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1.
J Orthop Surg Res ; 19(1): 244, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38622696

RESUMO

BACKGROUND: Ossification of ligamentum flavum (OLF) is a prevalent degenerative spinal disease, typically causing severe neurological dysfunction. Kruppel-like factor 5 (KLF5) plays an essential role in the regulation of skeletal development. However, the mechanism KLF5 plays in OLF remains unclear, necessitating further investigative studies. METHODS: qRT-PCR, immunofluorescent staining and western blot were used to measure the expression of KLF5. Alkaline Phosphatase (ALP) staining, Alizarin red staining (ARS), and the expression of Runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcin (OCN) were used to evaluate the osteogenic differentiation. Luciferase activity assay and ChIP-PCR were performed to investigate the molecular mechanisms. RESULTS: KLF5 was significantly upregulated in OLF fibroblasts in contrast to normal ligamentum flavum (LF) fibroblasts. Silencing KLF5 diminished osteogenic markers and mineralized nodules, while its overexpression had the opposite effect, confirming KLF5's role in promoting ossification. Moreover, KLF5 promotes the ossification of LF by activating the transcription of Connexin 43 (CX43), and overexpressing CX43 could reverse the suppressive impact of KLF5 knockdown on OLF fibroblasts' osteogenesis. CONCLUSION: KLF5 promotes the OLF by transcriptionally activating CX43. This finding contributes significantly to our understanding of OLF and may provide new therapeutic targets.


Assuntos
Ligamento Amarelo , Ossificação Heterotópica , Humanos , Células Cultivadas , Conexina 43/genética , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Ossificação Heterotópica/genética , Ossificação Heterotópica/metabolismo , Osteogênese/genética , Fatores de Transcrição/metabolismo
2.
World Neurosurg ; 185: e572-e581, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38382761

RESUMO

BACKGROUND: A low prognostic nutritional index (PNI) may reflect malnutrition, which has been associated with poor prognosis in patients with various clinical conditions. The aim of the systematic review and meta-analysis was to investigate the association between preoperative PNI and risk of postoperative complications in adult patients after spine surgery. METHODS: An extensive search was conducted on PubMed, Embase, and Web of Science to identify relevant cohort studies. Random-effects models were employed to combine the findings, taking into account the potential influence of heterogeneity. RESULTS: Ten cohort studies involving 3,249 patients receiving spine surgeries were included. Pooled results showed that a low preoperative prognostic nutritional index (PNI) was associated with an increased risk of overall postoperative complications in these patients (odds ratio [OR]: 1.82, 95% confidence interval [CI]: 1.42 to 2.34, P < 0.001; I2 = 49%). Specifically, a preoperative malnutrition as evidenced by a low PNI was associated with a higher incidence of postoperative delirium (OR: 2.36, 95% CI: 1.52 to 3.66, P < 0.001; I2 = 38%) and surgical site infection (OR: 1.41, 95% CI: 1.15 to 1.73, P = 0.001; I2 = 0%). Sensitivity analyses by excluding one study at a time did not significantly change the results (P all <0.05). CONCLUSIONS: A preoperative low prognostic nutritional index (PNI) may be a risk factor of increased incidence of overall postoperative complications, postoperative delirium, and surgical site infection in adult patients after spine surgeries.


Assuntos
Avaliação Nutricional , Complicações Pós-Operatórias , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Desnutrição , Fatores de Risco , Coluna Vertebral/cirurgia
3.
Eur J Cardiothorac Surg ; 64(5)2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37713465

RESUMO

OBJECTIVES: Sublobar resection, including wedge resection and segmentectomy, is non-inferior to lobectomy in early-stage non-small cell lung cancer treatment. We aimed to compare the risk of postoperative cognitive dysfunction (POCD) between sublobar resection and lobectomy. METHODS: We conducted a prospective cohort study. Patients with sublobar resection or lobectomy were divided into the sublobar group or the lobar group, respectively. Cognition was assessed before and after surgery with Montreal Cognitive Assessment and Minimum Mental State Examination tests. POCD is defined as Z score of Montreal Cognitive Assessment change ≤-1.96. Propensity score matching (PSM) was performed to make demographics well-balanced between the 2 groups. RESULTS: A total of 335 patients were enrolled. Both the postoperative 1-day POCD rate (sublobar 5.5% vs lobar 18.2%, P < 0.001) and the postoperative 1-month POCD rate (sublobar 7.9% vs lobar 21.8%, P < 0.001) were significantly lower in the sublobar group compared with lobar group, with demographics unbalanced between the 2 groups. In the 133 demographics-matched pairs obtained by PSM, both the postoperative 1-day POCD rate (sublobar 5.3% vs lobar 17.3%, P = 0.005) and the postoperative 1-month POCD rate (sublobar 8.3% vs lobar 18.8%, P = 0.018) remained significantly lower in the sublobar group than in the lobar group. The incidences of postoperative 1-day (P = 0.109) and postoperative 1-month (P = 0.026) Minimum Mental State Examination abnormity were also lower in the sublobar group than in the lobar group but only the latter was with statistical significance after PSM. CONCLUSIONS: Sublobar resection has an advantage over lobectomy in preventing POCD. Our findings might be a reference for selecting the most suitable type of resection for non-small-cell lung cancer patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Complicações Cognitivas Pós-Operatórias , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Complicações Cognitivas Pós-Operatórias/cirurgia , Estudos Prospectivos , Pneumonectomia , Estudos Retrospectivos , Estadiamento de Neoplasias
4.
Colloids Surf B Biointerfaces ; 216: 112592, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35636327

RESUMO

Oral administration of peptides/proteins with superior efficacy and fewer side effects is the most advantageous route of administration. In this study, we utilized controllable enzymatic (animal protease) hydrolysis technology to prepare active polypeptide self-assembling supramolecular (APs) from marine shellfish meat to explore the functional mechanism of APs in in vitro and in vivo (oral administration) experiments . In vitro experiments revealed that APs with self-assembly tendency had multifunctional activities. In vivo experiments indicated that oral administration of naturally safe APs could inhibited inflammation, promoted fibroblast proliferation and revascularization, and accelerated the epithelialization process, thus favoring a balanced repair tissue collagen I/III ratio and the promotion of hair follicle regeneration to achieve scarless healing, which was also relevant to "skin-gut" axis. These results showed that APs, as demonstrated in this study, promoted dermal wound healing in mice and may be developed and used to treat skin wounds.


Assuntos
Pele , Cicatrização , Animais , Folículo Piloso , Camundongos , Peptídeos/farmacologia , Frutos do Mar , Pele/lesões
5.
Clin Gastroenterol Hepatol ; 20(8): 1748-1756.e11, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-33823291

RESUMO

BACKGROUND & AIMS: Cow's milk protein (CMP) is the most common trigger of inflammation in children and adults with eosinophilic esophagitis (EoE). We sought to assess the clinical, endoscopic, and histologic efficacy of dietary elimination of all CMP-containing foods in EoE. METHODS: We performed a prospective observational study in children with EoE treated with the 1-food elimination diet (1FED), excluding all CMP. Children and their caretakers were educated by a registered dietitian regarding dietary elimination of all CMP-containing foods, with substitutions to meet nutritional needs for optimal growth and development, and daily meal planning. Upper endoscopy with biopsies was performed after 8 to 12 weeks of treatment. The primary end point was histologic remission, defined as fewer than 15 eosinophils per high-power field. Secondary end points were symptomatic, endoscopic, and quality-of-life (QOL) improvements. RESULTS: Forty-one children (76% male; ages, 9 ± 4 years; 88% white) underwent 1FED education and post-treatment endoscopy with biopsies. Histologic remission occurred in 21 (51%) children, with a decrease in peak eosinophils per high-power field from a median of 50 (interquartile range, 35-70) to a median of 1 (interquartile range, 0-6; P < .0001). Endoscopic abnormalities improved in 24 (59%) patients, while symptoms improved in 25 (61%). Improved symptoms included chest pain, dysphagia, and pocketing/spitting out food. Parents perceived worse QOL, while children perceived improved QOL with the 1FED. CONCLUSIONS: One-food elimination of CMP-containing foods from the diet induced histologic remission in more than 50% of children with EoE and led to significant improvement in symptoms and endoscopic abnormalities. The ease of implementation and adherence supports the 1FED as first-line dietary treatment.


Assuntos
Esofagite Eosinofílica , Animais , Bovinos , Feminino , Humanos , Masculino , Alérgenos , Dieta , Endoscopia Gastrointestinal , Esofagite Eosinofílica/patologia , Qualidade de Vida
6.
J Clin Med ; 10(24)2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34945137

RESUMO

BACKGROUND: Recurrent stress urinary incontinence (SUI) following male sling can be managed surgically with artificial urinary sphincter (AUS) insertion. Prior small, single-center retrospective studies have not demonstrated an association between having failed a sling procedure and worse AUS outcomes. The aim of this study was to compare outcomes of primary AUS placement in men who had or had not undergone a previous sling procedure. METHODS: A retrospective review of all AUS devices implanted at a single academic center during 2000-2018 was performed. After excluding secondary AUS placements, revision and explant procedures, 135 patients were included in this study, of which 19 (14.1%) patients had undergone prior sling procedures. RESULTS: There was no significant difference in demographic characteristics between patients undergoing AUS placement with or without a prior sling procedure. Average follow up time was 28.0 months. Prior sling was associated with shorter overall device survival, with an increased likelihood of requiring revision or replacement of the device (OR 4.2 (1.3-13.2), p = 0.015) as well as reoperation for any reason (OR 3.5 (1.2-9.9), p = 0.019). While not statistically significant, patients with a prior sling were more likely to note persistent incontinence at most recent follow up (68.8% vs. 42.7%, p = 0.10). CONCLUSIONS: Having undergone a prior sling procedure is associated with shorter device survival and need for revision or replacement surgery. When considering patients for sling procedures, patients should be counseled regarding the potential for worse AUS outcomes should they require additional anti-incontinence procedures following a failed sling.

7.
Anesth Analg ; 133(5): 1187-1196, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34319914

RESUMO

BACKGROUND: Asymptomatic brain ischemic injury detected with diffusion-weighted magnetic resonance imaging (DWI) is reported in more than one-half of patients after cardiac surgery. There are conflicting findings on whether DWI-detected covert stroke is associated with neurocognitive dysfunction after surgery, and it is unclear whether such ischemic injury affects quality of life or behavioral outcomes. The purpose of this study was to perform exploratory analysis on whether covert stroke after cardiac surgery is associated with delayed neurocognitive recovery 1 month after surgery, impaired quality of life, anxiety, or depression. METHODS: Analysis of data collected in a prospectively randomized study in patients undergoing cardiac surgery testing whether basing mean arterial pressure (MAP) targets during cardiopulmonary bypass to be above the lower limit of cerebral autoregulation versus usual practices reduces the frequency of adverse neurological outcomes. A neuropsychological testing battery was administered before surgery and then 1 month later. Patients underwent brain magnetic resonance imaging (MRI) between postoperative days 3 and 5. The primary outcome was DWI-detected ischemic lesion; the primary end point was change from baseline in domain-specific neurocognitive Z scores 1 month after surgery. Secondary outcomes included a composite indicator of delayed neurocognitive recovery, quality of life measures, state and trait anxiety, and Beck Depression Inventory scores. RESULTS: Of the 164 patients with postoperative MRI data, clinical stroke occurred in 10 patients. Of the remaining 154 patients, 85 (55.2%) had a covert stroke. There were no statistically significant differences for patients with or without covert stroke in the change from baseline in Z scores in any of the cognitive domains tested adjusted for sex, baseline cognitive score, and randomization treatment arm. The frequency of delayed neurocognitive recovery (no covert stroke, 15.1%; covert stroke, 17.6%; P = .392), self-reported quality of life measurements, anxiety rating, or depression scores were not different between those with or without DWI ischemic injury. CONCLUSIONS: More than one-half of patients undergoing cardiac surgery demonstrated covert stroke. In this exploratory analysis, covert stroke was not found to be significantly associated with neurocognitive dysfunction 1 month after surgery; evidence of impaired quality of life, anxiety, or depression, albeit a type II error, cannot be excluded.


Assuntos
Ansiedade/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Depressão/etiologia , Transtornos Neurocognitivos/etiologia , Acidente Vascular Cerebral/etiologia , Idoso , Ansiedade/diagnóstico , Ansiedade/psicologia , Doenças Assintomáticas , Circulação Cerebrovascular , Bases de Dados Factuais , Depressão/diagnóstico , Depressão/psicologia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/psicologia , Testes Neuropsicológicos , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
8.
Carcinogenesis ; 42(9): 1143-1153, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34170291

RESUMO

More and more studies indicated that extracellular vesicles (EVs) carrying miRNAs have been potential biomarkers of various cancers including colorectal cancer (CRC). This study aims to explore the function of miR-224-5p carried by EVs derived from cancer-associated fibroblasts (CAFs) in CRC. Here, we found that miR-224-5p was highly expressed while SLC4A4 was lowly expressed in CRC cells. Moreover, dual-luciferase reporter gene assay testified that miR-224-5p targeted SLC4A4. The expression of miR-224-5p in CAFs-derived EVs was found to be elevated. It was also testified that CAFs-derived EVs could transfer miR-224-5p into CRC cells. miR-224-5p in CAFs-derived EVs facilitated the proliferation, migration, invasion and anti-apoptosis of CRC cells. Overexpressing miR-224-5p increased the proliferative, migratory and invasive abilities of CRC cells and inhibit CRC cell apoptosis, while overexpressing SLC4A4 caused the opposite result. Research in vitro and in vivo further indicated that miR-224-5p promoted CRC cell progression via binding to its downstream target gene SLC4A4. Rescue assay also demonstrated that overexpressing miR-224-5p reversed the inhibitory effect of overexpressed SLC4A4 on cancer cell growth. In addition, in vivo assay identified that high level of miR-224-5p promoted the growth of cancer cells in mice in vivo. In conclusion, we explored the effect of miR-224-5p in CRC, which helps for further exploration of new methods for CRC targeted therapy.


Assuntos
Fibroblastos Associados a Câncer/metabolismo , Neoplasias Colorretais/patologia , Vesículas Extracelulares/metabolismo , MicroRNAs/metabolismo , Neoplasias/patologia , Simportadores de Sódio-Bicarbonato/metabolismo , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/metabolismo , Células HCT116 , Humanos , Invasividade Neoplásica
9.
South Med J ; 114(6): 344-349, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34075425

RESUMO

OBJECTIVES: To evaluate whether an institutionally created video-based educational module will improve obstetrics and gynecology residents' understanding of surgical anatomy and principles for performing abdominal hysterectomy. Secondary aims included evaluating the trainees' confidence levels and perceptions before and after the educational experience and ultimately implementing the module into the program curriculum, if successful. METHODS: In this prospective study, postgraduate obstetrics and gynecology resident physicians (n = 27) at the McGaw Medical Center of Northwestern University were assigned to watch an institutionally created video-based educational module on abdominal hysterectomy before the start of their gynecologic oncology rotation. A knowledge assessment and a postmodule survey were given to participants immediately following the module and repeated at the end of the 4-week rotation. RESULTS: Participants reported a median rating of 4 (n = 21, interquartile range 4-4) on a 5-point Likert scale when asked to rate the quality of the module. The module also was rated as equally effective both immediately after watching the module and after completing their gynecologic oncology rotation (median 4, interquartile range 3-4 at both times; p = 0.299, Wilcoxon signed rank test). Overall trends revealed that the video module had a greater impact on knowledge of surgical anatomy than on self-reported surgical skills and that postgraduate year 2 and postgraduate year 3 residents benefited more from the intervention. CONCLUSIONS: A video module can be a high-quality and effective educational tool for teaching the surgical principles, anatomy, and steps to perform abdominal hysterectomy to obstetrics and gynecology residents.


Assuntos
Currículo/tendências , Histerectomia/educação , Internato e Residência/normas , Adulto , Educação de Pós-Graduação em Medicina/métodos , Educação de Pós-Graduação em Medicina/normas , Educação de Pós-Graduação em Medicina/estatística & dados numéricos , Feminino , Ginecologia/educação , Humanos , Histerectomia/métodos , Internato e Residência/métodos , Internato e Residência/estatística & dados numéricos , Masculino , Obstetrícia/educação , Gravidez , Estudos Retrospectivos , Inquéritos e Questionários , Gravação de Videoteipe/normas , Gravação de Videoteipe/estatística & dados numéricos
10.
J Adolesc Health ; 68(6): 1135-1141, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33849759

RESUMO

PURPOSE: The purpose of this study was to determine the existence and strength of association between chest dysphoria and mental health in transmasculine and nonbinary adolescents. METHODS: This is a cross-sectional cohort study of transmasculine and nonbinary adolescents designated female at birth between 12 and 18 years old. None had undergone prior top surgery. Patients complete the Chest Dysphoria Measure and Youth Inventory-4 (YI-4) upon presentation to our institution. Outcomes were retrospectively reviewed. The primary outcome of interest was the association between chest dysphoria and anxiety and depression symptom severity, as measured by the YI-4. RESULTS: One hundred fifty-six patients met inclusion criteria. Mean age was 15.3 years (standard deviation [SD] = 1.7). Most patients identified as transmasculine (n = 132); 18 identified as nonbinary and 6 as questioning. Mean (SD) YI-4 symptom severity scores were 10.67 (6.64) for anxiety and 11.99 (7.83) for depression. Mean (SD) Chest Dysphoria Measure composite score was 30.15 (9.95); range 2-49. Chest dysphoria was positively correlated with anxiety (r = .146; p = .002) and depression (r = .207; p < .001). In multivariate linear regression models, chest dysphoria showed a significant, positive association with anxiety and depression, after accounting for gender dysphoria, degree of appearance congruence, and social transition status. CONCLUSIONS: Chest dysphoria is associated with higher anxiety and depression in transmasculine and nonbinary adolescents designated female at birth. This association is independent of level of gender dysphoria, degree of appearance congruence, and social transition status. Treatment options aimed at alleviating chest dysphoria should be made accessible to adolescents and tailored to individual needs.


Assuntos
Depressão , Pessoas Transgênero , Adolescente , Ansiedade/epidemiologia , Criança , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Recém-Nascido , Estudos Retrospectivos
11.
J Urol ; 205(4): 1180-1188, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33207136

RESUMO

PURPOSE: Kidney dysfunction in spina bifida is usually detected by low estimated glomerular filtration rate or ultrasound based hydronephrosis. We assessed the diagnostic test characteristics of hydronephrosis for detecting low estimated glomerular filtration rate, hypothesizing that hydronephrosis has low sensitivity compared to cystatin C based estimated glomerular filtration rate. MATERIALS AND METHODS: We conducted a single center, retrospective cohort study, including patients with spina bifida from 2012-2017 with 2 kidneys and complete data needed to calculate estimated glomerular filtration rate via multiple pediatric (age 1-17.9 years) or adult (age ≥18 years) estimating equations. We evaluated the association of hydronephrosis status (high grade, low grade or none) with estimated glomerular filtration rate, adjusting for small kidney size and scarring, and calculated diagnostic test characteristics of hydronephrosis for low estimated glomerular filtration rate. RESULTS: We analyzed 247 patients (176 children and 71 adults). Mean±SD age was 13.7±6.6 years, and 81% of patients had myelomeningocele. Hydronephrosis (77% low grade) was found in 35/176 children and 18/71 adults. Hydronephrosis was associated with low estimated glomerular filtration rate in stepwise fashion, independent of kidney size and scarring. However, across cystatin C based pediatric equations, any hydronephrosis (compared to none) had 23%-48% sensitivity, and high grade hydronephrosis (compared to none or low grade) had 4%-15% sensitivity for estimated glomerular filtration rate <90 ml/min/1.73 m2, which remained unchanged after excluding small kidneys and scarring. Across cystatin C based adult equations, any and high grade hydronephrosis had 55%-75% and 40%-100% sensitivity, respectively, for estimated glomerular filtration rate <90 ml/min/1.73 m2, although with wide confidence intervals. Specificity was higher with high grade vs any hydronephrosis. Sensitivities were higher for estimated glomerular filtration rate <60 ml/min/1.73 m2. CONCLUSIONS: Hydronephrosis was associated with low estimated glomerular filtration rate but had poor sensitivity for cystatin C based estimated glomerular filtration rate <90 ml/min/1.73 m2, especially among children with spina bifida.


Assuntos
Taxa de Filtração Glomerular , Hidronefrose/diagnóstico por imagem , Hidronefrose/etiologia , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/etiologia , Disrafismo Espinal/complicações , Ultrassonografia/métodos , Adolescente , Adulto , Biomarcadores/sangue , Criança , Pré-Escolar , Cistatina C/sangue , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos
12.
Proc Natl Acad Sci U S A ; 117(46): 28980-28991, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33139544

RESUMO

More than 70% of Epstein-Barr virus (EBV)-negative Hodgkin lymphoma (HL) cases display inactivation of TNFAIP3 (A20), a ubiquitin-editing protein that regulates nonproteolytic protein ubiquitination, indicating the significance of protein ubiquitination in HL pathogenesis. However, the precise mechanistic roles of A20 and the ubiquitination system remain largely unknown in this disease. Here, we performed high-throughput CRISPR screening using a ubiquitin regulator-focused single-guide RNA library in HL lines carrying either wild-type or mutant A20. Our CRISPR screening highlights the essential oncogenic role of the linear ubiquitin chain assembly complex (LUBAC) in HL lines, which overlaps with A20 inactivation status. Mechanistically, LUBAC promotes IKK/NF-κB activity and NEMO linear ubiquitination in A20 mutant HL cells, which is required for prosurvival genes and immunosuppressive molecule expression. As a tumor suppressor, A20 directly inhibits IKK activation and HL cell survival via its C-terminal linear-ubiquitin binding ZF7. Clinically, LUBAC activity is consistently elevated in most primary HL cases, and this is correlated with high NF-κB activity and low A20 expression. To further understand the complete mechanism of NF-κB activation in A20 mutant HL, we performed a specifically designed CD83-based NF-κB CRISPR screen which led us to identify TAK1 kinase as a major mediator for NF-κB activation in cells dependent on LUBAC, where the LUBAC-A20 axis regulates TAK1 and IKK complex formation. Finally, TAK1 inhibitor Takinib shows promising activity against HL in vitro and in a xenograft mouse model. Altogether, these findings provide strong support that targeting LUBAC or TAK1 could be attractive therapeutic strategies in A20 mutant HL.


Assuntos
Doença de Hodgkin/genética , Doença de Hodgkin/metabolismo , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/metabolismo , Ubiquitina/metabolismo , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Xenoenxertos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , NF-kappa B/metabolismo , Ligação Proteica , Transdução de Sinais , Proteína 3 Induzida por Fator de Necrose Tumoral alfa , Ubiquitinação
13.
Urology ; 145: 127-133, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32882305

RESUMO

OBJECTIVE: To determine predictive factors for antimicrobial resistance patterns and to develop an antimicrobial treatment algorithm for afebrile outpatients presenting with complicated cystitis. MATERIALS AND METHODS: We performed a retrospective, single-center, cross-sectional study of 2,891 outpatients with a diagnosed afebrile complicated cystitis from 2012 to 2018. For patients with confirmed urinary tract infection and antimicrobial sensitivities, univariate analyses and multivariable regression models were used to determine odds ratios for predicting resistance to trimethoprim-sulfamethoxazole, ciprofloxacin, nitrofurantoin, first-generation cephalosporin, and third-generation cephalosporin for the 2012-2016 data. Antimicrobial choice algorithms were created using 2012-2016 results and tested on 2017-2018 data. RESULTS: For afebrile outpatients presenting with complicated cystitis, overall prevalence of resistance for trimethoprim-sulfamethoxazole, ciprofloxacin, nitrofurantoin, first-generation cephalosporin, and third-generation cephalosporin was 25.6%, 19.5%, 19.1%, 15.0%, and 6.9%, respectively. Consistent predictive factors influencing resistance to all 5 antimicrobials were patient place of residence (ZIP code), status of host urinary tract (complicated vs uncomplicated), and prior resistance to the antimicrobial. Resulting treatment algorithm for complicated cystitis (whether or not prior microbiologic data was available) outperformed real-life provider choice and our previously published algorithm for uncomplicated cystitis. CONCLUSION: Treatment algorithms for urinary tract infections are dependent on patient place of residence (ZIP code), status of the host urinary tract (complicated or uncomplicated), and prior urine culture resistance data. When using our complicated cystitis treatment algorithm regardless of uropathogen, our results outperformed real-life scenario provider choice and our prior published algorithm for uncomplicated cystitis, which can help guide empiric antimicrobial choice.


Assuntos
Assistência Ambulatorial/métodos , Antibacterianos/uso terapêutico , Cistite/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Adulto , Algoritmos , Antibacterianos/farmacologia , Estudos Transversais , Cistite/complicações , Cistite/diagnóstico , Cistite/microbiologia , Farmacorresistência Bacteriana , Feminino , Geografia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos , Sistema Urinário/microbiologia , Infecções Urinárias/complicações , Infecções Urinárias/diagnóstico , Infecções Urinárias/microbiologia , Adulto Jovem
14.
Clin Cancer Res ; 26(15): 4093-4106, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32299816

RESUMO

PURPOSE: For patients with refractory/relapsed Hodgkin lymphoma (roughly 20% of total cases), few effective therapeutic options exist. Currently, brentuximab vedotin (BV), a drug-conjugated anti-CD30 antibody, is one of the most effective approved therapy agents for these patients. However, many patients do not achieve complete remission and ultimately develop BV-resistant disease, necessitating a more detailed understanding of the molecular circuitry that drives BV sensitivity and the mechanism of BV resistance. EXPERIMENTAL DESIGN: Here, we established a ubiquitin regulator-focused CRISPR library screening platform in Hodgkin lymphoma and carried out a drug sensitization screen against BV to identify genes regulating BV treatment sensitivity. RESULTS: Our CRISPR library screens revealed the ubiquitin-editing enzymes A20 and RBX1 as key molecule effectors that regulate BV sensitivity in Hodgkin lymphoma line L428. A20 negatively regulates NF-κB activity which is required to prevent BV cytotoxicity. In line with these results, the RNA-seq analysis of the BV-resistant single-cell clones demonstrated a consistent upregulation of NF-κB signature genes, as well as the ABC transporter gene ABCB1. Mechanically, NF-κB regulates BV treatment sensitivity through mediating ABCB1 expression. Targeting NF-κB activity synergized well with BV in killing Hodgkin lymphoma cell lines, augmented BV sensitivity, and overcame BV resistance in vitro and in Hodgkin lymphoma xenograft mouse models. CONCLUSIONS: Our identification of this previously unrecognized mechanism provides novel knowledge of possible BV responsiveness and resistance mechanisms in Hodgkin lymphoma, as well as leads to promising hypotheses for the development of therapeutic strategies to overcome BV resistance in this disease.


Assuntos
Brentuximab Vedotin/farmacologia , Proteínas de Transporte/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Doença de Hodgkin/tratamento farmacológico , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Animais , Brentuximab Vedotin/uso terapêutico , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Doença de Hodgkin/genética , Humanos , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , RNA-Seq , Indução de Remissão , Ubiquitinação/genética , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
15.
World J Urol ; 38(5): 1295-1301, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31332512

RESUMO

PURPOSE: Patients often receive antibiotic prophylaxis after urethroplasty to minimize the risk of urinary tract infection (UTI). The aim of this study was to determine the frequency of UTIs after urethroplasty and its impact on urethral and incisional healing. METHODS: Patients undergoing urethroplasty by a single surgeon from 2000 to 2012 were retrospectively reviewed. All patients received preoperative antibiotic prophylaxis and postoperative prophylaxis for 30 days or until catheter removal. We reviewed urine cultures obtained within 30 days after urethroplasty in symptomatic patients, and rates of stricture recurrence and wound complications. A positive culture was defined as > 1000 cfu/mL of an organism. RESULTS: 398 patients were included with a mean age of 43.5 years at time of surgery. We identified 102 positive urine cultures (25.6%) within 30 days of urethroplasty. 78 stricture recurrences (19.6%) occurred at an average of 3 years after surgery and 18 (4.5%) experienced a wound complication, with a 52 month mean follow-up. There were no significant differences in stricture recurrence (p = 0.36) or wound complications (p = 0.42) between patients who had a positive and negative urine culture. On multivariate analysis, positive urine cultures (HR 1.0, 95% CI 0.6-1.8, p = 0.88) were not associated with stricture recurrence, while lichen sclerosis (HR 3.2, 95% CI 1.1-9.2, p = 0.03) and previous urethroplasty (HR 2.3, 95% CI 1.1-4.6, p = 0.03) were. CONCLUSION: Bacterial colonization and UTIs despite antimicrobial prophylaxis are common in urethroplasty patients. This, however, does not appear to impair urethral healing or influence wound healing, suggesting that postoperative prophylaxis may in fact offer no benefit.


Assuntos
Antibioticoprofilaxia , Uretra/cirurgia , Estreitamento Uretral/cirurgia , Infecções Urinárias/prevenção & controle , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento , Procedimentos Cirúrgicos Urológicos Masculinos/métodos
16.
Zhonghua Wei Chang Wai Ke Za Zhi ; 20(8): 919-922, 2017 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-28836255

RESUMO

OBJECTIVE: To study the management for the perineal incision after laparoscopic-assisted abdominoperineal resection for rectal cancer. METHODS: Clinical data of 87 patients undergoing laparoscopic Miles operation for lower rectal cancer from June 2009 to February 2014 were collected and studied. Presacral space drainage group: presacral space drainage tube was applied in 42 patients. Combined drainage group: presacral space drainage tube combined with subcutaneous vacuum pressure suction was applied in 45 cases. In combined drainage group, except the presacral drainage tube, another drainage tube was placed subcutaneously and connected to a negative pressure ball, which was fixed on the lateral anterior of perineal wound by the further incision and drainage. After subcutaneous tube was placed for 2 weeks, as drainage fluid was limpid and <15 ml/d for 3 days, meanwhile no obvious pelvic fluid was detected by ultrasound, and the wound healed quite well without redness and edema, then the subcutaneous tube with the negative pressure ball could be removed. RESULTS: There were 51 males and 36 females with the mean age of 26-78(56.9±10.8) years old. The laparoscopic Miles operation was successfully completed in all the cases without death and complications. The drainage tube was placed for 4-13(8.0±2.5) days in presacral space drainage group, and for 4-14(6.7±2.4) days in combined drainage group. The subcutaneous tube was placed for 14-24(15.8±3.0) days. The primary healing rate of perineal wound in presacral space drainage group and combined drainage group was 66.7%(28/42) and 91.1%(41/45) respectively, while the perineal wound infection rate was 21.4%(9/42) and 4.4%(2/45) respectively, whose differences between two groups were both significant (χ2=7.911, P=0.005 and χ2=5.674, P=0.017). CONCLUSION: Presacral space drainage tube combined with subcutaneous vacuum pressure suction in laparoscopic-assisted abdominoperineal resection for rectal cancer has better efficacy and lower infection rate for perineal incision, which is worth wide application.


Assuntos
Drenagem/instrumentação , Tratamento de Ferimentos com Pressão Negativa/métodos , Protectomia/instrumentação , Neoplasias Retais/cirurgia , Adulto , Idoso , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Tratamento de Ferimentos com Pressão Negativa/instrumentação , Pelve/cirurgia , Períneo/cirurgia , Protectomia/métodos , Sucção , Vácuo
17.
Radiat Prot Dosimetry ; 158(4): 479-86, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24214908

RESUMO

After the Fukushima nuclear accident, there is a widespread concern over the radioactive contamination of the marine environment. To protect non-human species, a radiation dose rate calculation model for Western Pacific marine species was established. Ten kinds of marine species in the Western Pacific were modelled by Geant4 for Monte Carlo simulation. Organisms were modelled with two ellipsoids: one represented organs and the other represented muscle. The enhanced dose rates by 10 main kinds of nuclides were calculated. According to the reported activities of three main nuclides ((134)Cs, (137)Cs and (131)I) in seawater near Fukushima coastal, the radiation risks of marine species were estimated. The results showed that the marine species near the Fukushima accident drain outlets might be at risk. But organisms that were >15 km away from the drain outlets were relatively safe.


Assuntos
Acidente Nuclear de Fukushima , Monitoramento de Radiação/métodos , Radioisótopos/análise , Poluentes Radioativos da Água/análise , Algoritmos , Animais , Radioisótopos de Césio/análise , Método de Monte Carlo , Oceano Pacífico , Liberação Nociva de Radioativos , Risco , Água do Mar , Software
18.
Cancer Chemother Pharmacol ; 71(4): 921-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23355039

RESUMO

PURPOSE: To study the correlation between expression levels of ERCC1/TS mRNA and the susceptibility of preoperative chemotherapy for patients with gastric cancer. METHODS: A total of forty cases with advanced gastric cancer of T3-4N1-2M0 were treated with preoperative chemotherapy according to FLEEOX regimen based on endarterial-intravenous coadministration. Sufficient, fresh gastric tissue specimens were obtained with the help of gastroscope, and the expression levels of ERCC1/TS mRNA were detected by qRT-PCR before chemotherapy. The chemotherapeutic response was evaluated with Choi Criteria after chemotherapy, and pathologic remission extent was observed after surgery. The correlation between the expression levels of ERCC1/TS mRNA before chemotherapy and the chemotherapeutic effect based on imageology and pathology was analyzed. RESULTS: The response rate of Chemotherapy in this cohort was 80.0 % based on imageology and 51.43 % based on pathology. The expression levels of ERCC1/TS mRNA were significantly associated with imageology remission extent (P = 0.033, P = 0.025) and pathologic remission extent (P = 0.044, P = 0.016), respectively. The chemotherapeutic effect on patients with low-expression levels of ERCC1/TS mRNA was better. CONCLUSIONS: From the perspective of pathology and imageology evaluating the preoperative chemotherapeutic response for patients with gastric cancer, ERCC1 and TS were used as the molecular predictors and provided prognostic information in this study.


Assuntos
Proteínas de Ligação a DNA/genética , Endonucleases/genética , RNA Mensageiro/análise , Neoplasias Gástricas/tratamento farmacológico , Timidilato Sintase/genética , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios X
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