-
Journal of Alzheimer's Disease Reports 2024Alzheimer's disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in...
BACKGROUND
Alzheimer's disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in targeting core AD pathology, clinical studies are limited.
OBJECTIVE
A systematic review was performed to evaluate GLP-1 RAs in AD for their potential to target core AD pathology and improve cognition.
METHODS
Searches were conducted via three different databases (PubMed, Embase, and Cochrane Library). Search terms included Medical Subject Headings (MeSH) terms: 'glucagon-like peptide 1 receptor agonist' and 'Alzheimer's disease', as well as entry terms 'GLP-1 RA', 'AD', and three types of GLP-1 RA: 'liraglutide', 'exenatide', and 'lixisenatide'.
RESULTS
A total of 1,444 studies were screened. Six articles that met criteria were included (four randomized control trials [RCTs] and two protocol studies). Two RCTs with amyloid-β and tau biomarker endpoints did not observe an end of treatment difference between the placebo and treated groups. In three RCTs with cognitive endpoints, there was no end of treatment difference between placebo and treated groups. GLP-1 RA showed metabolic benefits, such as lower body mass index and improved glucose levels on oral glucose tolerance tests in treated groups. GLP-1 RA may mitigate the decline in cerebral glucose metabolism and show enhanced blood-brain glucose transport capacity using F-FDG PET, however, more data is needed.
CONCLUSIONS
GLP-1 RA therapy did not alter amyloid-β and tau biomarkers nor show improvements in cognition but showed potential metabolic and neuroprotective benefits.
PubMed: 38746639
DOI: 10.3233/ADR-230181 -
Journal of Cachexia, Sarcopenia and... Jun 2024Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary... (Review)
Review
Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary endpoints. To date, there has been no review of the most commonly selected measures or their potential sensitivity to detect changes resulting from the interventions being examined. The aim of this systematic review is to assess the frequency and diversity of body composition measures that have been used in cancer cachexia trials. MEDLINE, Embase and Cochrane Library databases were systematically searched between January 1990 and June 2021. Eligible trials examined adults (≥18 years) who had received an intervention aiming to treat or attenuate the effects of cancer cachexia for >14 days. Trials were also of a prospective controlled design and included body weight or at least one anthropometric, bioelectrical or radiological endpoint pertaining to body composition, irrespective of the modality of intervention (e.g., pharmacological, nutritional, physical exercise and behavioural) or comparator. Trials with a sample size of <40 patients were excluded. Data extraction used Covidence software, and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. This review was prospectively registered (PROSPERO: CRD42022276710). A total of 84 clinical trials, comprising 13 016 patients, were eligible for inclusion. Non-small-cell lung cancer and pancreatic cancer were studied most frequently. The majority of trial interventions were pharmacological (52%) or nutritional (34%) in nature. The most frequently reported endpoints were assessments of body weight (68 trials, n = 11 561) followed by bioimpedance analysis (BIA)-based estimates (23 trials, n = 3140). Sixteen trials (n = 3052) included dual-energy X-ray absorptiometry (DEXA)-based endpoints, and computed tomography (CT) body composition was included in eight trials (n = 841). Discrepancies were evident when comparing the efficacy of interventions using BIA-based estimates of lean tissue mass against radiological assessment modalities. Body weight, BIA and DEXA-based endpoints have been most frequently used in cancer cachexia trials. Although the optimal endpoints cannot be determined from this review, body weight, alongside measurements from radiological body composition analysis, would seem appropriate. The choice of radiological modality is likely to be dependent on the trial setting, population and intervention in question. CT and magnetic resonance imaging, which have the ability to accurately discriminate tissue types, are likely to be more sensitive and provide greater detail. Endpoints are of particular importance when aligned with the intervention's mechanism of action and/or intended patient benefit.
Topics: Humans; Cachexia; Neoplasms; Body Composition; Body Weight; Clinical Trials as Topic
PubMed: 38738581
DOI: 10.1002/jcsm.13478 -
Cancers May 2024Richter transformation is a rare phenomenon characterized by the transformation of cell chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma variant. The... (Review)
Review
The Diagnostic Performance of 2-[F]FDG PET/CT in Identifying Richter Transformation in Chronic Lymphocytic Leukemia: An Updated Systematic Review and Bivariate Meta-Analysis.
Richter transformation is a rare phenomenon characterized by the transformation of cell chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma variant. The early identification of CLLs with a high risk of RT is fundamental. In this field, 2-deoxy-2-[F]-fluoro-D-glucose positron emission tomography/computed tomography (2-[F]FDG PET/CT) has been shown to be a non-invasive and promising tool, but apparently, unclear data seem to be present in the literature. This systematic review and bivariate meta-analysis aimed to investigate the diagnostic performance of 2-[F]FDG PET/CT and its parameters in predicting RT. Between 2006 and 2024, 15 studies were published on this topic, including 1593 CLL patients. Among semiquantitative variables, SUV was the most investigated, and the best threshold derived for detecting RT was five. With this cut-off value, a pooled sensitivity of 86.8% (95% CI: 78.5-93.3), a pooled specificity of 48.1% (95% CI: 27-69.9), a pooled negative predictive value of 90.5% (95% CI: 88.4-92.4), a pooled negative likelihood ratio of 0.35 (95% CI: 0.17-0.70), a pooled positive likelihood ratio of 1.8 (95% CI: 1.3-2.4), and a pooled diagnostic odds ratio of 6.7 (3.5-12.5) were obtained. With a higher cut-off (SUV = 10), the specificity increased while the sensitivity reduced. The other metabolic features, like metabolic tumor volume, total lesion glycolysis, and radiomic features, were only marginally investigated with controversial evidence.
PubMed: 38730730
DOI: 10.3390/cancers16091778 -
Cancers Apr 2024In this systematic review and meta-analysis (PRISMA-compliant), we tried to investigate diagnostic and prognostic values of F-FDG PET in uveal melanoma. A systematic... (Review)
Review
In this systematic review and meta-analysis (PRISMA-compliant), we tried to investigate diagnostic and prognostic values of F-FDG PET in uveal melanoma. A systematic search was conducted on the main medical literature databases to include studies that evaluated F-FDG PET as the imaging modality to evaluate patients with uveal melanoma. Overall, 27 studies were included. Twelve had data about the detection rate of F-FDG PET in primary intra-ocular tumours. The pooled sensitivity was 45% (95%CI: 41-50%). Furthermore, studies showed that the larger the primary tumour, the higher its uptake. Among the included studies, 13 assessed F-FDG PET in detecting metastasis. The pooled sensitivity and specificity were 96% (95%CI: 81-99%) and 100% (95%CI: 94-100%), respectively. Regarding liver metastasis, they were 95% (95%CI: 79-99%) and 100% (95%CI: 91-100%), respectively. Noteworthy, the level of F-FDG uptake was a strong predictor of patient survival. Lastly, F-FDG PET could characterise lesions from the histopathology perspective, distinguishing high-risk from low-risk diseases. Overall, although not reliable in detecting primary intra-ocular tumours, F-FDG PET is highly accurate for diagnosing metastatic uveal melanomas. It can also be a highly valuable modality in terms of patient prognostication. Thus, F-FDG PET can be recommended in patients diagnosed with uveal melanoma to enhance decision-making and patient management.
PubMed: 38730664
DOI: 10.3390/cancers16091712 -
Pharmacopsychiatry May 2024Conventional antipsychotic drugs that attenuate dopaminergic neural transmission are ineffective in approximately one-third of patients with schizophrenia. This...
INTRODUCTION
Conventional antipsychotic drugs that attenuate dopaminergic neural transmission are ineffective in approximately one-third of patients with schizophrenia. This necessitates the development of non-dopaminergic agents.
METHODS
A systematic search was conducted for completed phase II and III trials of compounds for schizophrenia treatment using the US Clinical Trials Registry and the EU Clinical Trials Register. Compounds demonstrating significant superiority over placebo in the primary outcome measure in the latest phase II and III trials were identified. Collateral information on the included compounds was gathered through manual searches in PubMed and press releases.
RESULTS
Sixteen compounds were identified; four compounds (ulotaront, xanomeline/trospium chloride, vabicaserin, and roluperidone) were investigated as monotherapy and the remaining 12 (pimavanserin, bitopertin, BI 425809, encenicline, tropisetron, pregnenolone, D-serine, estradiol, tolcapone, valacyclovir, cannabidiol, and rimonabant) were examined as add-on therapy. Compared to the placebo, ulotaront, xanomeline/trospium chloride, vabicaserin, bitopertin, estradiol, cannabidiol, rimonabant, and D-serine showed efficacy for positive symptoms; roluperidone and pimavanserin were effective for negative symptoms; and encenicline, tropisetron, pregnenolone, tolcapone, BI 425809, and valacyclovir improved cognitive function.
DISCUSSION
Compounds that function differently from existing antipsychotics may offer novel symptom-specific therapeutic strategies for patients with schizophrenia.
PubMed: 38710208
DOI: 10.1055/a-2307-6484 -
Diseases of the Colon and Rectum Jun 2024A variety of definitions for a clinical near-complete response after neoadjuvant (chemo) radiotherapy for rectal cancer are currently used. This variety leads to...
BACKGROUND
A variety of definitions for a clinical near-complete response after neoadjuvant (chemo) radiotherapy for rectal cancer are currently used. This variety leads to inconsistency in clinical practice, long-term outcome, and trial enrollment.
OBJECTIVE
The aim of this study was to reach expert-based consensus on the definition of a clinical near-complete response after (chemo) radiotherapy.
DESIGN
A modified Delphi process, including a systematic review, 3 surveys, and 2 meetings, was performed with an international expert panel consisting of 7 surgeons and 4 radiologists. The surveys consisted of individual features, statements, and feature combinations (endoscopy, T2-weighted MRI, and diffusion-weighted MRI).
SETTING
The modified Delphi process was performed in an online setting; all 3 surveys were completed online by the expert panel, and both meetings were hosted online.
MAIN OUTCOME MEASURES
The main outcome was to reach consensus (80% or more agreement).
RESULTS
The expert panel reached consensus on a 3-tier categorization of the near-complete response category based on the likelihood of the response to evolve into a clinical complete response after a longer waiting interval. The panelists agreed that a near-complete response is a temporary entity only to be used in the first 6 months after (chemo)radiotherapy. Furthermore, consensus was reached that the lymph node status should be considered when deciding on a near-complete response and that biopsies are not always needed when a near-complete response is found. No consensus was reached on whether primary staging characteristics have to be taken into account when deciding on a near-complete response.
LIMITATIONS
This 3-tier subcategorization is expert-based; therefore, there is no supporting evidence for this subcategorization. Also, it is unclear whether this subcategorization can be generalized into clinical practice.
CONCLUSIONS
Consensus was reached on the use of a 3-tier categorization of a near-complete response, which can be helpful in daily practice as guidance for treatment and to inform patients with a near-complete response on the likelihood of successful organ preservation. See Video Abstract.
UN CONSENSO INTERNACIONAL BASADO EN EXPERTOS ACERCA DE LA DEFINICIN DE UNA RESPUESTA CLNICA CASI COMPLETA DESPUS DE QUIMIORADIOTERAPIA NEOADYUVANTE CONTRA EL CNCER DE RECTO
ANTECEDENTES:Actualmente, se utilizan una variedad de definiciones para una respuesta clínica casi completa después de quimioradioterapia neoadyuvante contra el cáncer de recto. Esta variedad resulta en inconsistencia en la práctica clínica, los resultados a largo plazo y la inscripción en ensayos.OBJETIVO:El objetivo de este estudio fue llegar a un consenso de expertos sobre la definición de una respuesta clínica casi completa después de quimioradioterapia.DISEÑO:Se realizó un proceso Delphi modificado que incluyó una revisión sistemática, 3 encuestas y 2 reuniones con un panel internacional de expertos compuesto por siete cirujanos y 4 radiólogos. Las encuestas consistieron en características individuales, declaraciones y combinaciones de características (endoscopía, T2W-MRI y DWI).AJUSTE:El proceso Delphi modificado se realizó en un entorno en línea; el panel de expertos completó las tres encuestas en línea y ambas reuniones se realizaron en línea.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue llegar a un consenso (≥80% de acuerdo).RESULTADOS:El panel de expertos llegó a un consenso sobre una categorización de tres niveles de la categoría de respuesta casi completa basada en la probabilidad de que la respuesta evolucione hacia una respuesta clínica completa después de un intervalo de espera más largo. Los panelistas coincidieron en que una respuesta casi completa es una entidad temporal que sólo debe utilizarse en los primeros 6 meses después de la quimioradioterapia. Además, se llegó a un consenso en que se debe considerar el estado de los nódulos linfáticos al decidir sobre una respuesta casi completa y que no siempre se necesitan biopsias cuando se encuentra una respuesta casi completa. No se llegó a un consenso sobre si se deben tener en cuenta las características primarias de estadificación al decidir una respuesta casi completa.LIMITACIONES:Esta subcategorización de 3 niveles está basada en expertos; por lo tanto, no hay evidencia que respalde esta subcategorización. Además, no está claro si esta subcategorización puede generalizarse a la práctica clínica.CONCLUSIONES:Se alcanzó consenso sobre el uso de una categorización de 3 niveles de una respuesta casi completa que puede ser útil en la práctica diaria como guía para el tratamiento y para informar a los pacientes con una respuesta casi completa sobre la probabilidad de una preservación exitosa del órgano. (Traducción - Dr. Aurian Garcia Gonzalez).
Topics: Humans; Rectal Neoplasms; Neoadjuvant Therapy; Delphi Technique; Consensus; Chemoradiotherapy; Treatment Outcome; Diffusion Magnetic Resonance Imaging
PubMed: 38701503
DOI: 10.1097/DCR.0000000000003209 -
JHEP Reports : Innovation in Hepatology Jun 2024Hepatocellular adenomas (HCAs) are rare benign liver tumours. Predisposing factors and complication rates appear to differ among children and adults. In the present... (Review)
Review
Hepatocellular adenomas (HCAs) are rare benign liver tumours. Predisposing factors and complication rates appear to differ among children and adults. In the present study, we aimed to systematically characterise paediatric HCAs and determine their course, complications, and management. Medical history, clinical symptoms, imaging, histopathology, and genetics of children with HCAs were collected through a systematic and comprehensive review of the published literature. A total of 316 children with HCAs were included in the present study. HCAs were diagnosed primarily in girls (59.3%) and at a mean age of 11.5 (range 0-17.7) years. The majority (83.6%) of HCAs occurred in children with predisposing diseases, of which glycogen storage disease was the most common, followed by portosystemic shunts and MODY3 (maturity-onset diabetes of the young type 3). Each of these diseases leads to a well-defined HCA molecular pattern. A significant number of HCAs either bled (24.7%) or transformed (14.8%) over time. HCA transformation was significantly more frequent in children with portosystemic shunts and in β-catenin-mutated HCAs, while haemorrhages were more frequent in children exposed to hormones and those with larger lesions. Management was primarily guided by any predisposing conditions and the number of lesions. Therefore, vascular shunts were closed when possible, while complicated lesions were resected. Liver transplantation has made it possible to treat adenomatosis, as well as any underlying diseases. Progress in understanding genetic and/or malformative contributions, which appear to be significant in paediatric HCAs, have provided insights into tumour pathogenesis and will further guide patient surveillance and management.
PubMed: 38699071
DOI: 10.1016/j.jhepr.2024.101078 -
In Vivo (Athens, Greece) 2024Primary omental torsion is uncommon, mimicking appendicitis and other acute abdominal pathologies. It often escapes diagnosis on imaging investigation or conventional...
BACKGROUND/AIM
Primary omental torsion is uncommon, mimicking appendicitis and other acute abdominal pathologies. It often escapes diagnosis on imaging investigation or conventional open laparotomy. This study aimed to evaluate the effect of laparoscopy on the various parameters of this entity, including incidence, diagnosis, and treatment.
MATERIALS AND METHODS
A systematic review was performed, including PubMed and Scopus databases, without a time limit, following the PRISMA principles. A total of 16 articles from January 2000 to December 2023, corresponding to 56 children with primary omental torsion, complied with the research criteria.
RESULTS
Primary omental torsion was associated with obesity. Symptoms were right abdomen oriented, often compared to those of acute appendicitis. Preoperative ultrasound displayed low diagnostic accuracy, whereas computerized tomography diagnosed only two thirds of cases. In all patients, the vermiform appendix was normal.
CONCLUSION
Laparoscopy affected both diagnosis and treatment of primary omental torsion in children. Easy peritoneal cavity access rendered possible the diagnosis of cases previously discharged as abdominal pain of unknown etiology. Combined with the increased pediatric obesity, it also affected primary omental torsion incidence. The recent pathogenetic theories may be better supported today, as laparoscopy provides a detailed view in situ, and facilitates harvesting of fat tissue from the omentum for molecular investigation. The diagnostic efficiency of laparoscopy is superior to ultrasonography and computerized tomography. Finally, the removal of the ischemic omentum is technically easier compared to the open laparotomy alternative with all the technical difficulties of traction of a vulnerable hemorrhagic tissue through a small incision.
Topics: Child; Female; Humans; Appendicitis; Laparoscopy; Omentum; Peritoneal Diseases; Tomography, X-Ray Computed; Torsion Abnormality; Ultrasonography; Male
PubMed: 38688642
DOI: 10.21873/invivo.13536 -
Epilepsia Apr 2024Up to 35% of individuals diagnosed with epilepsy continue to have seizures despite treatment, commonly referred to as drug-resistant epilepsy. Uncontrolled seizures can... (Review)
Review
Up to 35% of individuals diagnosed with epilepsy continue to have seizures despite treatment, commonly referred to as drug-resistant epilepsy. Uncontrolled seizures can directly, or indirectly, negatively impact an individual's quality of life. To inform clinical management and life decisions, it is important to be able to predict the likelihood of seizure control. Those likely to achieve seizure control will be able to return sooner to their usual work and leisure activities and require less follow-up, whereas those with a poor prognosis will need more frequent clinical attendance and earlier consideration of epilepsy surgery. This is a systematic review aimed at identifying demographic, clinical, physiological (e.g., electroencephalographic), and imaging (e.g., magnetic resonance imaging) factors that may be predictive of treatment outcomes in patients with newly diagnosed epilepsy (NDE). MEDLINE and Embase were searched for prediction models of treatment outcomes in patients with NDE. Study characteristics were extracted and subjected to assessment of risk of bias (and applicability concerns) using the PROBAST (Prediction Model Risk of Bias Assessment Tool) tool. Baseline variables associated with treatment outcomes are reported as prognostic factors. After screening, 48 models were identified in 32 studies, which generally scored low for concerns of applicability, but universally scored high for susceptibility to bias. Outcomes reported fit broadly into four categories: drug resistance, short-term treatment response, seizure remission, and mortality. Prognostic factors were also heterogenous, but the predictors that were commonly significantly associated with outcomes were those related to seizure characteristics/types, epilepsy history, and age at onset. Antiseizure medication response was often included as a baseline variable, potentially obscuring other factor relationships at baseline. Currently, outcome prediction models for NDE demonstrate a high risk of bias. Model development could be improved with a stronger adherence to recommended TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) practices. Furthermore, we outline actionable changes to common practices that are intended to improve the overall quality of prediction model development in NDE.
PubMed: 38687193
DOI: 10.1111/epi.17994 -
The Journal of Clinical Endocrinology... Jun 2024Use of artificial intelligence (AI) to predict clinical outcomes in thyroid nodule diagnostics has grown exponentially over the past decade. The greatest challenge is in...
CONTEXT
Use of artificial intelligence (AI) to predict clinical outcomes in thyroid nodule diagnostics has grown exponentially over the past decade. The greatest challenge is in understanding the best model to apply to one's own patient population, and how to operationalize such a model in practice.
EVIDENCE ACQUISITION
A literature search of PubMed and IEEE Xplore was conducted for English-language publications between January 1, 2015 and January 1, 2023, studying diagnostic tests on suspected thyroid nodules that used AI. We excluded articles without prospective or external validation, nonprimary literature, duplicates, focused on nonnodular thyroid conditions, not using AI, and those incidentally using AI in support of an experimental diagnostic outside standard clinical practice. Quality was graded by Oxford level of evidence.
EVIDENCE SYNTHESIS
A total of 61 studies were identified; all performed external validation, 16 studies were prospective, and 33 compared a model to physician prediction of ground truth. Statistical validation was reported in 50 papers. A diagnostic pipeline was abstracted, yielding 5 high-level outcomes: (1) nodule localization, (2) ultrasound (US) risk score, (3) molecular status, (4) malignancy, and (5) long-term prognosis. Seven prospective studies validated a single commercial AI; strengths included automating nodule feature assessment from US and assisting the physician in predicting malignancy risk, while weaknesses included automated margin prediction and interobserver variability.
CONCLUSION
Models predominantly used US images to predict malignancy. Of 4 Food and Drug Administration-approved products, only S-Detect was extensively validated. Implementing an AI model locally requires data sanitization and revalidation to ensure appropriate clinical performance.
Topics: Thyroid Nodule; Humans; Artificial Intelligence; Thyroid Neoplasms
PubMed: 38679750
DOI: 10.1210/clinem/dgae277