demographics, outcomes, and complications were compared. Results were weighted for national estimates. RESULTS: We analyzed 1306 newborns (64% premature) diagnosed with both IH and UT. IHR was performed at index admission in 30%. Repair was more common in premature babies (43% vs. 8% full-term, p < 0.001) and patients with congenital anomalies (33% vs. 27% without congenital anomaly, p = 0.012). There was no difference in readmission rates. Repair patients had higher rates of orchiectomy than did Deferral. No Deferral patients were readmitted for bowel resection, and <1% were readmitted for orchiectomy or hernia incarceration. CONCLUSION: In newborns with UT and IH, immediate repair is not associated with improved outcomes. Even with incarceration on initial presentation, rates of readmission with incarceration or bowel compromise for patients who undergo Deferral of surgery are minimal. Moreover, Repair newborns have higher rates of orchiectomy. We found no benefit to early operative intervention; thus, we recommend waiting until 6-12 months of age to reassess for surgery. LEVEL OF EVIDENCE: Level III TYPE OF STUDY: Retrospective Comparative Study.


Assuntos
Criptorquidismo , Hérnia Inguinal , Lactente , Masculino , Humanos , Recém-Nascido , Hérnia Inguinal/complicações , Hérnia Inguinal/cirurgia , Hérnia Inguinal/diagnóstico , Estudos Retrospectivos , Criptorquidismo/complicações , Criptorquidismo/cirurgia , Recém-Nascido Prematuro , Orquidopexia/métodos , Herniorrafia/métodos
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