Daily Sepsis Research Analysis
Three studies advance sepsis diagnostics and stewardship: an AI-assisted plasmonic coffee-ring biosensor achieves pg/mL protein detection (including procalcitonin) within 12 minutes; photoplethysmography features from routine pulse oximetry identify early deterioration in ED sepsis patients; and neonatal blood culture time-to-positivity data support stopping antibiotics at 36 hours in well-appearing infants with negative cultures.
Summary
Three studies advance sepsis diagnostics and stewardship: an AI-assisted plasmonic coffee-ring biosensor achieves pg/mL protein detection (including procalcitonin) within 12 minutes; photoplethysmography features from routine pulse oximetry identify early deterioration in ED sepsis patients; and neonatal blood culture time-to-positivity data support stopping antibiotics at 36 hours in well-appearing infants with negative cultures.
Research Themes
- Point-of-care diagnostics and biosensing for sepsis biomarkers
- Physiological waveform analytics to predict early deterioration
- Antibiotic stewardship in neonatal sepsis evaluations
Selected Articles
1. Plasmonic coffee-ring biosensing for AI-assisted point-of-care diagnostics.
This study introduces a dual-droplet, plasmonic coffee-ring biosensor coupled with a deep neural network to quantify proteins from smartphone images within 12 minutes at pg/mL sensitivity. It detected procalcitonin and other clinically relevant proteins across five orders of magnitude and outperformed lateral flow assays by >100-fold in saliva.
Impact: Provides a novel, low-cost, ultra-sensitive platform for point-of-care detection of sepsis biomarkers (e.g., procalcitonin) with AI-enabled readout. It could democratize early sepsis screening in resource-limited settings.
Clinical Implications: If clinically validated in blood or plasma, this platform could enable rapid triage and early antibiotic stewardship decisions using procalcitonin at the point of care, including ambulances and low-resource clinics.
Key Findings
- Dual-droplet coffee-ring biosensor achieved ~3 pg/mL limits of detection within 12 minutes.
- Quantitative readout via a deep neural model using smartphone photos enabled robust classification over five orders of magnitude.
- Procalcitonin (sepsis), SARS-CoV-2 N, CEA, and PSA were all detected; sensitivity surpassed lateral flow immunoassays by >100-fold in saliva.
Methodological Strengths
- Cross-analyte validation across four clinically relevant proteins
- Integration of generative and convolutional deep learning for smartphone-based quantification
Limitations
- No prospective clinical validation in sepsis patients; matrices beyond saliva (e.g., blood) not demonstrated in this report
- Environmental variability (humidity/temperature) may affect droplet evaporation and pattern formation
Future Directions: Prospective ED/ICU trials comparing to standard immunoassays, validation in whole blood/plasma, robustness testing across environments, and regulatory usability studies.
A major challenge in addressing global health issues is developing simple, affordable biosensors with high sensitivity and specificity. Significant progress has been made in at-home medical detection kits, especially during the COVID-19 pandemic. Here, we demonstrated a coffee-ring biosensor with ultrahigh sensitivity, utilizing the evaporation of two sessile droplets and the formation of coffee-rings with asymmetric nanoplasmonic patterns to detect disease-relevant proteins as low as 3 pg/ml, under 12 min. Experimentally, a protein-laden droplet dries on a nanofibrous membrane, pre-concentrating biomarkers at the coffee ring. A second plasmonic droplet with functionalized gold nanoshells is then deposited at an overlapping spot and dried, forming a visible asymmetric plasmonic pattern due to distinct aggregation mechanisms. To enhance detection sensitivity, a deep neural model integrating generative and convolutional networks was used to enable quantitative biomarker diagnosis from smartphone photos. We tested four different proteins, Procalcitonin (PCT) for sepsis, SARS-CoV-2 Nucleocapsid (N) protein for COVID-19, Carcinoembryonic antigen (CEA) and Prostate-specific antigen (PSA) for cancer diagnosis, showing a working concentration range over five orders of magnitude. Sensitivities surpass equivalent lateral flow immunoassays by over two orders of magnitude using human saliva samples. The detection principle, along with the device, and materials can be further advanced for early disease diagnostics.
2. Pulse oximetry beyond oxygen saturation: Early waveform characteristics in sepsis patients with adverse outcomes - A proof-of-concept study.
In a secondary analysis of 576 ED patients with early sepsis, specific PPG waveform features (lower SPA/DPA, shorter PI, lower APG b/a) identified those who deteriorated within 48 hours, whereas standard blood pressures did not differ. PPG may provide an early warning signal for clinical deterioration.
Impact: Leverages ubiquitous pulse oximetry to detect early hemodynamic compromise before conventional vitals diverge, supporting scalable risk stratification.
Clinical Implications: Incorporating PPG features into ED triage could identify at-risk sepsis patients earlier, prompting timely monitoring and interventions even when blood pressure appears stable.
Key Findings
- Among 576 early sepsis ED patients, 9.7% met the 48-hour composite endpoint (ICU admission and/or death).
- Deteriorating patients had lower SPA (1218 vs. 1490 AU), lower DPA (462 vs. 621 AU), shorter PI (0.540 vs. 0.609 s), and lower APG b/a (-0.881 vs. -0.802), all p < 0.001.
- Standard BP metrics (SBP/DBP/MAP) did not differ, while HR was higher and strongly correlated with PI (ρ = -0.921).
Methodological Strengths
- Prospective data source (Acutelines biobank) with standardized waveform capture
- Rich feature engineering of PPG/APG enabling physiologic interpretation
Limitations
- Secondary analysis without external validation or full predictive model performance reporting
- Potential confounding from motion artifacts and limited comparison to established risk scores
Future Directions: Develop and externally validate predictive algorithms integrating PPG features, and test clinical impact in prospective triage/intervention trials.
BACKGROUND: Sepsis is a life-threatening disorder with an in-hospital mortality rate of 10-40 %. Identifying patients at risk for deterioration is critical in guiding clinical decisions for patients with infection at the emergency department (ED). While pulse oximetry is known for estimating oxygen saturation, we hypothesize that photoplethysmography (PPG) can reflect early cardiovascular changes in sepsis. This study explores the potential use of pulse oximetry - PPG as a tool for predicting clinical deterioration in patients with early sepsis. METHODS: We conducted a secondary analysis of prospectively obtained data from the Acutelines data-biobank, involving 576 patients with early sepsis at the ED. Clinical and demographic data, vital signs, laboratory values, and PPG waveforms were collected. Groups were determined by a composite endpoint of intensive care unit (ICU) admission and/or in-hospital mortality within 48 h. PPG features were calculated and differences between groups were analyzed. FINDINGS: Within our study cohort, 9.7 % of patients were admitted to the ICU and/or deceased within 48 h after ED arrival. During the first 20 min after ED arrival, patients who deteriorated showed lower systolic peak amplitude (SPA: 1218 vs. 1490 AU, p < 0.001), lower diastolic peak amplitude (DPA: 462 vs. 621 AU, p < 0.001), and shorter pulse intervals (PI: 0.540 vs. 0.609 s, p < 0.001) on PPG. Additionally, the APG b/a ratio was lower (-0.881 vs. -0.802, p < 0.001). In contrast, systolic blood pressure (SBP: 123 vs. 129 mmHg, p = 0.186), diastolic blood pressure (DBP: 78 vs. 76 mmHg, p = 0.400), mean arterial pressure (MAP: 88 vs. 95 mmHg, p = 0.111) did not differ between groups. Heart rate (HR: 111 vs. 99 bpm, p = 0.001) and PPG-derived PI were both significantly different and strongly correlated (ρ = -0.921), as both reflect the duration of one interbeat interval. CONCLUSIONS: This study highlights the potential use of PPG as a valuable tool for detecting early cardiovascular changes in sepsis. These findings hold significance for developing novel tools that can facilitate early identification of patients at risk for deterioration, thereby improving clinical decisions and outcomes for ED patients with early sepsis.
3. Time to positive blood cultures in neonatal sepsis evaluations.
In 151 neonatal blood cultures, the median time to positivity was 17 hours. Nearly all gram-negatives were positive by 24 hours and most gram-positives by 36 hours, supporting antibiotic discontinuation at 36 hours in well-appearing infants with negative cultures.
Impact: Provides organism-specific time-to-positivity data that directly inform neonatal antibiotic stewardship and reduce unnecessary exposure.
Clinical Implications: NICUs can consider stopping empiric antibiotics at 36 hours in well-appearing infants with negative cultures and no source, potentially reducing antimicrobial resistance and adverse effects.
Key Findings
- Overall median time to blood culture positivity was 17 hours (IQR 12–23) in 151 neonatal cultures.
- 97.9% of gram-negative organisms were positive by 24 hours; 93.6% of gram-positive by 36 hours.
- All early-onset sepsis cultures were positive within 24 hours; most late-onset within 36 hours.
Methodological Strengths
- Organism-stratified time-to-positivity analysis with clinically actionable thresholds
- Focus on a defined NICU population with clear endpoints
Limitations
- Single-center retrospective design with modest sample size
- Did not assess clinical outcomes after implementing a 36-hour stop rule
Future Directions: Prospective multicenter validation of a 36-hour antibiotic stop protocol and integration with rapid diagnostics to further shorten unnecessary therapy.
OBJECTIVE: This study evaluates the time to blood culture positivity among neonates evaluated for sepsis to determine when antibiotics may be safely discontinued. STUDY DESIGN: Retrospective review of clinically relevant blood culture time to positivity from infants in a neonatal intensive care unit. The primary endpoint was overall median time to blood culture positivity. Secondary endpoints compared time to positivity among gram-positive versus gram-negative organisms, early versus late onset sepsis, and a sub-analysis excluding contaminants. RESULT: Among 151 cultures, the overall median time to positivity was 17 h (IQR 12-23). Most (47/48, 97.9%) gram-negative organisms resulted within 24 h and most (88/94, 93.6%) gram-positive by 36 h. All (13/13, 100%) early onset cultures resulted within 24 h and most (132/138, 95.7%) late onset by 36 h. CONCLUSION: Antibiotics for neonatal sepsis evaluation may be safely discontinued in well-appearing infants without an identified infection source with negative cultures at 36 h.