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1.
Radiographics ; 44(10): e240021, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39235963

RESUMEN

The widespread use of neck US and other imaging modalities has contributed to a phenomenon of increased detection of differentiated thyroid cancer (DTC). Most of these cancers remain indolent, without requiring surgical intervention. Nonetheless, a subset of patients who require surgical treatment experience subsequent disease recurrence. This most commonly occurs in the cervical lymph nodes and thyroid bed, followed by distant metastasis to the lungs and bones. Because imaging is an integral part of postoperative surveillance, radiologists play a central role in the detection of recurrent tumors and in guiding treatment in these patients. US is the primary imaging modality used for postoperative evaluation. Other modalities such as CT, MRI, radioactive iodine imaging, and PET/CT aid in the accurate diagnosis and characterization of recurrent disease. Therefore, radiologists must have a thorough understanding of the utility of these imaging techniques and the imaging characteristics of recurrent DTC when interpreting these multimodality studies. The interpretation of imaging findings should also be correlated with the clinical status of patients and their biochemical markers to minimize interpretative errors. The authors present a broad overview of the postoperative evaluation of DTC, including its initial primary management, staging, and prognostication; clinical risk stratification for recurrent disease; postoperative surveillance with imaging and evaluation of biochemical markers; and management of recurrent DTC. Published under a CC BY 4.0 license. Supplemental material is available for this article.


Asunto(s)
Recurrencia Local de Neoplasia , Neoplasias de la Tiroides , Tiroidectomía , Humanos , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Recurrencia Local de Neoplasia/diagnóstico por imagen , Estadificación de Neoplasias , Diagnóstico por Imagen/métodos
2.
Eur J Neurol ; : e16449, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39236309

RESUMEN

BACKGROUND AND PURPOSE: This study was undertaken to conduct a meta-analysis on the prevalence of aspiration pneumonia (AP) and hospital mortality in Parkinson disease (PD) as well as the risk of AP in PD patients compared to controls. METHODS: We searched MEDLINE and Embase from inception to 19 March 2024 to identify cross-sectional, cohort, and case-control studies comparing the frequency of AP and hospital mortality in PD patients. We computed risk ratios (RRs) with accompanying 95% confidence intervals (CIs) for each study and pooled the results using a random-effects meta-analysis. RESULTS: A total of 781 studies were initially screened, and 13 studies involving 541,785,587 patients were included. Patients with PD had >3 times higher risk of AP compared to controls (RR = 3.30, 95% CI = 1.82-6.00, p < 0.0001). This increased risk was similar in both cohort studies (RR = 3.01, 95% CI = 1.10-8.24, p = 0.03) and case-control studies (RR = 3.86, 95% CI = 3.84-3.87, p < 0.00001). The prevalence of AP in 12 studies was 2.74% (95% CI = 1.69-4.41), and hospital mortality was 10% in six studies (10.0%, 95% CI = 5.32-18.0). Prevalence of AP was higher in studies with smaller sample size (5.26%, 95% CI = 3.08-8.83 vs. 2.06%, 95% CI = 1.19-3.55, p = 0.02). CONCLUSIONS: Our meta-analysis showed that patients with PD had >3 times higher risk of AP, with an average 2.74% prevalence and 10.0% hospital mortality. Early recognition and treatment of AP in PD patients will help reduce morbidity and mortality. A multidisciplinary holistic approach is needed to address the multifactorial causes of AP.

3.
Oncology ; : 1-12, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39265556

RESUMEN

Introduction Early phase clinical trials (EPCT) enable access to novel therapies for patients who have exhausted standard of care treatment and contribute a crucial role in drug development and research. Culturally and linguistically diverse (CALD) or socially disadvantaged patients have notably lower rates of participation in these trials. We aimed to characterise the social and cultural demographics of patients enrolled on an EPCT in South Western Sydney. Methods We conducted a 10-year retrospective review of patients enrolled on a EPCT at Liverpool Hospital. CALD patients were defined as those born overseas or whose preferred language was other than English. The patient residential address was used to calculate distance travelled and the Index of Relative Socio-economic advantage and disadvantage (IRSD and IRSAD) scores were calculated and used as a surrogate for socioeconomic status (SES). Results Our study included 233 patients across 39 EPCTs. Ninety-one patients (39%) were identified as CALD. The median IRSD and IRSAD scores were 941 and 944 respectively with 62.7% - 67.4% of patients residing in an area with greater disadvantage compared to the median of Australia. The median distance travelled was 17 kilometres with only 12% of participants travelling more than 50 kilometres. CALD patients were more likely to reside in an area of low SES (OR 3.4, 95% CI 1.8 - 6.5, p<0.01) and travelled shorter median distances (10 vs 23 kilometres) when compared to non-CALD patients. Conclusion Our study cohort contained a lower proportion of CALD patients and a higher SES than what we might have expected from our local population. Furthermore, there was a trend toward greater SES disadvantage (lower IRSD/IRSAD scores) for the CALD population. This study provides novel Australian data to support the underrepresentation of culturally diverse or disadvantaged patients on EPCTs. Future efforts should be made to reduce barriers to participation and improve equity in clinical trial participation.

4.
Nutrients ; 16(16)2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39203903

RESUMEN

Background: Sarcopenia has been recognized as a determining factor in surgical outcomes and is associated with an increased risk of postoperative complications and readmission. Diagnosis is currently based on clinical guidelines, which includes assessment of skeletal muscle mass but not quality. Ultrasound has been proposed as a useful point-of-care diagnostic tool to assess muscle quality, but no validated cut-offs for sarcopenia have been reported. Using novel automated artificial intelligence (AI) software to interpret ultrasound images may assist in mitigating the operator-dependent nature of the modality. Our study aims to evaluate the fidelity of AI-aided ultrasound as a reliable and reproducible modality to assess muscle quality and diagnose sarcopenia in surgical patients. Methods: Thirty-six adult participants from an outpatient clinic were recruited for this prospective cohort study. Sarcopenia was diagnosed according to Asian Working Group for Sarcopenia (AWGS) 2019 guidelines. Ultrasonography of the rectus femoris muscle was performed, and images were analyzed by an AI software (MuscleSound® (Version 5.69.0)) to derive muscle parameters including intramuscular adipose tissue (IMAT) as a proxy of muscle quality. A receiver operative characteristic (ROC) curve was used to assess the predictive capability of IMAT and its derivatives, with area under the curve (AUC) as a measure of overall diagnostic accuracy. To evaluate consistency between ultrasound users of different experience, intra- and inter-rater reliability of muscle ultrasound parameters was analyzed in a separate cohort using intraclass correlation coefficients (ICC) and Bland-Altman plots. Results: The median age was 69.5 years (range: 26-87), and the prevalence of sarcopenia in the cohort was 30.6%. The ROC curve plotted with IMAT index (IMAT% divided by muscle area) yielded an AUC of 0.727 (95% CI: 0.551-0.904). An optimal cut-off point of 4.827%/cm2 for IMAT index was determined with a Youden's Index of 0.498. We also demonstrated that IMAT index has excellent intra-rater reliability (ICC = 0.938, CI: 0.905-0.961) and good inter-rater reliability (ICC = 0.776, CI: 0.627-0.866). In Bland-Altman plots, the limits of agreement were from -1.489 to 1.566 and -2.107 to 4.562, respectively. Discussion: IMAT index obtained via ultrasound has the potential to act as a point-of-care evaluation for sarcopenia screening and diagnosis, with good intra- and inter-rater reliability. The proposed IMAT index cut-off maximizes sensitivity for case finding, supporting its use as an easily implementable point-of-care test in the community for sarcopenia screening. Further research incorporating other ultrasound parameters of muscle quality may provide the basis for a more robust diagnostic tool to help predict surgical risk and outcomes.


Asunto(s)
Inteligencia Artificial , Sarcopenia , Ultrasonografía , Humanos , Sarcopenia/diagnóstico por imagen , Proyectos Piloto , Ultrasonografía/métodos , Femenino , Masculino , Estudios Prospectivos , Anciano , Persona de Mediana Edad , Reproducibilidad de los Resultados , Curva ROC , Adulto , Músculo Esquelético/diagnóstico por imagen , Anciano de 80 o más Años , Músculo Cuádriceps/diagnóstico por imagen
5.
Int J Mol Sci ; 25(16)2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39201360

RESUMEN

Caudal type homeobox transcription factor 2 (CDX2) is a gastrointestinal cancer biomarker that regulates epithelial development and differentiation. Absence or low levels of CDX2 have been associated with poor prognosis and proposed as a chemotherapy response predictor. Tumour tissue samples from 668 patients with stage I-IV colorectal cancer were stained for CDX2 and stratified into two subgroups according to expression levels. Statistical tests were used to evaluate CDX2's relationship with survival and chemotherapy response. Of 646 samples successfully stained, 51 (7.9%) had low CDX2 levels, and 595 (92.1%) had high levels. Low CDX2 staining was associated with poor differentiation and the presence of lymphovascular or perineural invasion and was more common in colon and right-sided tumours. Overall survival (p < 0.001) and disease-free survival (p = 0.009) were reduced in patients with low CDX2 expression. Multivariable analysis validated CDX2 as an independent poor prognostic factor after excluding confounding variables. There was no statistically significant improvement in survival with adjuvant chemotherapy in stage II colon cancer (p = 0.11). In the rectal cohort, there was no relationship between CDX2 levels and therapy response. While confirming the prognostic utility of CDX2 in colorectal cancer, our study highlights that larger studies are required to confirm its utility as a predictive chemotherapy biomarker, especially in left-sided and rectal cancers.


Asunto(s)
Biomarcadores de Tumor , Factor de Transcripción CDX2 , Neoplasias Colorrectales , Humanos , Factor de Transcripción CDX2/metabolismo , Factor de Transcripción CDX2/genética , Masculino , Femenino , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/tratamiento farmacológico , Persona de Mediana Edad , Pronóstico , Anciano , Biomarcadores de Tumor/metabolismo , Estadificación de Neoplasias , Adulto , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Quimioterapia Adyuvante
7.
bioRxiv ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-39005467

RESUMEN

Transfer RNA (tRNA) modifications have emerged as critical posttranscriptional regulators of gene expression affecting diverse biological and disease processes. While there is extensive knowledge about the enzymes installing the dozens of post-transcriptional tRNA modifications - the tRNA epitranscriptome - very little is known about how metabolic, signaling, and other networks integrate to regulate tRNA modification levels. Here we took a comprehensive first step at understanding epitranscriptome regulatory networks by developing a high-throughput tRNA isolation and mass spectrometry-based modification profiling platform and applying it to a Pseudomonas aeruginosa transposon insertion mutant library comprising 5,746 strains. Analysis of >200,000 tRNA modification data points validated the annotations of predicted tRNA modification genes, uncovered novel tRNA-modifying enzymes, and revealed tRNA modification regulatory networks in P. aeruginosa. Platform adaptation for RNA-seq library preparation would complement epitranscriptome studies, while application to human cell and mouse tissue demonstrates its utility for biomarker and drug discovery and development.

8.
Cancers (Basel) ; 16(11)2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38893125

RESUMEN

Given the crucial predictive implications of microsatellite instability (MSI) in colorectal cancer (CRC), MSI screening is commonly performed in those with and at risk for CRC. Here, we compared results from immunohistochemistry (IHC) and the droplet digital PCR (ddPCR) MSI assay on formalin-fixed paraffin-embedded tumor samples from 48 patients who underwent surgery for colon and rectal cancer by calculating Cohen's kappa measurement (k), revealing high agreement between the methods (k = 0.915). We performed Kaplan-Meier survival analyses and univariate and multivariate Cox regression to assess the prognostic significance of ddPCR-based MSI and to identify clinicopathological features associated with CRC outcome. Patients with MSI-high had better overall survival (OS; p = 0.038) and disease-free survival (DFS; p = 0.049) than those with microsatellite stability (MSS). When stratified by primary tumor location, right-sided CRC patients with MSI-high showed improved DFS, relative to those with MSS (p < 0.001), but left-sided CRC patients did not. In multivariate analyses, MSI-high was associated with improved OS (hazard ratio (HR) = 0.221, 95% confidence interval (CI): 0.026-0.870, p = 0.042), whereas the loss of DNA mismatch repair protein MutL homolog 1 (MLH1) expression was associated with worse OS (HR = 0.133, 95% CI: 0.001-1.152, p = 0.049). Our results suggest ddPCR is a promising tool for MSI detection. Given the opposing effects of MSI-high and MLH1 loss on OS, both ddPCR and IHC may be complementary for the prognostic assessment of CRC.

9.
Pathology ; 56(6): 786-794, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38918148

RESUMEN

KRAS G12C is the most common KRAS mutation in non-small cell lung carcinoma (NSCLC), for which targeted therapy has recently been developed. From the 732 cases of NSCLC that underwent next-generation sequencing at the Department of Anatomical Pathology, Liverpool Hospital, between July 2021 and May 2023, we retrieved 83 (11%) consecutive cases of KRAS G12C mutated NSCLC, and analysed their clinical, pathological, and molecular features. Of the 83 cases of KRAS G12C mutated NSCLC, there were 46 (55%) men and 37 (45%) women, with mean age of 72 years. Of the 49 cases with known clinical information, 94% were current or ex-smokers, and 49% were stage IV at diagnosis with median survival of 12 months. Sixty-three percent were histology cases and the remainder were cytology cases. Eighty-two percent were non-mucinous adenocarcinomas, with conventional histology including lepidic, acinar, solid, single cells and micropapillary patterns, and 62% were poorly differentiated. There were five (6%) cases of mucinous adenocarcinoma, one case of pleomorphic carcinoma and one case of high-grade fetal adenocarcinoma. TTF1 was positive in the majority (89%) of cases. Nineteen (23%) cases had TP53 co-mutation, and these cases had trends towards higher PD-L1 expression, poor differentiation, and presentation as stage IV disease, but the differences were not statistically significant. KRAS G12C mutated NSCLCs almost exclusively occurred in smokers and were mostly non-mucinous adenocarcinomas with conventional histological patterns which ranged from well to poorly differentiated. Around a quarter had TP53 co-mutation, the histological impacts and immune profile of which need to be assessed in a larger study.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Mutación , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Masculino , Femenino , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Adulto
10.
Clin Nucl Med ; 49(8): e415-e416, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38861378

RESUMEN

ABSTRACT: A 75-year-old woman with papillary thyroid carcinoma who underwent 131 I radioiodine treatment was incidentally found to have an established left cerebral infarct demonstrating 131 I uptake on posttherapy whole-body scan. False-positive iodine accumulation can occur in benign processes and other malignancies, necessitating awareness among nuclear medicine physicians to avoid misdiagnosing metastatic disease. SPECT/CT can be utilized to enhance diagnostic accuracy when needed.


Asunto(s)
Infarto Cerebral , Radioisótopos de Yodo , Imagen de Cuerpo Entero , Humanos , Anciano , Femenino , Infarto Cerebral/diagnóstico por imagen , Cáncer Papilar Tiroideo/diagnóstico por imagen , Cáncer Papilar Tiroideo/radioterapia , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/radioterapia , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Transporte Biológico
12.
Clin Genitourin Cancer ; 22(4): 102116, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38810324

RESUMEN

PURPOSE: Adherence to active surveillance in patients with stage 1 testicular cancers may be influenced by factors affecting capacity and motivation to attend appointments. The aims of this study were to assess adherence to active surveillance and analyze factors which may impact adherence. PATIENTS AND METHODS: A retrospective cohort study was conducted in patients diagnosed with stage 1 testicular cancer between 2005 and 2020, and managed with active surveillance at 3 institutions in South Western Sydney, Australia. Adherence with active surveillance was followed to 2023 and patients were subsequently classified into 3 groups: "Optimal," "Adequate" or "Loss to follow-up" (LTFU). Factors for adherence were analyzed using multivariable logistic regression. Disease recurrence was analyzed using multivariable Cox regression. RESULTS: In 125 patients, adherence with active surveillance was assessed as "Optimal" in 64 (51%), "Adequate" in 14 (11%), and LTFU in 47 (38%). Multivariable analysis demonstrated that patients had higher odds of being in the "Optimal" or "Adequate" categories if they were from a culturally and linguistically diverse background (OR 4.86, P = .026), nonsmokers (OR 7.63, P = .0002), not employed (OR 4.93, P = .0085), had a partner (OR 2.74, P = .0326), or were diagnosed after June 2016 (OR 5.22, P = .0016). Recurrence occurred in 21 patients (17%). The risk of recurrence increased with the presence of multiple pathological risk factors (HR 5.77, P = .0032), if patients were unemployed (HR 2.57, P = .032), or if they had "Optimal" or "Adequate" adherence (HR 12.74, P = .0136). CONCLUSION: Adherence with active surveillance was poorer in this cohort of stage 1 testicular cancer patients. Patients from culturally and linguistically diverse backgrounds and those who were nonsmokers, unemployed, with a partner, and later date of diagnosis, were more likely to be adherent with active surveillance.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Cooperación del Paciente , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Testiculares/psicología , Neoplasias Testiculares/patología , Neoplasias de Células Germinales y Embrionarias/psicología , Estudios Retrospectivos , Adulto , Factores de Riesgo , Cooperación del Paciente/estadística & datos numéricos , Espera Vigilante/estadística & datos numéricos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/psicología , Estadificación de Neoplasias , Australia , Adulto Joven
13.
Knee Surg Relat Res ; 36(1): 15, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38566254

RESUMEN

BACKGROUND: Chat Generative Pretrained Transformer (ChatGPT), a generative artificial intelligence chatbot, may have broad applications in healthcare delivery and patient education due to its ability to provide human-like responses to a wide range of patient queries. However, there is limited evidence regarding its ability to provide reliable and useful information on orthopaedic procedures. This study seeks to evaluate the accuracy and relevance of responses provided by ChatGPT to frequently asked questions (FAQs) regarding total knee replacement (TKR). METHODS: A list of 50 clinically-relevant FAQs regarding TKR was collated. Each question was individually entered as a prompt to ChatGPT (version 3.5), and the first response generated was recorded. Responses were then reviewed by two independent orthopaedic surgeons and graded on a Likert scale for their factual accuracy and relevance. These responses were then classified into accurate versus inaccurate and relevant versus irrelevant responses using preset thresholds on the Likert scale. RESULTS: Most responses were accurate, while all responses were relevant. Of the 50 FAQs, 44/50 (88%) of ChatGPT responses were classified as accurate, achieving a mean Likert grade of 4.6/5 for factual accuracy. On the other hand, 50/50 (100%) of responses were classified as relevant, achieving a mean Likert grade of 4.9/5 for relevance. CONCLUSION: ChatGPT performed well in providing accurate and relevant responses to FAQs regarding TKR, demonstrating great potential as a tool for patient education. However, it is not infallible and can occasionally provide inaccurate medical information. Patients and clinicians intending to utilize this technology should be mindful of its limitations and ensure adequate supervision and verification of information provided.

14.
Lancet Oncol ; 25(5): 563-571, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38621400

RESUMEN

BACKGROUND: Enzalutamide and lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [177Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer. METHODS: ENZA-p was an open-label, randomised, controlled phase 2 trial done at 15 hospitals in Australia. Participants were men aged 18 years or older with metastatic castration-resistant prostate cancer not previously treated with docetaxel or androgen receptor pathway inhibitors for metastatic castration-resistant prostate cancer, gallium-68 [68Ga]Ga-PSMA-PET-CT (PSMA-PET-CT) positive disease, Eastern Cooperative Oncology Group performance status of 0-2, and at least two risk factors for early progression on enzalutamide. Participants were randomly assigned (1:1) by a centralised, web-based system using minimisation with a random component to stratify for study site, disease burden, use of early docetaxel, and previous treatment with abiraterone acetate. Patients were either given oral enzalutamide 160 mg daily alone or with adaptive-dosed (two or four doses) intravenous 7·5 GBq [177Lu]Lu-PSMA-617 every 6-8 weeks dependent on an interim PSMA-PET-CT (week 12). The primary endpoint was prostate-specific antigen (PSA) progression-free survival, defined as the interval from the date of randomisation to the date of first evidence of PSA progression, commencement of non-protocol anticancer therapy, or death. The analysis was done in the intention-to-treat population, using stratified Cox proportional hazards regression. This trial is registered with ClinicalTrials.gov, NCT04419402, and participant follow-up is ongoing. FINDINGS: 162 participants were randomly assigned between Aug 17, 2020, and July 26, 2022. 83 men were assigned to the enzalutamide plus [177Lu]Lu-PSMA-617 group, and 79 were assigned to the enzalutamide group. Median follow-up in this interim analysis was 20 months (IQR 18-21), with 32 (39%) of 83 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 16 (20%) of 79 patients in the enzalutamide group remaining on treatment at the data cutoff date. Median age was 71 years (IQR 64-76). Median PSA progression-free survival was 13·0 months (95% CI 11·0-17·0) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 7·8 months (95% CI 4·3-11·0) in the enzalutamide group (hazard ratio 0·43, 95% CI 0·29-0·63, p<0·0001). The most common adverse events (all grades) were fatigue (61 [75%] of 81 patients), nausea (38 [47%]), and dry mouth (32 [40%]) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and fatigue (55 [70%] of 79), nausea (21 [27%]), and constipation (18 [23%]) in the enzalutamide group. Grade 3-5 adverse events occurred in 32 (40%) of 81 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 32 (41%) of 79 patients in the enzalutamide group. Grade 3 events that occurred only in the enzalutamide plus [177Lu]Lu-PSMA-617 group included anaemia (three [4%] of 81 participants) and decreased platelet count (one [1%] participant). No grade 4 or 5 events were attributed to treatment on central review in either group. INTERPRETATION: The addition of [177Lu]Lu-PSMA-617 to enzalutamide improved PSA progression-free survival providing evidence of enhanced anticancer activity in patients with metastatic castration-resistant prostate cancer with risk factors for early progression on enzalutamide and warrants further evaluation of the combination more broadly in metastatic prostate cancer. FUNDING: Prostate Cancer Research Alliance (Movember and Australian Federal Government), St Vincent's Clinic Foundation, GenesisCare, Roy Morgan Research, and Endocyte (a Novartis company).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Dipéptidos , Compuestos Heterocíclicos con 1 Anillo , Lutecio , Nitrilos , Feniltiohidantoína , Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Feniltiohidantoína/administración & dosificación , Feniltiohidantoína/uso terapéutico , Feniltiohidantoína/análogos & derivados , Anciano , Dipéptidos/uso terapéutico , Dipéptidos/administración & dosificación , Dipéptidos/efectos adversos , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Compuestos Heterocíclicos con 1 Anillo/administración & dosificación , Compuestos Heterocíclicos con 1 Anillo/efectos adversos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno Prostático Específico/sangre , Supervivencia sin Progresión , Radioisótopos/uso terapéutico , Anciano de 80 o más Años , Radiofármacos
15.
J Med Imaging Radiat Oncol ; 68(4): 412-420, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38632711

RESUMEN

Prostate cancer remains one of the leading causes of cancer-related death in the world. There have been significant advances in chemotherapy, hormonal therapy and targeted therapy options for patients with castrate-resistant disease. However, these systemic treatments are often associated with unwanted toxicities. Targeted therapy with radiopharmaceuticals has become of key interest to limit systemic toxicity and provides a more precision oncology approach to treatment. Strontium-89, Samarium-153 EDTMP and Radium-223 have been trialled with mixed results. Strontium-89 and Samarium-153 EDTMP have shown benefits in palliating metastatic bone pain but with no impact on survival outcomes. Early therapeutic radiopharmaceuticals targeting PSMA that were developed were beta-emitting agents, but recently alpha-emitting agents are being investigated as potentially superior options. Radium-223 is the first alpha-particle emitter therapeutic agent approved by the FDA, with phase III trial evidence showing benefits in overall survival and delay in symptomatic skeletal events for patients. Recently, 177-Lutetium-PSMA-617 has demonstrated significant survival advantages in pre-treated metastatic castrate-resistant cancer patients in a number of phase II and III studies. Furthermore, 225-Actinium-PSMA-617 also showed promise even in patients pre-treated with 177-Lutetium-PSMA-617. Hence, there has been an explosion of radiopharmaceutical treatment options for patients with prostate cancer. This review explores past and current theranostic capacities in the radiopharmaceutical treatment of metastatic castrate-resistant prostate cancer.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Radiofármacos , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Neoplasias de la Próstata Resistentes a la Castración/patología , Radiofármacos/uso terapéutico , Nanomedicina Teranóstica/métodos , Neoplasias Óseas/secundario , Neoplasias Óseas/radioterapia , Neoplasias Óseas/terapia , Neoplasias Óseas/diagnóstico por imagen , Radioisótopos/uso terapéutico
16.
Anticancer Res ; 44(5): 2095-2102, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38677731

RESUMEN

BACKGROUND/AIM: Early phase clinical trials (EPCTs) assess the tolerability of novel anti-cancer therapeutics in patients with advanced malignancy. Patient selection is important given the modest clinical benefit and time commitments for trials. Prognostic scores have been developed to facilitate identification of high-risk patients. This study aimed to compare five prognostic scores to predict survival for patients on an EPCT. PATIENTS AND METHODS: We performed a retrospective review of patients enrolled in EPCT at Liverpool Hospital, Sydney, from 2013 to 2023. Demographic, biochemical, and survival data were collected from electronic medical records. The score from five prognostic scoring systems (Royal Marsden hospital, MD Anderson Cancer centre, Gustave Roussy Immune, MD Anderson Immune Checkpoint Inhibitor and Princess Margaret Hospital Index) were calculated. Overall survival was measured using the Kaplan-Meier method and predictive discrimination was assessed using Harrell's c-index. RESULTS: A total of 218 patients across 36 EPCTs were included. The median overall survival was 9.8 months with 22% of patients dying in less than 90 days. Seventeen to thirty-four percent of patients were categorised as high-risk. The MDACC score obtained the highest predictability for overall survival for the whole cohort (c-index=0.67, 95%CI=0.62-0.72) and the immunotherapy-based cohort (c-index= 0.65, 95%CI=0.59-0.71). However, all scores performed similarly with a significant overlap in the confidence intervals. CONCLUSION: Our retrospective audit confirms the utility of prognostic scores to predict survival in an Australian EPCT cohort, with similar predictive discrimination across various scoring systems. Integration of these prognostic tools into EPCT screening processes may optimise benefits and reduce risks associated with EPCTs.


Asunto(s)
Neoplasias , Humanos , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Australia/epidemiología , Adulto , Anciano de 80 o más Años , Ensayos Clínicos como Asunto
18.
Asian J Urol ; 11(1): 55-64, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38312819

RESUMEN

Objective: To scrutinize the definitions of minimal invasive surgical therapy (MIST) and to investigate urologists' knowledge, attitudes, and practices for benign prostatic obstruction surgeries. Methods: A 36-item survey was developed with a Delphi method. Questions on definitions of MIST and attitudes and practices of benign prostatic obstruction surgeries were included. Urologists were invited globally to complete the online survey. Consensus was achieved when more than or equal to 70% responses were "agree or strongly agree" and less than or equal to 15% responses were "disagree or strongly disagree" (consensus agree), or when more than or equal to 70% responses were "disagree or strongly disagree" and less than or equal to 15% responses were "agree or strongly agree" (consensus disagree). Results: The top three qualities for defining MIST were minimal blood loss (n=466, 80.3%), fast post-operative recovery (n=431, 74.3%), and short hospital stay (n=425, 73.3%). The top three surgeries that were regarded as MIST were Urolift® (n=361, 62.2%), Rezum® (n=351, 60.5%), and endoscopic enucleation of the prostate (EEP) (n=332, 57.2%). Consensus in the knowledge section was achieved for the superiority of Urolift®, Rezum®, and iTIND® over transurethral resection of the prostate with regard to blood loss, recovery, day surgery feasibility, and post-operative continence. Consensus in the attitudes section was achieved for the superiority of Urolift®, Rezum®, and iTIND® over transurethral resection of the prostate with regard to blood loss, recovery, and day surgery feasibility. Consensus on both sections was achieved for EEP as the option with the better symptoms and flow improvement, lower retreatment rate, and better suitable for prostate more than 80 mL. Conclusion: Minimal blood loss, fast post-operative recovery, and short hospital stay were the most important qualities for defining MIST. Urolift®, Rezum®, and EEP were regarded as MIST by most urologists.

19.
J Clin Nurs ; 33(6): 2005-2018, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38379353

RESUMEN

AIM: The early warning scores (EWS), quick Sequential Organ Failure Assessment (qSOFA) and systemic inflammatory response syndrome (SIRS) criteria have been proposed as sepsis screening tools. This review aims to summarise and compare the performance of EWS with the qSOFA and SIRS criteria for predicting sepsis diagnosis and in-hospital mortality in patients with sepsis. DESIGN: A systematic review with meta-analysis. REVIEW METHODS: Seven databases were searched from January 1, 2016 until March 10, 2022. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Sensitivity, specificity, likelihood ratios and diagnostic odd ratios were pooled by using the bivariate random effects model. Overall performance was summarised by using the hierarchical summary receiver-operating characteristics curve. This paper adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines. RESULTS: Ten studies involving 52,474 subjects were included in the review. For predicting sepsis diagnosis, the pooled sensitivity of EWS (65%, 95% CI: 55, 75) was similar to SIRS ≥2 (70%, 95% CI: 49, 85) and higher than qSOFA ≥2 (37%, 95% CI: 20, 59). The pooled specificity of EWS (77%, 95% CI: 64, 86) was higher than SIRS ≥2 (62%, 95% CI: 41, 80) but lower than qSOFA ≥2 (94%, 95% CI: 86, 98). Results were similar for the secondary outcome of in-hospital mortality. CONCLUSIONS: Although no one scoring system had both high sensitivity and specificity, the EWS had at least equivalent values in most measures of diagnostic accuracy compared with SIRS or qSOFA. IMPLICATIONS FOR THE PROFESSION: Healthcare systems in which EWS is already in place should consider whether there is any clinical benefit in adopting qSOFA or SIRS. NO PATIENT OR PUBLIC CONTRIBUTION: This systematic review did not directly involve patient or public contribution to the manuscript.


Asunto(s)
Mortalidad Hospitalaria , Sepsis , Humanos , Sepsis/mortalidad , Sepsis/diagnóstico , Puntuación de Alerta Temprana , Puntuaciones en la Disfunción de Órganos , Adulto , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/mortalidad , Sensibilidad y Especificidad
20.
Medicina (Kaunas) ; 60(1)2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38256380

RESUMEN

Background and Objectives: Type 1 diabetes mellitus (T1DM) is a chronic and serious condition that is characterized by inadequate pancreatic-ß-cells' insulin production. The connection between T1DM and Helicobacter pylori infection remains uncertain. This study aimed to conduct a systematic meta-analysis to examine the association between H. pylori infection, hemoglobin A1c levels, and the development of T1DM. Materials and Methods: The initial search identified 451 articles on the association between H. pylori infection and T1DM. Among them, 12 articles had 2797 participants who met the inclusion criteria for an advanced meta-analysis. Results: A significant association was observed between H. pylori infection and T1DM (OR 1.77, 95% CI 1.47-2.12, p < 0.0001), with heterogeneity: Tau2 = 0.47; Chi2 = 57.07, df = 11 (p < 0.0001); I2 = 81%. Subgroup analysis showed that H. pylori infection was significantly associated with a longer duration of T1DM and higher hemoglobin A1c levels (p < 0.001 for both) but not with age at T1DM diagnosis (p = 0.306). Conclusions: These findings contribute to the understanding of the association between H. pylori infection and T1DM and highlight the potential role of H. pylori in influencing the duration and glycemic control of diabetes. Therefore, pediatric patients who have longstanding T1DM and poor glycemic control should be screened for H. pylori infection.


Asunto(s)
Diabetes Mellitus Tipo 1 , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Niño , Lactante , Diabetes Mellitus Tipo 1/complicaciones , Infecciones por Helicobacter/complicaciones , Hemoglobina Glucada , Control Glucémico
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