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2.
Anesthesiology ; 141(2): 300-312, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38700459

RESUMO

BACKGROUND: Propofol is a widely used intravenous hypnotic. Dosing is based mostly on weight, with great interindividual variation in consumption. Suggested factors affecting propofol requirements include age, sex, ethnicity, anxiety, alcohol consumption, smoking, and concomitant valproate use. Genetic factors have not been widely explored. METHODS: This study considered 1,000 women undergoing breast cancer surgery under propofol and remifentanil anesthesia. Depth of anesthesia was monitored with State Entropy (GE Healthcare, Finland). Propofol requirements during surgery were recorded. DNA from blood was genotyped with a genome-wide array. A multivariable linear regression model was used to assess the relevance of clinical variables and select those to be used as covariates in a genome-wide association study. Imputed genotype data were used to explore selected loci further. In silico functional annotation was used to explore possible consequences of the discovered genetic variants. Additionally, previously reported genetic associations from candidate gene studies were tested. RESULTS: Body mass index, smoking status, alcohol use, remifentanil dose (ln[mg · kg-1 · min-1]), and average State Entropy during surgery remained statistically significant in the multivariable model. Two loci reached genome-wide significance (P < 5 × 10-8). The most significant associations were for single-nucleotide polymorphisms rs997989 (30 kb from ROBO3), likely affecting expression of another nearby gene, FEZ1, and rs9518419, close to NALCN (sodium leak channel); rs10512538 near KCNJ2 encoding the Kir2.1 potassium channel showed suggestive association (P = 4.7 × 10-7). None of these single-nucleotide polymorphisms are coding variants but possibly affect the regulation of nearby genes. None of the single-nucleotide polymorphisms previously reported as affecting propofol pharmacokinetics or pharmacodynamics showed association in the data. CONCLUSIONS: In this first genome-wide association study exploring propofol requirements, This study discovered novel genetic associations suggesting new biologically relevant pathways for propofol and general anesthesia. The roles of the gene products of ROBO3/FEZ1, NALCN, and KCNJ2 in propofol anesthesia warrant further studies.


Assuntos
Anestésicos Intravenosos , Estudo de Associação Genômica Ampla , Propofol , Humanos , Estudo de Associação Genômica Ampla/métodos , Propofol/administração & dosagem , Feminino , Pessoa de Meia-Idade , Anestésicos Intravenosos/administração & dosagem , Adulto , Idoso , Relação Dose-Resposta a Droga , Polimorfismo de Nucleotídeo Único/genética
3.
J Stud Alcohol Drugs ; 85(3): 296-305, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38206664

RESUMO

OBJECTIVE: Characterization of population subgroups based on where they acquire cannabis is unexplored. We examine relationships between sociodemographic characteristics, cannabis use modality, risky cannabis use, and source of cannabis. METHOD: Analyzing a representative sample (unweighted n = 8,089) of U.S. adults living in medical cannabis-permitting states with past-year cannabis use from the 2021 National Survey on Drug Use and Health, we determined source of last cannabis used. Outcome groups were purchased from a dispensary, purchased from another source, or nonpurchased source. Incorporating the complex survey design, descriptive statistics and adjusted multinomial logistic regressions evaluated associations between sociodemographic, individual cannabis use characteristics, and source of cannabis. Secondary analyses described cannabis purchasing characteristics among the subsample who last purchased cannabis. RESULTS: Purchasing from a dispensary was the most common source of cannabis (42.5%). Significant relationships between sociodemographic characteristics, cannabis use modality, risky cannabis use, and source of cannabis were found. Recent cannabis initiates and those with cannabis vaporizer use had an increased likelihood of purchasing cannabis from a dispensary. Purchasing from a nondispensary source was most likely among those with daily cannabis use, past-month blunt use, past-year driving under the influence, cannabis use disorder, and cannabis and alcohol co-use. Among those purchasing cannabis, joints and other forms of cannabis were more likely to be purchased from a dispensary than purchased from other sources. CONCLUSIONS: We identified key sociodemographic and cannabis use characteristics that may influence where individuals obtain cannabis, which are important for cannabis behavior surveillance and cannabis use prevention and intervention strategies to consider.


Assuntos
Cannabis , Fatores Sociodemográficos , Humanos , Adulto , Estados Unidos/epidemiologia , Masculino , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Fumar Maconha/epidemiologia , Maconha Medicinal , Uso da Maconha/epidemiologia , Comércio/estatística & dados numéricos , Fatores Socioeconômicos , Idoso
5.
Glob Med Genet ; 10(4): 345-347, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38025191

RESUMO

In the clinical practice, it is not common for pediatricians to visit children with overgrowth phenotype. When it happens, it is important to focus on the age of manifestations and research the pathogenic causes using appropriate genetic test. Cowden syndrome is one of these rare causes; it is an autosomal dominant genodermatosis characterized by multiple hamartomas of ectodermal, mesodermal, and endodermal origin. It is caused by loss of function mutations in the phosphatase and tensin homolog (PTEN) gene located on chromosome 10q23.1 Loss of function of the PTEN gene contributes to overgrowth and risk for a variety of cancers including breast, thyroid, endometrium, skin, kidneys, and colon. The early diagnosis of Cowden disease allows a careful monitoring of the patients who are facing the risk of cancer transformation, which is the principal complication of the condition.

6.
Acta Obstet Gynecol Scand ; 102(9): 1176-1182, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37431247

RESUMO

INTRODUCTION: The pathogenesis and risk factors for hyperemesis gravidarum, excessive nausea and vomiting of pregnancy, are not adequately recognized. In our previous study, we found that women with a personal history of nausea in different situations and a family history of nausea and vomiting of pregnancy (NVP) were more likely to have severe NVP. The present study focuses on these themes in association with hyperemesis gravidarum in a hospital setting. MATERIAL AND METHODS: Women with hyperemesis gravidarum (n = 102) were recruited from among patients hospitalized due to hyperemesis gravidarum in Turku University Hospital, Finland. Our control group (Non-NVP group, n = 138) consisted of pregnant women with no NVP. Personal history of nausea in different situations was inquired about in relation to "motion sickness", "seasickness", "migraine", "other kind of headache", "after anesthesia", "during the use of contraception", and "other kinds of nausea". Relatives with NVP were divided into first-degree (mother and sisters) and second-degree (more distant) relatives. RESULTS: In univariate analysis, a personal history of motion sickness, seasickness, nausea related to migraine, nausea with other headache and nausea in other situations were associated with hyperemesis gravidarum. After adjusting for age, parity, pre-pregnancy body mass index, marital status, and smoking, motion sickness (adjusted odds ratio [aOR] 5.24, 95% confidence interval [CI] 2.67-10.31, p < 0.0001), seasickness (aOR 4.82, 95% CI 2.32-10.03, p < 0.0001), nausea related to migraine (aOR 3.00, 95% CI 1.58-5.70, p < 0.001), and nausea in other situations (aOR 2.65, 95% CI 1.13-6.20, p = 0.025) remained significant. In multivariable analysis with all history of nausea variables, motion sickness (OR 2.76, 95% CI 1.29-5.89, p = 0.009) and nausea related to migraine (OR 3.10, 95% CI 1.40-6.86, p = 0.005) were associated with hyperemesis gravidarum. Having any affected relative (OR 3.51, 95%CI 1.84-6.73, p = 0.0002), especially a first-degree relative (OR 3.06, 95% CI 1.62-5.79, p = 0.0006), was also associated with hyperemesis gravidarum. Adjustment did not change the results. CONCLUSIONS: Women with a personal history of nausea or a family history of NVP are more likely to suffer from hyperemesis gravidarum. These results are beneficial to better identify and help women at risk for hyperemesis gravidarum.


Assuntos
Cefaleia , Hiperêmese Gravídica , Náusea , Humanos , Feminino , Adulto , Hiperêmese Gravídica/epidemiologia , Náusea/epidemiologia , Náusea/etiologia , Gestantes , Finlândia/epidemiologia , Estudos de Casos e Controles , Cefaleia/complicações
7.
Acta Anaesthesiol Scand ; 67(8): 1018-1027, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37156489

RESUMO

BACKGROUND: The incidence of post-operative nausea and vomiting (PONV) remains at about 30% despite all therapeutic efforts to reduce it. The clinical risk factors guiding the prophylactic treatment are well established, but genetic factors associated with PONV remain poorly known. The aim of this study was to explore clinical and genetic factors impacting PONV by performing a genome-wide association study (GWAS) together with relevant clinical factors as covariates, and systematically attempt to replicate previously reported PONV associations. Relevant clinical factors are explored with logistic regression model. METHODS: This was an observational case control study in Helsinki University Hospital between 1 August 2006 and 31 December 2010. One thousand consenting women with elevated risk for PONV, undergoing breast cancer surgery with standardised propofol anaesthesia and antiemetics. After exclusions for clinical reasons and failed genotyping, 815 patients were included with 187 PONV cases and 628 controls. Emergence of PONV up to 7th post-operative day was recorded. PONV at 2-24 h after surgery was selected to be the primary outcome. The GWAS explored associations between PONV and 653 034 genetic variants. Replication attempts included 31 variants in 16 genes. RESULTS: The overall incidence of PONV up to 7th post-operative day was 35%, where 3% had PONV at 0-2 h and 23% at 2-24 h after surgery. Age, American Society of Anaesthesiologists status, the amount of oxycodone used in the post-anaesthesia care unit, smoking status, previous PONV, and history of motion sickness were statistically significant predictive factors in the logistic model. The receiver operating characteristic-area under the curve of 0.75 (95% CI 0.71-0.79) was calculated for the model. The GWAS identified six variants with suggestive association to PONV (p < 1 × 10-5 ). Of the previously reported variants, association with the DRD2 variant rs18004972 (TaqIA) was replicated (p = .028). CONCLUSIONS: Our GWAS approach did not identify any high-impact PONV susceptibility variants. The results provide some support for a role of dopamine D2 receptors in PONV.


Assuntos
Anestesia , Antieméticos , Propofol , Humanos , Feminino , Náusea e Vômito Pós-Operatórios/epidemiologia , Náusea e Vômito Pós-Operatórios/genética , Propofol/uso terapêutico , Estudos de Casos e Controles , Estudo de Associação Genômica Ampla , Antieméticos/uso terapêutico , Fatores de Risco
8.
Acta Neurol Belg ; 123(3): 903-909, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36068432

RESUMO

OBJECTIVE: To investigate the clinical characteristics, the neuroimaging features and associated anomalies observed in children affected by Dandy-Walker malformations (DWM) and variants (DWV) in a single tertiary hospital in Catania and compare our data to their existent in the literature. METHODS: A retrospective case series using the medical records has been performed on 28 children diagnosed with DWM and DWV admitted to a single tertiary section of Pediatric Neurology, Department of Catania, Italy from January 2005 to January 2021. We reviewed the neuroimaging using the new diagnostic criteria of Klein et al. RESULTS: Associated anomalies were frequently reported. Among these, hydrocephalus was found in 13/28 (48%), and hydrocephalus plus corpus callosum anomalies in three children (10%). We described corpus callosum, cardiac and genitourinary anomalies in 2/28 (7%), 3/28 (10%), and 3/28 (10%), respectively. The most common clinical features were the developmental delay and epilepsy observed in 19/28 (67%) and in 9/28 (32%) of the cases. The first exam at the diagnosis was MRI in 17/28 patients, followed by transfontanellar ultrasound in 5/28, computed tomography in 4/28 and prenatal ultrasound in 2/28. To note, a child with DWM was affected by Down syndrome and one by congenital disorders of N-linked glycosylation (CDG-IId). CONCLUSIONS: Children with DWV were more commonly observed than children with DWM. Hydrocephalus is an anomaly, frequently and equally reported in both DWM and DMV. Perinatal complications were frequent adverse events with severe respiratory distress and need for cardiopulmonary resuscitation. Cognitive involvement and epilepsy were the most common comorbidities. Single DWV is associated with a better developmental outcome.


Assuntos
Síndrome de Dandy-Walker , Hidrocefalia , Anormalidades Urogenitais , Gravidez , Feminino , Criança , Humanos , Síndrome de Dandy-Walker/complicações , Síndrome de Dandy-Walker/diagnóstico por imagem , Estudos Retrospectivos , Hidrocefalia/complicações , Anormalidades Urogenitais/complicações , Imageamento por Ressonância Magnética
9.
Eur Urol Open Sci ; 42: 1-8, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35911084

RESUMO

Background: Standardized methods for reporting surgical quality have been described for all the major urological procedures apart from radical nephroureterectomy (RNU). Objective: To propose a tetrafecta criterion for assessing the quality of RNU based on a consensus panel within the Young Association of Urology (YAU) Urothelial Group, and to test the impact of this tetrafecta in a multicenter, large contemporary cohort of patients treated with RNU for upper tract urothelial carcinoma (UTUC). Design setting and participants: This was a retrospective analysis of 1765 patients with UTUC treated between 2000 and 2021. Outcome measurements and statistical analysis: We interviewed the YAU Urothelial Group to propose and score a list of items to be included in the "RNU-fecta." A ranking was generated for the criteria with the highest sum score. These criteria were applied to a large multicenter cohort of patients. Kaplan-Meier curves were built to evaluate differences in overall survival (OS) rates between groups, and a multivariable logistic regression model was used to find the predictors of achieving the RNU tetrafecta. Results and limitations: The criteria with the highest score included three surgical items such as negative soft tissue surgical margins, bladder cuff excision, lymph node dissection according to guideline recommendations, and one oncological item defined by the absence of any recurrence in ≤12 mo. These items formed the RNU tetrafecta. Within a median follow-up of 30 mo, 52.6% of patients achieved the RNU tetrafecta. The 5-yr OS rates were significantly higher for patients achieving tetrafecta than for their counterparts (76% vs 51%). Younger age, lower body mass index, and robotic approach were found to be independent predictors of tetrafecta achievement. Conversely, a higher Eastern Cooperative Oncology Group score, higher clinical stage, and bladder cancer history were inversely associated with tetrafecta. Conclusions: Herein, we present a "tetrafecta" composite endpoint that may serve as a potential tool to assess the overall quality of the RNU procedure. Pending external validation, this tool could allow a comparison between surgical series and may be useful for assessing the learning curve of the procedure as well as for evaluating the impact of new technologies in the field. Patient summary: In this study, a tetrafecta criterion was developed for assessing the surgical quality of radical nephroureterectomy in patients with upper tract urothelial carcinoma. Patients who achieved tetrafecta had higher 5-yr overall survival rates than those who did not.

10.
Front Mol Biosci ; 9: 785232, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463966

RESUMO

The status of metabolomics as a scientific branch has evolved from proof-of-concept to applications in science, particularly in medical research. To comprehensively evaluate disease metabolomics, multiplatform approaches of NMR combining with mass spectrometry (MS) have been investigated and reported. This mixed-methods approach allows for the exploitation of each individual technique's unique advantages to maximize results. In this article, we present our findings from combined NMR and MS imaging (MSI) analysis of human lung and prostate cancers. We further provide critical discussions of the current status of NMR and MS combined human prostate and lung cancer metabolomics studies to emphasize the enhanced metabolomics ability of the multiplatform approach.

11.
Pharmacogenomics J ; 22(3): 166-172, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35197553

RESUMO

We demonstrate that CYP2D6 copy-number variation (CNV) can be imputed using existing imputation algorithms. Additionally, we report frequencies of key pharmacogenetic variants in individuals with a psychotic disorder from the genetically bottle-necked population of Finland. We combined GWAS chip and CYP2D6 CNV data from the Breast Cancer Pain Genetics study to construct an imputation panel (n = 902) for CYP2D6 CNV. The resulting data set was used as a CYP2D6 CNV imputation panel in 9262 non-related individuals from the SUPER-Finland study. Based on imputation of 9262 individuals we confirm the higher frequency of CYP2D6 ultrarapid metabolizers and a 22-fold enrichment of the UGT1A1 decreased function variant rs4148323 (UGT1A1*6) in Finland compared with non-Finnish Europeans. Similarly, the NUDT15 variant rs116855232 was highly enriched in Finland. We demonstrate that imputation of CYP2D6 CNV is possible and the methodology enables studying CYP2D6 in large biobanks with genome-wide data.


Assuntos
Citocromo P-450 CYP2D6 , Transtornos Psicóticos , Citocromo P-450 CYP2D6/genética , Finlândia , Frequência do Gene , Genótipo , Humanos , Variantes Farmacogenômicos
13.
Proc Natl Acad Sci U S A ; 118(51)2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34903652

RESUMO

The current high mortality of human lung cancer stems largely from the lack of feasible, early disease detection tools. An effective test with serum metabolomics predictive models able to suggest patients harboring disease could expedite triage patient to specialized imaging assessment. Here, using a training-validation-testing-cohort design, we establish our high-resolution magic angle spinning (HRMAS) magnetic resonance spectroscopy (MRS)-based metabolomics predictive models to indicate lung cancer presence and patient survival using serum samples collected prior to their disease diagnoses. Studied serum samples were collected from 79 patients before (within 5.0 y) and at lung cancer diagnosis. Disease predictive models were established by comparing serum metabolomic patterns between our training cohorts: patients with lung cancer at time of diagnosis, and matched healthy controls. These predictive models were then applied to evaluate serum samples of our validation and testing cohorts, all collected from patients before their lung cancer diagnosis. Our study found that the predictive model yielded values for prior-to-detection serum samples to be intermediate between values for patients at time of diagnosis and for healthy controls; these intermediate values significantly differed from both groups, with an F1 score = 0.628 for cancer prediction. Furthermore, values from metabolomics predictive model measured from prior-to-diagnosis sera could significantly predict 5-y survival for patients with localized disease.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Espectroscopia de Ressonância Magnética , Metabolômica , Idoso , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/metabolismo , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
14.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 73-79, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-34817365

RESUMO

Xanthan gum (XG) and polyvinylpyrrolidone (PVP) are two polymers with low toxicity, high biocompatibility, biodegradability, and high hydrophilicity, making them promising candidates for multiple medical aspects. The present work aimed to synthesize a hydrogel from a mixture of XG and PVP and crosslinked by gamma irradiation. We assessed the hydrogel through a series of physicochemical (FT-IR, TGA, SEM, and percentage of swelling) and biological (stability of the hydrogel in cell culture medium) methods that allowed to determine its applicability. The structural evaluation by infrared spectrum demonstrated that a crosslinked hydrogel was obtained from the combination of polymers. The calorimetric test and swelling percentage confirmed the formation of the bonds responsible for the crosslinked structure. The calorimetric test evidenced that the hydrogel was resistant to decomposition in contrast to non- irradiated material. The determination of the swelling degree showed constant behavior over time, indicating a structure resistant to hydrolysis. This phenomenon also occurred during the test of stability in a cell culture medium. Additionally, microscopic analysis of the sample revealed an amorphous matrix with the presence of porosity. Thus, the findings reveal the synthesis of a novel material that has desirable attributes for its potential application in pharmaceutical and biomedical areas.


Assuntos
Raios gama , Hidrogéis/efeitos da radiação , Polímeros/efeitos da radiação , Polissacarídeos Bacterianos/efeitos da radiação , Povidona/efeitos da radiação , Hidrogéis/síntese química , Hidrogéis/química , Microscopia Eletrônica de Varredura , Modelos Químicos , Estrutura Molecular , Polímeros/síntese química , Polímeros/química , Polissacarídeos Bacterianos/síntese química , Polissacarídeos Bacterianos/química , Porosidade , Povidona/síntese química , Povidona/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Temperatura , Termogravimetria/métodos
15.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 64-72, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-34817366

RESUMO

The purpose of our study was to obtain new wound dressings in the form of hydrogels that promote wound healing taking advantage of the broad activities of elastin (ELT) in physiological processes. The hydrogel of ELT and polyvinylpyrrolidone (PVP; ELT-PVP) was obtained by cross-linking induced by gamma irradiation at a dose of 25 kGy. The physicochemical changes attributed to cross-linking were analyzed through scanning electron microscopy (SEM), infrared spectroscopy analysis with Fourier transform (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Furthermore, we performed a rheological study to determine the possible changes in the fluidic macroscopic properties produced by the cross-linking method. Finally, we accomplished viability and proliferation analyses of human dermal fibroblasts in the presence of the hydrogel to evaluate its biological characteristics. The hydrogel exhibited a porous morphology, showing interconnected porous with an average pore size of 16 ± 8.42 µm. The analysis of FTIR, DSC, and TGA revealed changes in the chemical structure of the ELT-PVP hydrogel after the irradiation process. Also, the hydrogel exhibited a rheological behavior of a pseudoplastic and thixotropic fluid. The hydrogel was biocompatible, demonstrating high cell viability, whereas ELT presented low biocompatibility at high concentrations. In summary, the hydrogel obtained by gamma irradiation revealed the appropriate morphology to be applied as a wound dressing. Interestingly, the hydrogel exhibited a higher percentage of cell viability compared with ELT, suggesting that the cross-linking of ELT with PVP is a suitable strategy for biological applications of ELT without generating cellular damage.


Assuntos
Materiais Biocompatíveis/metabolismo , Elastina/metabolismo , Curativos Oclusivos , Polimerização/efeitos da radiação , Povidona/metabolismo , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Varredura Diferencial de Calorimetria/métodos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Elastina/química , Elastina/ultraestrutura , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Hidrogéis/química , Hidrogéis/metabolismo , Hidrogéis/farmacologia , Microscopia Eletrônica de Varredura , Povidona/química , Povidona/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Termogravimetria/métodos , Cicatrização/efeitos dos fármacos
16.
J Laryngol Otol ; 135(11): 970-975, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34482849

RESUMO

OBJECTIVE: This study aimed to evaluate the effectiveness of computed tomography and positron emission tomography-computed tomography prior to salvage surgery after head and neck carcinoma treated with bioradiotherapy and to look at the role of neck dissection in this setting. METHOD: This study was a retrospective chart review of a series of consecutive patients with locally advanced head and neck squamous cell carcinoma treated with bioradiotherapy. Radiological and pathological stages were compared to evaluate the accuracy of computed tomography and positron emission tomography-computed tomography in detecting occult neck metastasis in the context of recurrence of primary tumour. In order to assess the impact of neck dissection on survival, Kaplan-Meier survival curves after salvage surgery with and without neck dissection were derived. RESULTS: A total of 268 patients were identified, of which 22 underwent salvage surgery. The negative predictive value of computed tomography and positron emission tomography-computed tomography was excellent. Neck dissection did not represent an improvement on overall, disease specific and regional recurrence free survival (p = 0.67, p = 0.91 and p = 0.62, respectively) amongst clinically and radiologically negative necks. CONCLUSION: Conservative treatment of the neck should be considered when dealing with patients with primary site recurrence or persistent disease after bioradiotherapy without evidence of neck disease.


Assuntos
Tratamento Conservador , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Terapia de Salvação , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Feminino , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço/diagnóstico por imagem , Pescoço/patologia , Esvaziamento Cervical , Radioterapia , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
17.
Dalton Trans ; 50(30): 10593-10607, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34278398

RESUMO

Complexes trans,trans,trans-[Pt(N3)2(OH)(OCOR)(py)2] where py = pyridine and where OCOR = succinate (1); 4-oxo-4-propoxybutanoate (2) and N-methylisatoate (3) have been synthesized by derivation of trans,trans,trans-[Pt(OH)2(N3)2(py)2] (4) and characterised by NMR and EPR spectroscopy, ESI-MS and X-ray crystallography. Irradiation of 1-3 with green (517 nm) light initiated photoreduction to Pt(ii) and release of the axial ligands at a 3-fold faster rate than for 4. TD-DFT calculations showed dissociative transitions at longer wavelengths for 1 compared to 4. Complexes 1 and 2 showed greater photocytotoxicity than 4 when irradiated with 420 nm light (A2780 cell line IC50 values: 2.7 and 3.7 µM) and complex 2 was particularly active towards the cisplatin-resistant cell line A2780cis (IC50 3.7 µM). Unlike 4, complexes 1-3 were phototoxic under green light irradiation (517 nm), with minimal toxicity in the dark. A pKa(H2O) of 5.13 for the free carboxylate group was determined for 1, corresponding to an overall negative charge during biological experiments, which crucially, did not appear to impede cellular accumulation and photocytotoxicity.


Assuntos
Neoplasias Ovarianas , Linhagem Celular Tumoral , Feminino , Humanos , Compostos Organoplatínicos
18.
J Urol ; 206(4): 854-865, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34032495

RESUMO

PURPOSE: Sarcopenia, an age-related loss of muscle mass and function, may predict adverse outcomes for patients with urological cancers. However, the clinical implications and significance of sarcopenic obesity are not well understood. We systematically reviewed data on the prevalence and prognostic impact of sarcopenic obesity for patients with renal cell carcinoma, urothelial carcinoma and prostate cancer undergoing treatment. MATERIALS AND METHODS: We searched EMBASE®, PubMed®/MEDLINE® and Scopus® for relevant original articles and abstracts published between January 2010 and February 2021. Primary outcomes were overall survival (OS), cancer-specific survival (CSS) and progression-free survival. The secondary outcome was the prevalence of sarcopenic obesity. RESULTS: A total of 15 studies comprising 3,866 patients were included. Of the 10 studies that evaluated survival outcomes, the association between sarcopenic obesity and survival was mixed. One of 10 studies showed a significant association of sarcopenic obesity with OS (HR 0.7, 95% CI 0.51-0.98; p=0.04). One additional study showed reported a trend for shorter OS (p=0.05) associated with sarcopenic obesity. Others reported that it is an adverse prognostic factor for CSS (HR 5.0, 95% CI 1.4-16.7; p=0.01). All other studies did not demonstrate that sarcopenic obesity was of prognostic relevance with regard to OS, CSS and progression-free survival. Overall, its mean prevalence was 27% (range 11-63). CONCLUSIONS: There is considerable heterogeneity in methods used to define sarcopenic obesity in the literature, and current data are limited. Future studies are needed to further understand the relationship of obesity and sarcopenia on the clinical trajectory of patients with urological cancer.


Assuntos
Obesidade/epidemiologia , Sarcopenia/epidemiologia , Neoplasias Urológicas/mortalidade , Composição Corporal , Comorbidade , Humanos , Obesidade/complicações , Obesidade/diagnóstico , Prevalência , Prognóstico , Intervalo Livre de Progressão , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Sarcopenia/complicações , Sarcopenia/diagnóstico
19.
Arch Esp Urol ; 74(2): 254-260, 2021 Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33650541

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of prostatic artery embolization in the management of LUTS secondary to BPH in elderly patients unfit for surgery. MATERIALS AND METHODS: 17 elderly patients with moderate to severe LUTS/BPH were included in the study and treated with prostatic artery embolization. The patients were evaluated by transrectal ultrasonography (to assess prostate size), IPSS, and PVR urine volume preoperatively and 6 months after the procedure. RESULTS: The mean age of patients was 76.67 ± 7.69. The mean prostate volume was 139.8 ± 81.83 g. The mean preoperative IPSS and PVR were 23 ± 5.4, and 94.43 ± 88.94 ml, respectively. The mean operative time was 90 minutes. Only three patients suffered from postoperative complications (two patients suffered from urinary tract infection and one patient had partial penile necrosis). At 6 months follow up, there was a significant reduction in the prostate volume (101 ± 73.65 cc), IPSS (12.5 ± 3.65), and PVR urine volume (48.64 ± 43.55). CONCLUSION: prostatic artery embolization is a safe and effective nonsurgical alternative treatment of BPH/LUTS particularly in elderly patients with multiple comorbidities.


OBJETIVO: Evaluar la seguridad y eficacia de la embolización arteria prostática en el manejo de STUI secundarios a HBP en pacientes añosos no candidatos a cirugía.MATERIAL Y MÉTODOS: 17 pacientes añosos con STUI moderados/severos fueron incluidos en el estudio y tratados con ambolización de la arteria prostática. Los pacientes fueron evaluados con ecografía transrectal (para determinar el tamaño prostático), IPSS, y residuo post-miccional preoperatorio y a los 6 meses del procedimiento. RESULTADOS: La edad mediana de los pacientes fue de 76,67 ± 7,69. EL volumen prostático medio fue de 139,8 ± 81,83 g. EL IPSS preoperatorio y RPM medio fueron de 23 ± 5,4, y 94,43 ± 88,94 ml, respectivamente. El tiempo quirúrgico medio fue de 90 minutos Solamente 3 pacientes tuvieron complicaciones postoperatorias (2 pacientes tuvieron una infección tracto urinario y un paciente tuvo una necrosis peneana). A los 6 meses de seguimiento, hubo una reducción significativa del volumen prostático (101 ± 73,65 cc), IPSS (12,5 ± 3,65), y RPM volumen orina (48,64 ± 43,55). CONCLUSIONES: La embolización de la arteria prostática es un procedimiento seguro y efectivo como una alternativa no quirúrgica al tratamiento de HBP/STUI particularmente en pacientes añosos con múltiples comorbilidades.


Assuntos
Embolização Terapêutica , Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Idoso , Artérias , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/terapia , Masculino , Hiperplasia Prostática/complicações , Hiperplasia Prostática/terapia , Resultado do Tratamento
20.
World J Urol ; 39(10): 3875-3880, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33787986

RESUMO

PURPOSE: Rezum is the latest developed minimally invasive treatment for benign prostatic hyperplasia (BPH). We aimed to carefully assess the functional outcomes of patients treated with Rezum for BPH. METHODS: We prospectively followed 135 consecutive patients treated by Rezum at 5 institutions from June 2019 to August 2020. The International Prostate Symptom Score (IPSS), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI SF), the Overactive Bladder Questionnaire-Short Form (OAB-q SF) score, the International Index of Erectile Function (IIEF-5) and questions 9 and 10 to assess ejaculatory dysfunction were recorded. Election criteria were age > 18, no prior prostate interventions, IPSS ≥ 13, post-void residual ≤ 250 mL, prostate volume between 30 and 120 cc. RESULTS: The median operative time was 10.5 (IQR 8.7-15) min. All patients were dismissed few hours after surgery with indwelling urinary catheter that was removed after a median of 7 (IQR 7-10) days. A significantly decrease of IPSS from baseline at first (p = 0.001) and third (p < 0.0001) month after surgery was reported. No difference was reported in terms of ICIQ-UI SF score postoperatively. A mild reduction of the OAB-q SF score was reported at 1 month from surgery (p = 0.06) that turned significant at 3 months postoperatively (p < 0.0001). A slight but statistically significant increase of the IIEF-5 score was reported from baseline at 6 months (p = 0.04). Postoperatively, patients reported a significantly decrease of ejaculatory dysfunction after alpha-blocker interruption. CONCLUSION: Rezum treatment is a feasible minimally invasive option for patients with BPH symptoms and showed optimal early functional outcomes.


Assuntos
Hipertermia Induzida/instrumentação , Sintomas do Trato Urinário Inferior/terapia , Hiperplasia Prostática/complicações , Vapor , Idoso , Seguimentos , Humanos , Itália , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recuperação de Função Fisiológica , Inquéritos e Questionários , Resultado do Tratamento
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