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1.
Ann Surg Oncol ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969859

RESUMO

BACKGROUND: Analysis of temporal trends of urinary diversion (UD) and identification of predictive factors for continent urinary diversion (CUD) in patients with bladder cancer (BC) is scarce and data on large cohorts are missing. We aimed to describe longitudinal temporal trends and predictive factors for UD among patients with BC receiving radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analysed institutional data collected from patients undergoing RC from 1986 to 2022 to describe changes in patients' characteristics and UD. Primary end points were patients' characteristics associated with type of UD. Logistic regression analysis was used to determine predictive factors for CUD. RESULTS: In total, 2224 patients (77.16% male, 22.84% female) with a mean age of 66 years [standard deviation (SD), 10.64 years] were included. We observed an increase in mean age from 59.86 (10.8) years (1986-1990) to 69.85 (9.99) years (2016-2022) (p < 0.001). The proportion of CUD gradually declined from 43.72% (94/215; 1986-1990) to 18.38% (86/468; 2016-2022). Patients who were male [odds ratio (OR): 1.92, 95% confidence interval (CI): 1.43-2.57, p < 0.001), younger (OR: 0.88, 95% CI: 0.87-0.89, p < 0.001) and had no hydronephrosis prior to RC (OR: 2.2, 95% CI: 1.66-2.92, p < 0.001) were more likely to receive CUD. CONCLUSIONS: We report the largest European single-center cohort of UD after RC, demonstrating a significant shift from CUD to IUD, accompanied by an increasing age. Finally, our data mirrors the development and extensive experience with the Mainz Pouch-I in the 1980's and 1990's together with other colon pouches.

2.
World J Urol ; 42(1): 386, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918219

RESUMO

BACKGROUND: The last decades revealed new scientific knowledge regarding the fertility and potential malignancy of undescended testis AQ2(UDT). Accordingly, many guidelines changed their recommendation concerning timing of therapy, with the goal of an earlier time of surgery. METHODS: We analyzed the number of new diagnosis and performed surgeries in predefined age groups provided by the obligatory annual reports of German hospitals in the reimbursement.INFO"-tool between 2006 and 2020. RESULTS: Overall, 124,741 cases were analyzed. We showed a slight increase in performed surgeries in the first year by 2% per year with a main increase till 2011, a constant number of surgeries between first and 4th year and a decrease of surgeries between 5 and 14th year of living with a main decrease till 2009 by 3% per year. CONCLUSION: Even if our results illustrate an increasing adaption of the guideline's recommendation, there is still a significant number of patients who receive later treatment. More research about the reasons and circumstances for the latter is needed.


Assuntos
Criptorquidismo , Orquidopexia , Guias de Prática Clínica como Assunto , Criptorquidismo/cirurgia , Humanos , Masculino , Alemanha/epidemiologia , Criança , Adolescente , Pré-Escolar , Lactente , Fatores de Tempo , Adulto Jovem , Adulto
3.
Sci Adv ; 10(26): eadl0030, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38924398

RESUMO

How can short-lived molecules selectively maintain the potentiation of activated synapses to sustain long-term memory? Here, we find kidney and brain expressed adaptor protein (KIBRA), a postsynaptic scaffolding protein genetically linked to human memory performance, complexes with protein kinase Mzeta (PKMζ), anchoring the kinase's potentiating action to maintain late-phase long-term potentiation (late-LTP) at activated synapses. Two structurally distinct antagonists of KIBRA-PKMζ dimerization disrupt established late-LTP and long-term spatial memory, yet neither measurably affects basal synaptic transmission. Neither antagonist affects PKMζ-independent LTP or memory that are maintained by compensating PKCs in ζ-knockout mice; thus, both agents require PKMζ for their effect. KIBRA-PKMζ complexes maintain 1-month-old memory despite PKMζ turnover. Therefore, it is not PKMζ alone, nor KIBRA alone, but the continual interaction between the two that maintains late-LTP and long-term memory.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular , Potenciação de Longa Duração , Camundongos Knockout , Proteína Quinase C , Animais , Proteína Quinase C/metabolismo , Proteína Quinase C/genética , Camundongos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Memória/fisiologia , Memória de Longo Prazo/fisiologia , Sinapses/metabolismo , Sinapses/fisiologia , Ligação Proteica , Fosfoproteínas
5.
BMC Med Educ ; 24(1): 666, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886688

RESUMO

BACKGROUND: Advanced Trauma Life Support (ATLS) is the gold standard of initial assessment of trauma patients and therefore a widely used training program for medical professionals. Practical application of the knowledge taught can be challenging for medical students and inexperienced clinicians. Simulation-based training, including virtual reality (VR), has proven to be a valuable adjunct to real-world experiences in trauma education. Previous studies have demonstrated the effectiveness of VR simulations for surgical and technical skills training. However, there is limited evidence on VR simulation training specifically for trauma education, particularly within the ATLS curriculum. The purpose of this pilot study is to evaluate the feasibility, effectiveness, and acceptance of using a fully immersive VR trauma simulation to prepare medical students for the ATLS course. METHODS: This was a prospective randomised controlled pilot study on a convenience sample of advanced medical students (n = 56; intervention group with adjunct training using a commercially available semi-automated trauma VR simulation, n = 28, vs control group, n = 28) taking part in the ATLS course of the Military Physician Officer School. Feasibility was assessed by evaluating factors related to technical factors of the VR training (e.g. rate of interruptions and premature termination). Objective and subjective effectiveness was assessed using confidence ratings at four pre-specified points in the curriculum, validated surveys, clinical scenario scores, multiple choice knowledge tests, and ATLS final clinical scenario and course pass rates. Acceptance was measured using validated instruments to assess variables of media use (Technology acceptance, usability, presence and immersion, workload, and user satisfaction). RESULTS: The feasibility assessment demonstrated that only one premature termination occurred and that all remaining participants in the intervention group correctly stabilised the patient. No significant differences between the two groups in terms of objective effectiveness were observed (p = 0.832 and p = 0.237 for the pretest and final knowledge test, respectively; p = 0.485 for the pass rates for the final clinical scenario on the first attempt; all participants passed the ATLS course). In terms of subjective effectiveness, the authors found significantly improved confidence post-VR intervention (p < .001) in providing emergency care using the ATLS principles. Perceived usefulness in the TEI was stated with a mean of 4 (SD 0.8; range 0-5). Overall acceptance and usability of the VR simulation was rated as positive (System Usability Scale total score mean 79.4 (SD 11.3, range 0-100). CONCLUSIONS: The findings of this prospective pilot study indicate the potential of using VR trauma simulations as a feasible and acceptable supplementary tool for the ATLS training course. Where objective effectiveness regarding test and scenario scores remained unchanged, subjective effectiveness demonstrated improvement. Future research should focus on identifying specific scenarios and domains where VR can outperform or enhance traditional learning methods in trauma simulation.


Assuntos
Cuidados de Suporte Avançado de Vida no Trauma , Treinamento por Simulação , Realidade Virtual , Humanos , Projetos Piloto , Estudos Prospectivos , Masculino , Feminino , Adulto , Competência Clínica , Estudos de Viabilidade , Estudantes de Medicina , Currículo , Avaliação Educacional , Adulto Jovem
6.
Life Sci ; 351: 122841, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38897349

RESUMO

AIM: The cardiac surgery-related ischemia-reperfusion-related oxidative stress triggers the release of cytotoxic reactive oxygen and nitrogen species, contributing to organ failure and ultimately influencing patients' short- and long-term outcomes. Selenium is an essential co-factor for various antioxidant enzymes, thereby contributing to the patients' endogenous antioxidant and anti-inflammatory defense mechanisms. Given these selenium's pleiotropic functions, we investigated the effect of a high-dose selenium-based anti-inflammatory perioperative strategy on functional recovery after cardiac surgery. MATERIALS AND METHODS: This prospective study constituted a nested sub-study of the SUSTAIN CSX trial, a double-blinded, randomized, placebo-controlled multicenter trial to investigate the impact of high-dose selenium supplementation on high-risk cardiac surgery patients' postoperative recovery. Functional recovery was assessed by 6-min walk distance, Short Form-36 (SF-36) and Barthel Index questionnaires. KEY FINDINGS: 174 patients were included in this sub-study. The mean age (SD) was 67.3 (8.9) years, and 78.7 % of the patients were male. The mean (SD) predicted 30-day mortality by the European System for Cardiac Operative Risk Evaluation II score was 12.6 % (9.4 %). There was no difference at hospital discharge and after three months in the 6-min walk distance between the selenium and placebo groups (131 m [IQR: not performed - 269] vs. 160 m [IQR: not performed - 252], p = 0.80 and 400 m [IQR: 299-461] vs. 375 m [IQR: 65-441], p = 0.48). The SF-36 and Barthel Index assessments also revealed no clinically meaningful differences between the selenium and placebo groups. SIGNIFICANCE: A perioperative anti-inflammatory strategy with high-dose selenium supplementation did not improve functional recovery in high-risk cardiac surgery patients.


Assuntos
Anti-Inflamatórios , Procedimentos Cirúrgicos Cardíacos , Selênio , Humanos , Masculino , Feminino , Idoso , Procedimentos Cirúrgicos Cardíacos/métodos , Selênio/administração & dosagem , Selênio/farmacologia , Método Duplo-Cego , Pessoa de Meia-Idade , Estudos Prospectivos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Suplementos Nutricionais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos
7.
Urologie ; 63(7): 673-680, 2024 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-38811419

RESUMO

BACKGROUND: Stress urinary incontinence in men is predominantly iatrogenic after radical prostatectomy or transurethral interventions. Current studies show that there is a deficit in the availability of surgical therapy not only in Germany. The aim of this study is to investigate in more detail the structural health care situation of surgical treatment of male stress incontinence in Germany. MATERIALS AND METHODS: The evaluation of the surgical therapy of male stress incontinence in Germany is based on the OPS (Operationen- und Prozedurenschlüssel-German procedural classification) codes from hospital quality reports from 2011-2019. RESULTS: From 2012-2019, the number of male incontinence surgeries declined from 2191 to 1445. The number of departments performing incontinence surgeries decreased from 275 to 244. In the multivariate analysis, a high number (≥ 50) of radical prostatectomies/year (RPE/year) is an independent predictor of a high-volume centre (≥ 10 procedures/year; odds ratio [OR] 6.4 [2.3-17.6]; p < 0.001). The most significant decrease was in sling surgery (from 1091 to 410; p < 0.001). Here, the number of cases decreased especially in departments that implanted a high number of slings (≥ 10 slings/year; -69%; -62.4 ± 15.5 surgeries/year; p = 0.007). In addition, the number of departments implanting slings decreased over the investigated time period (from 34 to 10; p < 0.001). This particularly affected departments that also had a low number of RPE/year (from 9 to 0; -100%). CONCLUSION: The situation of surgical treatment of male stress urinary incontinence in Germany shows a clear decline in sling implantation, especially in small departments. On the one hand, this reflects the increasingly differentiated indications for sling implantation. On the other hand, it raises the suspicion that a gap in care has developed, as the decline was not compensated for by other surgical therapies.


Assuntos
Incontinência Urinária por Estresse , Humanos , Masculino , Incontinência Urinária por Estresse/cirurgia , Alemanha/epidemiologia , Prostatectomia/efeitos adversos , Idoso , Procedimentos Cirúrgicos Urológicos Masculinos , Pessoa de Meia-Idade
8.
Acta Neuropathol ; 147(1): 82, 2024 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722375

RESUMO

Aging affects all cell types in the CNS and plays an important role in CNS diseases. However, the underlying molecular mechanisms driving these age-associated changes and their contribution to diseases are only poorly understood. The white matter in the aging brain as well as in diseases, such as Multiple sclerosis is characterized by subtle abnormalities in myelin sheaths and paranodes, suggesting that oligodendrocytes, the myelin-maintaining cells of the CNS, lose the capacity to preserve a proper myelin structure and potentially function in age and certain diseases. Here, we made use of directly converted oligodendrocytes (dchiOL) from young, adult and old human donors to study age-associated changes. dchiOL from all three age groups differentiated in an comparable manner into O4 + immature oligodendrocytes, but the proportion of MBP + mature dchiOL decreased with increasing donor age. This was associated with an increased ROS production and upregulation of cellular senescence markers such as CDKN1A, CDKN2A in old dchiOL. Comparison of the transcriptomic profiles of dchiOL from adult and old donors revealed 1324 differentially regulated genes with limited overlap with transcriptomic profiles of the donors' fibroblasts or published data sets from directly converted human neurons or primary rodent oligodendroglial lineage cells. Methylome analyses of dchiOL and human white matter tissue samples demonstrate that chronological and epigenetic age correlate in CNS white matter as well as in dchiOL and resulted in the identification of an age-specific epigenetic signature. Furthermore, we observed an accelerated epigenetic aging of the myelinated, normal appearing white matter of multiple sclerosis (MS) patients compared to healthy individuals. Impaired differentiation and upregulation of cellular senescence markers could be induced in young dchiOL in vitro using supernatants from pro-inflammatory microglia. In summary, our data suggest that physiological aging as well as inflammation-induced cellular senescence contribute to oligodendroglial pathology in inflammatory demyelinating diseases such as MS.


Assuntos
Envelhecimento , Senescência Celular , Esclerose Múltipla , Oligodendroglia , Humanos , Oligodendroglia/patologia , Oligodendroglia/metabolismo , Senescência Celular/fisiologia , Envelhecimento/patologia , Esclerose Múltipla/patologia , Esclerose Múltipla/metabolismo , Adulto , Idoso , Pessoa de Meia-Idade , Masculino , Feminino , Adulto Jovem , Inflamação/patologia , Inflamação/metabolismo , Substância Branca/patologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21
10.
Nat Commun ; 15(1): 4120, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750052

RESUMO

5q-associated spinal muscular atrophy (SMA) is a motoneuron disease caused by mutations in the survival motor neuron 1 (SMN1) gene. Adaptive immunity may contribute to SMA as described in other motoneuron diseases, yet mechanisms remain elusive. Nusinersen, an antisense treatment, enhances SMN2 expression, benefiting SMA patients. Here we have longitudinally investigated SMA and nusinersen effects on local immune responses in the cerebrospinal fluid (CSF) - a surrogate of central nervous system parenchyma. Single-cell transcriptomics (SMA: N = 9 versus Control: N = 9) reveal NK cell and CD8+ T cell expansions in untreated SMA CSF, exhibiting activation and degranulation markers. Spatial transcriptomics coupled with multiplex immunohistochemistry elucidate cytotoxicity near chromatolytic motoneurons (N = 4). Post-nusinersen treatment, CSF shows unaltered protein/transcriptional profiles. These findings underscore cytotoxicity's role in SMA pathogenesis and propose it as a therapeutic target. Our study illuminates cell-mediated cytotoxicity as shared features across motoneuron diseases, suggesting broader implications.


Assuntos
Encéfalo , Células Matadoras Naturais , Neurônios Motores , Atrofia Muscular Espinal , Oligonucleotídeos , Humanos , Atrofia Muscular Espinal/tratamento farmacológico , Atrofia Muscular Espinal/patologia , Atrofia Muscular Espinal/genética , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/patologia , Neurônios Motores/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/efeitos dos fármacos , Feminino , Masculino , Proteína 2 de Sobrevivência do Neurônio Motor/genética , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Proteína 1 de Sobrevivência do Neurônio Motor/metabolismo , Análise de Célula Única , Citotoxicidade Imunológica/efeitos dos fármacos , Lactente , Pré-Escolar , Criança , Transcriptoma
11.
Biol Direct ; 19(1): 38, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741178

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC with high rates of metastasis. Targeted therapies such as tyrosine kinase and checkpoint inhibitors have improved treatment success, but therapy-related side effects and tumor recurrence remain a challenge. As a result, ccRCC still have a high mortality rate. Early detection before metastasis has great potential to improve outcomes, but no suitable biomarker specific for ccRCC is available so far. Therefore, molecular biomarkers derived from body fluids have been investigated over the past decade. Among them, RNAs from urine-derived extracellular vesicles (EVs) are very promising. METHODS: RNA was extracted from urine-derived EVs from a cohort of 78 subjects (54 ccRCC patients, 24 urolithiasis controls). RNA-seq was performed on the discovery cohort, a subset of the whole cohort (47 ccRCC, 16 urolithiasis). Reads were then mapped to the genome, and expression was quantified based on 100 nt long contiguous genomic regions. Cluster analysis and differential region expression analysis were performed with adjustment for age and gender. The candidate biomarkers were validated by qPCR in the entire cohort. Receiver operating characteristic, area under the curve and odds ratios were used to evaluate the diagnostic potential of the models. RESULTS: An initial cluster analysis of RNA-seq expression data showed separation by the subjects' gender, but not by tumor status. Therefore, the following analyses were done, adjusting for gender and age. The regions differentially expressed between ccRCC and urolithiasis patients mainly overlapped with small nucleolar RNAs (snoRNAs). The differential expression of four snoRNAs (SNORD99, SNORD22, SNORD26, SNORA50C) was validated by quantitative PCR. Confounder-adjusted regression models were then used to classify the validation cohort into ccRCC and tumor-free subjects. Corresponding accuracies ranged from 0.654 to 0.744. Models combining multiple genes and the risk factors obesity and hypertension showed improved diagnostic performance with an accuracy of up to 0.811 for SNORD99 and SNORA50C (p = 0.0091). CONCLUSIONS: Our study uncovered four previously unrecognized snoRNA biomarkers from urine-derived EVs, advancing the search for a robust, easy-to-use ccRCC screening method.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais , Vesículas Extracelulares , Neoplasias Renais , RNA Nucleolar Pequeno , Humanos , Carcinoma de Células Renais/urina , Carcinoma de Células Renais/genética , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Biomarcadores Tumorais/urina , Biomarcadores Tumorais/genética , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias Renais/urina , Neoplasias Renais/genética , Idoso , RNA Nucleolar Pequeno/genética , Estudos de Coortes , Adulto
12.
Oncogene ; 43(26): 2038-2050, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38750263

RESUMO

Docetaxel (DX) serves as a palliative treatment option for metastatic prostate cancer (PCa). Despite initial remission, acquired DX resistance is inevitable. The mechanisms behind DX resistance have not yet been deciphered, but a mesenchymal phenotype is associated with DX resistance. Mesenchymal phenotypes have been linked to metabolic rewiring, obtaining most ATP production by oxidative phosphorylation (OXPHOS) powered substantially by glutamine (Gln). Likewise, Gln is known to play an essential role in modulating bioenergetic, redox homeostasis and autophagy. Herein, investigations of Gln deprivation on DX-sensitive and -resistant (DR) PCa cells revealed that the DR cell sub-lines were susceptible to Gln deprivation. Mechanistically, Gln deprivation reduced OXPHOS and ATP levels, causing a disturbance in cell cycle progression. Genetic and chemical inhibition of the Gln-metabolism key protein GLS1 could validate the Gln deprivation results, thereby representing a valid therapeutic target. Moreover, immunohistological investigation of GLS1 revealed a high-expressing GLS1 subgroup post-docetaxel failure, exhibiting low overall survival. This subgroup presents an intriguing opportunity for targeted therapy focusing on glutamine metabolism. Thus, these findings highlight a possible clinical rationale for the chemical inhibition of GLS1 as a therapeutic strategy to target mesenchymal DR PCa cells, thereby delaying accelerated tumour progression.


Assuntos
Proliferação de Células , Docetaxel , Resistencia a Medicamentos Antineoplásicos , Glutamina , Neoplasias da Próstata , Masculino , Humanos , Glutamina/metabolismo , Docetaxel/farmacologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Fosforilação Oxidativa/efeitos dos fármacos , Glutaminase/metabolismo , Glutaminase/antagonistas & inibidores , Glutaminase/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
13.
Acta Neuropathol Commun ; 12(1): 51, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38576030

RESUMO

DNA methylation analysis based on supervised machine learning algorithms with static reference data, allowing diagnostic tumour typing with unprecedented precision, has quickly become a new standard of care. Whereas genome-wide diagnostic methylation profiling is mostly performed on microarrays, an increasing number of institutions additionally employ nanopore sequencing as a faster alternative. In addition, methylation-specific parallel sequencing can generate methylation and genomic copy number data. Given these diverse approaches to methylation profiling, to date, there is no single tool that allows (1) classification and interpretation of microarray, nanopore and parallel sequencing data, (2) direct control of nanopore sequencers, and (3) the integration of microarray-based methylation reference data. Furthermore, no software capable of entirely running in routine diagnostic laboratory environments lacking high-performance computing and network infrastructure exists. To overcome these shortcomings, we present EpiDiP/NanoDiP as an open-source DNA methylation and copy number profiling suite, which has been benchmarked against an established supervised machine learning approach using in-house routine diagnostics data obtained between 2019 and 2021. Running locally on portable, cost- and energy-saving system-on-chip as well as gpGPU-augmented edge computing devices, NanoDiP works in offline mode, ensuring data privacy. It does not require the rigid training data annotation of supervised approaches. Furthermore, NanoDiP is the core of our public, free-of-charge EpiDiP web service which enables comparative methylation data analysis against an extensive reference data collection. We envision this versatile platform as a useful resource not only for neuropathologists and surgical pathologists but also for the tumour epigenetics research community. In daily diagnostic routine, analysis of native, unfixed biopsies by NanoDiP delivers molecular tumour classification in an intraoperative time frame.


Assuntos
Epigenômica , Neoplasias , Humanos , Aprendizado de Máquina não Supervisionado , Computação em Nuvem , Neoplasias/diagnóstico , Neoplasias/genética , Metilação de DNA
14.
Sci Rep ; 14(1): 9600, 2024 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671028

RESUMO

Aim of this study was to evaluate the efficacy of switching treatment to faricimab in neovascular age-related macular degeneration (nAMD) from other anti-VEGF agents. Fifty-eight eyes of fifty-one patients with nAMD and a full upload series of four faricimab injections were included. Demographic data, multimodal imaging and treatment parameters were recorded. The primary outcome measures were changes in central subfield thickness (CST) and subfoveal choroidal thickness (SFCT). A subgroup analysis was performed for eyes with prior ranibizumab (R) or aflibercept (A) treatment. Mean injection intervals before and after switching were comparable (33.8 ± 11.2 vs. 29.3 ± 2.6 days; p = 0.08). Mean CST of 361.4 ± 108.1 µm prior to switching decreased significantly to 318.3 ± 97.7 µm (p < 0.01) after the third faricimab injection, regardless of prior anti-VEGF treatment (p < 0.01). Although SFCT slightly improved for the whole cohort from 165.8 ± 76.8 µm to 161.0 ± 82,8 µm (p = 0.029), subgroup analysis did not confirm this positive effect (subgroup R: p = 0.604; subgroup A: p = 0.306). In patients with a suboptimal response to aflibercept or ranibizumab in nAMD, farcimab can improve CST and slightly improve or maintain SFCT. Further prospective randomized trials are warranted.


Assuntos
Inibidores da Angiogênese , Corioide , Ranibizumab , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Humanos , Masculino , Feminino , Idoso , Ranibizumab/administração & dosagem , Ranibizumab/uso terapêutico , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/uso terapêutico , Corioide/efeitos dos fármacos , Corioide/diagnóstico por imagem , Corioide/patologia , Idoso de 80 Anos ou mais , Resultado do Tratamento , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Retina/patologia , Retina/efeitos dos fármacos , Retina/diagnóstico por imagem , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Degeneração Macular/patologia , Tomografia de Coerência Óptica , Acuidade Visual/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Substituição de Medicamentos
15.
World J Urol ; 42(1): 239, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630278

RESUMO

PURPOSE: An abnormal lower urinary tract poses significant challenges for transplant surgeons. Besides the ureteral anastomosis to an ileal conduit, there are diverse complex reconstructive solutions. Due to its rarity, standardization and teaching of complex urinary diversion is extremely difficult. METHODS: The indications and outcomes of complex urinary diversions after kidney transplantation (KT) were retrospectively investigated at eight urologic transplant centers including a current follow-up. RESULTS: Of 37 patients with 21 (56%) males, vesicoureteral reflux (24%), spina bifida (22%), and glomerulonephritis (12%) were the most common causes of terminal renal failure. In 30 (81%) patients, urinary diversion was performed before KT, at a median of 107.5 (range, 10; 545) months before. Transplantations were held at a median patient age of 43 (10; 68) years, including six (16%) living donations. Urinary diversion was modified during 12 (32%) transplantations. After KT, the ileal conduit was the most common incontinent urinary diversion in 25 (67%) patients; a Mainz pouch I and bladder augmentation were the most frequent continent diversions (each n = 3). At a median follow-up of 120 months (range 0; 444), 12 (32%) patients had a graft failure with a 5-year graft survival of 79% (95%CI 61; 90). The median overall survival was 227 months (168; 286) and the 5-year overall survival 89% (69.3; 96.4). CONCLUSION: The mid-term kidney transplant function with complex urinary diversion appears to be comparable to transplants with regular urinary diversions. Hence, complex urinary diversion should always be considered as a surgical option, even during transplantation, if necessary.


Assuntos
Transplante de Rim , Procedimentos de Cirurgia Plástica , Cirurgiões , Derivação Urinária , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto
16.
J Cancer Res Clin Oncol ; 150(4): 201, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630148

RESUMO

PURPOSE: We assessed factors that affect the utilization of sperm cryopreservation before 2021, when patients covered expenses, and the influence on quality of life. METHODS: Between 2011 and 2021, testicular cancer survivors (TCS) at our clinic completed a questionnaire, including EORTC QLQ-TC26, covering sperm cryopreservation, sociodemographic details, post-treatment births, and artificial insemination. RESULTS: After 5.7 ± 3.0 years, 279 participants (64%) responded to the questionnaire. Among them, 33% (91/279) of testicular cancer survivors chose sperm cryopreservation prior to treatment, with 11% (10/91) using it for insemination. Conversely, 2% (3/188) without cryopreservation reported unfulfilled desire to have children. Univariate analysis showed TCS with cryopreservation were younger (30.6 ± 7.1 (35 (21-59)) vs. 42.4 ± 10.9 (48 (22-81)) years; p = 0.001), had a lower BMI (24.2 ± 3.3 vs. 26.6 ± 4.6 kg/m2; p = 0.009) and a lower Charlson Score (> 3: 36% vs. 60%; p < 0.001). Multivariate analysis revealed older age (≥ 37 years: OR 13.1 (5.5-31.2), p < 0.001) and lower education (middle school or less: OR 3.3 (1.6-6.9), p = 0.001) as independent factors associated with not undergoing cryopreservation. Regarding quality of life, multivariate analysis identified a lower infertility anxiety score (OR 4.3 (2.0-9.0), p < 0.001) and higher age (≥ 44 years: OR 5.4 (2.6-11.3); p < 0.001) as predictors for the absence of prior cryopreservation. CONCLUSIONS: Age and education seem to impact the choice of undergoing paid sperm cryopreservation. Urologists should inform testicular cancer patients about costs and coverage. Importantly, the occurrence of unmet desires for parenthood is minimal among those who forego cryopreservation.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Criança , Humanos , Masculino , Adulto , Neoplasias Testiculares/terapia , Qualidade de Vida , Sêmen , Criopreservação , Espermatozoides
17.
J Am Coll Emerg Physicians Open ; 5(2): e13123, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38644807

RESUMO

Objectives: Clinical examination alone cannot reliably rule out significant traumatic abdominal injury. Computed tomography (CT) has become the primary method for evaluating blunt abdominal trauma and clinicians rely heavily on it to rule out abdominal injury. Ultrasound examination may miss significant abdominal injury particularly in stable patients. The use of a contrast agent improves ultrasound sensitivity to visceral abdominal injuries. The objective of this diagnostic study is to compare bedside contrast enhanced ultrasound (CEUS) performed by emergency physicians to CT in hemodynamically stable adults for the assessment of blunt abdominal trauma and evaluate CEUS accuracy outcomes. Methods: Hemodynamically stable patients with blunt trauma were prospectively enrolled in the trauma bay. After initial evaluation, we included patients at risk of abdominal injury and for whom an abdominal CT was planned by the trauma leader. Ultrasonography was performed prospectively and at the bedside by the emergency physician followed by abdominal CT used as a reference standard. Results: Thirty-three patients were enrolled in the study; among them, 52% showed positive traumatic findings in abdominal CT scans, and 42% were diagnosed with solid organ lesions. Compared to CT, a focused abdominal sonography (FOCUS) examination, looking for free fluid or perirenal hematoma, showed limited performance for traumatic findings with a sensitivity of 65% (95% confidence interval [CI]: 38%-86%), a specificity of 75% (95% CI: 48%-93%), a negative likelihood ratio (NLR) of 0.47 (95% CI: 0.23-0.95), and a positive likelihood ratio (PLR) of 2.59 (95% CI: 1.03-6.48). When combining FOCUS with CEUS, the sensitivity of the sonography increased to 94% (95% CI: 71%-100%) with a specificity of 75% (95% CI: 48%-93%). The PLR was 3.76 (95% CI: 1.6-8.87) and the NLR was 0.08 (95% CI: 0.01-0.54). In our population, abdominal sonography with contrast failed to identify a single positive abdominal CT with a grade 1 kidney injury. Conclusions: A FOCUS examination shows limited sensitivity and specificity to detect positive abdominal CT in stable adults with abdominal trauma. With the addition of contrast and careful inspection of solid organs, abdominal sonography with contrast performed by the emergency physician improves the ability to rule out traumatic findings on abdominal CT. CEUS performed by emergency physicians may miss injuries, especially in the absence of free fluid, in cases of low-grade injuries, simultaneous injuries, or poor-quality examinations.

19.
BJU Int ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506410

RESUMO

OBJECTIVE: To evaluate the nationwide online decision aid 'Entscheidungshilfe Prostatakrebs' (established in 2016, >11.000 users and 60 new users/week) for patients with non-metastatic prostate cancer (PCa), from the perspective of patients and urologists. PATIENTS AND METHODS: To provide personalised information, the tool collects most of the International Consortium for Health Outcomes Measurement standard set, personal preferences, psychological features, and a validated rating of the tool. To evaluate urologists' opinions, we developed a structured two-page questionnaire. All data were collected anonymously. RESULTS: From June 2016 to December 2020, 11 290 patients used the PCa decision aid. Their median (interquartile range [IQR]) age was 67 (61-72) years. The median (IQR) time from initial diagnosis to using the tool was 4 (3-7) weeks. In all, 87.7% of users reported high satisfaction. In a multivariable model, predictors for considering observation were higher knowledge, using the decision aid alone, lower oncological risk, normal erectile function, and respective personal preferences. Of 194 urologists, 91 (47%) had implemented the decision aid in their clinical practice. The urologists' mean (SD) satisfaction score (1 'very good'; 6 'unsatisfactory') with it was 1.45 (0.55), and 92% recommended it. Half of the urologists reported time savings. CONCLUSION: Patients and urologists report a very high level of acceptance and satisfaction with this online tool. It offers advantages in shared decision-making and time efficiency. The usage of the decision aid might improve the adoption of active surveillance and watchful waiting when indicated.

20.
NPJ Precis Oncol ; 8(1): 67, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461318

RESUMO

Genomic tumor testing (GTT) is an emerging technology aimed at identifying variants in tumors that can be targeted with genomically matched drugs. Due to limited resources, rural patients receiving care in community oncology settings may be less likely to benefit from GTT. We analyzed GTT results and observational clinical outcomes data from patients enrolled in the Maine Cancer Genomics Initiative (MCGI), which provided access to GTTs; clinician educational resources; and genomic tumor boards in community practices in a predominantly rural state. 1603 adult cancer patients completed enrollment; 1258 had at least one potentially actionable variant identified. 206 (16.4%) patients received a total of 240 genome matched treatments, of those treatments, 64% were FDA-approved in the tumor type, 27% FDA-approved in a different tumor type and 9% were given on a clinical trial. Using Inverse Probability of Treatment Weighting to adjust for baseline characteristics, a Cox proportional hazards model demonstrated that patients who received genome matched treatment were 31% less likely to die within 1 year compared to those who did not receive genome matched treatment (HR: 0.69; 95% CI: 0.52-0.90; p-value: 0.006). Overall, GTT through this initiative resulted in levels of genome matched treatment that were similar to other initiatives, however, clinical trials represented a smaller share of treatments than previously reported, and "off-label" treatments represented a greater share. Although this was an observational study, we found evidence for a potential 1-year survival benefit for patients who received genome matched treatments. These findings suggest that when disseminated and implemented with a supportive infrastructure, GTT may benefit cancer patients in rural community oncology settings, with further work remaining on providing genome-matched clinical trials.

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