Safety of robotic cholecystectomy as index training procedure: the UK experience.

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.

Standardized reporting for Head CT Scans in patients suspected of traumatic brain injury (TBI): An international expert endeavor.

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).

Clinical, Cultural, Computational, and Regulatory Considerations to Deploy AI in Radiology: Perspectives of RSNA and MICCAI Experts.

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, highlights the need to integrate clinical and medical imaging data, and introduces strategies to ensure smooth and incentivized integration. Keywords: Adults and Pediatrics, Computer Applications-General (Informatics), Diagnosis, Prognosis © RSNA, 2024.

MicroRNAs as Bile-based biomarkers in pancreaticobiliary cancers (MIRABILE): a cohort study.

BACKGROUND: Biliary obstruction can be due to both malignant and benign pancreaticobiliary disease. Currently, there are no biomarkers that can accurately help make this distinction. MicroRNAs (miRNAs) are stable molecules in tissue and biofluids that are commonly deregulated in cancer. The MIRABILE study aimed to identify miRNAs in bile that can differentiate malignant from benign pancreaticobiliary disease. MATERIALS AND METHODS: There were 111 patients recruited prospectively at endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) for obstructive jaundice, and bile was aspirated for cell-free RNA (cfRNA) extraction and analysis. In a discovery cohort of 78 patients (27 with pancreatic ductal adenocarcinoma (PDAC), 14 cholangiocarcinoma (CCA), 37 benign disease), cfRNA was subjected to small-RNA sequencing. LASSO regression was used to define bile miRNA signatures, and NormFinder to identify endogenous controls. In a second cohort of 87 patients (34 PDAC, 14 CCA, 39 benign disease), RT-qPCR was used for validation. RESULTS: LASSO regression identified 14 differentially-expressed bile miRNAs of which 6 were selected for validation. When comparing malignant and benign pancreaticobiliary disease, bile miR-340 and miR-182 were validated and significantly differentially expressed (P<0.05 and P<0.001, respectively). This generated an AUC of 0.79 (95%CI 0.70-0.88, sensitivity 65%; specificity 82%) in predicting malignant disease. CONCLUSION: Bile collected during biliary drainage contains miRNAs able to differentiate benign from malignant pancreaticobiliary diseases in patients with obstructive jaundice. These bile miRNAs have the potential to increase diagnostic accuracy.

Unlocking the diagnostic power of plasma extracellular vesicle miR-200 family in pancreatic ductal adenocarcinoma.

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.

CD5 deletion enhances the antitumor activity of adoptive T cell therapies.

Most patients treated with US Food and Drug Administration (FDA)-approved chimeric antigen receptor (CAR) T cells eventually experience disease progression. Furthermore, CAR T cells have not been curative against solid cancers and several hematological malignancies such as T cell lymphomas, which have very poor prognoses. One of the main barriers to the clinical success of adoptive T cell immunotherapies is CAR T cell dysfunction and lack of expansion and/or persistence after infusion. In this study, we found that CD5 inhibits CAR T cell activation and that knockout (KO) of CD5 using CRISPR-Cas9 enhances the antitumor effect of CAR T cells in multiple hematological and solid cancer models. Mechanistically, CD5 KO drives increased T cell effector function with enhanced cytotoxicity, in vivo expansion, and persistence, without apparent toxicity in preclinical models. These findings indicate that CD5 is a critical inhibitor of T cell function and a potential clinical target for enhancing T cell therapies.

Motivations for Endogamous Relationship Preferences.

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.

The microbial composition of pancreatic ductal adenocarcinoma: A systematic review of 16S rRNA gene sequencing.

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.

Predictors of cognitive change in cognitively healthy older women in Panama: the PARI-HD study.

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.

Application of artificial intelligence to chronic kidney disease mineral bone disorder.

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.

Primary care provider perspectives on the value of opportunistic CT screening.

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.

Semantic associative abilities and executive control functions predict novelty and appropriateness of idea generation.

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.

Parvimonas micra Bacteremia: A Rare Complication After Esophagogastroduodenoscopy for Upper Gastrointestinal Bleeding.

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.

Structural deviations of the posterior fossa and the cerebellum and their cognitive links in a neurodevelopmental deletion syndrome.

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.

Impact of tertiary lymphoid structures on prognosis and therapeutic response in pancreatic ductal adenocarcinoma.

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.

Renal Proximal Tubule Cell-specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed Western Diet.

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.

Is oncolytic adenoviral-mediated immunotherapy through p53-overexpression the solution to refractory pancreatic ductal adenocarcinoma?

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.

Enantiomeric profile of amphetamines in seized drug samples and in blood of impaired drivers in Iceland: The rise of (R)-methamphetamine?

Amphetamine (AMP) and methamphetamine (METH) use is increasing globally. Illegal AMP is generally a racemic mixture, whereas AMP-containing attention-deficit hyperactivity disorder drugs prescribed in Iceland consist of S-AMP. AMP is also a main metabolite of interest after METH intake. Distinguishing between legal and illegal AMP intake is vital in forensic toxicology. A chiral UPLC-MS-MS method was used to determine the enantiomeric profile of AMP and METH in circulation in Iceland by analysing blood samples from drivers suspected of driving under the influence of drugs (DUID) and seized drug samples from 2021 and 2022. All seized AMP samples (n = 48) were racemic, whereas all but one seized METH sample (n = 26) were enantiopure. Surprisingly, a large portion of the enantiopure METH samples was R-METH. DUID blood samples positive for AMP (n = 564) had a median blood concentration of 180 ng/mL (range 20-2770 ng/mL) and a median enantiomeric fraction (EFR) of 0.54 (range 0-0.73), whereas samples positive for METH (n = 236) had a median blood concentration of 185 ng/mL (range 20-2300 ng/mL) and a median EFR of 0.23 (range 0-1). The findings of this study show a significantly lower blood concentration in drivers with only S-AMP detected compared with when the R-isomer is also detected. No significant difference in blood concentration was detected between the sample groups containing S-METH, R-METH or both enantiomers. The occurrence of R-METH in both seized drug samples and DUID cases indicates a change in drug supply and a need for better scientific knowledge on R-METH abuse.