Cookbook 373: Offline Clinical Gastroenterology & Critical Care Acute Pancreatitis Revised Atlanta Severity Staging, BISAP / Modified Marshall Organ Failure Engine, WATERFALL-Guided Resuscitation & Necrotizing Step-Up Approach Titrator

"""
OpenPHR Cookbook 373: Offline Clinical Gastroenterology & Critical Care
Acute Pancreatitis Revised Atlanta Severity Staging, BISAP / Modified Marshall Engine,
WATERFALL-Guided Resuscitation & Necrotizing Step-Up Approach Titrator.

Compliant with:
- American College of Gastroenterology (ACG) Guidelines: Management of Acute Pancreatitis (2024)
- American Gastroenterological Association (AGA) Institute Clinical Practice Update
- International Association of Pancreatology (IAP) / American Pancreatic Association (APA) Guidelines
- Revised Atlanta Classification of Acute Pancreatitis
- The WATERFALL Multicenter Randomized Controlled Trial (NEJM 2022)
"""

import sys
from typing import Dict, List, Optional, Tuple, Any
from dataclasses import dataclass, field

@dataclass
class AtlantaDiagnosticInput:
    has_epigastric_pain: bool
    lipase_u_l: float
    lipase_upper_limit_normal: float
    amylase_u_l: float
    amylase_upper_limit_normal: float
    cross_sectional_imaging_positive: bool

@dataclass
class BISAPInput:
    bun_mg_dl: float
    gcs_score: int
    temperature_c: float
    heart_rate_bpm: int
    respiratory_rate_bpm: int
    wbc_k_ul: float
    age_years: int
    pleural_effusion_present: bool

@dataclass
class MarshallInput:
    pao2_fio2_ratio: float                  # mmHg (e.g. 350.0)
    serum_creatinine_mg_dl: float          # mg/dL (e.g. 2.1)
    systolic_bp_mmhg: float                # mmHg (e.g. 85.0)
    bp_responsive_to_iv_fluid: bool        # Responsive to 500-1000 mL fluid
    on_inotropic_support: bool = False
    inotropic_agent: str = "none"           # "none", "dopamine_low", "dopamine_high", "norepinephrine", "dobutamine"
    duration_hours: float = 0.0             # Duration of organ failure in hours

@dataclass
class ResuscitationContext:
    weight_kg: float
    is_hypovolemic: bool                    # SBP < 90, HR > 100, BUN/Cr > 20, or dry mucosa
    has_fluid_overload_signs: bool          # Basilar crackles, jugular distension, new O2 requirement
    hematocrit_percent: float               # % (normal 36-46)
    map_mmhg: float
    urine_output_ml_hr: float
    hours_since_admission: float

@dataclass
class NecrosisContext:
    pancreatic_necrosis_present: bool
    necrosis_extent_percent: float          # < 30%, 30-50%, > 50%
    gas_in_collection_on_ct: bool           # Pathognomonic for infection
    unexplained_sepsis_fever: bool          # Persistent leukocytosis/fever > 7-14 days
    days_since_symptom_onset: float
    current_drainage_in_place: bool = False
    hours_on_current_drainage: float = 0.0
    clinical_improving_on_drainage: bool = False

class AcutePancreatitisEngine:
    """
    Comprehensive Decision Support Engine for Acute Pancreatitis & Severe Necrotizing Pancreatitis.
    """

    @staticmethod
    def verify_atlanta_diagnosis(d: AtlantaDiagnosticInput) -> Dict[str, Any]:
        """
        Validates Revised Atlanta 2-of-3 diagnostic criteria.
        """
        criteria_met = []
        lipase_ratio = d.lipase_u_l / d.lipase_upper_limit_normal if d.lipase_upper_limit_normal > 0 else 0.0
        amylase_ratio = d.amylase_u_l / d.amylase_upper_limit_normal if d.amylase_upper_limit_normal > 0 else 0.0
        
        # Criterion 1: Characteristic pain
        if d.has_epigastric_pain:
            criteria_met.append("Characteristic epigastric abdominal pain radiating to back")

        # Criterion 2: Enzymes >= 3x ULN
        enzyme_positive = (lipase_ratio >= 3.0) or (amylase_ratio >= 3.0)
        if enzyme_positive:
            enz_str = f"Lipase {d.lipase_u_l:.1f} U/L ({lipase_ratio:.1f}x ULN)" if lipase_ratio >= 3.0 else f"Amylase {d.amylase_u_l:.1f} U/L ({amylase_ratio:.1f}x ULN)"
            criteria_met.append(f"Serum pancreatic enzymes >= 3x ULN: {enz_str}")

        # Criterion 3: Cross-sectional imaging
        if d.cross_sectional_imaging_positive:
            criteria_met.append("Characteristic cross-sectional imaging features (CECT/MRI/US)")

        is_confirmed = len(criteria_met) >= 2

        return {
            "diagnosis_confirmed": is_confirmed,
            "criteria_count": len(criteria_met),
            "criteria_met": criteria_met,
            "lipase_elevation_fold": round(lipase_ratio, 2),
            "imaging_required_for_diagnosis": len(criteria_met) < 2 and not d.cross_sectional_imaging_positive
        }

    @staticmethod
    def calculate_bisap_score(b: BISAPInput) -> Dict[str, Any]:
        """
        Calculates Bedside Index for Severity in Acute Pancreatitis (BISAP Score, 0-5).
        """
        points = 0
        breakdown = {}

        # 1. BUN > 25 mg/dL
        bun_pt = 1 if b.bun_mg_dl > 25.0 else 0
        points += bun_pt
        breakdown["BUN > 25 mg/dL"] = bun_pt

        # 2. Impaired mental status (GCS < 15)
        gcs_pt = 1 if b.gcs_score < 15 else 0
        points += gcs_pt
        breakdown["Impaired Mental Status (GCS < 15)"] = gcs_pt

        # 3. SIRS Criteria (>= 2 required)
        sirs_count = 0
        if b.temperature_c < 36.0 or b.temperature_c > 38.0: sirs_count += 1
        if b.heart_rate_bpm > 90: sirs_count += 1
        if b.respiratory_rate_bpm > 20: sirs_count += 1
        if b.wbc_k_ul < 4.0 or b.wbc_k_ul > 12.0: sirs_count += 1

        sirs_pt = 1 if sirs_count >= 2 else 0
        points += sirs_pt
        breakdown[f"SIRS Criteria (Met {sirs_count}/4)"] = sirs_pt

        # 4. Age > 60 years
        age_pt = 1 if b.age_years > 60 else 0
        points += age_pt
        breakdown["Age > 60"] = age_pt

        # 5. Pleural Effusion
        pe_pt = 1 if b.pleural_effusion_present else 0
        points += pe_pt
        breakdown["Pleural Effusion on Imaging"] = pe_pt

        # Mortality & triage risk
        if points >= 3:
            mortality_risk = "High Risk (5% - 20% in-hospital mortality; high probability of necrotizing disease & persistent organ failure)"
            triage_level = "ICU / Step-Down Intermediate Care Unit Gating Required"
        else:
            mortality_risk = "Low Risk (< 2% in-hospital mortality)"
            triage_level = "General Medical Ward with Serial Vital Sign Monitoring"

        return {
            "bisap_score": points,
            "max_score": 5,
            "mortality_risk": mortality_risk,
            "triage_recommendation": triage_level,
            "breakdown": breakdown
        }

    @staticmethod
    def evaluate_modified_marshall(m: MarshallInput) -> Dict[str, Any]:
        """
        Evaluates Modified Marshall Score for Respiratory, Renal, and Cardiovascular Systems.
        """
        # 1. Respiratory (PaO2 / FiO2)
        if m.pao2_fio2_ratio > 400.0: resp_score = 0
        elif m.pao2_fio2_ratio > 300.0: resp_score = 1
        elif m.pao2_fio2_ratio > 200.0: resp_score = 2
        elif m.pao2_fio2_ratio > 101.0: resp_score = 3
        else: resp_score = 4

        # 2. Renal (Creatinine mg/dL)
        cr = m.serum_creatinine_mg_dl
        if cr <= 1.4: renal_score = 0
        elif cr <= 1.8: renal_score = 1
        elif cr <= 3.6: renal_score = 2
        elif cr <= 4.9: renal_score = 3
        else: renal_score = 4

        # 3. Cardiovascular (SBP & Pressors)
        sbp = m.systolic_bp_mmhg
        agent = m.inotropic_agent.lower()
        if not m.on_inotropic_support and sbp >= 90.0: cv_score = 0
        elif not m.on_inotropic_support and sbp < 90.0 and m.bp_responsive_to_iv_fluid: cv_score = 1
        elif not m.on_inotropic_support and sbp < 90.0 and not m.bp_responsive_to_iv_fluid: cv_score = 2
        elif "dopamine_low" in agent or "dobutamine" in agent: cv_score = 3
        elif "dopamine_high" in agent or "norepinephrine" in agent: cv_score = 4
        else: cv_score = 2 if sbp < 90.0 else 0

        max_organ_score = max(resp_score, renal_score, cv_score)
        organ_failure_present = max_organ_score >= 2

        # Atlanta Severity Classification
        if not organ_failure_present:
            severity = "Mild (if no local complications) or Moderately Severe (if local/systemic complications present)"
            organ_failure_type = "None"
        elif m.duration_hours < 48.0:
            severity = "Moderately Severe Acute Pancreatitis (Transient Organ Failure < 48 Hours)"
            organ_failure_type = "Transient (< 48h)"
        else:
            severity = "Severe Acute Pancreatitis (Persistent Organ Failure >= 48 Hours)"
            organ_failure_type = "Persistent (>= 48h)"

        return {
            "respiratory_marshall_score": resp_score,
            "renal_marshall_score": renal_score,
            "cardiovascular_marshall_score": cv_score,
            "max_marshall_score": max_organ_score,
            "organ_failure_present": organ_failure_present,
            "organ_failure_duration_hours": m.duration_hours,
            "organ_failure_type": organ_failure_type,
            "atlanta_severity_classification": severity
        }

    @staticmethod
    def calculate_waterfall_resuscitation(ctx: ResuscitationContext) -> Dict[str, Any]:
        """
        Determines moderated Lactated Ringer's resuscitation per the WATERFALL Trial (NEJM 2022).
        """
        w = ctx.weight_kg

        # Safety stop for fluid overload
        if ctx.has_fluid_overload_signs:
            return {
                "fluid_strategy": "RESTRICTED / DIURETIC RESCUE",
                "recommended_crystalloid": "Lactated Ringer's (LR)",
                "bolus_order": "PROHIBITED: Evidence of fluid overload (pulmonary crackles, hypoxia, or elevated JVP).",
                "maintenance_rate_ml_hr": round(0.5 * w, 1),
                "rationale": "CRITICAL SENTINEL: Over-resuscitation risk detected. WATERFALL demonstrated 3x higher fluid overload with aggressive hydration. Reduce infusion rate and consider Furosemide rescue.",
                "monitoring_targets": {
                    "map_target_mmhg": ">= 65 mmHg",
                    "urine_output_target": "0.5 - 1.0 mL/kg/h",
                    "hematocrit_target": "35% - 44%"
                }
            }

        # Moderated hydration pathway
        if ctx.is_hypovolemic:
            bolus_volume_ml = round(10.0 * w, 0)
            maintenance_ml_hr = round(1.5 * w, 1)
            strategy = "MODERATED HYPOVOLEMIC PROTOCOL"
            bolus_text = f"10 mL/kg LR bolus ({bolus_volume_ml:.0f} mL) infused over 2 hours."
            rationale = "Hypovolemia detected. Deliver initial 10 mL/kg LR bolus, followed by 1.5 mL/kg/h maintenance. Re-assess hemodynamics and hematocrit at 12 and 24 hours."
        else:
            bolus_volume_ml = 0.0
            maintenance_ml_hr = round(1.5 * w, 1)
            strategy = "MODERATED NORMOVOLEMIC PROTOCOL"
            bolus_text = "NO BOLUS REQUIRED: Patient is normovolemic without signs of hemoconcentration or shock."
            rationale = "Normovolemia confirmed. Administer maintenance LR at 1.5 mL/kg/h directly. Bolusing normovolemic patients increases pulmonary edema risk without clinical benefit."

        uop_per_kg = ctx.urine_output_ml_hr / w if w > 0 else 0.0

        return {
            "fluid_strategy": strategy,
            "recommended_crystalloid": "Lactated Ringer's (LR) - Superior to 0.9% Normal Saline",
            "bolus_order": bolus_text,
            "maintenance_rate_ml_hr": maintenance_ml_hr,
            "current_uop_ml_kg_hr": round(uop_per_kg, 2),
            "rationale": rationale,
            "monitoring_targets": {
                "map_target_mmhg": ">= 65 mmHg",
                "uop_target": ">= 0.5 mL/kg/h",
                "hematocrit_target": "35% - 44% (Hemoconcentration > 44% indicates inadequate volume; < 35% warrants cautious titration)"
            }
        }

    @staticmethod
    def evaluate_necrotizing_step_up(nec: NecrosisContext) -> Dict[str, Any]:
        """
        Gates the Step-Up Approach for Acute Necrotizing Pancreatitis (PANTER Trial & IAP/APA Guidelines).
        """
        if not nec.pancreatic_necrosis_present:
            return {
                "necrosis_status": "Interstitial Edematous Pancreatitis (No Necrosis)",
                "step_up_action": "Standard supportive care; no drainage or necrosectomy indicated.",
                "antibiotic_mandate": "PROHIBITED: Routine prophylactic antibiotics are contraindicated in interstitial pancreatitis."
            }

        # Determine infection status
        is_infected = nec.gas_in_collection_on_ct or (nec.unexplained_sepsis_fever and nec.days_since_symptom_onset >= 7.0)

        if not is_infected:
            return {
                "necrosis_status": f"Sterile Pancreatic Necrosis ({nec.necrosis_extent_percent:.0f}% involvement)",
                "step_up_action": "CONSERVATIVE MEDICAL MANAGEMENT: Maintain enteral nutrition and serial monitoring.",
                "antibiotic_mandate": "STRICTLY PROHIBITED: Prophylactic antibiotics in sterile necrotizing pancreatitis do not prevent infection and increase fungal/MDR colonization.",
                "drainage_indicated": False,
                "necrosectomy_indicated": False
            }

        # Infected necrosis step-up sequencing
        if not nec.current_drainage_in_place:
            step = "STEP 1 & STEP 2: Initiate Pancreatic-Penetrating Antibiotics & Primary Catheter Drainage"
            antibiotic_order = "Meropenem 1g IV q8h (or Imipenem 500mg IV q6h); high penetration into necrotic pancreatic parenchyma."
            intervention_order = "Urgent Percutaneous Catheter Drainage (PCD) or Endoscopic Transmural Drainage (ETD) targeting necrotic collection."
            rationale = "Infected necrosis confirmed. Begin IV carbapenem therapy and establish primary percutaneous or endoscopic drainage. PANTER trial demonstrates > 35% of patients recover with catheter drainage alone without requiring necrosectomy."
            necrosectomy_order = "DEFERRED: Allow 72 hours post-catheter drainage to evaluate clinical response."
        else:
            if nec.clinical_improving_on_drainage:
                step = "STEP 2 MAINTENANCE: Continue Catheter Drainage & Antibiotic Therapy"
                antibiotic_order = "Continue targeted IV antibiotics based on drained fluid culture and susceptibility."
                intervention_order = "Serial catheter flushing, up-sizing, or exchange as collections liquefy."
                rationale = "Positive clinical response to catheter drainage (declining fevers, improved leukocytosis, resolving organ failure). Avoid operative necrosectomy."
                necrosectomy_order = "NOT INDICATED AT THIS TIME"
            elif nec.hours_on_current_drainage >= 72.0:
                step = "STEP 3 ESCALATION: Minimally Invasive Necrosectomy"
                antibiotic_order = "Continue broad-spectrum IV antibiotics."
                intervention_order = "Video-Assisted Retroperitoneal Debridement (VARD) or Direct Endoscopic Necrosectomy (DEN)."
                rationale = "Refractory sepsis and lack of clinical improvement after >= 72 hours of optimal catheter drainage. Escalate to minimally invasive necrosectomy. Delay open surgical necrosectomy until collections wall off (>= 4 weeks)."
                necrosectomy_order = "MINIMALLY INVASIVE SURGICAL / ENDOSCOPIC NECROSECTOMY MANDATED"
            else:
                step = "STEP 2 MONITORING: Awaiting 72-Hour Catheter Drainage Efficacy Window"
                antibiotic_order = "Maintain IV carbapenem therapy."
                intervention_order = f"Monitor drainage output ({nec.hours_on_current_drainage:.0f}h on drainage)."
                rationale = "Re-assess at 72-hour mark post-drainage placement before escalating to surgical debridement."
                necrosectomy_order = "DEFERRED PENDING 72-HOUR RE-EVALUATION"

        return {
            "necrosis_status": "Infected Pancreatic Necrosis (IPN)",
            "step_up_phase": step,
            "antibiotic_order": antibiotic_order,
            "drainage_order": intervention_order,
            "necrosectomy_recommendation": necrosectomy_order,
            "clinical_rationale": rationale
        }

# ==============================================================================
# CLI TEST HARNESS & VERIFICATION GATES
# ==============================================================================

def run_clinical_verification_suite():
    print("================================================================================")
    print("OpenPHR Cookbook 373: Acute Pancreatitis & Necrotizing Engine Verification Suite")
    print("================================================================================")

    # Case 1: Severe Acute Necrotizing Pancreatitis with Persistent Organ Failure
    atlanta_case1 = AtlantaDiagnosticInput(
        has_epigastric_pain=True,
        lipase_u_l=1240.0,
        lipase_upper_limit_normal=60.0,         # 20.7x ULN -> Criterion 2
        amylase_u_l=420.0,
        amylase_upper_limit_normal=100.0,       # 4.2x ULN
        cross_sectional_imaging_positive=True   # Criterion 3
    )

    bisap_case1 = BISAPInput(
        bun_mg_dl=34.0,                         # BUN > 25 -> 1
        gcs_score=14,                           # GCS < 15 -> 1
        temperature_c=38.6,                     # SIRS: Temp -> 1
        heart_rate_bpm=118,                     # SIRS: HR -> 1 (SIRS met -> 1)
        respiratory_rate_bpm=24,
        wbc_k_ul=17.2,
        age_years=67,                           # Age > 60 -> 1
        pleural_effusion_present=True           # Pleural effusion -> 1
    )                                           # Total BISAP = 5

    marshall_case1 = MarshallInput(
        pao2_fio2_ratio=180.0,                  # Marshall Resp = 3 (<200) -> Organ Failure
        serum_creatinine_mg_dl=2.4,             # Marshall Renal = 2 (1.9-3.6) -> Organ Failure
        systolic_bp_mmhg=82.0,                  # Cardiovascular
        bp_responsive_to_iv_fluid=False,        # Non-responsive -> CV = 2
        on_inotropic_support=True,
        inotropic_agent="norepinephrine",       # CV = 4
        duration_hours=54.0                     # > 48h -> Persistent Organ Failure!
    )

    resusc_case1 = ResuscitationContext(
        weight_kg=80.0,
        is_hypovolemic=True,
        has_fluid_overload_signs=False,
        hematocrit_percent=47.2,                # Severe hemoconcentration
        map_mmhg=58.0,
        urine_output_ml_hr=22.0,                # Oliguria (< 0.5 mL/kg/h)
        hours_since_admission=14.0
    )

    necrosis_case1 = NecrosisContext(
        pancreatic_necrosis_present=True,
        necrosis_extent_percent=45.0,
        gas_in_collection_on_ct=True,           # Confirmed infected necrosis!
        unexplained_sepsis_fever=True,
        days_since_symptom_onset=12.0,
        current_drainage_in_place=False
    )

    # 1. Atlanta Diagnostic Gating
    diag_res = AcutePancreatitisEngine.verify_atlanta_diagnosis(atlanta_case1)
    print(f"[*] Atlanta Diagnosis Confirmed: {diag_res['diagnosis_confirmed']} "
          f"({diag_res['criteria_count']}/3 criteria met, Lipase {diag_res['lipase_elevation_fold']}x ULN)")
    assert diag_res['diagnosis_confirmed'] is True, "Assertion Failure: Case 1 must confirm acute pancreatitis."

    # 2. BISAP Score
    bisap_res = AcutePancreatitisEngine.calculate_bisap_score(bisap_case1)
    print(f"[*] BISAP Score: {bisap_res['bisap_score']} / {bisap_res['max_score']} -> {bisap_res['triage_recommendation']}")
    assert bisap_res['bisap_score'] == 5, f"Assertion Failure: Expected BISAP 5, got {bisap_res['bisap_score']}"

    # 3. Modified Marshall & Atlanta Severity
    marshall_res = AcutePancreatitisEngine.evaluate_modified_marshall(marshall_case1)
    print(f"[*] Marshall Scores - Resp: {marshall_res['respiratory_marshall_score']}, "
          f"Renal: {marshall_res['renal_marshall_score']}, CV: {marshall_res['cardiovascular_marshall_score']}")
    print(f"[*] Organ Failure: {marshall_res['organ_failure_present']} ({marshall_res['organ_failure_type']})")
    print(f"[*] Atlanta Staging: {marshall_res['atlanta_severity_classification']}")
    assert marshall_res['organ_failure_present'] is True, "Assertion Failure: Case 1 must have organ failure."
    assert "Severe" in marshall_res['atlanta_severity_classification'], "Assertion Failure: Case 1 must be Severe Acute Pancreatitis."

    # 4. WATERFALL Moderated Resuscitation
    resusc_res = AcutePancreatitisEngine.calculate_waterfall_resuscitation(resusc_case1)
    print(f"[*] Resuscitation Protocol: {resusc_res['fluid_strategy']}")
    print(f"[*] Bolus: {resusc_res['bolus_order']}")
    print(f"[*] Maintenance: {resusc_res['maintenance_rate_ml_hr']} mL/hr of {resusc_res['recommended_crystalloid']}")
    assert "MODERATED HYPOVOLEMIC" in resusc_res['fluid_strategy'], "Assertion Failure: Case 1 must use moderated hypovolemic strategy."
    assert resusc_res['maintenance_rate_ml_hr'] == 120.0, f"Expected 120 mL/hr, got {resusc_res['maintenance_rate_ml_hr']}"

    # 5. Necrotizing Step-Up Gating
    nec_res = AcutePancreatitisEngine.evaluate_necrotizing_step_up(necrosis_case1)
    print(f"[*] Necrosis Status: {nec_res['necrosis_status']}")
    print(f"[*] Step-Up Action: {nec_res['step_up_phase']}")
    print(f"[*] Antibiotic: {nec_res['antibiotic_order']}")
    print(f"[*] Drainage: {nec_res['drainage_order']}")
    assert "Infected" in nec_res['necrosis_status'], "Assertion Failure: Gas on CT must confirm infected necrosis."
    assert "STEP 1 & STEP 2" in nec_res['step_up_phase'], "Assertion Failure: Initial infected necrosis requires Step 1 & 2."

    print("\n>>> ALL VERIFICATION GATES PASSED (100% CLINICAL CONCORDANCE) <<<")

if __name__ == "__main__":
    run_clinical_verification_suite()