Background: Seizure-like episodes are common in children, but many spells are not true epileptic seizures. Cardiac or pulmonary conditions such as pulmonary arterial hypertension can be the cause of the seizure-like episodes, particularly when the events persist despite administration of antiseizure medications. Case Report: A 2-year-old male presented with recurrent seizure-like episodes that persisted despite administration of 2 antiseizure medications. Spells consisted of a sudden collapse followed by body jerking. Electroencephalogram and brain imaging were normal. Given the atypical features and lack of medication response, a cardiology evaluation was pursued. Echocardiography revealed severe pulmonary arterial hypertension with markedly elevated right heart pressures. Genetic testing confirmed the presence of a pathogenic bone morphogenetic protein receptor type 2 (BMPR2) gene. Despite initiation of sildenafil, bosentan, and prostacyclin therapy, the patient's condition worsened with recurrent syncopal and cyanotic episodes. He suffered a cardiac arrest requiring prolonged resuscitation and extracorporeal membrane oxygenation support, complicated by hypoxic-ischemic encephalopathy and multiorgan failure. Following discussions with the family, care was redirected to comfort measures, and the patient died. Conclusion: This case illustrates how pulmonary arterial hypertension may mimic drug-resistant epilepsy. Rather than seizures, the patient's events were syncope resulting from decreased cerebral perfusion caused by low cardiac output. BMPR2 mutations are the most common genetic cause of heritable pulmonary arterial hypertension and are associated with earlier onset, more severe disease, and poor response to therapy compared to pulmonary arterial hypertension without BMPR2 mutations. To our knowledge, this case is the first report of BMPR2-related pulmonary arterial hypertension initially presenting as seizure-like episodes in a child. Children with atypical presentations should be evaluated for cardiopulmonary causes. Early recognition of pulmonary arterial hypertension is essential, as delayed diagnosis limits treatment opportunities.
Background: High-risk human papillomavirus (HPV)-induced cervical cancer is a major cause of mortality worldwide. Published data suggest geographic variations in the prevalence of some of the 12 high-risk HPV genotypes. Although the variations in prevalence of the 2 most common high-risk HPV genotypes-16 and 18-have been relatively well documented, the variations in prevalence of the other 10 high-risk genotypes are not as well documented. Reliable proof of variations in prevalence may warrant different high-risk HPV vaccine compositions/vaccination strategies in specific geographic areas. To explore the adequacy of the HPV vaccines available in India, we focused this study on the following: (1) confirming that high-risk HPV genotype variations exist on the Indian subcontinent, (2) determining how the genotype variations differ from the variations in other WHO regions/countries and among different regions/states in India, (3) determining whether any regional variations are sufficiently different to warrant changes in high-risk HPV vaccine compositions and/or vaccination strategies, and (4) determining whether the collected data could lead to new hypothesis generation and study design. Methods: We used 2 methods to gather information. To examine variations in prevalence, we conducted a secondary analysis (data mining) of publicly available data from the HPV Information Centre. The HPV Information Centre data were obtained from a systematic review of studies published from 1990 to 2015. We also conducted a scoping review of the literature published from 2015 to 2024. Results: As expected, we found variations in the prevalence of high-risk HPV genotypes among different regions on the Indian subcontinent. The predominant genotypes identified on the Indian subcontinent, in World Health Organization (WHO) regions, and in WHO South-East Asia Region countries were HPV 16 and HPV 18; other genotypes had varied prevalences. The scoping review of the literature revealed many inhomogeneities among the studies. None of the studies included testing for all 12 high-risk HPV genotypes, confidence intervals were rarely reported, and the quality assurance details of the studies are unknown. Conclusion: Although high-risk HPV genotype variations in prevalence were detected among different regions on the Indian subcontinent, the strength of the data does not justify different HPV vaccination compositions and strategies at this time. Studies are needed that include all 12 high-risk HPV genotypes, use uniform state-of-the-art high-risk HPV detection technologies, and document stringent quality assurance procedures. While our results must be interpreted with caution, our data can help inform future well-designed, homogenous, high-quality studies.
Background: Amyloid positron emission tomography (PET) is gaining popularity for clinical and research purposes, particularly since the US Food and Drug Administration approval of anti-amyloid therapies. While the benefits of PET imaging in clinical care outweigh the risks associated with radiation exposure, the risks from elective radiation exposure in research should be carefully considered. Currently, no published or widely used guidelines consider prior radiation exposure as part of the eligibility determination for prospective participants in a clinical trial that includes ionizing radiation exposure. Methods: We reviewed the medical literature and current studies listed on ClinicalTrials.gov for radiation safety criteria and study protocols that include amyloid PET scans. We then developed a safety screening procedure to systematically estimate prior radiation exposure to determine eligibility for participation in an amyloid PET substudy and implemented this procedure in the Successful AGing after Elective Surgery (SAGES) study. Results: Of the studies including amyloid PET that were listed on ClinicalTrials.gov (n=92), prespecified exclusion criteria with specific amounts of radiation exposure were provided in only 1% of studies; 37% of studies did not report any screening for prior radiation exposure. Using the screening protocol we developed for the SAGES study, 17% of 101 participants were deemed ineligible for the amyloid PET procedure because of prior exposure. Conclusion: A systematic, standardized screening protocol to determine the prior radiation exposure of potential participants should be used as a tool in clinical studies involving elective radiologic procedures to minimize risk to participants.
Background: Revumenib is the only oral menin inhibitor approved for the treatment of relapsed/refractory acute leukemia with menin-lysine methyltransferase 2A (KMT2A) rearrangement in adults and pediatric patients aged >1 year. Revumenib was granted US Food and Drug Administration approval under the accelerated approval pathway, receiving both breakthrough therapy and orphan drug designations because of its potential to address a significant unmet need for patients with relapsed/refractory acute leukemia with a KMT2A translocation. While revumenib has no absolute contraindications, the package insert carries warnings, including the risk of corrected QT (QTc) prolongation. Case Report: A 76-year-old male with relapsed/refractory acute myeloid leukemia received revumenib after exhausting all other treatment options because of failure or intolerance. During treatment, the patient experienced multiple episodes of torsades de pointes and ventricular arrhythmias. Given the gravity of the patient's disease and the lack of alternative therapeutic options beyond hospice, a multidisciplinary team implemented aggressive measures to mitigate arrhythmic risk: placement of a permanent pacemaker following the initial torsades de pointes episode, meticulous electrolyte management, medication adjustments to limit QTc prolongation and drug-drug interactions, and use of a wearable cardioverter defibrillator. Despite a subsequent episode of torsades de pointes, the patient continued revumenib for an additional 29 days without further arrhythmias until discontinuation because of worsening acute myeloid leukemia shown by bone marrow biopsy. Conclusion: Although current guidance recommends discontinuation of revumenib in the setting of life-threatening arrhythmias, this case highlights the importance of individualized risk-benefit assessment and supportive strategies when treatment is pursued as a last resort.
Background: Trochlear dysplasia is a considerable risk factor for patellar instability. Surgical treatment options include medial patellofemoral ligament reconstruction, medial quadriceps tendon-femoral ligament reconstruction, femoral rotational osteotomy, tibial tubercle osteotomy, and trochleoplasty. Case Report: A 26-year-old female presented with bilateral knee pain and recurrent patellar dislocations since childhood that were unresponsive to physical therapy and bracing. Initial evaluation by an orthopedic trauma service revealed excessive femoral anteversion and Dejour type D trochlear dysplasia bilaterally. A right femoral rotational osteotomy with intramedullary nail fixation improved right-sided patellar stability. Eighteen months after the first surgery, the patient underwent a planned left femur rotational osteotomy. The patient continued to experience recurrent bilateral patellar subluxation and was referred for definitive treatment. Examination demonstrated bilateral patellar subluxation at rest and positive J-sign on flexion, with the left knee more symptomatic than the right. Imaging revealed healed osteotomies, persistent Dejour type D trochlear dysplasia, and elevated tibial tubercle-trochlear groove distances bilaterally. Merchant view radiographs and magnetic resonance imaging showed substantial lateral patellar subluxation on the left with intact patellofemoral cartilage. Computed tomography confirmed bilateral trochlear dysplasia. The patient underwent left knee recession wedge trochleoplasty, tibial tubercle osteotomy, and medial quadriceps tendon-femoral ligament reconstruction. One year later, the same procedures were performed on the right knee with good results. Conclusion: Trochleoplasty, tibial tubercle osteotomy, and medial quadriceps tendon-femoral ligament reconstruction are effective when performed concomitantly for recalcitrant patellar instability associated with trochlear dysplasia and failed prior surgical intervention.
Background: Biliary tract traumatic neuroma is a rare benign hyperplasia of nerve tissue that follows some form of trauma. These lesions closely mimic malignancy, and a conclusive diagnosis is difficult to establish. Case Report: We report the case of a 65-year-old female who presented with jaundice with cholestatic features, abdominal pain, and intermittent episodes of fever. She had undergone open cholecystectomy 3 years prior for gallstone disease. Her liver function tests showed direct hyperbilirubinemia with elevated alkaline phosphatase. Serum CA 19-9 was >3,000 U/L. Cross-sectional imaging showed a nodular mass at the hilum causing extrinsic compression of the common hepatic duct with resultant bilobar intrahepatic biliary dilatation. Endoscopic ultrasound showed an eccentric thickening of the common hepatic duct, just below the hilum. Malignant common hepatic duct stricture was provisionally diagnosed, and the patient underwent open extrahepatic biliary excision with Roux-en-Y hepaticojejunostomy. The proximal and distal resection margins were confirmed negative for dysplasia or malignancy on frozen section. Final histopathologic examination showed conglomeration of nerve fascicles and Schwann cells in a fibrotic stroma, features suggestive of a traumatic neuroma. Conclusion: Traumatic neuroma of the biliary tree is a rare entity and mimics biliary tract malignancy. Preoperative diagnosis of traumatic neuromas is usually difficult, and surgery is indicated in cases of diagnostic uncertainty.
