Pulmonary arteriovenous malformations (PAVMs) are rare vascular anomalies most commonly seen in hereditary hemorrhagic telangiectasia (HHT), a condition associated with mutations in ENG, ACVRL1, SMAD4, or GDF2. In contrast, BMPR2 variants are well-established in heritable pulmonary arterial hypertension (PAH), but their relationship to PAVMs remains poorly understood. We report the case of a 41-year-old woman with an incidentally discovered PAVM, initially treated with embolization and subsequent surgical resection. She remained asymptomatic for several years until progressive exertional dyspnea led to a diagnosis of severe precapillary PAH. Genetic testing identified a heterozygous BMPR2 splice-site variant (c.967 + 5G>A), previously reported in a PAH cohort but currently classified as a variant of uncertain significance. This report is notable for the delayed evolution from isolated PAVM to PAH in the context of a BMPR2 variant, raising the possibility of a mechanistic link outside the canonical HHT pathway. We review published reports of BMPR2-associated PAVMs, some of which include subtle HHT-like features, such as mucocutaneous telangiectases and epistaxis, despite negative testing for classical HHT genes. These observations suggest a potential phenocopy vascular syndrome driven by disruption of the shared bone morphogenetic protein 9 (BMP9)-ALK1 signaling axis. We also discuss the implications of sotatercept, a transforming growth factor-beta (TGF-β) superfamily ligand trap, which in this case was associated with symptomatic improvement and stable shunt burden. These findings contribute to the emerging recognition of atypical vascular phenotypes in BMPR2 variant carriers, particularly those presenting with PAVMs in the absence of HHT. It highlights the importance of considering genetic testing in isolated AVM presentations, as well as the need for longitudinal surveillance and mechanistic investigation into overlapping TGF-β/BMP signaling disorders.

Alpha-2 antiplasmin (α2AP) deficiency is a rare fibrinolytic disorder characterized by unregulated plasmin activity and premature clot breakdown. Mechanistically, α2AP restrains fibrinolysis by (i) forming a covalent serpin complex with plasmin, (ii) blocking plasminogen binding to fibrin, and (iii) undergoing factor XIIIa-mediated cross-linking into fibrin to harden clots against local lysis. We describe a woman with decades of delayed postoperative bleeding, transfusion dependence, and a presumed diagnosis of von Willebrand disease, ultimately found to have congenital α2AP deficiency. Her evaluation showed normal coagulation studies, platelet function, and von Willebrand factor assays, with persistently low α2AP activity and a homozygous SERPINF2 variant confirming the diagnosis. Standard hemostatic panels may fail to detect α2AP deficiency, and testing with functional activity assays or genetic analysis is required. This case highlights diagnostic pitfalls and underscores the importance of considering fibrinolytic disorders in patients with unexplained or delayed bleeding.

Oral telangiectasias in hereditary hemorrhagic telangiectasia (HHT) can significantly impair quality of life. While sclerotherapy is an established treatment for HHT-related epistaxis, it is rarely used for oral telangiectasias. We retrospectively reviewed HHT patients who underwent oral sclerotherapy between 2021 and 2024 at a tertiary academic center. Eleven patients (64% female, mean age 61.3 years, 82% ACVRL1 genotype) underwent sclerotherapy using a 1:4 mixture of 3% sodium tetradecyl sulfate and air. Lesions treated included the lip (36%), tongue (36%), hard palate (18%), and gingiva (9%). Presenting symptoms included oral bleeding with eating and dietary limitations. Adverse effects included transient lip swelling (n = 2) and tongue burning (n = 1). At an average follow-up of 6 months, 10/11 patients with follow-up data had complete symptomatic and clinical resolution. Our findings suggest that oral sclerotherapy is a safe, effective, and minimally invasive treatment for HHT-related oral bleeding that clinicians should consider.

Hereditary haemorrhagic telangiectasia (HHT) is a genetic disorder characterised by epistaxis, mucocutaneous telangiectasias and arteriovenous malformations. Iron deficiency due to chronic bleeding events is a common manifestation that produces a range of nonspecific symptoms. We report on a patient with HHT with longstanding fatigue and exercise intolerance, which was persistently attributed to iron deficiency, who was revealed to have glycogen storage disease type V, an autosomal recessive metabolic myopathy caused by deficiency of myophosphorylase due to PYGM variants. Genetic testing revealed a pathogenic common exon mutation of one allele and a pathogenic intronic mutation of the other, possibly suggestive of a milder phenotype. We not only detail the first case of concurrent HHT and glycogen storage disease in the literature but more importantly emphasise the need for clinician awareness of the disorders to avoid perpetuating a biased clinical impression and delay in diagnosis as well as prevent potentially harmful interventions.

Partial anomalous pulmonary venous return (PAPVR) is a rare congenital anomaly in which one or more pulmonary veins drain into the systemic venous system, creating a left-to-right shunt and potentially causing right-sided volume overload. Frequently associated with atrial septal defects, PAPVR may present with non-specific symptoms such as exertional dyspnoea and is often misdiagnosed as pulmonary hypertension of other origins. We describe a woman with progressive exertional dyspnoea and lower extremity oedema in the setting of newly identified precapillary pulmonary hypertension. Imaging revealed severe right atrial enlargement and a left-to-right shunt from the right superior pulmonary vein draining into the superior vena cava, consistent with PAPVR. She underwent successful surgical correction with the Warden procedure resulting in functional recovery. This case highlights the importance of recognising unexplained right atrial enlargement as a clue to PAPVR and demonstrates the potential for symptomatic and physiological resolution following timely surgical intervention.

Autoimmune pulmonary alveolar proteinosis is a heterogenous clinical syndrome of disordered surfactant clearance due to a dysfunctional granulocyte–macrophage colony-stimulating factor signaling axis in the setting of polyclonal autoantibody generation. Recent advancements identifying key mechanistic drivers of this disease have been made. This clinical review summarizes current knowledge of autoimmune pulmonary alveolar proteinosis with an emphasis on contemporary findings on pathogenesis and emerging therapies. A disturbed granulocyte–macrophage colony-stimulating factor signaling axis leads to downstream dysregulation of cholesterol export within alveolar macrophages. Accumulation of cholesterol impedes surfactant clearance and propagates the syndrome’s disease process. Whole lung lavage therapy is an invasive procedure performed under general anesthesia which remains the standard of care for autoimmune pulmonary alveolar proteinosis. Augmentation of the defective signaling axis with recombinant human granulocyte-macrophage colony-stimulating factor is a promising treatment modality.

Passenger lymphocyte syndrome is an immunologic disorder observed in solid organ and haematopoietic stem cell transplantation in which B lymphocytes within a donor graft are transferred to the recipient and subsequently produce circulating antibodies against host red blood cell antigens. The syndrome is most likely to occur in minor ABO blood group mismatched or Rh incompatible transplantation. Although generally mild and self-limited, the resulting haemolytic burden has the potential to increase the risk of infection, graft failure and death. The phenomenon is observed in the transplantation of any solid organ with lymphoid tissue, including the liver. We present a structured case report of passenger lymphocyte syndrome following minor ABO-mismatched liver transplantation, which was initially complicated by blood loss anaemia early in the postoperative period. By reviewing the limited literature of this disorder following liver transplantation, we emphasise common clinical findings and treatment strategies as well as introduce chimerism analysis to confirm resolution.

Myelodysplastic neoplasms (MDS) define clonal hematopoietic malignancies characterized by heterogeneous mutational and clinical spectra typically seen in the elderly. Curative treatment entails allogeneic hematopoietic stem cell transplant, which is often not a feasible option due to older age and significant comorbidities. Immunotherapy has the cytotoxic capacity to elicit tumor-specific killing with long-term immunological memory. While a number of platforms have emerged, therapeutic vaccination presents as an appealing strategy for MDS given its promising safety profile and amenability for commercialization. Several preclinical and clinical trials have investigated the efficacy of vaccines in MDS; these include peptide vaccines targeting tumor antigens, whole cell-based vaccines and dendritic cell-based vaccines. These therapeutic vaccines have shown acceptable safety profiles, but consistent clinical responses remain elusive despite robust immunological reactions. Combining vaccines with immunotherapeutic agents holds promise and requires further investigation. Herein, we highlight therapeutic vaccine trials while reviewing challenges and future directions of successful vaccination strategies in MDS.

Drug-induced lupus is an autoimmune phenomenon characterized by the development of systemic lupus erythematosus-like clinical features after drug exposure. The entity is a clinical diagnosis. Evaluation consists of recognizing systemic lupus erythematosus-like features, identifying an appropriate causative agent, observing elevations of characteristic autoantibodies, and obtaining positive response with drug discontinuation. Vedolizumab is an anti-alpha 4 beta 7 antibody used in the treatment of ulcerative colitis and Crohn's disease. We report a novel case of drug-induced lupus recurrence secondary to vedolizumab use in a patient with Crohn's disease, emphasizing diagnostic evaluation, and provide a brief review of the published literature.

Case Presentation A 35-year-old woman at 36 weeks and 4 days gestation with known complete anterior placenta previa and no other medical history presented for routine obstetric follow-up. She reported increasing fatigue in the prior week but otherwise endorsed no new concerns. She denied recent vaginal bleeding or discharge, abdominal pain, contractions, or extremity swelling. On evaluation, her BP was 126/74 mm Hg with a heart rate of 72 beats per min. The results from the physical examination were normal. There was a category II fetal heart rate tracing and a 6/10 biophysical profile (ie, no fetal breathing movements, nonreactive nonstress test), which prompted referral to the hospital. On admission, sonogram confirmed cephalic presentation and redemonstrated complete anterior placenta previa with no evidence of hemorrhage. She received antenatal steroids and was scheduled for a cesarean section delivery. She received bupivacaine spinal anesthesia for the procedure. The surgical procedure progressed with a low transverse uterine incision and subsequent delivery of the baby with no complications noted. Immediately after delivery of the baby and during gentle traction of the placenta, the patient experienced rapid cardiovascular collapse in the form of hypotension and bradycardia.

The urachus is a vestigial structure that connects the bladder to the allantois in utero and subsequently obliterates into the fibrous median umbilical ligament. Urachal adenocarcinoma (UrC) is an extremely rare malignancy, comprising less than 1% of all bladder tumors, and may arise from any remnant component of the urachus—most often from the dome of the bladder. 1 Paner GP Lopez-Beltran A Sirohi D Amin MB Updates in the pathologic diagnosis and classification of epithelial neoplasms of urachal origin. Adv Anat Pathol. 2016; 23: 71-83 Crossref PubMed Scopus (50) Google Scholar ,2 Pinthus JH Haddad R Trachtenberg J et al. Population based survival data on urachal tumors. J Urol. 2006; 175: 2042-2047 Crossref PubMed Scopus (111) Google Scholar The clinical course of UrC involves nonspecific signs and symptoms often leading to eventual detection only after local spread. Overall prognosis is poor with an estimated 5-year survival of 20% to 50%. 2 Pinthus JH Haddad R Trachtenberg J et al. Population based survival data on urachal tumors. J Urol. 2006; 175: 2042-2047 Crossref PubMed Scopus (111) Google Scholar ,3 Gopalan A Sharp DS Fine SW et al. Urachal carcinoma: a clinicopathologic analysis of 24 cases with outcome correlation. Am J Surg Pathol. 2009; 33: 659-668 Crossref PubMed Scopus (197) Google Scholar Diagnostic criteria are debated but frequently emphasize the presence of a tumor at the dome of a bladder with no evidence of a primary neoplasm elsewhere. 3 Gopalan A Sharp DS Fine SW et al. Urachal carcinoma: a clinicopathologic analysis of 24 cases with outcome correlation. Am J Surg Pathol. 2009; 33: 659-668 Crossref PubMed Scopus (197) Google Scholar , 4 Sheldon CA Clayman RV Gonzalez R Williams RD Fraley EE Malignant urachal lesions. J Urol. 1984; 131: 1-8 Crossref PubMed Scopus (434) Google Scholar , 5 Mostofi FK Thomson RV Dean AL Mucous adenocarcinoma of the urinary bladder. Cancer. 1955; 8: 741-758 Crossref PubMed Scopus (277) Google Scholar In fact, metastatic adenocarcinomas of unknown primary origin may often be due to an unidentified urachal malignancy, although there remains a paucity of data on its incidence. 6 Sahu KK Pandey D Mishra AK et al. Mystery of neck lump: an uncommon presentation of urachal cancer. BMJ Case Rep. 2019; 12e230215 Crossref Scopus (3) Google Scholar ,7 Suzuki K Kai Y Matsuda M et al. A rare case of urachal carcinoma with multiple lung metastasis that required differentiation from primary lung carcinoma. Respirol Case Rep. 2022; 10: e0890 Crossref PubMed Scopus (1) Google Scholar In the most recent classification of genitourinary tumors, urachal epithelial malignancies are divided histologically into glandular, nonglandular and mixed neoplasms with further subtypes; the majority of urachal malignancies are glandular adenocarcinomas with mucinous or enteric features. 1 Paner GP Lopez-Beltran A Sirohi D Amin MB Updates in the pathologic diagnosis and classification of epithelial neoplasms of urachal origin. Adv Anat Pathol. 2016; 23: 71-83 Crossref PubMed Scopus (50) Google Scholar ,8 Humphrey PA Moch H Cubilla AL Ulbright TM Reuter VE The 2016 WHO Classification of tumours of the urinary system and male genital organs—Part B: prostate and bladder tumours. Eur Urol. 2016; 70: 106-119 Abstract Full Text Full Text PDF PubMed Scopus (1036) Google Scholar ,9 Netto GJ Amin MB Berney DM et al. The 2022 World Health Organization classification of tumors of the urinary system and male genital organs—Part B: prostate and urinary tract tumors. Eur Urol. 2022; 82: 469-482 Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar The prognostic relevance of these subtypes is currently unclear. 1 Paner GP Lopez-Beltran A Sirohi D Amin MB Updates in the pathologic diagnosis and classification of epithelial neoplasms of urachal origin. Adv Anat Pathol. 2016; 23: 71-83 Crossref PubMed Scopus (50) Google Scholar ,10 Benerjee N Parmar K Vaiphei K Primary signet-ring cell carcinoma of the urinary bladder. Autops Case Rep. 2021; 11e2021264 Crossref PubMed Google Scholar The mainstay of treatment for all subtypes is en bloc resection. 4 Sheldon CA Clayman RV Gonzalez R Williams RD Fraley EE Malignant urachal lesions. J Urol. 1984; 131: 1-8 Crossref PubMed Scopus (434) Google Scholar There is remarkable molecular overlap between UrC and colorectal adenocarcinoma (CRC). Global transcriptome profiling and targeted exon sequencing of UrC has shown high similarity of RNA expression (via clustering analysis) as well as genetic alterations (eg, APC, SMAD4, KRAS, microsatellite instability) between UrC and CRC. 11 Kardos J Wobker SE Woods ME et al. Comprehensive molecular characterization of urachal adenocarcinoma reveals commonalities with colorectal cancer, including a hypermutable phenotype. JCO Precis Oncol. 2017; 1 (PO.17.00027) Google Scholar The enteric subtype of UrC also demonstrates a histologic pattern of stratified columnar epithelium similar to that of CRC. Thus, 5-fluorouracil (5-FU) based therapies have often been employed with moderate efficacy in metastatic cases of UrC. 12 Siefker-Radtke AO Gee J Shen YU et al. Multimodality management of urachal carcinoma: The M. D. Anderson Cancer Center Experience. J Urol. 2003; 169: 1295-1298 Crossref PubMed Scopus (223) Google Scholar The role of targeted therapies and immunotherapies has increasingly been investigated in contemporary single case reports. We present the cases of 5 patients with UrC and review literature regarding emerging therapies.

A53-YEAR-OLD WOMAN presented to the emergency department with 6 months of progressively worsening episodic upper abdominal pain. The pain was sharp and radiating to the back and exacerbated by eating, which caused her to avoid oral intake and led to a more than 12-kg (26.5-lb) weight loss. She also described intermittent nausea and fatigue but had no fevers, yellowing of the eyes or skin, pruritis, swelling, vomiting, diarrhea, constipation, or bloody stools. She had no history of tobacco, alcohol, or illicit drug use and had no significant travel history. rent epistaxis that started in adolescence, followed by the emergence of telangiectasis involving her lips,

Pulmonary hamartomas are abnormal growths of mature cell or tissue types, including cartilage, epithelium, fat or muscle. Although most cases are benign, asymptomatic and often incidentally discovered, these masses may provoke significant complications via predisposition to obstruction, ischaemia or infection. Pulmonary hamartomas located within the tracheal lumen are exceedingly rare clinical entities which produce symptoms of dyspnoea, cough, stridor, wheezing or angina. Significant clinical consequences include airway obstruction and cardiovascular collapse. Most cases of tracheal hamartoma are initially diagnosed as obstructive pulmonary disease. We present a structured case report of a tracheal hamartoma identified in a patient with recent coronary artery bypass grafting who was initially evaluated for persistent ischaemic pathology, resulting in delay of diagnosis. By review of limited literature of this disorder, we emphasise the need for clinicians to be aware of this indolent and rare entity.

An older patient with hereditary hemorrhagic telangiectasia and right lower lobe segmental pulmonary embolism presented with dyspnea that had worsened over 5 years; physical examination and laboratory testing showed jugular venous distension, a cardiac systolic murmur, right ventricular heave, bilateral lower extremity edema to the knees, and elevated brain-type natriuretic peptide level. What is the diagnosis and what would you do next?

Arrhythmogenic cardiomyopathy is a non-ischaemic cardiomyopathy characterised by the presence of myocardial dysfunction and inherited conduction disease that predisposes patients to malignant ventricular arrhythmias and sudden cardiac death. There is a growing awareness of the diverse phenotypic presentation of arrhythmogenic cardiomyopathy, which may demonstrate preferential involvement of the left, right or both ventricles. A subset of arrhythmogenic cardiomyopathy may be due to mutations of desmosomes, intercellular junctions of the myocardium that promote structural and electrical integrity. Mutations of desmoplakin, encoded by the DSP gene and a critical constituent protein of desmosomes, have been implicated in the onset of arrhythmogenic cardiomyopathy. We present a structured case report of desmoplakin arrhythmogenic cardiomyopathy secondary to novel heterozygous DSP mutations (c.1061T>C and c.795G>C) manifesting as early onset non-ischaemic cardiomyopathy and recurrent ventricular tachycardia refractory to multiple modalities of therapy, including oral antiarrhythmics, cardiac ablation and bilateral sympathectomy, as well as frequent implantable cardioverter-defibrillator discharges.

Immune-mediated herb-induced liver injury (HILI) is an acute or chronic inflammatory liver disease precipitated by a hepatotoxic agent with a presentation similar to acute autoimmune hepatitis. It is distinguished in clinical course from true autoimmune hepatitis by remission on drug discontinuation and immunosuppressive treatment. We report a potential case of immune-mediated HILI associated with artemisinin use, an herb underlying first-line malarial treatments, in a woman undergoing radiotherapy for right-sided pelvic sarcoma. A probable association in this case is supported by causality assessment using the updated Roussel Uclaf Causality Assessment Method (score of 6). She achieved clinical improvement with a course of oral corticosteroids and remained stable without relapse following discontinuation. Increased awareness of this complication is imperative, as literature to date only documents direct hepatocellular and cholestatic liver injury from artemisinin use, and should augment clinician counsel regarding complementary medicine administration, especially in high-risk individuals like those with cancer.

Background: As the number of elderly patients referred to and undergoing allogeneic hematopoietic cell transplantation (alloHCT) continues to rise, there is a growing need for a comprehensive risk assessment model to accurately predict transplantation outcomes in this specific patient population. The widely used Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) does not fully capture factors influencing transplant outcomes in elderly patients. This study aims to enhance risk stratification for elderly patients undergoing alloHCT by integrating additional functional, nutritional, and clinical indicators. Methods: This is a retrospective study utilizing the data registry of HCT patients who received their treatment at UF Health Cancer Center. The inclusion criteria included all patients age > 65 years, who underwent their first alloHSCT between January 2012 and December 2022, regardless of graft type, conditioning regimen, donor type, or graft source. Patient data were extracted through chart review. The primary endpoint was 1-year Overall Survival (OS). Prognostic significance of each variable was assessed using Cox proportional hazard models. We subsequently used all variables to build a comprehensive prediction model to assess 1-year survival outcomes in elderly patients undergoing alloHCT. The predictive model's performance was measured by the Concordance-statistic (c-statistic). Results: A total of 69 patients satisfied the inclusion criteria and were included in the analysis. Median age was 69 years (range 66-81) and 65.2% were male. Unrelated donors were used in 66.6% of patients, while the remainder received grafts from related donors. Most patients received peripheral blood stem cell grafts (91%). Myeloid malignancies comprised the most common indication for alloHCT in this group of patients (89.8%). 59.4% had abnormal cytogenetics. 35 variables were considered in the analysis. In the univariate analysis, variables with impact on 1-year OS post-transplant included creatinine (HR 3.35, CI 1.62-6.91, p=0.001), blood urea nitrogen (HR 1.03, CI 1.01-1.06, p=0.007), estimated glomerular filtration rate (HR 0.93, CI 0.89-0.93, p=0.001), hemoglobin (HR 0.8, CI 0.66-0.97, p=0.02), abnormal cytogenetics (HR 2.27, CI 1.20-4.31, p=0.012) and high and very high disease risk index (HR 0.51, CI 0.27-0.98, p=0.04). Notably, both hemoglobin and cytogenetics demonstrated a c-statistic greater than 0.6 in the univariate analysis. In the multivariate analysis, variables impacting 1-year OS included hemoglobin (HR 0.69, CI 0.48-0.99, p=0.04), remission status at the time of transplant i.e., not reached (NR) vs complete remission 1 (CR1) (HR 0.05, CI 0.00-0.71, p=0.027), and abnormal cytogenetics (HR 7.55, CI 2.32-24.58, p=0.001). Interestingly, the HCT-CI did not significantly impact 1-year OS in the univariate analysis (c-statistic 0.51, HR 0.99, CI 0.85-1.15, p=0.896). Our prediction model showed good performance with a mean area under the receiver operating characteristic curve of 0.82. Conclusion: We developed a comprehensive prediction model to assess 1-year OS in elderly patients undergoing alloHCT to overcome some of the limitations of the HCT-CI in this unique age group. This model holds potential to enhance decision-making regarding candidacy for elderly patients undergoing alloHCT.