Differences in intratumor innate lymphoid cell composition between orthotopic and spontaneous pancreatic mouse models.

Pancreatic cancer remains an unmet medical need. Late diagnosis and the lack of efficient treatment significantly impact the prognosis of patients suffering from pancreatic cancer. Improving patient outcomes requires a deeper comprehension of the tumor ecosystem. To achieve this, a thorough exploration of the tumor microenvironment using pre-clinical models that accurately replicate human disease is imperative, particularly in understanding the dynamics of immune cell subsets. Surprisingly, the impact of model variations on the composition of the tumor microenvironment has been largely neglected. In this study, we introduce an orthotopic model of pancreatic ductal adenocarcinoma and a spontaneous model of insulinoma. Our findings reveal striking differences in the innate lymphoid cell infiltrate, highlighting the importance of considering model-specific influences when investigating the tumor microenvironment.

Characterization of innate lymphoid cell subsets infiltrating melanoma and epithelial ovarian tumors.

The innate lymphoid cell (ILC) family is composed of heterogeneous innate effector and helper immune cells that preferentially reside in tissues where they promote tissue homeostasis. In cancer, they have been implicated in driving both pro- and anti-tumor responses. This apparent dichotomy highlights the need to better understand differences in the ILC composition and phenotype within different tumor types that could drive seemingly opposite anti-tumor responses. Here, we characterized the frequency and phenotype of various ILC subsets in melanoma metastases and primary epithelial ovarian tumors. We observed high PD-1 expression on ILC subsets isolated from epithelial ovarian tumor samples, while ILC populations in melanoma samples express higher levels of LAG-3. In addition, we found that the frequency of cytotoxic ILCs and NKp46+ILC3 in tumors positively correlates with monocytic cells and conventional type 2 dendritic cells, revealing potentially new interconnected immune cell subsets in the tumor microenvironment. Consequently, these observations may have direct relevance to tumor microenvironment composition and how ILC subset may influence anti-tumor immunity.

Generation of an Inhibitory NK Cell Subset by TGF-ß1/IL-15 Polarization.

NK cells have been shown to exhibit inflammatory and immunoregulatory functions in a variety of healthy and diseased settings. In the context of chronic viral infection and cancer, distinct NK cell populations that inhibit adaptive immune responses have been observed. To understand how these cells arise and further characterize their immunosuppressive role, we examined in vitro conditions that could polarize human NK cells into an inhibitory subset. TGF-ß1 has been shown to induce regulatory T cells in vitro and in vivo; we therefore investigated if TGF-ß1 could also induce immunosuppressive NK-like cells. First, we found that TGF-ß1/IL-15, but not IL-15 alone, induced CD103+CD49a+ NK-like cells from peripheral blood NK cells, which expressed markers previously associated with inhibitory CD56+ innate lymphoid cells, including high expression of GITR and CD101. Moreover, supernatant from ascites collected from patients with ovarian carcinoma also induced CD103+CD49a+ NK-like cells in vitro in a TGF-ß-dependent manner. Interestingly, TGF-ß1/IL-15-induced CD103+CD56+ NK-like cells suppressed autologous CD4+ T cells in vitro by reducing absolute number, proliferation, and expression of activation marker CD25. Collectively, these findings provide new insight into how NK cells may acquire an inhibitory phenotype in TGF-ß1-rich environments.

Ex vivo activation of the GCN2 pathway metabolically reprograms T cells, leading to enhanced adoptive cell therapy.

The manipulation of T cell metabolism to enhance anti-tumor activity is an area of active investigation. Here, we report that activating the amino acid starvation response in effector CD8+ T cells ex vivo using the general control non-depressible 2 (GCN2) agonist halofuginone (halo) enhances oxidative metabolism and effector function. Mechanistically, we identified autophagy coupled with the CD98-mTOR axis as key downstream mediators of the phenotype induced by halo treatment. The adoptive transfer of halo-treated CD8+ T cells into tumor-bearing mice led to robust tumor control and curative responses. Halo-treated T cells synergized in vivo with a 4-1BB agonistic antibody to control tumor growth in a mouse model resistant to immunotherapy. Importantly, treatment of human CD8+ T cells with halo resulted in similar metabolic and functional reprogramming. These findings demonstrate that activating the amino acid starvation response with the GCN2 agonist halo can enhance T cell metabolism and anti-tumor activity.

Comparison of pre-operative computed tomography cholangiography and intraoperative cholangiography in laparoscopic cholecystectomy: a retrospective analysis.

BACKGROUND: The role of intra-operative cholangiography (IOC) in laparoscopic cholecystectomy (LC) is controversial. CT cholangiography (CTC) provides a reliable assessment of biliary anatomy, potentially reducing operating times, open conversion, and complication rates. This study aims to assess the safety and effectiveness of routine pre-operative CTC. METHODS: A single centre retrospective analysis was undertaken of all elective laparoscopic cholecystectomies between 2017 and 2021. Information was obtained from a general surgical database alongside hospital electronic medical records. T-tests and Chi2 tests were used to assess statistical significance. RESULTS: Of 1079 patients, 129 (12.0%) underwent routine pre-operative CTC, 786 (72.8%) routine IOC, and 161 patients (14.9%) neither modality. Comparing CTC and IOC, the CTC group had higher rates of open conversion (3.1% vs. 0.6%, p 0.009), subtotal cholecystectomies (3.1% vs. 0.8%, p 0.018), and length of stay (1.47 vs. 1.18 nights, p 0.015). Comparing the prior groups together against those utilising neither modality, the latter had reduced operative time (66.29 vs. 72.47, p 0.011), but increased rate of bile leak (1.9% vs. 0.4%, p 0.037) and bile duct injury (1.2% vs. 0.2%, p 0.049). Co-dependence between operative complications was noted in linear regression. CONCLUSION: Biliary imaging with either CTC or IOC is beneficial in reducing bile leak and bile duct injury, and its routine use LC is recommended. However, routine CTC is inferior to routine IOC in preventing conversions to open surgery and subtotal cholecystectomy. Further research may be undertaken to evaluate criteria for a selective CTC protocol.

A Review of Quantitative Systems Pharmacology Models of the Coagulation Cascade: Opportunities for Improved Usability.

Despite the numerous therapeutic options to treat bleeding or thrombosis, a comprehensive quantitative mechanistic understanding of the effects of these and potential novel therapies is lacking. Recently, the quality of quantitative systems pharmacology (QSP) models of the coagulation cascade has improved, simulating the interactions between proteases, cofactors, regulators, fibrin, and therapeutic responses under different clinical scenarios. We aim to review the literature on QSP models to assess the unique capabilities and reusability of these models. We systematically searched the literature and BioModels database reviewing systems biology (SB) and QSP models. The purpose and scope of most of these models are redundant with only two SB models serving as the basis for QSP models. Primarily three QSP models have a comprehensive scope and are systematically linked between SB and more recent QSP models. The biological scope of recent QSP models has expanded to enable simulations of previously unexplainable clotting events and the drug effects for treating bleeding or thrombosis. Overall, the field of coagulation appears to suffer from unclear connections between models and irreproducible code as previously reported. The reusability of future QSP models can improve by adopting model equations from validated QSP models, clearly documenting the purpose and modifications, and sharing reproducible code. The capabilities of future QSP models can improve from more rigorous validation by capturing a broader range of responses to therapies from individual patient measurements and integrating blood flow and platelet dynamics to closely represent in vivo bleeding or thrombosis risk.

Innate lymphoid cells in early tumor development.

Innate and adaptive immune cells monitor, recognize, and eliminate transformed cells. Innate lymphoid cells (ILCs) are innate counterparts of T cells that play a key role in many facets of the immune response and have a profound impact on disease states, including cancer. ILCs regulate immune responses by responding and integrating a wide range of signals within the local microenvironment. As primarily tissue-resident cells, ILCs are ideally suited to sense malignant transformation and initiate anti-tumor immunity. However, as ILCs have been associated with anti-tumor and pro-tumor activities in established tumors, they could potentially have dual functions during carcinogenesis by promoting or suppressing the malignant outgrowth of premalignant lesions. Here we discuss emerging evidence that shows that ILCs can impact early tumor development by regulating immune responses against transformed cells, as well as the environmental cues that potentially induce ILC activation in premalignant lesions.

Innate Lymphoid Cells: Role in Immune Regulation and Cancer.

Immune regulation is composed of a complex network of cellular and molecular pathways that regulate the immune system and prevent tissue damage. It is increasingly clear that innate lymphoid cells (ILCs) are also armed with immunosuppressive capacities similar to well-known immune regulatory cells (i.e., regulatory T cells). In cancer, immunoregulatory ILCs have been shown to inhibit anti-tumour immune response through various mechanisms including: (a) direct suppression of anti-tumour T cells or NK cells, (b) inhibiting T-cell priming, and (c) promoting other immunoregulatory cells. To provide a framework of understanding the role of immunosuppressive ILCs in the context of cancer, we first outline a brief history and challenges related to defining immunosuppressive ILCs. Furthermore, we focus on the mechanisms of ILCs in suppressing anti-tumour immunity and consequentially promoting tumour progression.

Jejunal diverticulosis - A case series and literature review.

Introduction: Scant literature is available regarding in vivo jejunal diverticulosis, in part due to its typically asymptomatic course. This is made more difficult by the difficulty in establishing its diagnosis. This case series examines a number of patients presenting to our hospital with jejunal diverticular disease, and their varying clinical courses. Methods: A number of cases that had presented to our hospital with jejunal diverticulosis were reviewed retrospectively in keeping with PROCESS guidelines. Their presentations, investigations, and management rationale are discussed in brief. Discussion: The presentation of jejunal diverticulosis is varies significantly along a spectrum, with a number of symptoms similar to other common intra-abdominal pathologies. The imaging modalities of choice are a barium small bowel series, CT scans, and enteroclysis, varying in sensitivity and complexity. Decision making with regards to operative vs. non-operative management is typically in line with that of colonic diverticulosis, though no strict guidelines have been established. Conclusion: Jejunal diverticulosis is an uncommon, with scarce data available on the appropriate investigation and management pathways. Its presentation is difficult to differentiate from other intra-abdominal pathology, and its investigations either poorly sensitive or costly and technically challenging. The general consensus on its management is similar to that of colonic diverticula, though more research needs is warranted.

Overproduction of IFNγ by Cbl-b-Deficient CD8+ T Cells Provides Resistance against Regulatory T Cells and Induces Potent Antitumor Immunity.

Regulatory T cells (Treg) are an integral component of the adaptive immune system that negatively affect antitumor immunity. Here, we investigated the role of the E3 ubiquitin ligase casitas B-lineage lymphoma-b (Cbl-b) in establishing CD8+ T-cell resistance to Treg-mediated suppression to enhance antitumor immunity. Transcriptomic analyses suggested that Cbl-b regulates pathways associated with cytokine signaling and cellular proliferation. We showed that the hypersecretion of IFNγ by Cbl-b-deficient CD8+ T cells selectively attenuated CD8+ T-cell suppression by Tregs. Although IFNγ production by Cbl-b-deficient T cells contributed to phenotypic alterations in Tregs, the cytokine did not attenuate the suppressive function of Tregs. Instead, IFNγ had a profound effect on CD8+ T cells by directly upregulating interferon-stimulated genes and modulating T-cell activation. In murine models of adoptive T-cell therapy, Cbl-b-deficient T cells elicited superior antitumor immune response. Furthermore, Cbl-b-deficient CD8+ T cells were less susceptible to suppression by Tregs in the tumor through the effects of IFNγ. Collectively, this study demonstrates that the hypersecretion of IFNγ serves as a key mechanism by which Cbl-b-deficient CD8+ T cells are rendered resistant to Tregs. See related Spotlight by Wolf and Baier, p. 370.

Ischaemic gastritis and perforation.

INTRODUCTION: Gastric perforation is a common general surgical emergency. Ischaemia of the stomach is uncommon due to its rich vascular supply, and is an uncommon cause of perforation. Minimal literature is available on the topic of ischaemic gastritis, with the few cases available linked to gastric dilation. PRESENTATION OF CASE: A 52 year old lady presents with a syncopal episode, nausea, vomiting, malaise, and abdominal discomfort. A chest X-ray identified free subdiaphragmatic gas, and her examination revealed a peritonitic abdomen, prompting urgent surgical intervention. She was found to have ischaemic gastritis with multiple perforations along the greater curvature, necessitating a sleeve gastrectomy. Her post-operative course was stormy, requiring significant haemodynamic and respiratory support in the intensive care unit with progressive multi-organ dysfunction. She eventually developed extensive bowel ischaemia, and further management was considered futile. She passed away 13 days post-operatively. CLINICAL DISCUSSION: The vascular supply of the stomach is rich with collaterals, making ischaemia unlikely. Its occurrence requires either a proximal insult, global ischaemia from pressure, or a systemic coagulopathy. Aside from perforation, it may also present with GI bleeding. Depending on its aetiology, the disease has been managed successfully either conservatively, interventionally, or operatively. CONCLUSION: Ischaemic gastritis is uncommon and likely underdiagnosed. Timely recognition of its aetiology early in its course is important, for choosing the appropriate management and to improve patient outcomes. Its management is dependent on the aetiology of the perforation.

Immune Checkpoints and Innate Lymphoid Cells-New Avenues for Cancer Immunotherapy.

Immune checkpoints (IC) are broadly characterized as inhibitory pathways that tightly regulate the activation of the immune system. These molecular "brakes" are centrally involved in the maintenance of immune self-tolerance and represent a key mechanism in avoiding autoimmunity and tissue destruction. Antibody-based therapies target these inhibitory molecules on T cells to improve their cytotoxic function, with unprecedented clinical efficacies for a number of malignancies. Many of these ICs are also expressed on innate lymphoid cells (ILC), drawing interest from the field to understand their function, impact for anti-tumor immunity and potential for immunotherapy. In this review, we highlight ILC specificities at different tissue sites and their migration potential upon inflammatory challenge. We further summarize the current understanding of IC molecules on ILC and discuss potential strategies for ILC modulation as part of a greater anti-cancer armamentarium.

Jejunal diverticulitis secondary to a gastrointestinal stromal tumor: A case report.

INTRODUCTION: The common manifestations of gastrointestinal stromal tumors (GIST) are well established. However, jejunal diverticulosis is an uncommon phenomenon to be associated with this lesion, with its rarity compounded by the relative difficulty associated with its diagnosis. Limited literature is available on this topic. This article examines one such case of jejunal diverticulitis as a result of a GIST, and the intervention of said disease. CASE PRESENTATION: A 69 year old lady presented with abdominal pain, vomiting, and low grade fevers, on a background of ulcerative colitis. She was peritonitic, raising concerns of an acute abdomen. Her imaging identified an intra-abdominal contained perforation, prompting a transfer to theatres overnight for a laparotomy, which identified a jejunal diverticulum, which resembled a contained perforation. This was resected, and sent for histopathological analysis, identifying the lesion as a GIST. DISCUSSION: Unlike other forms of jejunal diverticular disease, those arising from GISTs tend to present perforated, necessitating resection. This disease displays a tendency towards formation on the anti-mesenteric border of the small bowel. Additionally, this particular form of GIST shows macroscopic and histopathological uniformity across reported cases to date despite significant geographical disparity. CONCLUSION: A scant number of case reports worldwide have identified jejunal diverticulitis from GISTs. We suggest diverticula be excised if perforation is suspected, while incidental findings of such be left untouched. However, overall management should be undertaken at the discretion of the operating surgeon.

Chemotherapy-induced changes in tumor consistency can allow gross total resection of previously unresectable brainstem pilocytic astrocytoma.

BACKGROUND: Low-grade gliomas (LGG) are described by the World Health Organization as Grades I and II. Among LGGs, the most common primary brain tumor is pilocytic astrocytoma (PA) and carries an excellent prognosis when treated with complete surgical resection. Cases, in which this is not possible, are associated with less favorable outcomes and worse progression-free survival. CASE DESCRIPTION: This report describes a case of a 22-year-old male, who presented with progression of a primary brainstem tumor previously treated with stereotactic radiosurgery and chemotherapy. Patient underwent surgical exploration and was diagnosed with juvenile PA, but debulking was limited by the very dense and fibrous tumor. Complete surgical resection was not possible at this time. Despite efforts to treat with chemotherapy, the patient presented a year later with clinical deterioration and severe neurologic deficits, prompting surgical re-exploration. During the second operation, the tumor was found to have undergone very significant softening in consistency, allowing for gross total resection (GTR). CONCLUSION: Aggressive treatment of brainstem LGG should be pursued whenever possible, given its generally favorable prognosis. Repeat microsurgical resection, even with a different approach, might be reasonable and safe. Finally, chemotherapy may be associated with changes in the tumor consistency that can render previously unresectable lesions amenable to successful aggressive resection.

A comparison of electronically-delivered and face to face cognitive behavioural therapies in depressive disorders: A systematic review and meta-analysis.

BACKGROUND: Cognitive behavioural therapy (CBT) is a widely used treatment for depression. However, limited resource availability poses several barriers to patients seeking access to care, including lengthy wait times and geographical limitations. This has prompted health care services to introduce electronically delivered CBT (eCBT) to facilitate access. Although previous reviews have compared the effects of eCBT to face-to-face CBT, there is an overall lack of adequately powered and up-to-date evidence in the literature to provide a reliable comparison between the two modes of administration. The purpose of this study is to evaluate the effects of eCBT compared to face-to-face CBT through a systematic review of the literature. METHODS: To be eligible for this review, studies needed to be randomized controlled trials evaluating the clinical effectiveness of any form of eCBT compared to face-to-face CBT. These encompassed studies evaluating a wide range of outcomes including severity of symptoms, adverse outcomes, clinically relevant outcomes, global functionality, participant satisfaction, quality of life, and affordability. There were no restrictions on participant age or sex.We searched MEDLINE, EMBASE, Psych Info, Cochrane CENTRAL and CINAHL databases from inception to February 20th, 2020 using a comprehensive search strategy. All stages of literature screening and data extraction were completed independently in duplicate. Data extraction and risk of bias analyses, including GRADE ratings, were conducted on studies meeting inclusion criteria. Qualitative measures are reported in a narrative summary. We pooled quantitative data in meta-analyses to provide an estimated summary effect. This review adheres to PRISMA reporting guidelines. FINDINGS: In total, we included 17 studies in our analyses. Our results demonstrated that eCBT was more effective than face-to-face CBT at reducing depression symptom severity (Standardized mean difference [SMD]: -1.73; 95% confidence interval [CI]: -2.72, -0.74; GRADE: moderate quality of evidence). There were no significant differences between the two interventions on participant satisfaction (SMD 0.13 95%; CI -0.32, 0.59; GRADE: low quality of evidence). One RCT reported eCBT to be less costly than face-to-face CBT (GRADE: low quality of evidence). Results did not differ when stratified by subgroups such as participant age and study location. INTERPRETATION: Although we found eCBT to have moderate evidence of effectiveness in reducing symptoms of depression, high heterogeneity among studies precludes definitive conclusions for all outcomes. With the current reliance and accessibility of technology to increasing number of people worldwide, serious consideration in utilizing technology should be given to maximize accessibility for depression treatments. Our results found eCBT is at least as effective as face to face CBT, thus eCBT should be offered if preferred by patients and therapists. FUNDING: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Extreme Intracranial Hypotension With Brain Herniation Treated With Repeat Bolus Intrathecal Infusions.

Intracranial hypotension (IH) is a relatively common condition associated with low cerebrospinal (CSF) pressure. The most typical symptom is orthostatic headache, although neurological deficits and changes in the level of consciousness, such as encephalopathy, stupor, and coma, may also occur. Uncomplicated CSF hypotension headaches generally resolve with rest, hydration, and analgesia. However, persistent cases may require an epidural blood patch (EBP) for resolution. Our report presents the case of a 50-year-old male with a history of intravenous (IV) drug abuse, positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) antibodies, who was admitted for new-onset headache and brain magnetic resonance imaging (MRI) findings suggesting CSF hypotension. The patient subsequently developed altered mental status with agonizing respirations, prompting intubation and admission to the intensive care unit (ICU) with neurosurgery consult. The initial exam revealed fixed and dilated pupils, suggestive of severe IH with brain herniation and the decision was made to proceed with an emergent intrathecal infusion with intraparenchymal intracranial pressure (ICP) monitoring, combined with EBP. A substantial clinical improvement was noted following the procedure. Within 45 minutes, the patient's mental status improved to normal and pupillary dilation and areflexia were no longer observed. While the procedure may need to be repeated in cases of late deterioration, this report provides evidence that intrathecal bolus saline infusion with simultaneous ICP monitoring may be considered an effective measure to treat extreme cases of IH with associated brain herniation. If performed in a timely fashion, improvement of ICP numbers, and clinical resolution can be quite rapid.

Overproduction of IL-2 by Cbl-b deficient CD4+ T cells provides resistance against regulatory T cells.

Regulatory T cells are integral to the regulation of autoimmune and anti-tumor immune responses. However, several studies have suggested that changes in T cell signaling networks can result in T cells that are resistant to the suppressive effects of regulatory T cells. Here, we investigated the role of Cbl-b, an E3 ubiquitin ligase, in establishing resistance to Treg-mediated suppression. We found that the absence of Cbl-b, a negative regulator of multiple TCR signaling pathways, rendered T cells impartial to Treg suppression by regulating cytokine networks leading to improved anti-tumor immunity despite the presence of Treg cells in the tumor. Specifically, Cbl-b KO CD4+FoxP3- T cells hyper-produced IL-2 and together with IL-2 Rα upregulation served as an essential mechanism to escape suppression by Treg cells. Furthermore, we report that IL-2 serves as the central molecule required for cytokine-induced Treg resistance. Collectively our data emphasize the role of IL-2 as a key mechanism that renders CD4+ T cells resistant to the inhibitory effects of Treg cells.

Microsurgical Clip Suspension to Prevent Optic Neuropathy Following Ligation of Anterior Communicating Artery Aneurysm: A Technical Report and Surgical Video.

Anterior communicating artery (ACoA) aneurysms are among the most common intracerebral aneurysms. Complications of ACoA aneurysm include subarachnoid hemorrhage, which may occur spontaneously or as a result of trauma. While prognosis of microsurgical clip ligation is excellent, iatrogenic afferent pupillary defect secondary to mechanical compression of the optic nerve by the clips is a known complication. Our report presents a case of a 59-year-old female status post resection of a pituitary macroadenoma one year ago with a three- to four-week history of progressively worsening headache found to have a 6.5 x 5.4 mm wide neck and irregularly dysplastic aneurysmal dilation of the ACoA. During the operation, two of the longer clips appeared to be touching the optic nerve and we utilized a clip suspension technique to relieve compression. This gently elevated and suspended the two clips up to the dura, allowing for a 2 mm gap between the optic nerve and clips. This maneuver relieved mechanical compression against the optic nerve and potentially mitigated the need for surgical re-exploration in the future.

Acceptability of the Fitbit in behavioural activation therapy for depression: a qualitative study.

INTRODUCTION: Major depressive disorder is characterised by low mood and poor motivation. Literature suggests that increased physical activity has positive effects on alleviating depression. Fitness-tracking devices may complement behavioural activation (BA) therapy to improve physical activity and mental health in patients with depression. OBJECTIVES: To understand patients' perceived benefit from the Fitbit and explore themes associated with patient experiences. To compare perceived benefit, patient factors, Fitbit usage and Beck's Depression Inventory (BDI) scores. METHODS: Semistructured interviews were conducted with patients (n=36) who completed a 28-week BA group programme in a mood disorders outpatient clinic. All patients were asked to carry a Fitbit One device. We conducted thematic analyses on the interviews and exploratory quantitative analyses on patient characteristics, Fitbit usage, steps recorded, perceived benefit and BDI scores. FINDINGS: Twenty-three patients found the Fitbit helpful for their physical activity. Themes of positive experiences included self-awareness, peer motivation and goal-setting opportunities. Negative themes included inconvenience, inaccuracies and disinterest. Age, baseline and change in BDI scores, prior physical activity goals and familiarity with technology were not associated with perceived benefit from the Fitbit or usage. Perceived benefit was significantly (p<0.01) associated with usage. CONCLUSIONS: Overall, the Fitbit is an acceptable tool to complement BA therapy for patients with depression. Many positive themes were concordant with current literature; however, patients also reported negative aspects that may affect use. CLINICAL IMPLICATIONS: Clinicians and researchers should consider both strengths and limitations of activity trackers when implementing them to motivate patients with depression. TRIAL REGISTRATION NUMBER: NCT02045771; Pre-results.

Next generation patient monitor powered by in-silico physiology.

The goal of this paper is to introduce a next generation patient monitoring technology that relies on objective and continuous data analytics to alleviate the data overload in the critical care unit. The technology provides the foundation for increasing the consistency and efficacy of data use in clinical practice and improving outcomes. This paper presents results for applying the approach to the hemodynamic monitoring of infants immediately following cardiac surgery and demonstrates its efficacy of estimating the probability of inadequate systemic oxygen delivery, which is an essential risk attribute in the management of critically ill patients.