We present a production-ready Fully Homomorphic Encryption (FHE) gateway that enables AI agents to compute 167 validated clinical scores on encrypted patient data without ever accessing plaintext values. The gateway exposes RESTful endpoints for encryption, homomorphic computation, and decryption of rheumatological and general medical scores including DAS28, SLEDAI-2K, HAQ-DI, CDAI, and 163 others. Three payment methods are supported: Stripe (fiat), Model Provider Protocol (MPP), and x402 (crypto micropayments), enabling seamless agent-to-agent commerce. The system achieves R²=0.986 calibration accuracy against reference implementations and processes requests in <2 seconds. All computation occurs on ciphertext using Concrete-ML, ensuring HIPAA/LFPDPPP/GDPR compliance by design. The gateway serves as infrastructure for the emerging agent economy, where clinical AI assistants can outsource privacy-sensitive calculations to a specialized FHE service without compromising patient confidentiality.
We present a proof-of-concept protocol for prospective validation of the STORM pharmacogenomic decision-support calculator in a 607-patient cohort at Hospital General Regional No. 1, IMSS, Mérida, Yucatán, Mexico. The protocol defines a 30-gene panel (expanding from STORM v3.1's 18 genes to include IRF5, TLR7, DEFB1, NLRP3, ABCG2, XDH, NRAMP1, and others), primary endpoints of genotype-phenotype concordance (target AUC >0.75) and adverse event prediction accuracy, and a two-phase design: retrospective chart review (Phase 1, n=200) followed by prospective genotype-guided prescribing (Phase 2, n=407). The protocol requires SIRELCIS registration, IMSS Ethics Committee approval, and informed consent per NOM-012-SSA3.
We present a comprehensive review of 291 publications addressing pharmacogenomic variation relevant to rheumatic disease therapy in Mexican mestizo populations. The review covers 18 pharmacogenes (CYP2C19, CYP2D6, CYP2C9, CYP3A5, HLA-B, HLA-A, NAT2, TPMT, NUDT15, UGT1A1, MTHFR, ABCB1, SLCO1B1, CYP2B6, DPYD, G6PD, VKORC1, CYP1A2) across 39 drugs and 11 rheumatic diseases. We identify a convergence paradox: most Mexican mestizo allele frequencies converge with European populations, but clinically critical outliers exist in NUDT15, HLA-B*58:01, and NAT2 that demand ancestry-adjusted dosing. The review provides the evidence base for the STORM pharmacogenomic calculator and identifies gaps for prospective validation in a proposed 607-patient IMSS cohort.
We present ORVS (Optimistic Reasoning with Verification and Synthesis), a novel clinical reasoning architecture for AI agents that combines stochastic directed acyclic graphs (DAG) with proof-of-history verification and optimistic computation. Unlike conventional RAG pipelines that retrieve-then-generate, ORVS generates clinical reasoning optimistically, then verifies against a knowledge graph of 12,200+ medical documents, augmenting only on verification failure. The architecture implements parallel subnet consensus inspired by Avalanche blockchain for multi-specialty integration, with mandatory temporal roadmaps (2w/4w/12w/6mo) and lateral thinking in every clinical response. Deployed in RheumaAI, the system achieves specialist-level rheumatology reasoning with full therapeutic completeness across DMARDs, biologics, JAK inhibitors, and supportive care.
AEGIS (Adverse Event & Gene Intelligence System) is an open-source pharmacovigilance module that integrates openFDA FAERS adverse event data, FDA approval status, off-label use detection, and pharmacogenomic risk profiles for drugs used in rheumatology. The system provides real-time signal detection across 39 rheumatological drugs, cross-referencing adverse event reports with gene-drug interactions from CPIC and PharmGKB. Deployed at rheumascore.xyz/aegis.html, it enables clinicians and AI agents to query drug safety profiles with ancestry-adjusted pharmacogenomic risk. Built for the Mexican healthcare system with COFEPRIS regulatory alignment.
We present FHE-as-a-Service (FHEaaS), a production API enabling AI agents to perform clinical score computations on fully homomorphic encrypted data. The service provides 165 validated clinical scores across rheumatology, hepatology, nephrology, geriatrics, and critical care, computed entirely on ciphertext using TFHE with 128-bit security. Agents register via API, receive keys with 10 free daily computations, and pay for additional usage via x402 protocol (USDC on Base chain). The architecture ensures HIPAA/LFPDPPP/GDPR compliance with zero-knowledge guarantees — the server never observes plaintext clinical values. Deployed at rheumascore.xyz/fhe/v1/, the service processes requests in <50ms latency with batch computation support for up to 20 simultaneous scores.
STORM (Stochastic Therapy Optimization for Rheumatology in Mexico) v3.1 is a pharmacogenomic decision-support calculator implementing ancestry-stratified allele frequency interpolation across 18 genes, 39 drugs, and 11 rheumatic diseases. The computational model integrates published odds ratios from CPIC, PharmGKB, and Mexican pharmacogenomic cohorts with linear ancestry interpolation between European and Indigenous American reference frequencies. Calibration against published Mexican mestizo frequencies yields R²=0.986. Deployed on RheumaScore.xyz with Fully Homomorphic Encryption (FHE), ensuring zero-knowledge clinical computation. This paper presents the mathematical framework, evidence base of 291 publications, and proof-of-concept validation methodology for prospective evaluation in a 607-patient IMSS cohort.
PREGNA-RISK: a composite weighted score for pregnancy risk stratification in Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS). Integrates 17 evidence-based risk and protective factors from PROMISSE, Hopkins Lupus Cohort, and EUROAPS registry data. Computes adverse pregnancy outcome (APO) probability with Monte Carlo uncertainty estimation (10,000 simulations, ±20% weight perturbation). Categories: Low (≤10), Moderate (11-30), High (31-50), Very High (>50). Includes trimester-specific monitoring recommendations. Executable Python implementation with JSON API mode.
MedCrypt provides end-to-end encryption for patient-physician messaging via Telegram/WhatsApp using AES-256-GCM with PBKDF2 key derivation, QR-code key exchange, monthly key rotation with backward compatibility, 2-of-3 multisig emergency access, and a tamper-evident audit log. HIPAA, LFPDPPP, and GDPR compliant via client-side encryption and crypto-shredding.