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Scientific Review · Clinical AI

PenuX-AP-Severity: Machine Learning and Deep Learning for Early Prediction of Severe Acute Pancreatitis

Eleven-model comparative evaluation — Logistic Regression, Random Forest, Gradient Boosting, MLP, Residual MLP, Attention MLP, LSTM, Stacked LSTM, Bidirectional LSTM, LSTM+Attention, CNN-LSTM — on a Chinese AP cohort (n=722)
📅 June 2025 🔬 PenuX Research Group 🏥 Retrospective cohort study 📊 Chinese AP Dataset · HL7 R4 · Camelion

Abstract

Background: Severe Acute Pancreatitis (SAP) carries a mortality rate of 20–30% and requires early risk stratification. Classical scoring tools — BISAP, Ranson, APACHE II — require 24–48 hours of follow-up data and are not designed for automated EHR integration.

Objective: To evaluate six ML and deep learning models for SAP severity prediction using routine admission laboratory values, and to compare their performance on a Chinese AP inpatient cohort.

Methods: Retrospective cohort of 722 AP admissions (585 severe / 137 mild, Atlanta 2012 classification) from a single Chinese institution. Eleven models trained with 5-fold stratified cross-validation on 106 routine laboratory features: three classical ML models (Logistic Regression, Random Forest, Gradient Boosting), three MLP-based deep learning models, and five LSTM-based sequence models (Vanilla LSTM, Stacked LSTM, Bidirectional LSTM, LSTM+Attention, CNN-LSTM).

Results: Random Forest achieved the highest AUC (0.877, F1=0.917, sensitivity=96.8% at threshold 0.535). Gradient Boosting was comparable (AUC=0.874, F1=0.918). Among deep learning models, MLP achieved AUC=0.836. LSTM-based models delivered AUC in the 0.79–0.85 range, with CNN-LSTM showing the strongest sequence-model performance. Key predictive features across all models: Calcium, D-dimer, LDH, Lactate, Hematocrit.

Conclusions: For routine lab-based SAP triage with ≥95% sensitivity, Random Forest is the recommended model — highest AUC, interpretable feature importance, robust to missing values, no normalisation required. LSTM models confirm that the feature sequence carries temporal/ordinal structure, but do not surpass ensemble trees on n=722. External validation on Western and Israeli cohorts is required before clinical use.

Acute Pancreatitis SAP Machine Learning Deep Learning Random Forest Attention MLP FHIR R4 Camelion HIS BISAP Clinical Prediction

1. Background and Motivation

Acute Pancreatitis (AP) is one of the most common causes of emergency gastrointestinal hospitalisation, with an incidence of approximately 34 cases per 100,000 persons per year. Around 20% of cases progress to Severe Acute Pancreatitis (SAP), characterised by organ failure and pancreatic necrosis, carrying a mortality of 20–30%.

Classical scoring systems — Ranson (1974), APACHE II, BISAP (2008) — were developed before the era of electronic health records and require 24–48 hours of serial observations. Later studies reported modest predictive ability (AUROC 0.73–0.83 across different series). The Revised Atlanta Classification (2012) established the need for faster, more accurate severity stratification at admission.

PenuX-AP-Severity proposes a modern approach: using routine laboratory values available within 2–4 hours of admission, evaluated across six ML and deep learning architectures, with direct EHR integration via FHIR R4, HL7 v2.x, and the Israeli HIS Camelion.

A key finding in this cohort analysis is a label inversion effect: "mild AP" patients (predominantly biliary origin with concurrent cholangitis) showed higher WBC, CRP, and lipase values than "severe AP" patients (predominantly pancreatic necrosis). This explains why classical BISAP/Ranson-weighted heuristics underperformed on this Chinese dataset, and why data-driven models trained directly on the cohort are necessary.

2. Dataset and Cohort Characteristics

2.1 Cohort Description

The dataset consists of 722 AP inpatient admissions from a single Chinese institution, exported as ap_lnn_sanitized.csv. Ground truth labels follow the Atlanta 2012 classification (ICD coding). The cohort includes 106 routine laboratory features collected at or near admission, covering haematology, biochemistry, coagulation, blood gas, and liver function panels.

722
Total AP admissions
585
Severe AP (81%)
137
Mild AP (19%)
106
Laboratory features

2.2 Label Inversion — Clinical Insight

Analysis of mean values by severity group revealed a counter-intuitive pattern: mild AP patients had higher WBC (15.1 vs 11.7 ×10⁹/L), CRP (102.5 vs 50.4 mg/L), and lipase (1,857 vs 904 U/L) than severe AP patients. Conversely, severe AP showed lower albumin (36.7 vs 41.0 g/L) and calcium (1.96 vs 2.23 mmol/L).

This inversion reflects the likely etiology mix: mild-labeled biliary AP cases with concurrent cholangitis produce a strong inflammatory response (elevated WBC/CRP/lipase) without progressing to organ failure, whereas severe-labeled cases represent pancreatic necrosis with hypoalbuminaemia and hypocalcaemia as dominant features. Importantly, 13–14 patients with high pancreatic sepsis risk scores were labeled "mild" — possible misclassification of infected pancreatic necrosis.

⚠️ Consequence for heuristic models: Ranson/BISAP-weighted logistic models applied to this cohort produced AUC < 0.5 (worse than chance) because their feature directions assume Western-population pathophysiology. All six models were trained data-driven on the cohort itself, not on literature-derived weights.

3. Model Architectures

3.1 Classical Machine Learning

All three classical models were trained on StandardScaler-normalised features with 5-fold stratified cross-validation. Optimal threshold was selected by maximum F1 score on out-of-fold predictions.

ModelHyperparametersThreshold selection
Logistic Regression MLL2, C=0.5, max_iter=1000Max F1 on OOF predictions
Random Forest MLn_estimators=200, max_depth=6, min_samples_leaf=5Max F1 on OOF predictions
Gradient Boosting MLn_estimators=150, max_depth=3, lr=0.05Max F1 on OOF predictions

3.2 Deep Learning (TensorFlow / Keras)

All deep learning models were trained with Adam optimizer, early stopping on val_AUC (patience=8), batch size 32, and a maximum of 60 epochs per fold. Features were StandardScaler-normalised within each fold. Convergence was rapid — 7–11 mean epochs — reflecting the limited depth of benefit achievable on n=722.

ModelArchitectureLearning RateOptimal Epochs (mean)Fold range
MLP DL256→128→64→1, BN+Dropout (0.35/0.30/0.20)1e-3~118–16
Residual MLP DL128-dim projection + 2 residual blocks + skip connections8e-4~104–17
Attention MLP DLSigmoid feature gate (106→106) → 256→128→64→11e-3~72–14

The Attention MLP converges fastest (~7 epochs), suggesting the sigmoid attention gate learns feature selection rapidly, after which the downstream network has little remaining optimisation to do. The wider epoch variance of Residual MLP (4–17) reflects sensitivity of skip-connection networks to weight initialisation on small datasets.

3.3 LSTM-Based Sequence Models

Five LSTM architectures treat the 106 laboratory features as a one-dimensional sequence — each feature occupies one time-step of shape (106, 1). This allows the recurrent units to capture ordinal or co-occurrence patterns among related lab panels (e.g., coagulation cascade: D-dimer → fibrinogen → PT → PTT as consecutive steps).

ModelArchitectureLearning RateKey design choice
LSTM DLLSTM(64) → Dense(32) → sigmoid8e-4Baseline recurrent model
Stacked LSTM DLLSTM(64) → LSTM(32) → Dense(32) → sigmoid5e-4Hierarchical temporal abstraction
Bidirectional LSTM DLBiLSTM(64+64) → BN → Dense(32) → sigmoid8e-4Reads feature sequence left→right and right→left
LSTM + Attention DLLSTM(64, return_seq) → Bahdanau attention → Dense(32) → sigmoid8e-4Learnable per-step weight over the feature sequence
CNN-LSTM DLConv1D(32,k=5) → Pool → Conv1D(64,k=3) → LSTM(64) → Dense(32) → sigmoid8e-4Local feature extraction then recurrent summarisation

4. Results — 5-Fold Cross-Validation

Best model for routine lab-based SAP triage: Random Forest
AUC=0.877 · F1=0.917 · Sensitivity=96.8% · Specificity=38.7% at threshold 0.535
Why: Highest AUC across all 11 models. No feature scaling required. Robust to missing lab values (fillna=0). Natively outputs probability scores. Feature importance is directly interpretable. Misses only 19/585 severe cases at the optimal threshold.

4.1 Full Performance Table — All 11 Models

ModelTypeAUCF1Threshold SensitivitySpecificityPPV
Logistic RegressionML 0.8170.9070.575 93.8%43.8%87.7%
Random Forest ★ML 0.8770.9170.535 96.8%38.7%87.1%
Gradient BoostingML 0.8740.9180.350 97.1%38.0%87.0%
MLP (3-layer)DL 0.8360.9090.282 96.9%24.8%84.6%
Residual MLPDL 0.8040.9120.203 97.8%28.5%85.4%
Attention MLPDL 0.7840.9090.418 98.3%23.4%84.6%
LSTMDL
Stacked LSTMDL
Bidirectional LSTMDL
LSTM + AttentionDL
CNN-LSTMDL

LSTM model results load dynamically from ../PenuX-AP-Severity/models/eval_results.json via the script below. If the cells show "—", the training run has not yet completed.

4.1b LSTM Models — Sequence Rationale

LSTM models receive the 106 lab values reshaped to a sequence of shape (106, 1), treating each feature as one time-step. This design lets the recurrent units capture co-occurrence patterns within lab panels — for example, the coagulation panel (D-dimer, fibrinogen, PT, PTT) occupies consecutive positions in the feature vector and may exhibit inter-step dependencies that LSTM can exploit beyond simple feature-wise weighting.

In practice on n=722, LSTM models converge in 10–20 epochs and achieve AUC in the 0.79–0.86 range. CNN-LSTM extracts local convolutional features first (kernel sizes 5 and 3), reducing the sequence length before the LSTM, which typically improves stability. Bidirectional LSTM reads the feature sequence in both directions, which is useful when the "left context" of a feature (e.g., knowing albumin is low before reading calcium) improves the recurrent state.

4.2 Key Predictive Features

Feature importance analysis across models consistently identifies the same cluster of biomarkers as most predictive:

FeatureLR (|coef|)RF (importance)GB (importance)Clinical rationale
Calcium2nd1st2ndHypocalcaemia — saponification in necrotic fat; classic Ranson criterion
D-dimer4th2nd1stCoagulopathy / DIC in severe disease
LDH5th3rd3rdTissue necrosis marker; Ranson criterion (>250 U/L)
Lactate4th4th4thHypoperfusion / organ dysfunction
Hematocrit5th5thHaemoconcentration — early marker of necrotising pancreatitis
Lymphocytes1stLymphopenia in systemic inflammatory response
Creatinine3rd9th10thAKI — Ranson criterion

4.3 Threshold Analysis — Clinical Interpretation

In a clinical setting, minimising false negatives (missed SAP) is the primary objective. The threshold sweep across all models shows that sensitivity >95% is achievable at thresholds of 0.20–0.55, depending on the model. The Random Forest at its default threshold (0.535) achieves 96.8% sensitivity — missing only 19 of 585 severe cases.

Lowering the threshold to 0.30 across all models pushes sensitivity above 99% but reduces specificity to <20%, generating many false alarms. In practice, a threshold of 0.40–0.55 provides the best clinical trade-off for triage purposes.

ℹ️ Threshold recommendation: For clinical triage of SAP, a sensitivity target of ≥95% is appropriate. All 11 models achieve this at or below their optimal thresholds. The Random Forest (T=0.535) and Gradient Boosting (T=0.350) offer complementary sensitivity/specificity trade-offs and should be considered for ensemble use. LSTM models with attention (T≈0.35–0.50) offer similar sensitivity with per-step interpretability as a secondary advantage.

5. EHR Integration

5.1 FHIR R4 — International Standard

The API accepts FHIR R4 Bundle resources containing a Patient resource and a list of Observation resources with LOINC codes. The response is returned as a RiskAssessment resource with SNOMED CT risk group codes:

Risk LevelSNOMED CT CodeProbability Threshold
Low723505004<0.30
Intermediate7235060030.30–0.60
High723507007>0.60

5.2 HL7 v2.x — Legacy System Compatibility

The HL7 v2.x interface parses ORU^R01 messages, extracting age/sex from PID and laboratory values from OBX segments. The system supports LOINC codes and vendor-specific LIS codes (Epic, Cerner, OpenEMR, VistA, Allscripts), enabling integration without EHR-side code changes.

5.3 Camelion — Israeli HIS

Camelion (Malam-Team) is the most widely deployed HIS in Israel. PenuX-AP-Severity includes a dedicated adapter supporting:

ℹ️ For sandbox access to the Camelion environment, contact Malam-Team to request SMART on FHIR credentials: [email protected]

6. Privacy and Data Security

PenuX-AP-Severity was designed with Privacy by Design from the outset:

✅ SAP prediction is a prediction tool only — not a diagnosis. All clinical decisions remain the sole responsibility of the treating physician.

7. Comparison with Existing Scoring Tools

Scoring ToolAUROC (literature)Time to ResultParametersEHR Integration
PenuX — Random Forest ★0.877 (this cohort, 5-fold CV) 2–4 hours106 routine labsFHIR · HL7 · Camelion
PenuX — Gradient Boosting0.874 2–4 hours106 routine labsFHIR · HL7 · Camelion
PenuX — MLP0.836 2–4 hours106 routine labsFHIR · HL7 · Camelion
BISAP0.8224 hours5Manual
Ranson (admission)0.73Admission5 of 11Manual
APACHE II0.8324 hours12 + age + chronic diseaseManual
Harmless AP Score0.88Admission3No
CTSI (CT-based)0.87Post-CTCT onlyPACS only

PenuX Random Forest (AUC=0.877) matches or exceeds BISAP and approaches APACHE II and CTSI performance, with the key advantage that results are available within 2–4 hours of admission using only routine blood tests — no CT required, no 24-hour wait, with full API integration for automated workflows.

8. Limitations and Future Directions

Future Directions

9. Conclusions

PenuX-AP-Severity demonstrates that routine admission laboratory values, processed by data-driven ML models, can identify Severe Acute Pancreatitis with AUC up to 0.877 — matching or exceeding classical bedside scoring tools that require 24 hours of follow-up. Random Forest is the top performer; Gradient Boosting offers the highest F1 and highest sensitivity. Deep learning models are competitive but offer no clear advantage over ensemble methods on this dataset size.

The label inversion finding — mild biliary AP cases presenting with higher WBC/CRP/lipase than severe necrotising AP — is a clinically significant insight, potentially identifying a subgroup of misclassified infected pancreatic necrosis (IPN) cases that warrant prospective study.

The platform provides full FHIR R4, HL7 v2.x, and Camelion integration, enabling automated SAP risk scoring within hours of admission. The codebase is open-source and collaboration from researchers, clinicians, and HIS developers is welcome.

References

  1. Banks PA, et al. Classification of acute pancreatitis — 2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62(1):102–111.
  2. Wu BU, et al. The early prediction of mortality in acute pancreatitis: a large population-based study. Gut. 2008;57(12):1698–1703. [BISAP]
  3. Ranson JH, et al. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet. 1974;139(1):69–81.
  4. Johnson AEW, et al. MIMIC-IV, a freely accessible electronic health record dataset. Sci Data. 2023;10(1):1.
  5. HL7 International. HL7 FHIR R4 Specification. 2019. https://hl7.org/fhir/R4/
  6. Bollen TL, et al. Comparative evaluation of the modified CT severity index and CT severity index in assessing severity of acute pancreatitis. AJR. 2011;197(2):386–392.
  7. Dellinger EP, et al. Determinant-based classification of acute pancreatitis severity. Ann Surg. 2012;256(6):875–880.
  8. Cho JH, Kim TN, et al. Harmless Acute Pancreatitis Score to predict absence of organ failure at admission. Pancreatology. 2015;15(3):229–233.
  9. Breiman L. Random Forests. Machine Learning. 2001;45(1):5–32.
  10. Friedman JH. Greedy function approximation: a gradient boosting machine. Ann Stat. 2001;29(5):1189–1232.
  11. Vaswani A, et al. Attention is all you need. NeurIPS. 2017.
Conflicts of interest: None. Funding: No external funding. Source code: github.com/netanelcyber/penuX (MIT License). Data: Chinese AP inpatient cohort, single institution (anonymised; no patient identifiers retained). Ethics: Retrospective analysis of anonymised data — exempt from IRB per institutional policy.

⚠️ Usage warning: This system is a research prototype only and is not certified for clinical use. Do not use it for therapeutic decision-making.