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1.
Surg Endosc ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38955837

RESUMO

AIMS: To evaluate the safety profile of robotic cholecystectomy performed within the United Kingdom (UK) Robotic Hepatopancreatobiliary (HPB) training programme. METHODS: A retrospective evaluation of prospectively collected data from eleven centres participating in the UK Robotic HPB training programme was conducted. All adult patients undergoing robotic cholecystectomy for symptomatic gallstone disease or gallbladder polyp were considered. Bile duct injury, conversion to open procedure, conversion to subtotal cholecystectomy, length of hospital stay, 30-day re-admission, and post-operative complications were the evaluated outcome parameters. RESULTS: A total of 600 patients were included. The median age was 53 (IQR 65-41) years and the majority (72.7%; 436/600) were female. The main indications for robotic cholecystectomy were biliary colic (55.5%, 333/600), cholecystitis (18.8%, 113/600), gallbladder polyps (7.7%, 46/600), and pancreatitis (6.2%, 37/600). The median length of stay was 0 (IQR 0-1) days. Of the included patients, 88.5% (531/600) were discharged on the day of procedure with 30-day re-admission rate of 5.5% (33/600). There were no bile duct injuries and the rate of conversion to open was 0.8% (5/600) with subtotal cholecystectomy rate of 0.8% (5/600). CONCLUSION: The current study confirms that robotic cholecystectomy can be safely implemented to routine practice with a low risk of bile duct injury, low bile leak rate, low conversion to open surgery, and low need for subtotal cholecystectomy.

2.
Neuroradiology ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963424

RESUMO

BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) is a major source of health loss and disability worldwide. Accurate and timely diagnosis of TBI is critical for appropriate treatment and management of the condition. Neuroimaging plays a crucial role in the diagnosis and characterization of TBI. Computed tomography (CT) is the first-line diagnostic imaging modality typically utilized in patients with suspected acute mild, moderate and severe TBI. Radiology reports play a crucial role in the diagnostic process, providing critical information about the location and extent of brain injury, as well as factors that could prevent secondary injury. However, the complexity and variability of radiology reports can make it challenging for healthcare providers to extract the necessary information for diagnosis and treatment planning. METHODS/RESULTS/CONCLUSION: In this article, we report the efforts of an international group of TBI imaging experts to develop a clinical radiology report template for CT scans obtained in patients suspected of TBI and consisting of fourteen different subdivisions (CT technique, mechanism of injury or clinical history, presence of scalp injuries, fractures, potential vascular injuries, potential injuries involving the extra-axial spaces, brain parenchymal injuries, potential injuries involving the cerebrospinal fluid spaces and the ventricular system, mass effect, secondary injuries, prior or coexisting pathology).

3.
J Exp Clin Cancer Res ; 43(1): 189, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38978141

RESUMO

BACKGROUND: Distinguishing benign from malignant pancreaticobiliary disease is challenging because of the absence of reliable biomarkers. Circulating extracellular vesicles (EVs) have emerged as functional mediators between cells. Their cargos, including microRNAs (miRNAs), are increasingly acknowledged as an important source of potential biomarkers. This multicentric, prospective study aimed to establish a diagnostic plasma EV-derived miRNA signature to discriminate pancreatic ductal adenocarcinoma (PDAC) from benign pancreaticobiliary disease. METHODS: Plasma EVs were isolated using size exclusion chromatography (SEC) and characterised using nanoparticle tracking analysis, electron microscopy and Western blotting. EV-RNAs underwent small RNA sequencing to discover differentially expressed markers for PDAC (n = 10 benign vs. 10 PDAC). Candidate EV-miRNAs were then validated in a cohort of 61 patients (n = 31 benign vs. 30 PDAC) by RT-qPCR. Logistic regression and optimal thresholds (Youden Index) were used to develop an EV-miR-200 family model to detect cancer. This model was tested in an independent cohort of 95 patients (n = 30 benign, 33 PDAC, and 32 cholangiocarcinoma). RESULTS: Small RNA sequencing and RT-qPCR showed that EV-miR-200 family members were significantly overexpressed in PDAC vs. benign disease. Combined expression of the EV-miR-200 family showed an AUC of 0.823. In an independent validation cohort, application of this model showed a sensitivity, specificity and AUC of 100%, 88%, and 0.97, respectively, for diagnosing PDAC. CONCLUSIONS: This is the first study to validate plasma EV-miR-200 members as a clinically-useful diagnostic biomarker for PDAC. Further validation in larger cohorts and clinical trials is essential. These findings also suggest the potential utility in monitoring response and/or recurrence.


Assuntos
Carcinoma Ductal Pancreático , Vesículas Extracelulares , MicroRNAs , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , MicroRNAs/sangue , MicroRNAs/genética , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Idoso , Biomarcadores Tumorais/sangue , Estudos Prospectivos
4.
Radiol Artif Intell ; : e240225, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984986

RESUMO

"Just Accepted" papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. The Radiological Society of North of America (RSNA) and the Medical Image Computing and Computer Assisted Intervention (MICCAI) Society have led a series of joint panels and seminars focused on the present impact and future directions of artificial intelligence (AI) in radiology. These conversations have collected viewpoints from multidisciplinary experts in radiology, medical imaging, and machine learning on the current clinical penetration of AI technology in radiology, and how it is impacted by trust, reproducibility, explainability, and accountability. The collective points-both practical and philosophical-define the cultural changes for radiologists and AI scientists working together and describe the challenges ahead for AI technologies to meet broad approval. This article presents the perspectives of experts from MICCAI and RSNA on the clinical, cultural, computational, and regulatory considerations-coupled with recommended reading materials-essential to adopt AI technology successfully in radiology and more generally in clinical practice. The report emphasizes the importance of collaboration to improve clinical deployment and highlights the need to integrate clinical and medical imaging data and introduces strategies to ensure smooth and incentivized integration. ©RSNA, 2024.

5.
Arch Sex Behav ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888703

RESUMO

People tend to select romantic partners who belong to the same social group as themselves (i.e., endogamy). However, there is limited research on the proximal psychological motivations for choosing endogamous relationship partners. The purpose of this research was to develop a measure of motivations for endogamous relationship preferences and to assess whether such motivations were associated with actual dating experiences and attitudes toward endogamy across four common social categories: race and/or ethnicity, religion, social class, and education. Data from an online sample of participants (Study 1, n = 341) were used to generate items assessing motivations for endogamous relationship preferences. This initial set of items was administered to a new sample of participants (Study 2, n = 193) to establish the component structure of the measure and to examine whether the motivational components were associated with participants' past exogamous dating experiences as well as the perceived importance of dating within one's own racial and/or ethnic, religious, socioeconomic, and educational group. Endogamy motivations characterized by intergroup prejudice were the strongest and most consistent correlates of endogamous relationships and the perceived importance of endogamy. Study 3 (n = 332) replicated the component structure of the measure and the general pattern of associations documented in Study 2, and provided evidence for the measure's construct validity. The overall findings suggest that intergroup prejudice partially explains preferences for endogamous relationships.

6.
Clin Kidney J ; 17(6): sfae143, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38899159

RESUMO

The global derangement of mineral metabolism that accompanies chronic kidney disease (CKD-MBD) is a major driver of the accelerated mortality for individuals with kidney disease. Advances in the delivery of dialysis, in the composition of phosphate binders, and in the therapies directed towards secondary hyperparathyroidism have failed to improve the cardiovascular event profile in this population. Many obstacles have prevented progress in this field including the incomplete understanding of pathophysiology, the lack of clinical targets for early stages of chronic kidney disease, and the remarkably wide diversity in clinical manifestations. We describe in this review a novel approach to CKD-MBD combining mathematical modelling of biologic processes with machine learning artificial intelligence techniques as a tool for the generation of new hypotheses and for the development of innovative therapeutic approaches to this syndrome. Clinicians need alternative targets of therapy, tools for risk profile assessment, and new therapies to address complications early in the course of disease and to personalize therapy to each individual. The complexity of CKD-MBD suggests that incorporating artificial intelligence techniques into the diagnostic, therapeutic, and research armamentarium could accelerate the achievement of these goals.

7.
Int J Surg ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874485

RESUMO

BACKGROUND: Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), continues to pose a significant clinical and scientific challenge. The most significant finding of recent years is that PDAC tumours harbour their specific microbiome, which differs amongst tumour entities and is distinct from healthy tissue. This review aims to evaluate and summarise all PDAC studies that have used the next-generation technique, 16S rRNA gene amplicon sequencing within each bodily compartment. As well as establishing a causal relationship between PDAC and the microbiome. MATERIALS AND METHODS: This systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. A comprehensive search strategy was designed, and 1727 studies were analysed. RESULTS: In total, 38 studies were selected for qualitative analysis and summarised significant PDAC bacterial signatures. Despite the growing amount of data provided, we are not able to state a universal 16S rRNA gene microbial signature that can be used for PDAC screening. This is most certainly due to the heterogeneity of the presentation of results, lack of available datasets and the intrinsic selection bias between studies. CONCLUSION: Several key studies have begun to shed light on causality and the influence the microbiome constituents and their produced metabolites could play in tumorigenesis and influencing outcomes. The challenge in this field is to shape the available microbial data into targetable signatures. Making sequenced data readily available is critical, coupled with the coordinated standardisation of data and the need for consensus guidelines in studies investigating the microbiome in PDAC.

8.
Clin Imaging ; 112: 110210, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38850710

RESUMO

BACKGROUND: Clinical adoption of AI applications requires stakeholders see value in their use. AI-enabled opportunistic-CT-screening (OS) capitalizes on incidentally-detected findings within CTs for potential health benefit. This study evaluates primary care providers' (PCP) perspectives on OS. METHODS: A survey was distributed to US Internal and Family Medicine residencies. Assessed were familiarity with AI and OS, perspectives on potential value/costs, communication of results, and technology implementation. RESULTS: 62 % of respondents (n = 71) were in Family Medicine, 64.8 % practiced in community hospitals. Although 74.6 % of respondents had heard of AI/machine learning, 95.8 % had little-to-no familiarity with OS. The majority reported little-to-no trust in AI. Reported concerns included AI accuracy (74.6 %) and unknown liability (73.2 %). 78.9 % of respondents reported that OS applications would require radiologist oversight. 53.5 % preferred OS results be included in a separate "screening" section within the Radiology report, accompanied by condition risks and management recommendations. The majority of respondents reported results would likely affect clinical management for all queried applications, and that atherosclerotic cardiovascular disease risk, abdominal aortic aneurysm, and liver fibrosis should be included within every CT report regardless of reason for examination. 70.5 % felt that PCP practices are unlikely to pay for OS. Added costs to the patient (91.5 %), the healthcare provider (77.5 %), and unknown liability (74.6 %) were the most frequently reported concerns. CONCLUSION: PCP preferences and concerns around AI-enabled OS offer insights into clinical value and costs. As AI applications grow, feedback from end-users should be considered in the development of such technology to optimize implementation and adoption. Increasing stakeholder familiarity with AI may be a critical prerequisite first step before stakeholders consider implementation.


Assuntos
Tomografia Computadorizada por Raios X , Humanos , Atenção Primária à Saúde , Inquéritos e Questionários , Atitude do Pessoal de Saúde , Programas de Rastreamento , Estados Unidos , Masculino , Feminino , Inteligência Artificial , Achados Incidentais
9.
Commun Biol ; 7(1): 703, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849461

RESUMO

Novelty and appropriateness are two fundamental components of creativity. However, the way in which novelty and appropriateness are separated at behavioral and neural levels remains poorly understood. In the present study, we aim to distinguish behavioral and neural bases of novelty and appropriateness of creative idea generation. In alignment with two established theories of creative thinking, which respectively, emphasize semantic association and executive control, behavioral results indicate that novelty relies more on associative abilities, while appropriateness relies more on executive functions. Next, employing a connectome predictive modeling (CPM) approach in resting-state fMRI data, we define two functional network-based models-dominated by interactions within the default network and by interactions within the limbic network-that respectively, predict novelty and appropriateness (i.e., cross-brain prediction). Furthermore, the generalizability and specificity of the two functional connectivity patterns are verified in additional resting-state fMRI and task fMRI. Finally, the two functional connectivity patterns, respectively mediate the relationship between semantic association/executive control and novelty/appropriateness. These findings provide global and predictive distinctions between novelty and appropriateness in creative idea generation.


Assuntos
Criatividade , Função Executiva , Imageamento por Ressonância Magnética , Semântica , Humanos , Função Executiva/fisiologia , Masculino , Feminino , Adulto , Adulto Jovem , Conectoma , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem
10.
ACG Case Rep J ; 11(6): e01378, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38854806

RESUMO

Parvimonas micra bacteremia is rarely encountered in clinical practice. When it is, patients usually have underlying periodontal disease or colorectal carcinoma. To the best of our knowledge, this is the first case of P. micra bacteremia in a patient without the predisposing risk factors listed above. We postulate that this occurred because of translocation across an interrupted gut-blood barrier in the setting of an acute upper gastrointestinal bleed. We present this case to highlight the importance of identifying and treating P. micra bacteremia because it can prevent commonly encountered sequelae of untreated bacteremia and improve outcomes.

12.
Front Glob Womens Health ; 5: 1353657, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38939750

RESUMO

Background: Evidence suggests that a combination of biological and social factors influence risk of dementia differently for women and men. In healthy older women, several factors may contribute to changes in cognition. Objective: Describe the characteristics associated with variation in cognition in a sample of cognitively healthy older Panamanian women. Methods: The study includes cross-sectional analyses of cognitive domains at baseline (n = 357) and 17-month (SD = 2.0) follow-up (n = 200) for women aged 60 years and older enrolled in the Panama Aging Research Initiative-Health Disparities (PARI-HD) study. Instruments included clinical questionnaires, physiological measures, and a neuropsychological test battery assessing global cognition and seven cognitive domains. Multiple regression analyses examined the associations between demographic and clinical characteristics and cognition at baseline. Repeated measures analyses were used to investigate changes in cognition from baseline to follow-up. Results: On average, participants were 68.6 years of age (SD = 5.9) with 16.1 years of education (SD = 4.7). Age, income, and education showed robust associations with baseline cognition. Subjective cognitive impairment was associated with lower performance in global cognition, verbal learning, and memory domains. Only performance in the attention domain decreased at follow-up, and subjective health state and depressive symptoms significantly predicted the change in attention. Discussion: Our study findings contribute to the investigation of cognitive health in older Hispanic women and to the understanding of sociodemographic and health-related factors associated with cognitive decline and the progression to cognitive impairment and dementia.

13.
Nutrients ; 16(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38732516

RESUMO

BACKGROUND AND METHODS: Pancreatico-duodenectomy (PD) carries significant morbidity and mortality, with very few modifiable risk factors. Radiological evidence of sarcopenia is associated with poor outcomes. This retrospective study aimed to analyse the relationship between easy-to-use bedside nutritional assessment techniques and radiological markers of muscle loss to identify those patients most likely to benefit from prehabilitation. RESULTS: Data were available in 184 consecutive patients undergoing PD. Malnutrition was present in 33-71%, and 48% had a high visceral fat-to-skeletal muscle ratio, suggestive of sarcopenic obesity (SO). Surgical risk was higher in patients with obesity (OR 1.07, 95%CI 1.01-1.14, p = 0.031), and length of stay was 5 days longer in those with SO (p = 0.006). There was no correlation between skeletal muscle and malnutrition using percentage weight loss or the malnutrition universal screening tool (MUST), but a weak correlation between the highest hand grip strength (HGS; 0.468, p < 0.001) and the Global Leadership in Malnutrition (GLIM) criteria (-0.379, p < 0.001). CONCLUSIONS: Nutritional assessment tools give widely variable results. Further research is needed to identify patients at significant nutritional risk prior to PD. In the meantime, those with malnutrition (according to the GLIM criteria), obesity or low HGS should be referred to prehabilitation.


Assuntos
Desnutrição , Músculo Esquelético , Avaliação Nutricional , Estado Nutricional , Pancreaticoduodenectomia , Sarcopenia , Humanos , Masculino , Feminino , Estudos Retrospectivos , Sarcopenia/etiologia , Sarcopenia/diagnóstico , Idoso , Desnutrição/diagnóstico , Desnutrição/etiologia , Pessoa de Meia-Idade , Pancreaticoduodenectomia/efeitos adversos , Força da Mão , Obesidade/cirurgia , Obesidade/complicações , Fatores de Risco , Idoso de 80 Anos ou mais
14.
bioRxiv ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38798535

RESUMO

Background: Pharmacological inhibition of megalin (also known as low-density lipoprotein receptor-related protein 2: LRP2) attenuates atherosclerosis in hypercholesterolemic mice. Since megalin is abundant in renal proximal tubule cells (PTCs), the purpose of this study was to determine whether PTC-specific deletion of megalin reduces hypercholesterolemia-induced atherosclerosis in mice. Methods: Female Lrp2 f/f mice were bred with male Ndrg1-Cre ERT2 +/0 mice to develop PTC-LRP2 +/+ and -/- littermates. To study atherosclerosis, all mice were to bred to an LDL receptor -/- background and fed a Western diet to induce atherosclerosis. Results: PTC-specific megalin deletion did not attenuate atherosclerosis in LDL receptor -/- mice in either sex. Serendipitously, we discovered that PTC-specific megalin deletion led to interstitial infiltration of CD68+ cells and tubular atrophy. The pathology was only evident in male PTC-LRP2 -/- mice fed the Western diet, but not in mice fed a normal laboratory diet. Renal pathologies were also observed in male PTC-LRP2 -/- mice in an LDL receptor +/+ background fed the same Western diet, demonstrating that the renal pathologies were dependent on diet and not hypercholesterolemia. By contrast, female PTC-LRP2 -/- mice had no apparent renal pathologies. In vivo multiphoton microscopy demonstrated that PTC-specific megalin deletion dramatically diminished albumin accumulation in PTCs within 10 days of Western diet feeding. RNA sequencing analyses demonstrated the upregulation of inflammation-related pathways in kidney. Conclusions: PTC-specific megalin deletion does not affect atherosclerosis, but leads to tubulointerstitial nephritis in mice fed Western diet, with severe pathologies in male mice.

15.
JCI Insight ; 9(12)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743496

RESUMO

Diabetes increases the risk of both cardiovascular disease and kidney disease. Notably, most of the excess cardiovascular risk in people with diabetes is in those with kidney disease. Apolipoprotein C3 (APOC3) is a key regulator of plasma triglycerides, and it has recently been suggested to play a role in both type 1 diabetes-accelerated atherosclerosis and kidney disease progression. To investigate if APOC3 plays a role in kidney disease in people with type 2 diabetes, we analyzed plasma levels of APOC3 from the Veterans Affairs Diabetes Trial. Elevated baseline APOC3 levels predicted a greater loss of renal function. To mechanistically test if APOC3 plays a role in diabetic kidney disease and associated atherosclerosis, we treated black and tan, brachyury, WT and leptin-deficient (OB; diabetic) mice, a model of type 2 diabetes, with an antisense oligonucleotide (ASO) to APOC3 or a control ASO, all in the setting of human-like dyslipidemia. Silencing APOC3 prevented diabetes-augmented albuminuria, renal glomerular hypertrophy, monocyte recruitment, and macrophage accumulation, partly driven by reduced ICAM1 expression. Furthermore, reduced levels of APOC3 suppressed atherosclerosis associated with diabetes. This suggests that targeting APOC3 might benefit both diabetes-accelerated atherosclerosis and kidney disease.


Assuntos
Apolipoproteína C-III , Aterosclerose , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Apolipoproteína C-III/genética , Apolipoproteína C-III/sangue , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Animais , Aterosclerose/metabolismo , Aterosclerose/etiologia , Camundongos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Oligonucleotídeos Antissenso/farmacologia , Modelos Animais de Doenças
16.
HPB (Oxford) ; 26(7): 873-894, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38729813

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is known to have a heterogeneous desmoplastic tumour microenvironment (TME) with a large number of immunosuppressive cells. Recently, high B-cell infiltration in PDAC has received growing interest as a potential therapeutic target. METHODS: Our literature review summarises the characteristics of tumour-associated tertiary lymphoid structures (TLSs) and highlight the key studies exploring the clinical outcomes of TLSs in PDAC patients and the direct effect on the TME. RESULTS: The location, density and maturity stages of TLSs within tumours play a key role in determining the prognosis and is a new emerging target in cancer immunotherapy. DISCUSSION: TLS development is imperative to improve the prognosis of PDAC patients. In the future, studying the genetics and immune characteristics of tumour infiltrating B cells and TLSs may lead towards enhancing adaptive immunity in PDAC and designing personalised therapies.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Estruturas Linfoides Terciárias , Microambiente Tumoral , Humanos , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/patologia , Estruturas Linfoides Terciárias/imunologia , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Prognóstico , Linfócitos do Interstício Tumoral/imunologia , Resultado do Tratamento , Imunoterapia/métodos
17.
Artigo em Inglês | MEDLINE | ID: mdl-38818792

RESUMO

Evaluation of: Araki H, Tazawa H, Kanaya N, et al. Oncolytic virus-mediated p53 overexpression promotes immunogenic cell death and efficacy of PD-1 blockade in pancreatic cancer. Mol Ther Oncolytics. 2022;27:3-13.Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis. PDAC has a dense, desmoplastic stroma and immunosuppressive microenvironment, which impedes current treatment options. Immunotherapy delivered via oncolytic virotherapy is one potential solution to these barriers. Immune checkpoint inhibitors may facilitate immunogenic cell death by improving immune cell infiltration in cancer cells. PD-1 blockade shows better clinical outcomes for certain cancers. The addition of p53 to stimulate cell cycle arrest remains a novel field of research. The evaluated article by Araki et al. explores the efficacy of PD-1 blockade with oncolytic adenovirus platforms on immunogenic cell death and the possibility of combining PD-1 blockade and p53-activation. In vitro analysis showed increased cell death in multiple cell lines infected with AdV mediating p53 expression. The underlying process may attribute to apoptosis and autophagy, with evidence of increased immunogenic cell death. In vivo models demonstrated improved efficacy of p53-expressing AdV, particularly with the addition of PD-1 blockade which appears to be related to CD8+ cell infiltration.

18.
Mol Psychiatry ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744992

RESUMO

High-impact genetic variants associated with neurodevelopmental disorders provide biologically-defined entry points for mechanistic investigation. The 3q29 deletion (3q29Del) is one such variant, conferring a 40-100-fold increased risk for schizophrenia, as well as high risk for autism and intellectual disability. However, the mechanisms leading to neurodevelopmental disability remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in individuals with 3q29Del (N = 24) and neurotypical controls (N = 1608) using structural MRI. Given prior radiology reports of posterior fossa abnormalities in 3q29Del, we focused our investigation on the cerebellum and its tissue-types and lobules. Additionally, we compared the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del and controls and examined the association between neuroanatomical findings and quantitative traits to probe gene-brain-behavior relationships. 3q29Del participants had smaller cerebellar cortex volumes than controls, before and after correction for intracranial volume (ICV). An anterior-posterior gradient emerged in finer grained lobule-based and voxel-wise analyses. 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction and displayed elevated rates of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Cerebellar white matter and subregional gray matter volumes were associated with visual-perception and visual-motor integration skills as well as IQ, while cystic/cyst-like malformations yielded no behavioral link. In summary, we find that abnormal development of cerebellar structures may represent neuroimaging-based biomarkers of cognitive and sensorimotor function in 3q29Del, adding to the growing evidence identifying cerebellar pathology as an intersection point between syndromic and idiopathic forms of neurodevelopmental disabilities.

19.
Eur J Surg Oncol ; 50(6): 108353, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38701690

RESUMO

INTRODUCTION: Patients undergoing pancreaticoduodenectomy for distal cholangiocarcinoma (dCCA) often develop cancer recurrence. Establishing timing, patterns and risk factors for recurrence may help inform surveillance protocol strategies or select patients who could benefit from additional systemic or locoregional therapies. This multicentre retrospective cohort study aimed to determine timing, patterns, and predictive factors of recurrence following pancreaticoduodenectomy for dCCA. MATERIALS AND METHODS: Patients who underwent pancreaticoduodenectomy for dCCA between June 2012 and May 2015 with five years of follow-up were included. The primary outcome was recurrence pattern (none, local-only, distant-only or mixed local/distant). Data were collected on comorbidities, investigations, operation details, complications, histology, adjuvant and palliative therapies, recurrence-free and overall survival. Univariable tests and regression analyses investigated factors associated with recurrence. RESULTS: In the cohort of 198 patients, 129 (65%) developed recurrence: 30 (15%) developed local-only recurrence, 44 (22%) developed distant-only recurrence and 55 (28%) developed mixed pattern recurrence. The most common recurrence sites were local (49%), liver (24%) and lung (11%). 94% of patients who developed recurrence did so within three years of surgery. Predictors of recurrence on univariable analysis were cancer stage, R1 resection, lymph node metastases, perineural invasion, microvascular invasion and lymphatic invasion. Predictors of recurrence on multivariable analysis were female sex, venous resection, advancing histological stage and lymphatic invasion. CONCLUSION: Two thirds of patients have cancer recurrence following pancreaticoduodenectomy for dCCA, and most recur within three years of surgery. The commonest sites of recurrence are the pancreatic bed, liver and lung. Multiple histological features are associated with recurrence.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Recidiva Local de Neoplasia , Pancreaticoduodenectomia , Humanos , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Feminino , Masculino , Estudos Retrospectivos , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Recidiva Local de Neoplasia/epidemiologia , Idoso , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia
20.
Expert Rev Gastroenterol Hepatol ; 18(4-5): 133-139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38712525

RESUMO

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, and multimodal treatment including high-quality surgery can improve survival outcomes. Pancreaticoduodenectomy (PD) has evolved with minimally invasive approaches including the implementation of robotic PD (RPD). In this special report, we review the literature whilst evaluating the 'true benefits' of RPD compared to open approach for the treatment of PDAC. AREAS COVERED: We have performed a mini-review of studies assessing PD approaches and compared intraoperative characteristics, perioperative outcomes, post-operative complications and oncological outcomes. EXPERT OPINION: RPD was associated with similar or longer operative times, and reduced intra-operative blood loss. Perioperative pain scores were significantly lower with shorter lengths of stay with the robotic approach. With regards to post-operative complications, post-operative pancreatic fistula rates were similar, with lower rates of clinically relevant fistulas after RPD. Oncological outcomes were comparable or superior in terms of margin status, lymph node harvest, time to chemotherapy and survival between RPD and OPD. In conclusion, RPD allows safe implementation of minimally invasive PD. The current literature shows that RPD is either equivalent, or superior in certain aspects to OPD. Once more centers gain sufficient experience, RPD is likely to demonstrate clear superiority over alternative approaches.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Robóticos , Humanos , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/mortalidade , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Duração da Cirurgia , Fatores de Risco
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