Irman Forghani

Importance. Cancer is the second leading cause of death among patients in the Caribbean, where outcomes are associated with delayed clinical navigation to screening, diagnosis, and treatment. Artificial intelligence is increasingly used to guide patients with cancer to care, but whether these systems provide clinically actionable, facility-verified guidance for individuals in this population, and whether governance of the system is associated with the quality of that guidance, has not been evaluated. Objective. We tested whether a governed community learning platform navigates Caribbean cancer patients better than four ungoverned AI systems, and we tracked how community intelligence accumulates over time. Design, Setting, and Participants. We deployed a community learning ledger (CaribChat.ai) across ten Caribbean jurisdictions beginning March 2, 2026, and report all sessions through June 1, 2026 (N=207). An initial actively-promoted accrual period (March 2 - April 6, 2026; 168 sessions) was followed by continued organic use after active clinical promotion ceased. We then submitted the same 28 patient screening queries to ChatGPT (GPT-4o), Claude Haiku 4.5, DeepSeek-Chat, and OpenEvidence on April 5-6, 2026. Claude Haiku 4.5 powers CaribChat; testing it without governance isolates the governance effect. The platform requires no registration. Exempt under 45 CFR 46.104(d)(4)(ii). Main Outcomes and Measures. We classified 207 community sessions by thematic domain and temporal phase. We scored each of five systems on Caribbean facility citation, actionable navigation, and US-resource leakage across 28 screening queries. Results. The ledger accumulated 207 sessions - 168 during an actively-promoted accrual period (March 2 - April 6) and 39 after active clinical promotion ceased. Community engagement evolved from screening questions to active treatment navigation and diaspora engagement. CaribChat cited verified Caribbean facilities in 28/28 (100%) responses versus 10/28 (35.7%) for ChatGPT and 9/28 (32.1%) for OpenEvidence. CaribChat provided actionable navigation in 28/28 (100%) versus 2/28 (7.1%) for OpenEvidence (P<=.001). The same model scored 100% with governance and 54% without (P<=.001). DeepSeek cited US resources in 57.1% of Caribbean responses. After active clinical promotion ceased, off-codebook queries rose from 2.4% to 26.7% across phases while the governance contract continued to reject every adversarial probe - the community persisted but drifted from the cancer codebook absent clinician curation. The deployment operated within the OECS Health Strategy 2030 and CARICOM regional health frameworks, with queries originating across Caribbean jurisdictions led by Trinidad and Tobago. Conclusions and Relevance. Every ungoverned AI system we tested failed Caribbean cancer navigation. The best scored 68%. The most widely adopted physician platform scored 7%. The same foundation model scored 100% with governance and 54% without. Community intelligence accumulated from the population it serves, not published literature, is what makes health AI work in SIDS. The post-promotion decay shows the requirement is bidirectional: sustained, on-codebook engagement depends on patients and clinicians working together - community participation and active clinical curation are jointly necessary for maximum AI leverage.

Demographic representation in clinical trials and downstream genomic databases has been documented to be skewed across two decades, but the structural origin of the skew remains contested. Here we test whether a single upstream protocol-writing bias drives demographic skew on both axes (race and sex) at the population scale of clinical-trial enrollment, and whether the same skew compounds at the genomic-database layer that informs precision-medicine inference. The hypothesis is anchored to a previously characterized clinical-care bias. The senior author has previously shown that the named sex disparity in coronary artery bypass grafting (CABG) does not originate at the operating-room door but in diagnostic timing, with women experiencing significantly longer first-encounter to diagnostic-catheterization intervals than men, while no sex difference appears in cath to CABG timing ⁹ . The bedside record shows what looks like sex-biased surgery; the upstream record reveals a bias set in who is investigated for cardiac disease at all. CABG is the bedside template; clinicaltrial enrollment is the population-scale analogue. In the trial record, the CABG signature reproduces, on both demographic axes. On the race axis, African-derived enrollment declines Phase I → Phase III monotonically across all sponsor classes; the industry × academia joint trial shows the steepest gradient of all (Phase III 8.2%; Δ Phase I → III = +4.65 pp; OR = 1.62; P < 10 ⁻¹⁰⁰ ), with academic execution under industry-written protocols laundering catchment-area diversity out. On the sex axis, female enrollment runs the opposite phase direction (Phase I 41.4% → Phase III 48.7% in the eligibility-ALL subset, n = 37,737), with the inversion concentrated in industry-solo trials (+10.0 pp); 99.3% of trials report sex against 61.6% reporting race. The two axes are statistically independent at the trial level (joint CABG-bias quadrant occupancy 24.81% vs 24.76% expected under independence; χ ² = 0.13, P = 0.72; Pearson r = 0.016), one upstream cause with two parallel readouts, not one reinforcing race × sex effect. Extended to the genomic-database layer, the pattern compounds. The GEI ranks European-derived populations at 0.98; eight others score 0.58 or below; the global equity gap is 3.94 billion people receiving precision medicine calibrated for the 11% of humanity who are European-derived. The race-axis primary-data recomputation of GWAS Catalog ancestry share yields 88.3% European-derived participation, not the published 78% (Mills & Rahal 2020), the gap has widened, not narrowed. Top and bottom GEI rankings are robust in 100% of 10,000 Dirichlet weight permutations. The same architecture is portable to a parallel Sex Equity Index for the orthogonal axis. The hypothesis is supported at every layer we measured. The structural locus across all three, bedside, trial, genomic database, is one upstream governance function. Boards and credentialing bodies that govern protocol design, independent of the sponsor, are the structural intervention point at every layer.

Why do pandemics keep emerging despite decades of surveillance and response? Paleopathology, the study of disease traces in ancient remains, has been revolutionized by ancient DNA (aDNA) analysis and next-generation sequencing (NGS). Reconstructing pathogen genomes from archaeological material enables the identification of extinct lineages, the refinement of disease chronologies, and the characterization of long-term host-pathogen co-evolution. This provides context for public health challenges, including the emergence of pandemics and antimicrobial resistance (AMR). Infectious diseases are increasingly understood as complex phenomena arising from biological, ecological, and sociopolitical forces. Integrating paleopathology, aDNA, and paleomicrobiology supports a deep-time syndemic framework, revealing how recurring biosocial drivers have structured infectious disease risk throughout history. Ancient resistome studies demonstrate that AMR predates modern antibiotic use, reframing resistance as an intrinsic ecological feature rather than solely a modern phenomenon. Coronavirus disease 2019 (COVID-19) reaffirmed how infection intersects with chronic disease, health system fragility, and social inequities. This review highlights how integrating evolutionary perspectives into One Health shifts surveillance from a reactive approach to upstream risk mitigation and spillover prevention.

Background/Objectives: Hypermobile Ehlers–Danlos syndrome (hEDS) is the most common subtype of Ehlers–Danlos syndromes (EDS), a heterogeneous group of hereditary connective tissue disorders. The hallmark features of hEDS include generalized joint hypermobility (GJH), soft or velvety skin, and persistent joint pain. The molecular etiology of hEDS remains unknown, and diagnosis is primarily clinical. The updated diagnostic criteria for hEDS requires the fulfillment of three criteria: (1) GJH, (2) a combination of musculoskeletal and systemic manifestations consistent with a connective tissue disorder, and (3) the exclusion of alternative diagnoses. However, the exclusion process and the role of genetic testing have not yet been fully refined. Methods: This retrospective review utilized data from the Hereditary Connective Tissue Disorders (HCTD) patient registry at the University of Miami, which includes individuals evaluated at the HCTD Clinic using a standardized internal clinical and genetic protocol. We analyzed data from 907 patients referred for hEDS evaluation between June 2019 and December 2022. Results: Among these patients, 178 met the 2017 diagnostic criteria for hEDS. Genetic testing identified an alternative or additional diagnosis in 47 of these individuals (26.4%), with clinical implications requiring distinct management strategies. Conclusions: These findings underscore the importance of criterion three—exclusion of alternative diagnoses—and highlight the critical yet underutilized role of genetic testing in the assessment of joint hypermobility. Furthermore, the results suggest that hypermobility may present a shared phenotype across a spectrum of disorders, including inflammatory diseases, monogenic syndromes, and chromosomal abnormalities.

Phenotypic features of a hereditary connective tissue disorder, including craniofacial characteristics, hyperextensible skin, joint laxity, kyphoscoliosis, arachnodactyly, inguinal hernia, and diverticulosis associated with biallelic pathogenic variants in EFEMP1 have been previously described in four patients. Genome sequencing on a proband and her mother with comparable phenotypic features revealed that both patients were heterozygous for a stop‐gain variant c.1084C>T (p.Arg362*). Complementary RNA‐seq on fibroblasts revealed significantly reduced levels of mutant EFEMP1 transcript. Considering the absence of other molecular explanations, we extrapolated that EFEMP1 could be the cause of the patient's phenotypes. Furthermore, nonsense‐mediated decay was demonstrated for the mutant allele as the principal mechanism for decreased levels of EFEMP1 mRNA. We provide strong clinical and genetic evidence for the haploinsufficiency of EFEMP1 due to nonsense‐medicated decay to cause severe kyphoscoliosis, generalized hypermobility of joints, high and narrow arched palate, and potentially severe diverticulosis. To the best of our knowledge, this is the first report of an autosomal dominant EFEMP1‐associated hereditary connective tissue disorder and therefore expands the phenotypic spectrum of EFEMP1 related disorders.

Cardiovascular system involvements have been frequently reported in hypermobile Ehlers‐Danlos Syndrome (hEDS). Mitral valve prolapse (MVP) and aortic root dilatation are included in the 2017 international classification criteria for hEDS. Different studies have found conflicting results regarding the significance of cardiac involvement in hEDS patients. We conducted a retrospective review of cardiac involvement in patients diagnosed with hEDS based on the 2017 International diagnostic criteria to provide further evidence toward more defined and reliable diagnostic criteria and recommended cardiac surveillance. A total of 75 hEDS patients with at least one diagnostic cardiac evaluation were included in the study. The most common reported cardiovascular complaints were lightheadedness (80.6%), followed by palpitations (77.6%), fainting (44.8%), and chest pain (32.8%). Of the 62 echocardiogram reports, 57 (91.9%) showed trace/trivial to mild valvular insufficiency, and 13 (21%) had additional abnormalities such as grade I diastolic dysfunction, mild aortic sclerosis, and trivial or small pericardial effusion. Of the 60 electrocardiograms (ECG) reports, 39 (65%) were normal, and 21 (35%) reported minor abnormalities or normal variants. Even though many hEDS patients in our cohort experienced cardiac symptoms, the presence of a significant cardiac abnormality was very low.

Osteogenesis imperfecta (OI) is a rare connective tissue disorder with clinical and genetic heterogeneity. The cardinal features of OI are bone fragility and low bone mineral density (BMD). Pathogenic variants in COL1A1 and COL1A2 genes, which encode the pro alpha-1(I) and pro alpha-2(I) chains of Type 1 collagen, are the most common causes of OI. Mutations disrupting the carboxy-terminal propeptide cleavage site of the pro alpha-1(I) and pro alpha-2(I) chains have recently been reported as rare causes of OI with paradoxically normal to high BMD. This report describes a father and daughter with OI who are heterozygous for a novel likely pathogenic variant at the carboxy-terminal propeptide cleavage site of COL1A1 (NM_000088.4): c.3656A>G; (p.Asp1219Gly). We describe their intrafamilial phenotypic variability and overlapping features with other COL1A1-related disorders.

Identifying hereditary syndromes among patients with renal cell carcinoma (RCC) is essential for surveillance of affected individuals and their at‐risk family members and for treatment optimization. We conducted a chart review to determine the percentage of patients with RCC who were seen at the University of Miami Health System (UHealth), and met the American College of Medical Genetics (ACMG) and the National Society of Genetic Counselors (NSGC) genetic referral criteria at the University of Miami. Subsequently, we determined the percentage of those who went on to receive genetic evaluation. Patients selected by International Classification of Diseases (ICD) 9/10 codes corresponding to kidney cancer who were at least 18 years of age at the time of diagnosis were included in the study. We included a total of 1443 patients in the final analysis, and after exclusion of charts with incorrect ICD codes, insufficient clinical data, unknown pathology, and patients who were not seen. We used chi‐square analysis, ANOVA, and t ‐test. Of 1443 charts reviewed, 65.7% were male and 34.3% were female. 47.7% self‐identified as White, 39.2% as Hispanic, 9.1% as Black, and 4.0% as “other.” The mean age of RCC diagnosis was 60.0 ± 12.4 years old. In total, 47.0% of patients met ACMG/NSGC referral criteria for genetic evaluation. Of those, only 4.2% had documented genetic assessment. This study showed a low adherence to ACMG/NSGC genetic referral guidelines at our institution and a need for increasing patients' and practitioners' awareness about the significance of genetic assessment for RCC patients and their family members.

Peroxisomes play an essential role in lipid metabolism via interaction with other intracellular organelles. The information about the role of the Acyl‐CoA‐binding domain containing‐protein 5 (ACBD5) in these interactions in human cells is emerging. Moreover, a few patients with retinal dystrophy and leukodystrophy caused by pathogenic variants in ACBD5 have been recently introduced. Here, we present a 36‐year‐old female with retinal dystrophy, leukodystrophy, and psychomotor regression due to a novel homozygous variant in ACBD5. Our study adds to the growing knowledge of this peroxisomal disorder by providing phenotypic details of the first adult patient.

We report the first case of blood chimerism involving a pathogenic RB1 variant in naturally conceived monochorionic‐dizygotic twins (MC/DZ) with the twin–twin‐transfusion syndrome (TTTS), presumably caused by the exchange of stem‐cells. Twin A developed bilateral retinoblastoma at 7 months of age. Initial genetic testing identified a de novo RB1 pathogenic variant, with a 20% allelic ratio in both twins' blood. Subsequent genotyping of blood and skin confirmed dizygosity, with the affected twin harboring the RB1 pathogenic variant in skin and blood, and the unaffected twin carrying the variant only in blood.