Malnutrition risk assessment using a machine learning-based screening tool: A multicentre retrospective cohort.

BACKGROUND: Malnutrition is associated with increased morbidity, mortality, and healthcare costs. Early detection is important for timely intervention. This paper assesses the ability of a machine learning screening tool (MUST-Plus) implemented in registered dietitian (RD) workflow to identify malnourished patients early in the hospital stay and to improve the diagnosis and documentation rate of malnutrition. METHODS: This retrospective cohort study was conducted in a large, urban health system in New York City comprising six hospitals serving a diverse patient population. The study included all patients aged ≥ 18 years, who were not admitted for COVID-19 and had a length of stay of ≤ 30 days. RESULTS: Of the 7736 hospitalisations that met the inclusion criteria, 1947 (25.2%) were identified as being malnourished by MUST-Plus-assisted RD evaluations. The lag between admission and diagnosis improved with MUST-Plus implementation. The usability of the tool output by RDs exceeded 90%, showing good acceptance by users. When compared pre-/post-implementation, the rate of both diagnoses and documentation of malnutrition showed improvement. CONCLUSION: MUST-Plus, a machine learning-based screening tool, shows great promise as a malnutrition screening tool for hospitalised patients when used in conjunction with adequate RD staffing and training about the tool. It performed well across multiple measures and settings. Other health systems can use their electronic health record data to develop, test and implement similar machine learning-based processes to improve malnutrition screening and facilitate timely intervention.

Dysregulation of core neurodevelopmental pathways-a common feature of cancers with perineural invasion.

Background: High nerve density in tumors and metastasis via nerves (perineural invasion-PNI) have been reported extensively in solid tumors throughout the body including pancreatic, head and neck, gastric, prostate, breast, and colorectal cancers. Ablation of tumor nerves results in improved disease outcomes, suggesting that blocking nerve-tumor communication could be a novel treatment strategy. However, the molecular mechanisms underlying this remain poorly understood. Thus, the aim here was to identify molecular pathways underlying nerve-tumor crosstalk and to determine common molecular features between PNI-associated cancers. Results: Analysis of head and neck (HNSCC), pancreatic, and gastric (STAD) cancer Gene Expression Omnibus datasets was used to identify differentially expressed genes (DEGs). This revealed extracellular matrix components as highly dysregulated. To enrich for pathways associated with PNI, genes previously correlated with PNI in STAD and in 2 HNSCC studies where tumor samples were segregated by PNI status were analyzed. Neurodevelopmental genes were found to be enriched with PNI. In datasets where tumor samples were not segregated by PNI, neurodevelopmental pathways accounted for 12%-16% of the DEGs. Further dysregulation of axon guidance genes was common to all cancers analyzed. By examining paralog genes, a clear pattern emerged where at least one family member from several axon guidance pathways was affected in all cancers examined. Overall 17 different axon guidance gene families were disrupted, including the ephrin-Eph, semaphorin-neuropilin/plexin, and slit-robo pathways. These findings were validated using The Cancer Genome Atlas and cross-referenced to other cancers with a high incidence of PNI including colon, cholangiocarcinoma, prostate, and breast cancers. Survival analysis revealed that the expression levels of neurodevelopmental gene families impacted disease survival. Conclusion: These data highlight the importance of the tumor as a source of signals for neural tropism and neural plasticity as a common feature of cancer. The analysis supports the hypothesis that dysregulation of neurodevelopmental programs is a common feature associated with PNI. Furthermore, the data suggested that different cancers may have evolved to employ alternative genetic strategies to disrupt the same pathways. Overall, these findings provide potential druggable targets for novel therapies of cancer management and provide multi-cancer molecular biomarkers.

Output force and ratio of laparoscopic graspers: an evaluation of operating room ergonomics.

BACKGROUND: "Laparoscopist's thumb," or thenar paresthesia, can result from prolonged or excessive grip force during laparoscopy, as can more general syndromes, such as carpal tunnel syndrome. This is particularly relevant in gynecology, where laparoscopic procedures are standard. Although this method of injury is well known, there is a paucity of data to guide surgeons in selecting more efficient, ergonomic instruments. OBJECTIVE: This study compared the ratio of applied tissue force and required surgeon input in a sample of common ratcheting laparoscopic graspers in a small-handed surgeon, to provide potential metrics applicable to surgical ergonomics and surgeon instrument choice. STUDY DESIGN: Laparoscopic graspers with varied ratcheting mechanisms and tip shapes were evaluated. Brands included Snowden-Pencer, Covidien, Aesculap, and Ethicon. A Kocher was used as an open instrument comparison. Flexiforce A401 thin-film force sensors were used to measure applied forces. Data were collected and calibrated using an Arduino Uno microcontroller board with Arduino and MATLAB software. Single-handed, complete closure of each device's ratcheting mechanism was performed 3 times. The maximum required input force in Newtons was recorded and averaged. The average output force was measured with a bare sensor and the same sensor between 2 different thicknesses of LifeLike BioTissue. RESULTS: The most ergonomic ratcheting grasper for a small-handed surgeon was identified by the output ratio: the highest output force relative to the required surgeon input (the most force for the least amount of effort). The Kocher required an average input force of 33.66 N, with its highest output ratio of 3.46 (112 N output). The Covidien Endo Grasp was the most ergonomic, with an output ratio of 0.96 on the bare force sensor (31.4 N output). The Snowden-Pencer Wavy grasper was the least ergonomic, with an output ratio of 0.06 when applied to the bare force sensor (5.9 N output). All graspers except for the Endo Grasp had improving output ratios as tissue thickness and subsequent grasper contact area increased. Input force above that provided by the ratcheting mechanisms did not increase output force in a clinically relevant amount for any of the instruments evaluated. CONCLUSION: Laparoscopic graspers vary widely in their ability to provide reliable tissue force without requiring excessive input by the surgeon, and a point of diminishing returns often exists with increased surgeon input over designed ratcheting mechanisms. Output force and output ratio are potential quantitative measures of the efficiency of laparoscopic instruments. Providing users with this type of data could assist in optimizing instrument ergonomics.

Intraoperative Transesophageal Echocardiography in Management of Acute Type I Aortic Dissection With Malperfusion: A Case Report.

Acute type I aortic dissection is a life-threatening emergency with potentially devastating complications, including end-organ malperfusion. Early detection of malperfusion with intraoperative imaging allows for efficient transition to appropriate interventions. We present a case of a 65-year-old male with acute type I aortic dissection who underwent emergent surgical repair of the aortic root and hemiarch followed by acutely worsening distal malperfusion. The use of intraoperative transesophageal echocardiography played a critical role in visualizing diversion of flow to the false lumen, prompting urgent vascular surgery consultation and life-saving thoracic endovascular aortic repair.

Not Your Average Mediastinal Mass: A Case of a Large Mediastinal Teratoma in a Patient With a History of Polio Disease.

Mediastinal masses can be challenging to the surgical team and anesthetic considerations vary according to the location, pathology, surgical approach, and patient comorbidities. We report the case of a 21 cm symptomatic intrathoracic teratoma in a postpartum patient with a history of poliomyelitis. Significant challenges were presented for anesthetic induction, potential extracorporeal membrane oxygenation, and the use of neuraxial pain techniques and neuromuscular blockade. This case report demonstrates techniques to safely manage a patient with a large symptomatic mediastinal mass and potential neuromuscular disease.

MUST-Plus: A Machine Learning Classifier That Improves Malnutrition Screening in Acute Care Facilities.

OBJECTIVE: Malnutrition among hospital patients, a frequent, yet under-diagnosed problem is associated with adverse impact on patient outcome and health care costs. Development of highly accurate malnutrition screening tools is, therefore, essential for its timely detection, for providing nutritional care, and for addressing the concerns related to the suboptimal predictive value of the conventional screening tools, such as the Malnutrition Universal Screening Tool (MUST). We aimed to develop a machine learning (ML) based classifier (MUST-Plus) for more accurate prediction of malnutrition. METHOD: A retrospective cohort with inpatient data consisting of anthropometric, lab biochemistry, clinical data, and demographics from adult (≥ 18 years) admissions at a large tertiary health care system between January 2017 and July 2018 was used. The registered dietitian (RD) nutritional assessments were used as the gold standard outcome label. The cohort was randomly split (70:30) into training and test sets. A random forest model was trained using 10-fold cross-validation on training set, and its predictive performance on test set was compared to MUST. RESULTS: In all, 13.3% of admissions were associated with malnutrition in the test cohort. MUST-Plus provided 73.07% (95% confidence interval [CI]: 69.61%-76.33%) sensitivity, 76.89% (95% CI: 75.64%-78.11%) specificity, and 83.5% (95% CI: 82.0%-85.0%) area under the receiver operating curve (AUC). Compared to classic MUST, MUST-Plus demonstrated 30% higher sensitivity, 6% higher specificity, and 17% increased AUC. CONCLUSIONS: ML-based MUST-Plus provided superior performance in identifying malnutrition compared to the classic MUST. The tool can be used for improving the operational efficiency of RDs by timely referrals of high-risk patients.

Germline Variant in SLCO2B1 and Response to Abiraterone Acetate Plus Prednisone (AA) in New-onset Metastatic Castration-resistant Prostate Cancer (mCRPC).

There are many treatment options available for men with metastatic castration-resistant prostate cancer (mCRPC). Yet, biomarkers predictive of differential response to treatment are currently unavailable. A recent translational study suggested that SLCO2B1 genotype could predict response to abiraterone acetate for men with advanced prostate cancer. Here, we investigate whether germline variants in SLCO2B1 are predictive of response to first-line abiraterone acetate in men with new mCRPC. Clinical data and samples were analyzed from a prospective prostate cancer registry at the University of Utah (Salt Lake City, UT). Genotyping was performed using the Illumina OmniExpress genotyping platform. Primary endpoint was progression-free survival (PFS) on first-line abiraterone acetate in men with mCRPC. We performed a prespecified multivariate Cox regression analysis to assess the independent predictive value of rs12422149 and rs1789693 on PFS on abiraterone acetate. Of 401 men with advanced prostate cancer genotyped, 323 were homozygous wild-type for rs12422149 (80.5%), 74 were heterozygous (18.5%), and 4 were homozygous variant (1.0%). In a multivariate analysis of 79 men treated with first-line abiraterone acetate for mCRPC, men heterozygous for rs12422149 had significantly improved median PFS compared with the homozygous wild-type group (8.9 months vs. 6.3 months; HR, 0.46; 95% confidence interval, 0.23-0.94; P = 0.03). No significant difference in median PFS was seen by rs1789693 genotype. In this first clinical validation of translational data reported by Mostaghel and colleagues, germline variant alleles in rs12422149 of SLCO2B1 are common and predict improved response to first-line abiraterone acetate in men with mCRPC.

Commissural axonal corridors instruct neuronal migration in the mouse spinal cord.

Unravelling how neurons are guided during vertebrate embryonic development has wide implications for understanding the assembly of the nervous system. During embryogenesis, migration of neuronal cell bodies and axons occurs simultaneously, but to what degree they influence each other's development remains obscure. We show here that within the mouse embryonic spinal cord, commissural axons bisect, delimit or preconfigure ventral interneuron cell body position. Furthermore, genetic disruption of commissural axons results in abnormal ventral interneuron cell body positioning. These data suggest that commissural axonal fascicles instruct cell body position by acting either as border landmarks (axon-restricted migration), which to our knowledge has not been previously addressed, or acting as cellular guides. This study in the developing spinal cord highlights an important function for the interaction of cell bodies and axons, and provides a conceptual proof of principle that is likely to have overarching implications for the development of neuronal architecture.

Netrin 1 and Dcc signalling are required for confinement of central axons within the central nervous system.

The establishment of anatomically stereotyped axonal projections is fundamental to neuronal function. While most neurons project their axons within the central nervous system (CNS), only axons of centrally born motoneurons and peripherally born sensory neurons link the CNS and peripheral nervous system (PNS) together by navigating through specialized CNS/PNS transition zones. Such selective restriction is of importance because inappropriate CNS axonal exit could lead to loss of correct connectivity and also to gain of erroneous functions. However, to date, surprisingly little is known about the molecular-genetic mechanisms that regulate how central axons are confined within the CNS during development. Here, we show that netrin 1/Dcc/Unc5 chemotropism contributes to axonal confinement within the CNS. In both Ntn1 and Dcc mutant mouse embryos, some spinal interneuronal axons exit the CNS by traversing the CNS/PNS transition zones normally reserved for motor and sensory axons. We provide evidence that netrin 1 signalling preserves CNS/PNS axonal integrity in three ways: (1) netrin 1/Dcc ventral attraction diverts axons away from potential exit points; (2) a Dcc/Unc5c-dependent netrin 1 chemoinhibitory barrier in the dorsolateral spinal cord prevents interneurons from being close to the dorsal CNS/PNS transition zone; and (3) a netrin 1/Dcc-dependent, Unc5c-independent mechanism that actively prevents exit from the CNS. Together, these findings provide insights into the molecular mechanisms that maintain CNS/PNS integrity and, to the best of our knowledge, present the first evidence that chemotropic signalling regulates interneuronal CNS axonal confinement in vertebrates.

The expression profile of the tumor suppressor gene Lzts1 suggests a role in neuronal development.

BACKGROUND: Neuronal circuit assembly comprises a number of developmental processes that ultimately underlie function. Identifying the molecular events that dictate these processes can give key insights into how neuronal circuit formation is coordinated. To begin to identify such molecular mechanisms, we have analysed the expression of a candidate gene of entirely unknown function within the nervous system. Here we reveal the spatial and temporal distribution of Lzts1 in mouse and chick embryonic spinal cord and propose potential biological functions. RESULTS: Lzts1 mRNA is transiently expressed at the border of the ventricular and mantle zones in subsets of sensory and motor spinal neurons. The protein is localized to the cell body, axon, and trailing process of motor, commissural, and dorsal root neurons during development. CONCLUSIONS: Taken together, the spatial and temporal distribution of Lzts1 is consistent with a potential function(s) in cell cycle regulation, axon growth or guidance, and/or migration of neurons.

Adult parenteral nutrition utilization at a tertiary care hospital.

BACKGROUND: Guidelines from the American Society for Parenteral and Enteral Nutrition promote appropriate use of parenteral nutrition (PN). In addition, involvement of multidisciplinary nutrition support teams (NSTs) has led to a reduction of inappropriate PN administration. This study evaluated the effect of introducing hospital-wide PN guidelines and a PN review committee on PN prescription behavior of NSTs in the authors' hospital. METHODS: A PN guidelines form with established indications was developed and made available to the NSTs. A PN review committee was formed to assess the appropriateness of PN prescriptions and educate the NSTs if an inappropriate PN prescription was noted. The initial-phase PN prescriptions were compared with those in a later (established) phase. RESULTS: Of a total of 614 PN prescriptions, 8.1% did not meet the established indications. The initial phase recorded 312 PN prescriptions, and the established phase had 302 prescriptions. The number of inappropriate PN prescriptions decreased significantly from 11.9% in the initial phase to 4.3% in the established phase (P = .001). CONCLUSION: The incidence of inappropriate PN prescription was low when NSTs were closely involved in patient care. Availability of written guidelines and continuous oversight of NSTs promoted appropriate PN usage.

A molecular program for contralateral trajectory: Rig-1 control by LIM homeodomain transcription factors.

Despite increasing evidence for transcriptional control of neural connectivity, how transcription factors regulate discrete steps in axon guidance remains obscure. Projection neurons in the dorsal spinal cord relay sensory signals to higher brain centers. Some projection neurons send their axons ipsilaterally, whereas others, commissural neurons, send axons contralaterally. We show that two closely related LIM homeodomain proteins, Lhx2 and Lhx9, are expressed by a set of commissural relay neurons (dI1c neurons) and are required for the dI1c axon projection. Midline crossing by dI1c axons is lost in Lhx2/9 double mutants, a defect that results from loss of expression of Rig-1 from dI1c axons. Lhx2 binds to a conserved motif in the Rig-1 gene, suggesting that Lhx2/9 regulate directly the expression of Rig-1. Our findings reveal a link between the transcriptional programs that define neuronal subtype identity and the expression of receptors that guide distinctive aspects of their trajectory.