Rosmarinic acid enhances CHO cell productivity and proliferation through activation of the unfolded protein response and the mTOR pathway.

Rosmarinic acid (RA) has gained attraction in bioprocessing as a media supplement to improve cellular proliferation and protein production. Here, we observe up to a two-fold increase in antibody production with RA-supplementation, and a concentration-dependent effect of RA on cell proliferation for fed-batch Chinese hamster ovary (CHO) cell cultures. Contrary to previously reported antioxidant activity, RA increased the reactive oxygen species (ROS) levels, stimulated endoplasmic reticulum (ER) stress, activated the unfolded protein response (UPR), and elicited DNA damage. Despite such stressful events, RA appeared to maintained cell health via mammalian target of rapamycin (mTOR) pathway activation; both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) were stimulated in RA-supplemented cultures. By reversing such mTOR pathway activity through either chemical inhibitor addition or siRNA knockdown of genes regulating the mTORC1 and mTORC2 complexes, antibody production, UPR signaling, and stress-induced DNA damage were reduced. Further, the proliferative effect of RA appeared to be regulated selectively by mTORC2 activation and have reproduced this observation by using the mTORC2 stimulator SC-79. Analogously, knockdown of mTORC2 strongly reduced X-box binding protein 1 (XBP1) splicing, which would be expected to reduce antibody folding and secretion, sugging that reduced mTORC2 would correlate with reduced antibody levels. The crosstalk between mTOR activation and UPR upregulation may thus be related directly to the enhanced productivity. Our results show the importance of the mTOR and UPR pathways in increasing antibody productivity, and suggest that RA supplementation may obviate the need for labor-intensive genetic engineering by directly activating pathways favorable to cell culture performance.

Factors Associated With Post-Extubation Stridor in Infants Intubated in the Pediatric ICU.

BACKGROUND: Post-extubation stridor (PES) is a common problem in the pediatric intensive care unit (PICU) and is associated with extubation failure, longer length of stay, and increased mortality. Infants represent a large proportion of PICU admissions and are at higher risk for PES, making identification and mitigation of factors associated with PES important in this age group. RESEARCH QUESTION: What factors are associated with PES in infants (age less than 1 year) intubated in the PICU? STUDY DESIGN & METHODS: The primary outcome was PES as defined by the need for racemic epinephrine within 6 h of extubation. Secondary outcomes were heliox administration and reintubation. Statistical analyses were performed with Fisher's exact test for univariate analyses and multivariate logistic regression. RESULTS: 518 patient charts were retrospectively reviewed. 24.1% of patients developed PES. Duration of mechanical ventilation greater than 48 h was associated with increased risk of PES (odds ratio [OR] = 1.75, 95% confidence interval [CI] 1.13-2.71, P = .01), as was nonelective intubation (OR = 2.92, 95% CI 1.91-4.46, P < .01). The presence of a cuff, gastroesophageal reflux disease, prematurity, and known upper airway abnormality had no association with PES. 4.0 endotracheal tubes (ETTs) had an increased association with PES compared to 3.5 ETTs (OR = 1.96, 95% CI 1.18-3.27, P < .01). There was no difference in risk of PES between 3.5 and 3.0 ETTs. INTERPRETATION: In infants intubated in the PICU, mechanical ventilation greater than 48 h and nonelective intubation were associated with PES. 4.0 ETTs were associated with higher risk of PES compared to 3.5 ETTs. These findings may help providers in ETT selection and to identify infants that may be at increased risk of PES.

Rapid Remission of Chronic, Progressive Conditions and Reducing Polypharmacy by Utilizing Lifestyle Therapy to Target Insulinemic Lifestyle Components.

This case study provides evidence that homeostatic control in a patient with hyperglycemia and other metabolic abnormalities associated with insulin resistance can be rapidly restored utilizing lifestyle therapy. The patient, an overweight, non-Hispanic White male aged 70 years, had been medicated for hypertension and Type 2 diabetes mellitus for 12 years. From baseline during 21 months of follow-up, HbA1c decreased from 6.6% to 5.4%, mean fasting glucose decreased from 125 mg/dL to 94 mg/dL, blood pressure decreased from 130/85 mmHg to 100/64 mmHg, estimated glomerular filtration rate increased from 50 ml/min/1.73m² to 58 ml/min/1.73m², waist circumference decreased from 118.8 cm to 90.8 cm, and liver function improved with aspartate transaminase decreasing from 44 IU/L to 17 IU/L and alanine transaminase decreasing from 34 IU/L to 21 IU/L. Each of these metabolic corrections was observed while eliminating respective disease-specific medications. These metabolic improvements were achieved using primary recommended lifestyle therapy specifically targeting known insulinemic lifestyle components. This case study shows that the utilization of primary recommended, ongoing lifestyle therapy targeting insulinemic lifestyle components can rapidly improve markers of insulin resistance and normalize abnormal laboratory values while eliminating the risk of polypharmacy and the direct costs of medication.

Use of single analytic tool to quantify both absolute N-glycosylation and glycan distribution in monoclonal antibodies.

Recombinant proteins represent almost half of the top selling therapeutics-with over a hundred billion dollars in global sales-and their efficacy and safety strongly depend on glycosylation. In this study, we showcase a simple method to simultaneously analyze N-glycan micro- and macroheterogeneity of an immunoglobulin G (IgG) by quantifying glycan occupancy and distribution. Our approach is linear over a wide range of glycan and glycoprotein concentrations down to 25 ng/mL. Additionally, we present a case study demonstrating the effect of small molecule metabolic regulators on glycan heterogeneity using this approach. In particular, sodium oxamate (SOD) decreased Chinese hamster ovary (CHO) glucose metabolism and reduced IgG glycosylation by 40% through upregulating reactive oxygen species (ROS) and reducing the UDP-GlcNAc pool, while maintaining a similar glycan profile to control cultures. Here, we suggest glycan macroheterogeneity as an attribute should be included in bioprocess screening to identify process parameters that optimize culture performance without compromising antibody quality.

Rapid In-Process Measurement of Live Virus Vaccine Potency Using Laser Force Cytology: Paving the Way for Rapid Vaccine Development.

Vaccinations to prevent infectious diseases are given to target the body's innate and adaptive immune systems. In most cases, the potency of a live virus vaccine (LVV) is the most critical measurement of efficacy, though in some cases the quantity of surface antigen on the virus is an equally critical quality attribute. Existing methods to measure the potency of viruses include plaque and TCID50 assays, both of which have very long lead times and cannot provide real time information on the quality of the vaccine during large-scale manufacturing. Here, we report the evaluation of LumaCyte's Radiance Laser Force Cytology platform as a new way to measure the potency of LVVs in upstream biomanufacturing process in real time and compare this to traditional TCID50 potency. We also assess this new platform as a way to detect adventitious agents, which is a regulatory expectation for the release of commercial vaccines. In both applications, we report the ability to obtain expedited and relevant potency information with strong correlation to release potency methods. Together, our data propose the application of Laser Force Cytology as a valuable process analytical technology (PAT) for the timely measurement of critical quality attributes of LVVs.

Progress toward rapid, at-line N-glycosylation detection and control for recombinant protein expression.

Proteins continue to represent a large fraction of the therapeutics market, reaching over a hundred billion dollars in market size globally. One key feature of protein modification that can affect both structure and function is the addition of glycosylation following protein folding, leading to regulatory requirements for the accurate assessment of protein attributes, including glycan structures. The non-template-driven, innately heterogeneous N-glycosylation process thus requires accurate detection to robustly generate protein therapies. A challenge exists in the timely detection of protein glycosylation without labor-intensive manipulation. In this article, we discuss progress toward N-glycoprotein control, focusing on novel control strategies and the advancement of rapid, high-throughput analysis methods.

Best Practices in Medical Documentation: A Curricular Module.

OBJECTIVE: To create and validate a checklist for high-quality documentation and pilot a multi-modal, immersive educational module across multiple institutions. We hypothesized that this module would improve knowledge, skills, and attitudes in medical documentation. METHODS: Module design was grounded in an established curriculum design framework. We conducted the study across 12 pediatric critical care fellowship programs between September 2017 and January 2018. Workshops were allotted 90 minutes for completion. We utilized a pre-/post- study design to determine the workshop's impact. Changes in knowledge were assessed through pre and post testing. Changes in skills were evaluated with a validated checklist for inclusion of key documentation elements. Changes in attitudes were determined through learner self-assessment RESULTS: 83 of 138 eligible fellows (60%) started the module and 62 of 83 (75%) completed data sets for analysis. Immediate post-testing demonstrated modest statistically significant improvement in knowledge, skills, and attitudes. The workshop was easily disseminated and deployed CONCLUSIONS: This study demonstrates that a multi-modal educational intervention can lead to improvement in medical documentation knowledge, skills, and attitudes in a cohort of PCCM fellows and be easily disseminated for use by other specialties and types of clinicians.

Viral adventitious agent detection using laser force cytology: Intrinsic cell property changes with infection and comparison to in vitro testing.

Adventitious agent testing in biomanufacturing requires assays of broad detection capability to screen for as many infectious agents as possible. The current gold standard for general infectious adventitious virus screening is the in vitro assay in which test articles are cultured onto a panel of different cell lines and observed for cytopathic effect (CPE). However, this assay is inherently subjective due to the nature of visual observation of cell morphology and labor and time intensive, requiring highly trained personnel to identify CPE. Laser force cytology (LFC) is an alternative, automated analytical method that uses a combination of optical and fluidic forces along with imaging to objectively and quantitatively assess CPE in cell culture. Importantly, because LFC uses no labels or antibodies, the assay is appropriate for general adventitious agent testing. Using LFC, changes in cellular features associated with virally infected cells were identified using principal component analysis. Using these features of infected cells, the sensitivity and earliness of detection with LFC was directly compared with the in vitro assay for a diverse panel of viruses incubated with chinese hamster ovary (CHO), Vero, and Medical Research Council cell strain 5 (MRC-5) cells. LFC detected viral infection with a sensitivity equal to the in vitro assay on average, but in certain virus and cell combinations including mouse minute virus (MMV) and reovirus 3 in CHO cells, detection was 4 days earlier and for MMV, the limit of detection was 10-fold lower. Overall, these results demonstrate the ability of LFC to serve as a biopharmaceutical adventitious agent testing methodology with sensitivity equivalent to the in vitro assay, but in an objective and automated manner.

Blood pressure variability during pediatric cardiac surgery is associated with acute kidney injury.

BACKGROUND: Blood pressure variability (BPV), defined as the degree of variation between discrete blood pressure readings, is associated with poor outcomes in acute care settings. Acute kidney injury (AKI) is a common and serious postoperative complication of cardiac surgery with cardiopulmonary bypass (CPB) in children. No studies have yet assessed the association between intraoperative BPV during cardiac surgery with CPB and the development of AKI in children. METHODS: A retrospective chart review of children undergoing cardiac surgery with CPB was performed. Intraoperative BPV was calculated using average real variability (ARV) and standard deviation (SD). Multiple regression models were used to examine the association between BPV and outcomes of AKI, hospital and intensive care unit (PICU) length of stay, and length of mechanical ventilation. RESULTS: Among 231 patients (58% males, median age 8.6 months) reviewed, 51.5% developed AKI (47.9% Stage I, 41.2% Stage II, 10.9% Stage III). In adjusted models, systolic and diastolic ARV were associated with development of any stage AKI (OR 1.40, 95% CI 1.08-1.8 and OR 1.4, 95% CI 1.05-1.8, respectively). Greater diastolic SD was associated with longer PICU length of stay (ß 0.94, 95% CI 0.62-1.2). When stratified by age, greater systolic ARV and SD were associated with AKI in infants ≤ 12 months, but there was no relationship in children > 12 months. CONCLUSIONS: Greater BPV during cardiac surgery with CPB was associated with development of postoperative AKI in infants, suggesting that BPV is a potentially modifiable risk factor for AKI in this high-risk population.

Acute kidney injury and kidney recovery after cardiopulmonary bypass in children.

BACKGROUND: Acute kidney injury (AKI) that improves in the pediatric intensive care unit (PICU) is associated with better outcomes compared to AKI that persists, but no study has investigated whether this also occurs in children undergoing cardiopulmonary bypass (CPB). METHODS: A retrospective study of children ≤18 years who underwent CPB in three children's hospitals was conducted. Patients were classified into groups by kidney recovery after AKI according to Acute Disease Quality Initiative (ADQI) guidelines. Adjusted regression models evaluated associations between kidney recovery group and hospital outcomes. RESULTS: Among 3620 children, AKI developed in 701 (19.4%): 610 transient AKI, 47 persistent AKI, and 44 acute kidney disease (AKD). Mortality increased with severity of kidney recovery group: 4.5% in the never developed AKI group, 8.9% in the transient AKI group, 25.5% in the persistent AKI group, and 31.8% in the AKD group (p <0.0001). In adjusted analysis, transient AKI (HR 1.4, CI 1.02, 2), persistent AKI (HR 22.4, CI 10.2, 49.2), and AKD (HR 3.7, CI 1.7, 7.9) had a greater hazard of mortality when compared to the never developed AKI group. Patients with transient AKI had a longer length of PICU stay than those with never developed AKI (HR 5.1, CI 2.9, 7.3). CONCLUSIONS: Patterns of kidney recovery after AKI were associated with worse PICU outcomes in children after CPB compared to those who did not develop AKI, even after rapid AKI recovery. Identification of factors that increase risk for these AKI patterns is necessary for prevention of AKI during CPB in children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Rapid, multiplexed detection of the let-7 miRNA family using γPNA amphiphiles in micelle-tagging electrophoresis.

miRNA is a promising class of biomarkers whose levels can be assayed to detect various forms of cancer and other serious diseases. These short, noncoding nucleic acids are difficult to detect due to their low abundance and the marginal stability of their duplexes with DNA probes. In addition, miRNAs within the same family have high sequence homology, and often, related miRNA differ in sequence by only a single base. In this report, we demonstrate an independent detection seven members of the let-7 family of miRNA in a single run. Key to success is the use of mini-PEG-substituted PNA amphiphiles (γPNAA) and highly fluorescent DNA nanotags in micelle tagging electrophoresis (MTE). Multiplexed detection is accomplished in capillary electrophoresis (CE) using oligomeric nanotags of pre-programmed lengths where the presence of a specific miRNA links its nanotag to a micelle drag-tag, which shifts the nanotag elution time to a defined region for detection. We further demonstrate that the peak shape and elution time are unaffected by the presence of up to 10 mg/ml of serum protein in the sample, with a total runtime of less than 4 min and a LOD of 10-100 pM. We discuss efforts to substantially decrease the detection limit using nanotags that are >1000 bp in length.

Acute kidney injury in pediatric patients hospitalized with acute COVID-19 and multisystem inflammatory syndrome in children associated with COVID-19.

This study describes the incidence, associated clinical characteristics and outcomes of acute kidney injury in a pediatric cohort with COVID-19 and Multisystem Inflammatory Syndrome in Children (MIS-C). We performed a retrospective study of patients 18 years of age and under admitted to four New York hospitals in the Northwell Health System interned during the height of the COVID-19 pandemic, between March 9 and August 13, 2020. Acute kidney injury was defined and staged according to Kidney Disease: Improving Global Outcomes criteria. The cohort included 152 patients; 97 acute-COVID-19 and 55 with MIS-C associated with COVID-19. Acute kidney injury occurred in 8 with acute-COVID-19 and in 10 with MIS-C. Acute kidney injury, in unadjusted models, was associated with a lower serum albumin level (odds ratio 0.17; 95% confidence interval 0.07, 0.39) and higher white blood cell counts (odds ratio 1.11; 95% confidence interval 1.04, 1.2). Patients with MIS-C and acute kidney injury had significantly greater rates of systolic dysfunction, compared to those without (80% vs 49%). In unadjusted models, patients with acute kidney injury had 8.4 days longer hospitalizations compared to patients without acute kidney injury (95% confidence interval, 4.4-6.7). Acute kidney injury in acute-COVID-19 and MIS-C may be related to inflammation and/or dehydration. Further research in larger pediatric cohorts is needed to better characterize risk factors for acute kidney injury in acute-COVID-19 and with MIS-C consequent to COVID-19.

Determination of the zeta potential of planar solids in nonpolar liquids.

ZetaSpin determines zeta potential by measuring the streaming potential generated by rotating a disk-shaped sample about its axis while submerged in the liquid. The apparatus and procedure developed for ZetaSpin in aqueous solutions was adapted for use in highly nonpolar fluids like surfactant-doped alkanes. Perhaps most unexpected is the need for up to 10 min (instead of a fraction of one second for aqueous solutions) for the electrometer to display changes in streaming potential in response to changes in rotation speed. Four tests (suggested by theory) confirm that the potential finally reported by the electrometer was indeed the streaming potential. Compared to electrophoresis, ZetaSpin does not require a value for the Debye length, avoids the complication caused by the electric-field-dependence of electrophoretic mobility and can be used with planar samples as well as colloidal particles.

Characteristics and risk factors associated with critical illness in pediatric COVID-19.

BACKGROUND: While much has been reported regarding the clinical course of COVID-19 in children, little is known regarding factors associated with organ dysfunction in pediatric COVID-19. We describe critical illness in pediatric patients with active COVID-19 and identify factors associated with PICU admission and organ dysfunction. This is a retrospective chart review of 77 pediatric patients age 1 day to 21 years admitted to two New York City pediatric hospitals within the Northwell Health system between February 1 and April 24, 2020 with PCR + SARS-CoV-2. Descriptive statistics were used to describe the hospital course and laboratory results and bivariate comparisons were performed on variables to determine differences. RESULTS: Forty-seven patients (61%) were admitted to the general pediatric floor and thirty (39%) to the PICU. The majority (97%, n = 75) survived to discharge, 1.3% (n = 1) remain admitted, and 1.3% (n = 1) died. Common indications for PICU admission included hypoxia (50%), hemodynamic instability (20%), diabetic ketoacidosis (6.7%), mediastinal mass (6.7%), apnea (6.7%), acute chest syndrome in sickle cell disease (6.7%), and cardiac dysfunction (6.7%). Of PICU patients, 46.7% experienced any significant organ dysfunction (pSOFA > = 2) during admission. Patients aged 12 years or greater were more likely to be admitted to a PICU compared to younger patients (p = 0.015). Presence of an underlying comorbidity was not associated with need for PICU admission (p = 0.227) or organ dysfunction (p = 0.87). Initial white blood cell count (WBC), platelet count, and ferritin were not associated with need for PICU admission. Initial C-reactive protein was associated with both need for PICU admission (p = 0.005) and presence of organ dysfunction (p = 0.001). Initial WBC and presenting thrombocytopenia were associated with organ dysfunction (p = 0.034 and p = 0.003, respectively). CONCLUSIONS: Age over 12 years and initial CRP were associated with need for PICU admission in COVID-19. Organ dysfunction was associated with elevated admission CRP, elevated WBC, and thrombocytopenia. These factors may be useful in determining risk for critical illness and organ dysfunction in pediatric COVID-19.

Clinical characteristics and outcomes of critically ill patients with COVID-19 admitted to an intensive care unit in London: A prospective observational cohort study.

BACKGROUND: Cohorts of severely ill patients with COVID-19 have been described in several countries around the globe, but to date there have been few published reports from the United Kingdom (UK). Understanding the characteristics of the affected population admitted to intensive care units (ICUs) in the UK is crucial to inform clinical decision making, research and planning for future waves of infection. METHODS: We conducted a prospective observational cohort study of all patients with COVID-19 admitted to a large UK ICU from March to May 2020 with follow-up to June 2020. Data were collected from health records using a standardised template. We used multivariable logistic regression to analyse the factors associated with ICU survival. RESULTS: Of the 156 patients included, 112 (72%) were male, 89 (57%) were overweight or obese, 68 (44%) were from ethnic minorities, and 89 (57%) were aged over 60 years of age. 136 (87%) received mechanical ventilation, 77 (57% of those intubated) were placed in the prone position and 95 (70% of those intubated) received neuromuscular blockade. 154 (99%) patients required cardiovascular support and 44 (28%) required renal replacement therapy. Of the 130 patients with completed ICU episodes, 38 (29%) died and 92 (71%) were discharged alive from ICU. In multivariable models, age (OR 1.13 [95% CI 1.07-1.21]), obesity (OR 3.06 [95% CI 1.16-8.74]), lowest P/F ratio on the first day of admission (OR 0.82 [95% CI 0.67-0.98]) and PaCO2 (OR 1.52 [95% CI 1.01-2.39]) were independently associated with ICU death. CONCLUSIONS: Age, obesity and severity of respiratory failure were key determinants of survival in this cohort. Multiorgan failure was prevalent. These findings are important for guiding future research and should be taken into consideration during future healthcare planning in the UK.

Positional and angular tracking of HDR 192 Ir source for brachytherapy quality assurance using radiochromic film dosimetry.

PURPOSE: To quantify and verify the dosimetric impact of high-dose rate (HDR) source positional uncertainty in brachytherapy, and to introduce a model for three-dimensional (3D) position tracking of the HDR source based on a two-dimensional (2D) measurement. This model has been utilized for the development of a comprehensive source quality assurance (QA) method using radiochromic film (RCF) dosimetry including assessment of different digitization uncertainties. METHODS: An algorithm was developed and verified to generate 2D dose maps of the mHDR-V2 192 Ir source (Elekta, Veenendaal, Netherlands) based on the AAPM TG-43 formalism. The limits of the dosimetric error associated with source (0.9 mm diameter) positional uncertainty were evaluated and experimentally verified with EBT3 film measurements for 6F (2.0 mm diameter) and 4F (1.3 mm diameter) size catheters at the surface (4F, 6F) and 10 mm further (4F only). To quantify this uncertainty, a source tracking model was developed to incorporate the unique geometric features of all isodose lines (IDLs) within any given 2D dose map away from the source. The tracking model normalized the dose map to its maximum, then quantified the IDLs using blob analysis based on features such as area, perimeter, weighted centroid, elliptic orientation, and circularity. The Pearson correlation coefficients (PCCs) between these features and source coordinates (x, y, z, θy , θz ) were calculated. To experimentally verify the accuracy of the tracking model, EBT3 film pieces were positioned within a Solid Water® (SW) phantom above and below the source and they were exposed simultaneously. RESULTS: The maximum measured dosimetric variations on the 6F and 4F catheter surfaces were 39.8% and 36.1%, respectively. At 10 mm further, the variation reduced to 2.6% for the 4F catheter which is in agreement with the calculations. The source center (x, y) was strongly correlated with the low IDL-weighted centroid (PCC = 0.99), while the distance to source (z) was correlated with the IDL areas (PCC = 0.96) and perimeters (PCC = 0.99). The source orientation θy was correlated with the difference between high and low IDL-weighted centroids (PCC = 0.98), while θz was correlated with the elliptic orientation of the 60-90% IDLs (PCC = 0.97) for a maximum distance of z = 5 mm. Beyond 5 mm, IDL circularity was significant, therefore limiting the determination of θz (PCC ≤ 0.48). The measured positional errors from the film sets above and below the source indicated a source position at the bottom of the catheter (-0.24 ± 0.07 mm). CONCLUSIONS: Isodose line features of a 2D dose map away from the HDR source can reveal its spatial coordinates. RCF was shown to be a suitable dosimeter for source tracking and dosimetry. This technique offers a novel source QA method and has the potential to be used for QA of commercial and customized applicators.

Veno-venous extracorporeal membrane oxygenation for COVID-19-associated pediatric acute respiratory distress syndrome.

BACKGROUND: The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) coronavirus has emerged as a highly contagious respiratory pathogen causing severe acute lung injury. Extracorporeal membrane oxygenation is a standard tool for the management of life-threatening acute respiratory distress syndrome, but the use of this resource-intensive therapy has come into question due to strained medical systems and limited proven treatments for COVID-19. CASE SUMMARY: A 16-year-old female with obesity presented with fever, myalgias, cough, and tachypnea and was diagnosed with COVID-19. She progressed to severe pediatric acute respiratory distress syndrome requiring intubation on hospital day 4 and cannulation to veno-venous extracorporeal membrane oxygenation on hospital day 6. The patient received remdesivir, steroids, and anakinra. The patient was successfully decannulated on hospital day 12 and was discharged home on hospital day 21. CONCLUSION: We report the use of veno-venous extracorporeal membrane oxygenation as a bridge to lung recovery in a pediatric patient with severe pediatric acute respiratory distress syndrome due to COVID-19.

Characteristics, Cardiac Involvement, and Outcomes of Multisystem Inflammatory Syndrome of Childhood Associated with severe acute respiratory syndrome coronavirus 2 Infection.

We report on the presentation and course of 33 children with multisystem inflammatory syndrome in children and confirmed severe acute respiratory syndrome coronavirus 2 infection. Hemodynamic instability and cardiac dysfunction were prominent findings, with most patients exhibiting rapid resolution following anti-inflammatory therapy.

Is coffee ground vomiting important? Findings from a large bleeding unit database and outcomes at 30 days.

OBJECTIVES: 'Coffee ground' vomiting (CGV) has classically been considered a sign of upper gastrointestinal bleeding. There is a paucity of data concerning endoscopic findings and outcomes in patients presenting with CGV. The aim of this study was to analyze endoscopic yield and 30-day outcomes in CGV patients. METHODS: Analysis was performed over the period 1992-2005 and four groups were identified: CGV alone, hematemesis alone, melena alone, and hematemesis and melena. Endoscopic yield, requirement for blood transfusion, rebleeding, and mortality rate at 30 days were calculated and compared using logistic regression analysis. RESULTS: 6054 patients (mean age 61.3 years, 3538 male) were included in the study. The hematemesis group was younger compared with the other groups. Therefore, endoscopic yield was adjusted for age and sex. CGV was associated with a significantly lower risk of gastric ulcer, duodenal ulcer, varices, gastric cancer, esophageal cancer, and Mallory-Weiss tears compared with some or all of the other groups. CGV was associated with an increased risk of esophagitis and no source was found. CGV was associated with a lower rate of blood transfusion and rebleeding (all P < 0.0001) but 30-day mortality rates were similar. CGV was less likely to require endoscopic intervention compared with the other groups (all P < 0.001). CONCLUSIONS: CGV is associated with a lower endoscopic yield, requirement for blood transfusion, rebleeding rate, and potential for intervention compared to those with hematemesis, melena or both. Mortality rates are similar suggesting a nonbleeding cause and therefore questions the role of endoscopy in CGV.