Derivation and External Validation of the Ottawa Bloodstream Infection Model for Acutely Ill Adults.

BACKGROUND: Knowing the probability that patients have a bloodstream infection (BSI) could influence the ordering of blood cultures and interpretation of their preliminary results. Many previous BSI probability models have limited applicability and accuracy. This study used currently recommended modeling techniques and a large sample to derive and validate the Ottawa BSI Model. METHODS: At a tertiary care teaching hospital, we retrieved a random sample of 4180 adults having blood cultures in our emergency department or during the initial 48 h of the encounter. Variable selection was based on clinical experience and a systematic review of previous model performance. Model performance was measured in a temporal external validation group of 4680 patients. RESULTS: A total of 327 derivation patients had a BSI (8.0%). BSI risk increased with increased number of culture sets (2 sets: adjusted odds ratio [aOR] 1.52 [1.10-2.11]; 3 sets: 1.99 [0.86-4.58]); with indwelling catheter (aOR 2.07 [1.34-3.20); with increasing temperature, heart rate, and neutrophil-lymphocyte ratio; and with decreasing systolic blood pressure, platelet count, urea-creatinine ratio, and estimated glomerular filtration rate. In the temporal external validation group, model discrimination was good (c-statistic 0.71 [0.69-0.74]) and calibration was very good (integrated calibration index .016 [.010-.024]). Exclusion of validation patients with acute SARS-CoV-2 infection improved discrimination slightly (c-statistic 0.73 [0.69-0.76]). CONCLUSIONS: The Ottawa BSI Model uses commonly available data to return an expected BSI probability for acutely ill patients. However, it cannot exclude BSI and its complexity requires computational assistance to use.

Reactive oxygen species (ROS) are a key determinant of cancer's metabolic phenotype.

Cancer cells exhibit a wide range of metabolic phenotypes, ranging from strict aerobic glycolysis to increased mitochondrial respiration. The cause and utility of this metabolic variation is poorly understood. Given that cancer cells experience heavy selection within their microenvironment, survival requires metabolic adaptation to both extracellular and intracellular conditions. Herein, we suggest that reactive oxygen species (ROS) are a key determinant of cancer's metabolic phenotype. Intracellular ROS levels can be modified by an assortment of critical parameters including oxygenation, glucose availability and growth factors. ROS act as integrators of environmental information as well as downstream effectors of signaling pathways. Maintaining ROS within a narrow range allows malignant cells to enhance growth and invasion while limiting their apoptotic susceptibility. Cancer cells actively modify their metabolism to optimize intracellular ROS levels and thereby improve survival. Furthermore, we highlight distinct metabolic phenotypes in response to oxidative stress and their tumorigenic drivers.

The Independent Association of Plasma and Red Blood Cell Zinc Concentrations with Long-Term Outcomes of Hospitalized Patients.

Background: Plasma and RBC zinc values are unrelated in hospitalized patients. The independent association of these values with important patient outcomes is unknown. Objectives: Measure the independent association of plasma and RBC zinc with outcomes in hospitalized patients. Methods: Plasma and RBC zinc concentrations were prospectively measured within 48 h of hospitalization in consenting patients. Data were linked deterministically with population-based health administrative data to measure each association of zinc measures with 2 outcomes (time to death from any cause and likelihood of death or urgent readmission to hospital within 30-d of discharge) after adjusting for validated outcome risk scores. Results: In total, 250 people admitted to medical services were studied. Patients were ill with a 1-y baseline expected death risk (IQR) of 19.9% (6.3%-37.2%). The observed 1-y and 2-y all-cause death risks were 24.5% (95% CI: 19.6%, 30.3%) and 33.2% (95% CI: 27.3%, 39.9%), respectively. Death risk increased significantly as plasma zinc concentrations decreased (P = 0.0001). This association persisted even after adjusting for the baseline expected death risk (P = 0.02) with every 2-µmol/L decrease in plasma zinc concentrations being independently associated with, on average, a 35% increase in the death risk. RBC zinc concentrations were not associated with the death risk. Neither plasma nor RBC zinc concentrations were significantly associated with the 30-d death or urgent readmission rate. Conclusions: Plasma, but not RBC, zinc concentrations are independently associated with the all-cause death risk in hospitalized medical patients. Further study is required to determine whether this association is causal and identify its potential causal pathways. Curr Dev Nutr 2023;x:xx.

Concurrent external validation of bloodstream infection probability models.

OBJECTIVE: Accurately estimating the likelihood of bloodstream infection (BSI) can help clinicians make diagnostic and therapeutic decisions. Many multivariate models predicting BSI probability have been published. This study measured the performance of BSI probability models within the same patient sample. METHODS: We retrieved validated BSI probability models included in a recently published systematic review that returned a patient-level BSI probability for adults. Model applicability, discrimination, and accuracy was measured in a simple random sample of 4485 admitted adults having blood cultures ordered in the emergency department or the initial 48 hours of hospitalization. RESULTS: Ten models were included (publication years 1991-2015). Common methodological threats to model performance included overfitting and continuous variable categorization. Restrictive inclusion criteria caused seven models to apply to <15% of validation patients. Model discrimination was less than originally reported in derivation groups (median c-statistic 60%, range 48-69). The observed BSI risk frequently deviated from expected (median integrated calibration index 4.0%, range 0.8-12.4). Notable disagreement in expected BSI probabilities was seen between models (median (25th-75th percentile) relative difference between expected risks 68.0% (28.6-113.6%)). DISCUSSION: In a large randomly selected external validation population, many published BSI probability models had restricted applicability, limited discrimination and calibration, and extensive inter-model disagreement. Direct comparison of model performance is hampered by dissimilarities between model-specific validation groups.

Relationship between Plasma Zinc and Red Blood Cell Zinc Levels in Hospitalized Patients.

BACKGROUND: Patient zinc stores are quantified with plasma or red blood cell (RBC) measures. The relationship between these 2 measures of zinc status has not been determined in a broad population of hospitalized patients. METHODS: Both plasma zinc and RBC zinc were prospectively collected and measured in 252 consenting patients admitted urgently to hospital. Plasma and RBC zinc levels were measured within 48 h of admission. We collected demographic, vitals, and laboratory data for use in multivariate regression models that included markers of acute disease severity and systemic inflammation. RESULTS: Plasma zinc and RBC zinc levels were low in 63% and 10% of hospitalized patients, respectively. Categorized zinc levels based on normal intervals for plasma and RBC zinc values were not related (χ2 0.47 [2 df] P = 0.79). The Pearson correlation coefficient between plasma zinc and RBC zinc was -0.09 (P = 0.15). After adjustments for multiple clinical covariates, the correlation coefficient remained insignificant (r = -0.11, P = 0.08). Plasma zinc was inversely associated with markers of inflammation including the neutrophil-to-lymphocyte ratio and temperature. CONCLUSIONS: Patient-specific plasma and RBC zinc are unrelated in hospitalized patients, possibly due to decreased values with acute illness seen in the former but not the latter. Future studies are required to determine which of these measures best predicts outcomes in hospitalized patients.

The Prognostic Value of Serum Zinc Levels in Acutely Hospitalized Patients: a Systematic Review.

Several small studies have identified possible associations between low serum zinc levels and worse outcomes in patients acutely hospitalized for a variety of diseases. This study systematically evaluated all published literature to determine whether serum zinc might independently predict important outcomes in hospitalized patients. PubMed, Embase, and Cochrane Libraries databases were searched from 1970 to 2019 to identify all citations having the keyword "zinc" with hospital outcomes. Studies were included if they measured the association between serum zinc levels in non-electively hospitalized patients with survival, length of stay, or unplanned readmission. Data were double-abstracted to evaluate the association between zinc levels and these outcomes. Our search returned 1091 citations of which 12 studies met the inclusion criteria. Studies were small (median 112.5 patients) using unspecified sampling methods. Seven studies were restricted to critically ill patients. Mean zinc levels ranged from 27.5 to 85.3 µg/dL. Baseline mean zinc levels were significantly lower (p < 0.05) in patients who eventually died in 1 of 7 studies. Five of seven studies found significantly increased risk of death in hospital with lower zinc levels. Associations between zinc levels and critical care or hospital length of stay were unclear. In 1 study, lower zinc levels were associated with a significantly increased risk of unplanned readmission. Current studies measuring the association between serum zinc levels and outcomes in acutely hospitalized patients are limited by their sample sizes, select patient populations, and limited statistical analyses. The association of zinc levels with hospital patient outcomes is unclear.

Factors associated with zinc levels in hospitalized patients: An observational study using routinely collected data.

BACKGROUND: Zinc deficiency is easily treated and has been associated with worse outcomes in hospitalized patients. Zinc testing is time-consuming and relatively costly. We identified every zinc level measured at our teaching hospital and quantified how much zinc variation is explained by other hospital factors. METHODS: We linked tables from our hospital data warehouse from 1996 to 2019 to identify all patients who had at least 1 serum zinc measured during their admission. We determined the status of factors that could influence zinc levels including severity of illness, presence of bleeding or inflammation, and factors influencing zinc absorption. RESULTS: We identified only 318 adult patients having zinc measurement during their hospitalization. Patients were elderly (median age 71 [IQR 56-78]) and arrived by ambulance 45% of the time. Zinc was measured a median of 5 days into the hospitalization (IQR 3-13) with 154 (51.6%) recording a low level. Almost half of patients were missing at least one covariable laboratory test. Multilinear regression models using complete case analysis returned more extreme parameter estimate values and deemed as significant only two thirds of the factors identified as significant in models using data with missing values imputed. Imputed models found significant associations between lower zinc levels and recent surgery, decreased albumin, creatinine, and sodium, earlier hospitalization day of sampling, and increased patient comorbidity. These models explained 32% of zinc variation. CONCLUSIONS: Zinc testing is rare, low zinc levels are very common, and one third of its variation in hospitalized patients is explained by other covariables.

Detection methods of circulating tumor cells in cutaneous melanoma: a systematic review.

The vast majority of melanoma-related deaths are due to disseminated malignancy. Many treated patients who are clinically disease-free will go on to relapse. Therefore, new prognostic tools must be developed to better assess metastatic potential and assist in patient management. Circulating tumor cells are a widely studied metastatic biomarker with promising prognostic utility, as the shedding of cells from the primary tumor into peripheral blood is a necessary step in disease dissemination. An assortment of technologies and techniques has been developed to isolate and detect circulating melanoma cells (CMCs), but a standardized method is yet to be established. It is the aim of this study to systematically review the diverse enrichment and detection methods of circulating tumor cells in cutaneous melanoma. A literature search yielded 351 articles, of which 74 were deemed eligible according to inclusion criteria, the primary requirement being the reporting of patient CMC positivity status stratified by the stage of melanoma. Pertinent studies were used to evaluate the advantages and disadvantages of each method. Additionally, we calculated the sensitivity and specificity of seven common melanoma-associated markers based on the available literature.