Cookbook 381: Offline Clinical Oncology, Endocrinology & ICU Severe Hypercalcemic Crisis Albumin-Correction Staging, PTHrP / 1,25-VitD Etiology Sieve, Aggressive Saline-Calcitonin-Zoledronic Acid / Denosumab Titrator & Dialysis Engine

#!/usr/bin/env python3
"""
OpenPHR Cookbook 381: Offline Clinical Oncology & Critical Care Engine
Severe Hypercalcemic Crisis Staging, Four-Pathway Etiology Sieve,
Calcitonin/Bisphosphonate/Denosumab Titrator & Hemodialysis Protocol.

Dependencies: Python 3.8+ (Standard Library Only).
"""

from dataclasses import dataclass, field
from enum import Enum
from typing import Dict, List, Optional, Tuple, Union


class HypercalcemiaSeverityTier(Enum):
    CRISIS_SEVERE = "Severe Hypercalcemic Crisis (Corrected Ca >= 14.0 mg/dL or Life-Threatening Encephalopathy)"
    MODERATE = "Moderate Hypercalcemia (Corrected Ca 12.0 - 13.9 mg/dL)"
    MILD = "Mild Hypercalcemia (Corrected Ca 10.5 - 11.9 mg/dL)"
    NORMAL_EUCALCEMIA = "Eucalcemia (Corrected Ca 8.5 - 10.4 mg/dL)"
    HYPOCALCEMIA = "Hypocalcemia (Corrected Ca < 8.5 mg/dL)"


class HypercalcemiaEtiology(Enum):
    PTH_DEPENDENT = "Primary / Tertiary Hyperparathyroidism (Elevated / Inappropriately Normal Intact PTH)"
    HUMORAL_MALIGNANCY_PTHRP = "Humoral Hypercalcemia of Malignancy (HHM - Elevated PTHrP with Suppressed PTH)"
    VITAMIN_D_CALCITRIOL_MEDIATED = "Calcitriol-Mediated Hypercalcemia (Elevated 1,25-OH2 Vit D: Lymphoma or Granulomatous Disease)"
    LOCAL_OSTEOLYTIC_METASTASES = "Local Osteolytic Hypercalcemia (Multiple Myeloma or Extensive Skeletal Metastases)"
    EXOGENOUS_TOXICITY = "Exogenous Toxicity / Milk-Alkali / Medication-Induced (Thiazides, Lithium, Vitamin D Toxicity)"
    INDETERMINATE = "Indeterminate Etiology - Requires Full PTH, PTHrP, and Calcitriol Panel"


class AntiResorptiveAgent(Enum):
    ZOLEDRONIC_ACID = "Zoledronic Acid (Reclast / Zometa) 4 mg IV over 15 minutes"
    DENOSUMAB = "Denosumab (Xgeva) 120 mg Subcutaneous Injection"
    PAMIDRONATE = "Pamidronate Disodium (Aredia) 60 to 90 mg IV over 2 to 4 hours"
    GLUCOCORTICOIDS_ONLY = "Systemic Glucocorticoids (Prednisone 40-60 mg/day PO or Hydrocortisone 100 mg IV q8h)"
    HEMODIALYSIS_ONLY = "Low-Calcium / Zero-Calcium Hemodialysis (Severe Refractory / GFR < 15 with Overload)"


@dataclass
class HypercalcemiaPatientPresentation:
    # Patient demographics
    age_years: float
    weight_kg: float
    is_adult: bool
    # Laboratory parameters
    measured_total_calcium_mg_dl: float
    serum_albumin_g_dl: float
    serum_creatinine_mg_dl: float
    estimated_gfr_ml_min: float
    serum_potassium_meq_l: float = 4.0
    serum_magnesium_mg_dl: float = 2.0
    serum_phosphorus_mg_dl: float = 2.8
    ionized_calcium_mmol_l: Optional[float] = None
    # Endocrine & Tumor markers
    intact_pth_pg_ml: Optional[float] = None
    pthrop_pmol_l: Optional[float] = None  # Normal < 2.0 pmol/L
    vit_d_25_hydroxy_ng_ml: Optional[float] = None  # Calcidiol
    vit_d_1_25_dihydroxy_pg_ml: Optional[float] = None  # Calcitriol (Normal 20-76 pg/mL)
    spep_free_light_chains_positive: bool = False
    known_malignancy_type: Optional[str] = None  # e.g., "Squamous Cell Lung", "Multiple Myeloma", "Breast"
    known_sarcoidosis_or_tb: bool = False
    # Clinical manifestations
    severe_encephalopathy_coma_stupor: bool = False
    qtc_interval_shortened: bool = False
    cardiac_arrhythmias_present: bool = False
    volume_overload_pulmonary_edema: bool = False
    anuric_or_oliguric_aki: bool = False


@dataclass
class PayneAlbuminCorrectionResult:
    measured_total_calcium_mg_dl: float
    serum_albumin_g_dl: float
    corrected_calcium_mg_dl: float
    corrected_calcium_mmol_l: float
    severity_tier: HypercalcemiaSeverityTier
    is_crisis: bool
    clinical_interpretation: str


@dataclass
class HypercalcemiaDecisionReport:
    albumin_correction: PayneAlbuminCorrectionResult
    etiology_classification: HypercalcemiaEtiology
    etiology_rationale: str
    saline_resuscitation_protocol: Dict[str, Union[str, float]]
    calcitonin_bridge_protocol: Dict[str, Union[str, float]]
    antiresorptive_selection: AntiResorptiveAgent
    antiresorptive_dosing_instructions: Dict[str, str]
    furosemide_loop_diuretic_sentinel: Dict[str, str]
    steroid_protocol_for_calcitriol: Optional[Dict[str, str]]
    emergent_dialysis_evaluation: Dict[str, Union[bool, str, List[str]]]


class AcuteHypercalcemiaEngine:
    """
    Clinical Decision Support Engine for Severe Hypercalcemic Crisis Staging,
    Etiology Identification, Anti-Resorptive Titration, and Dialysis Gating.
    """

    @staticmethod
    def calculate_payne_corrected_calcium(
        total_ca: float, albumin: float, has_encephalopathy: bool
    ) -> PayneAlbuminCorrectionResult:
        """
        Calculates albumin-corrected calcium using the validated Payne equation:
        Corrected Calcium (mg/dL) = Total Calcium (mg/dL) + 0.8 * (4.0 - Albumin g/dL).
        """
        corrected_ca = round(total_ca + 0.8 * (4.0 - albumin), 2)
        corrected_mmol = round(corrected_ca * 0.25, 2)

        if corrected_ca >= 14.0 or has_encephalopathy:
            tier = HypercalcemiaSeverityTier.CRISIS_SEVERE
            is_crisis = True
            interp = (
                f"Severe Hypercalcemic Crisis (Corrected Ca {corrected_ca} mg/dL [{corrected_mmol} mmol/L]). "
                "Immediate inpatient ICU admission, aggressive IV isotonic hydration, salmon calcitonin bridge, "
                "and targeted anti-resorptive therapy indicated."
            )
        elif corrected_ca >= 12.0:
            tier = HypercalcemiaSeverityTier.MODERATE
            is_crisis = False
            interp = (
                f"Moderate Hypercalcemia (Corrected Ca {corrected_ca} mg/dL). Saline volume expansion and "
                "anti-resorptive therapy indicated to prevent escalation to crisis."
            )
        elif corrected_ca >= 10.5:
            tier = HypercalcemiaSeverityTier.MILD
            is_crisis = False
            interp = (
                f"Mild Hypercalcemia (Corrected Ca {corrected_ca} mg/dL). Outpatient/inpatient oral hydration "
                "and diagnostic etiology workup indicated."
            )
        elif corrected_ca >= 8.5:
            tier = HypercalcemiaSeverityTier.NORMAL_EUCALCEMIA
            is_crisis = False
            interp = f"Normal corrected serum calcium ({corrected_ca} mg/dL)."
        else:
            tier = HypercalcemiaSeverityTier.HYPOCALCEMIA
            is_crisis = False
            interp = f"Hypocalcemia (Corrected Ca {corrected_ca} mg/dL)."

        return PayneAlbuminCorrectionResult(
            measured_total_calcium_mg_dl=total_ca,
            serum_albumin_g_dl=albumin,
            corrected_calcium_mg_dl=corrected_ca,
            corrected_calcium_mmol_l=corrected_mmol,
            severity_tier=tier,
            is_crisis=is_crisis,
            clinical_interpretation=interp,
        )

    @staticmethod
    def identify_etiology(
        p: HypercalcemiaPatientPresentation
    ) -> Tuple[HypercalcemiaEtiology, str]:
        """
        Triages hypercalcemia across the 4 primary mechanistic pathways:
        1. PTH-Dependent: Intact PTH >= 20 pg/mL (inappropriately normal or high).
        2. Humoral Malignancy: Suppressed PTH (< 10-15) + Elevated PTHrP (> 2.0 pmol/L).
        3. Calcitriol Mediated: Suppressed PTH + Elevated 1,25-(OH)2 Vit D (> 70 pg/mL).
        4. Local Osteolytic: Suppressed PTH + Normal PTHrP + Multiple Myeloma / Bone Mets.
        """
        if p.intact_pth_pg_ml is not None:
            if p.intact_pth_pg_ml >= 20.0:
                return (
                    HypercalcemiaEtiology.PTH_DEPENDENT,
                    f"Intact PTH is inappropriately elevated/normal ({p.intact_pth_pg_ml} pg/mL in the setting of hypercalcemia). Confirms PTH-dependent hyperparathyroidism.",
                )

        if p.vit_d_1_25_dihydroxy_pg_ml is not None and p.vit_d_1_25_dihydroxy_pg_ml > 70.0:
            return (
                HypercalcemiaEtiology.VITAMIN_D_CALCITRIOL_MEDIATED,
                f"Elevated 1,25-(OH)2 Vitamin D ({p.vit_d_1_25_dihydroxy_pg_ml} pg/mL > 70 pg/mL) with suppressed PTH. Confirms extra-renal 1-alpha-hydroxylase calcitriol synthesis (Lymphoma or Granulomatous Disease).",
            )

        if p.pthrop_pmol_l is not None and p.pthrop_pmol_l >= 2.0:
            return (
                HypercalcemiaEtiology.HUMORAL_MALIGNANCY_PTHRP,
                f"Suppressed PTH with elevated PTHrP ({p.pthrop_pmol_l} pmol/L >= 2.0 pmol/L). Confirms Humoral Hypercalcemia of Malignancy (HHM).",
            )

        if p.spep_free_light_chains_positive or (
            p.known_malignancy_type and "myeloma" in p.known_malignancy_type.lower()
        ):
            return (
                HypercalcemiaEtiology.LOCAL_OSTEOLYTIC_METASTASES,
                "Suppressed PTH with paraproteinemia / Multiple Myeloma or extensive skeletal metastases. Confirms Local Osteolytic Hypercalcemia.",
            )

        if p.known_sarcoidosis_or_tb:
            return (
                HypercalcemiaEtiology.VITAMIN_D_CALCITRIOL_MEDIATED,
                "Clinical history of active granulomatous disease (Sarcoidosis/TB) with suppressed PTH. Presumed Calcitriol-mediated hypercalcemia.",
            )

        return (
            HypercalcemiaEtiology.INDETERMINATE,
            "Suppressed PTH without definitive PTHrP, 1,25-Vit D, or skeletal imaging confirmation. Complete diagnostic panel pending.",
        )

    @staticmethod
    def calculate_saline_resuscitation(
        weight_kg: float, is_overloaded: bool
    ) -> Dict[str, Union[str, float]]:
        """
        Calculates aggressive isotonic crystalloid volume expansion.
        Most hypercalcemic crisis patients have a 3 to 6 liter intravascular volume deficit
        due to calcium-induced nephrogenic diabetes insipidus and vomiting.
        """
        if is_overloaded:
            return {
                "initial_bolus_ml": 0.0,
                "maintenance_rate_ml_hr": 50.0,
                "fluid_type": "0.9% Normal Saline (Restricted)",
                "clinical_guidance": (
                    "CAUTION: Patient has baseline congestive heart failure / volume overload. "
                    "Aggressive saline boluses are contraindicated. Maintain slow infusion with invasive CVP "
                    "or bedside lung ultrasound (B-line) monitoring. Prepare for emergent hemodialysis."
                ),
            }

        initial_bolus = 1000.0  # 1-2 L in first 2-4 hours
        maint_rate = 250.0  # 200 - 300 mL/hr titrated to urine output 100 - 150 mL/hr

        return {
            "initial_bolus_ml": initial_bolus,
            "maintenance_rate_ml_hr": maint_rate,
            "fluid_type": "0.9% Normal Saline (Isotonic Crystalloid)",
            "infusion_protocol": (
                f"Administer {initial_bolus:.0f} mL 0.9% Normal Saline over the first 1-2 hours. "
                f"Continue maintenance at {maint_rate:.0f} mL/hour. Titrate to target urine output of "
                "100 to 150 mL/hour to drive proximal tubule calcium excretion."
            ),
            "monitoring_sentinels": (
                "Monitor serum sodium, potassium, and magnesium every 4-6 hours. Saline-induced kaliuresis "
                "and magnesiuria require proactive replacement to prevent secondary hypokalemia / hypomagnesemia."
            ),
        }

    @staticmethod
    def calculate_calcitonin_bridge(
        weight_kg: float
    ) -> Dict[str, Union[str, float]]:
        """
        Calculates Salmon Calcitonin bridging regimen:
        Dose: 4 to 8 IU/kg IM or SubQ every 12 hours.
        Rapid onset (2-4 hours), but efficacy wanes after 48 hours due to tachyphylaxis.
        """
        dose_4iu = round(weight_kg * 4.0, 0)
        dose_8iu = round(weight_kg * 8.0, 0)

        return {
            "recommended_agent": "Salmon Calcitonin (Miacalcin) Injection",
            "dose_range_iu": f"{dose_4iu:.0f} - {dose_8iu:.0f} IU (4 to 8 IU/kg)",
            "route_and_frequency": "Subcutaneous or Intramuscular injection every 12 hours (can increase to q6h in refractory crisis)",
            "onset_of_action": "Rapid: 2 to 4 hours (Lowers corrected calcium by 1.0 to 2.0 mg/dL)",
            "duration_and_tachyphylaxis_sentinel": (
                "MANDATORY DISCONTINUATION AT 48 HOURS: Calcitonin receptors rapidly down-regulate, "
                "leading to tachyphylaxis and loss of efficacy after 48 hours. Calcitonin is strictly a "
                "fast-acting bridge while waiting 48-72 hours for bisphosphonates or denosumab to take effect."
            ),
        }

    @classmethod
    def select_antiresorptive_therapy(
        cls,
        egfr: float,
        etiology: HypercalcemiaEtiology,
        is_dialysis_dependent: bool,
    ) -> Tuple[AntiResorptiveAgent, Dict[str, str]]:
        """
        Selects optimal anti-resorptive therapy respecting renal safety gates:
        - eGFR >= 30 mL/min: Zoledronic acid 4 mg IV (preferred first-line).
        - eGFR < 30 mL/min or Dialysis: Denosumab 120 mg SC (avoids bisphosphonate nephrotoxicity).
        - Calcitriol-mediated: Systemic glucocorticoids first-line.
        """
        if etiology == HypercalcemiaEtiology.VITAMIN_D_CALCITRIOL_MEDIATED:
            agent = AntiResorptiveAgent.GLUCOCORTICOIDS_ONLY
            instructions = {
                "drug": "Prednisone (or IV Hydrocortisone / Methylprednisolone)",
                "dose": "Prednisone 40 to 60 mg PO daily (or IV Methylprednisolone 20-40 mg q12h)",
                "mechanism": "Inhibits 1-alpha-hydroxylase activity and decreases intestinal calcium absorption in calcitriol-driven hypercalcemia.",
                "renal_adjustment": "No dose adjustment required for renal impairment.",
            }
            return agent, instructions

        if egfr < 30.0 or is_dialysis_dependent:
            agent = AntiResorptiveAgent.DENOSUMAB
            instructions = {
                "drug": "Denosumab (Xgeva) Monoclonal Antibody (RANKL Inhibitor)",
                "dose": "120 mg Subcutaneously on Day 1, Day 8, Day 15, and then every 4 weeks",
                "mechanism": "Binds and neutralizes RANKL, preventing osteoclast maturation and bone resorption.",
                "renal_advantage": (
                    "ZERO RENAL TOXICITY: Denosumab is cleared via the reticuloendothelial system and does not "
                    "undergo renal filtration. It is the MANDATED agent when eGFR < 30 mL/min, where Zoledronic Acid "
                    "is strictly contraindicated due to risk of irreversible acute tubular necrosis."
                ),
                "hypocalcemia_sentinel": (
                    "HIGH RISK OF PROTRACTED SEVERE HYPOCALCEMIA in severe CKD/dialysis patients. "
                    "Monitor serum calcium closely for 2-4 weeks post-injection."
                ),
            }
            return agent, instructions

        # Standard eGFR >= 30 mL/min: Zoledronic Acid
        agent = AntiResorptiveAgent.ZOLEDRONIC_ACID
        instructions = {
            "drug": "Zoledronic Acid (Zometa / Reclast) Intravenous Bisphosphonate",
            "dose": "4.0 mg in 100 mL Normal Saline or D5W infused IV over AT LEAST 15 MINUTES",
            "mechanism": "Inhibits farnesyl pyrophosphate synthase in mature osteoclasts, inducing osteoclast apoptosis.",
            "renal_safety_gate": (
                f"Permissible based on patient's eGFR ({egfr} mL/min >= 30 mL/min cutoff). "
                "Ensure patient is fully hydrated before infusion to prevent acute phase nephrotoxicity."
            ),
            "onset": "Takes 48 to 72 hours to achieve nadir calcium; paired with salmon calcitonin for early 48h coverage.",
        }
        return agent, instructions

    @staticmethod
    def evaluate_loop_diuretic_sentinel(
        is_overloaded: bool, uremic_failure: bool
    ) -> Dict[str, str]:
        """
        Enforces strict safety guardrails on loop diuretics (furosemide).
        Loop diuretics are strictly contraindicated until full euvolemia is restored.
        """
        if is_overloaded:
            status = "PERMITTED WITH CAUTION (Strictly for Volume Overload Management)"
            rule = (
                "Furosemide (20 - 40 mg IV) is permitted ONLY to manage clinical pulmonary edema or "
                "iatrogenic volume overload following saline resuscitation. It does NOT replace hemodialysis "
                "in oliguric renal failure."
            )
        else:
            status = "STRICTLY CONTRAINDICATED IN DEHYDRATED PATIENTS"
            rule = (
                "DO NOT ADMINISTER FUROSEMIDE OR LOOP DIURETICS TO DEHYDRATED PATIENTS. "
                "Early loop diuretic use aggravates hypovolemia, impairs GFR, stimulates proximal tubular "
                "calcium reabsorption, and increases mortality. Modern Endocrine Society guidelines strictly "
                "forbid routine diuretic use unless overt hypervolemia/pulmonary edema supervenes."
            )

        return {
            "sentinel_status": status,
            "clinical_rule": rule,
        }

    @staticmethod
    def evaluate_dialysis_criteria(
        corrected_ca: float,
        p: HypercalcemiaPatientPresentation,
    ) -> Dict[str, Union[bool, str, List[str]]]:
        """
        Evaluates emergency low-calcium hemodialysis criteria:
        - Corrected Calcium >= 18.0 mg/dL (4.5 mmol/L)
        - Corrected Calcium >= 14.0 mg/dL with severe neurological compromise (coma, stupor)
        - Severe oliguric/anuric AKI or advanced CKD unable to tolerate saline volume expansion
        - Volume overload / pulmonary edema with refractory hypercalcemia
        """
        reasons = []
        if corrected_ca >= 18.0:
            reasons.append(f"Extreme life-threatening hypercalcemia (Corrected Ca {corrected_ca} mg/dL >= 18.0 mg/dL)")

        if corrected_ca >= 14.0 and p.severe_encephalopathy_coma_stupor:
            reasons.append("Severe acute encephalopathy / coma refractory to medical therapy")

        if p.anuric_or_oliguric_aki or (p.estimated_gfr_ml_min < 15.0 and p.volume_overload_pulmonary_edema):
            reasons.append("Anuric/oliguric acute kidney injury or severe heart failure unable to tolerate saline hydration")

        if p.cardiac_arrhythmias_present:
            reasons.append("Life-threatening cardiac dysrhythmias / severe QTc shortening")

        needs_dialysis = len(reasons) > 0

        dialysate_protocol = (
            "Dialysis Prescription: Perform emergent hemodialysis using ZERO-CALCIUM (0.0 mmol/L) or "
            "LOW-CALCIUM (1.0 mmol/L) dialysate bath. Continuous Renal Replacement Therapy (CRRT / CVVHDF) "
            "with regional citrate anticoagulation provides rapid, smooth calcium clearance without rebound."
            if needs_dialysis
            else "Patient does not meet emergent hemodialysis criteria; proceed with medical pharmacotherapy cascade."
        )

        return {
            "dialysis_indicated": needs_dialysis,
            "triggers_identified": reasons if reasons else ["None - Medical management appropriate"],
            "dialysis_prescription": dialysate_protocol,
        }

    @classmethod
    def run_clinical_assessment(
        cls, p: HypercalcemiaPatientPresentation
    ) -> HypercalcemiaDecisionReport:
        """
        Runs the end-to-end clinical assessment.
        """
        correction = cls.calculate_payne_corrected_calcium(
            p.measured_total_calcium_mg_dl,
            p.serum_albumin_g_dl,
            p.severe_encephalopathy_coma_stupor,
        )

        etiology, etiology_rationale = cls.identify_etiology(p)

        saline = cls.calculate_saline_resuscitation(
            p.weight_kg, p.volume_overload_pulmonary_edema
        )

        calcitonin = cls.calculate_calcitonin_bridge(p.weight_kg)

        antiresorptive_agent, antiresorptive_dosing = cls.select_antiresorptive_therapy(
            p.estimated_gfr_ml_min,
            etiology,
            p.anuric_or_oliguric_aki or p.estimated_gfr_ml_min < 15.0,
        )

        furosemide_sentinel = cls.evaluate_loop_diuretic_sentinel(
            p.volume_overload_pulmonary_edema, p.anuric_or_oliguric_aki
        )

        steroids = None
        if etiology == HypercalcemiaEtiology.VITAMIN_D_CALCITRIOL_MEDIATED:
            steroids = {
                "indication": "Calcitriol-Mediated Hypercalcemia (Lymphoma / Sarcoidosis / Granulomatous)",
                "regimen": "Prednisone 40 to 60 mg PO daily (or IV Methylprednisolone 20-40 mg q12h)",
                "duration": "Continue for 7 to 10 days until calcium normalizes, then taper under specialist guidance.",
            }

        dialysis = cls.evaluate_dialysis_criteria(correction.corrected_calcium_mg_dl, p)

        return HypercalcemiaDecisionReport(
            albumin_correction=correction,
            etiology_classification=etiology,
            etiology_rationale=etiology_rationale,
            saline_resuscitation_protocol=saline,
            calcitonin_bridge_protocol=calcitonin,
            antiresorptive_selection=antiresorptive_agent,
            antiresorptive_dosing_instructions=antiresorptive_dosing,
            furosemide_loop_diuretic_sentinel=furosemide_sentinel,
            steroid_protocol_for_calcitriol=steroids,
            emergent_dialysis_evaluation=dialysis,
        )


# =====================================================================
# SELF-CONTAINED CLINICAL VALIDATION SUITE
# =====================================================================

def verify_clinical_scenarios():
    print("=" * 80)
    print("OpenPHR Cookbook 381: Severe Hypercalcemic Crisis & Anti-Resorptive Suite")
    print("=" * 80)

    # Test Case 1: Severe Squamous Lung HHM in Renal Failure (eGFR 22, Total Ca 13.6, Alb 2.0 -> Corr Ca 15.2)
    pt_hhm = HypercalcemiaPatientPresentation(
        age_years=66.0,
        weight_kg=72.0,
        is_adult=True,
        measured_total_calcium_mg_dl=13.6,
        serum_albumin_g_dl=2.0,  # Corrected Ca = 13.6 + 0.8*(4.0 - 2.0) = 15.2 mg/dL!
        serum_creatinine_mg_dl=2.8,
        estimated_gfr_ml_min=22.0,  # Severe CKD / AKI (GFR < 30)
        intact_pth_pg_ml=6.0,  # Suppressed PTH
        pthrop_pmol_l=5.4,  # High PTHrP -> HHM
        known_malignancy_type="Squamous Cell Lung Carcinoma",
        severe_encephalopathy_coma_stupor=True,
        qtc_interval_shortened=True,
    )

    rep1 = AcuteHypercalcemiaEngine.run_clinical_assessment(pt_hhm)

    assert rep1.albumin_correction.is_crisis is True, "Must be crisis with corrected Ca 15.2 mg/dL"
    assert rep1.albumin_correction.corrected_calcium_mg_dl == 15.2
    assert rep1.etiology_classification == HypercalcemiaEtiology.HUMORAL_MALIGNANCY_PTHRP
    assert rep1.antiresorptive_selection == AntiResorptiveAgent.DENOSUMAB, "Must select Denosumab because GFR < 30"
    assert rep1.emergent_dialysis_evaluation["dialysis_indicated"] is True, "Encephalopathy + Ca >= 14 triggers dialysis readiness"

    print("[*] Test Case 1 (Severe HHM with GFR 22 mL/min - Denosumab Gate) PASSED")
    print(f"    - Measured Total Ca: {rep1.albumin_correction.measured_total_calcium_mg_dl} mg/dL | Albumin: {rep1.albumin_correction.serum_albumin_g_dl} g/dL")
    print(f"    - Payne Corrected Ca: {rep1.albumin_correction.corrected_calcium_mg_dl} mg/dL ({rep1.albumin_correction.severity_tier.value})")
    print(f"    - Etiology: {rep1.etiology_classification.value}")
    print(f"    - Anti-Resorptive Selected: {rep1.antiresorptive_selection.value}")
    print(f"    - Calcitonin Dose: {rep1.calcitonin_bridge_protocol['dose_range_iu']} ({rep1.calcitonin_bridge_protocol['route_and_frequency']})")

    # Test Case 2: Sarcoidosis Calcitriol-Mediated Hypercalcemia (eGFR 65, 1,25-VitD 110 pg/mL)
    pt_sarcoid = HypercalcemiaPatientPresentation(
        age_years=38.0,
        weight_kg=68.0,
        is_adult=True,
        measured_total_calcium_mg_dl=12.4,
        serum_albumin_g_dl=3.5,  # Corrected Ca = 12.4 + 0.8*(0.5) = 12.8 mg/dL
        serum_creatinine_mg_dl=1.1,
        estimated_gfr_ml_min=65.0,
        intact_pth_pg_ml=8.0,
        vit_d_1_25_dihydroxy_pg_ml=110.0,  # High Calcitriol
        known_sarcoidosis_or_tb=True,
    )

    rep2 = AcuteHypercalcemiaEngine.run_clinical_assessment(pt_sarcoid)

    assert rep2.etiology_classification == HypercalcemiaEtiology.VITAMIN_D_CALCITRIOL_MEDIATED
    assert rep2.antiresorptive_selection == AntiResorptiveAgent.GLUCOCORTICOIDS_ONLY
    assert rep2.steroid_protocol_for_calcitriol is not None

    print("\n[*] Test Case 2 (Sarcoidosis Calcitriol-Mediated - Glucocorticoid Protocol) PASSED")
    print(f"    - Corrected Ca: {rep2.albumin_correction.corrected_calcium_mg_dl} mg/dL")
    print(f"    - Etiology: {rep2.etiology_classification.value}")
    print(f"    - Primary Therapy: {rep2.steroid_protocol_for_calcitriol['regimen']}")

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


if __name__ == "__main__":
    verify_clinical_scenarios()