Clinical History Research Articles

An update on nonsteroidal anti-inflammatory drug-induced urticaria.

Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (HR-NSAIDs) are common adverse events related to the widespread use of over-the-counter NSAIDs for the treatment of a variety of inflammatory conditions. Urticaria is the most commonly reported immediate cutaneous clinical sign of HR-NSAIDs, but it can be a manifestation of pathophysiologically different clinical entities that require different therapeutic strategies. The aim of this study is to ease the identification of the correct phenotype of HR-NSAIDs in patients reporting urticaria associated with the intake of NSAIDs and provide updated information about their diagnosis and management. The study is a narrative review conducted by collecting the most relevant and up-to-date data related to the classification, pathophysiology, severity, and prognosis of NSAID hypersensitivity reactions. PubMed and Embase scientific databases were used as search engines to select relevant articles. Patients developing HR-NSAIDs can be divided into two categories: selective responders (SR), who develop reactions after the administration of a single specific NSAID due to an underlying IgE or T-cell mediated hypersensitivity mechanism, or cross-intolerant (CI), who develop reactions to more than one chemically unrelated NSAIDs due to abnormalities in the biochemical pathways related with prostaglandin metabolism, independently from an underlying immunological mechanism. Five major different categories of HR-NSAIDs have been identified: NSAIDs-exacerbated cutaneous disease (NECD), NSAIDs-induced urticaria/angioedema with/without respiratory and systemic symptoms of anaphylaxis (NIUAA), and NSAIDs-exacerbated respiratory disease (NERD), which are developed by CI patients, and single NSAIDs-induced urticaria, angioedema and/ or anaphylaxis (SNIUAA) and single NSAIDs-induced delayed hypersensitivity reactions (SNIDHR), which are developed by CI patients. In vivo and in vitro diagnostic tests have rarely been shown to be reliable in all these entities and therefore are not routinely used in clinical practice. The management in SR patients consists of strict avoidance of the culprit drug, while for cross-intolerance reactions oral tolerance tests with safe alternative drugs (e.g. weak COX-1 inhibitors or selective COX-2 inhibitors) can be performed. HR-NSAIDs are being observed with increasing frequency, however, the pathogenesis behind some NSAIDS-associated clinical entities is still unclear. Diagnosis is mostly based on a thorough clinical history and confirmed by a drug challenge test. Clinical management is based on strict avoidance and use of alternative tolerated medications. Overall, all therapeutic decisions depend on the correct identification of the type of reaction the patient experienced.

Does Adjuvant Gamma Knife Stereotactic Radiosurgery Have a Role in Treating Optic Nerve Sheath Meningiomas?

Meningiomas arising from or adjacent to the optic nerve sheath meningioma (ONSM) are management challenges because of their risk of visual loss. Stereotactic radiosurgery (SRS) is a minimally invasive modality that can be added as adjuvant treatment for patients whose tumor has progressed or recurred after initial resection. The authors retrospectively reviewed 2,030 meningioma patients who underwent SRS between 1987 and 2022. In total, 7 patients (4 females; median age = 49) were found with tumors originating from the optic nerve sheath. None of the patients had tumors that engulfed the optic nerve as such tumors typically undergo fractionated radiation therapy (FRT) to preserve vision. The clinical history, visual function, and radiographic and neurological findings were characterized. Outcome measures included visual status, tumor control, and the need for additional management. All patients underwent either initial gross total (n = 1) or partial surgical resection (n = 6) before SRS. Two patients with progressive tumor growth also had SRS after failing additional fractionated radiation after surgery (54 Gy, 30 fractions for both patients). The median time between the date of surgery and the SRS procedure date was 38 months. The Leksell Gamma Knife was used to deliver a margin dose of 12 Gy (range: 8-14 Gy) to a median cumulative tumor volume of 3.3 cc (range: 1.2-18 cc). The median maximal optic nerve radiation dose was 6.5 Gy (range: 1.9-8.1 Gy). After SRS, the median follow-up time was 130 months (range: 26-169 months). Two patients showed local tumor progression at 20 and 55 months after SRS. Four had stable visual function, 2 experienced improved visual acuity, and 1 patient had visual deterioration. Meningiomas arising from (but not engulfing the optic nerve) represent management quandaries after failed initial surgical removal. In this experience, salvage SRS was associated with tumor control and vision preservation in 5 of 7 patients. Additional experience with this strategy may further define the role of SRS both as a salvage and primary option.

Introduction to the assessment and management of persistent postural-perceptual dizziness.

Persistent postural-perceptual dizziness classifies patients with chronic dizziness, often triggered by an acute episode of vestibular dysfunction or threat to balance. Unsteadiness and spatial disorientation vary in intensity but persist for over three months, exacerbated by complex visual environments. Literature suggests diagnosis relies on a clinical history of persistent subjective dizziness and normal vestibular and neurological examination findings. Behavioural diagnostic biomarkers have been proposed, to facilitate diagnosis. Research has focused on understanding the neural mechanisms that underpin this perceptual disorder, with imaging data supporting altered connectivity between neural brain networks that process vision, motion and emotion. Behavioural research identified the perceptual and motor responses to a heightened perception of imbalance. Management utilises head and body motion detection, and downregulation of visual motion excitability, reducing postural hypervigilance and anxiety. Combinations of physical and cognitive therapies, with antidepressant medications, help if the condition is associated with mood disorder.

Calcineurin inhibitor-related hyperkalemia is caused by hyporeninemic hypoaldosteronism and fludrocortisone is an effective treatment: Report of a case series and review of the literature.

Calcineurin inhibitors (CNIs) are widely used in transplantation. Although CNI-related hyperkalemia is common (10%-60.6%), the underlying pathogenetic mechanism is not well-elucidated and may lead to dose adjustment or treatment withdrawal. The aim of this study is to describe CNI-related hyperkalemia due to hyporeninemic hypoaldosteronism in pediatric transplant recipients who were successfully treated with fludrocortisone. In a total of 55 hematopoietic stem cell (HSCT) and 35 kidney transplant recipients followed according to institutional immunosuppression protocols, recipients diagnosed with CNI-related hyperkalemia were reviewed. Recipients who were receiving intravenous fluid, potassium, or were diagnosed with hemolysis, acute graft rejection, or had an eGFR < 30 mL/min/1.73m2, were excluded. A detailed analysis of clinical history as well as biochemical studies was carried out to reveal possible pathophysiology. Three pediatric transplant recipients (one HSCT, two kidney transplantation) with findings of hyperkalemia, hyponatremia, and a mild elevation in blood urea nitrogen while on CNIs were recruited. Urinary potassium excretion was diminished while sodium excretion was increased. Plasma aldosterone levels were low, and renin was not increased in response. Primary adrenal insufficiency was ruled out, and hyporeninemic hypoaldosteronism was diagnosed. CNI-related hyperkalemia was detected earlier in case 1, who had HSCT (22 days), than in the second and third cases, who had kidney transplantation (24 and 30 months post-transplantation, respectively). The discrepancy was hypothesized to be explained by higher overall CNI dose due to higher serum target CNI used in HSCT than kidney transplantation. Electrolyte imbalance was reversed upon administration of physiologic dose fludrocortisone (0.05 mg, daily), while fludrocortisone was ceased after CNI withdrawal in case 1, which is additional evidence for the etiological association of CNIs and hyporeninemic hypoaldosteronism. Our three cases strengthen the premise that CNI-related hyperkalemia may be due to hyporeninemic hypoaldosteronism, and the timing and severity may be related to CNI dose. Fludrocortisone is a safe and effective treatment in CNI-related hyperkalemia, providing maintenance of CNIs, which are one of the essential therapeutic agents for pediatric transplantation.

Common and Uncommon Mimics of Thoracic Malignancy on PET/CT: Part 2—Pearls and Pitfalls of Lung Parenchyma and Mediastinum

In the thorax, there are multiple benign entities that may demonstrate hypermetabolism of fluorodeoxyglucose (FDG) leading to false-positive interpretation. Part 2 of this article aims to provide an overview of some benign thoracic entities that may mimic malignancy on positron emission tomography (PET)/CT in the lung parenchyma and mediastinum. Clinical history, anatomical correlation, and imaging features can help in narrowing the differential diagnosis. This review is divided into two parts: part 1 covers the pleura and chest wall; part 2 will cover lung parenchyma and mediastinum.

A case report of Steven Johnson’s Syndrome (SJS) /Toxic Epidermal Necrolysis(TEN) overlap caused by Nimesulide

Introduction: Stevens–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare, acute and life-threatening mucocutaneous diseases that are nearly always drug-related. Incidence of SJS and TEN is 0.05 to 2 persons per million populations per year. In India, Nimesulide is easily available as an over the counter drug (OTC), different cutaneous reactions associated with, Nimesulide including angioedema, maculo-papular rash, severe urticaria, pityriasis rosea and worsening of preexisting psoriasis. Patient concern (Case summary): A 17 years old female patient complained about fever and she was prescribed with Tab.Nimesulide twice daily by private practitioner. On the 3rd day of intake of oral Nimesulide, patient developed skin lesions over face, trunk, back and all four limbs. This reaction was diagnosed as Stevens–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) overlap by Nimesulide based on clinical picture and drug history. Interventions: Tab. Nimesulide was stopped and patient was admitted in dermatology ward. Patient was treated with Inj.Hydrocortisone sodium succinate 100mg iv twice daily, Inj.Cefotaxime 1gm iv thrice a daily, Inj. Metronidazole 500mg once a day and Liquid Cyclosporine 50mg twice a day for 10days. Other treatments included Inj. Albumin 100ml i.v slowly for 3 days given. Patient recovered and was discharged after 10 days. Conclusion: We are presenting a case of SJS-TEN overlap caused by Nimesulide, which is commonly used as an over the counter drug (OTC). Our aims to minimize this type of serious ADR by making alert to physicians and other healthcare professionals, we can avoid hospital admissions because of ADR, reduce economic burden of the patients and health related quality of life of the patient can be improved.

Retrospective review of the pathology of American pikas.

American pikas (Ochotona princeps) are small lagomorphs that live in mountainous talus areas of western North America. Studies on the histopathology of American pikas are limited. We summarize here the clinical histories, and gross and histologic findings of 12 American pikas, including 9 captive (wild-caught) and 3 wild animals. Death was often attributed to stress (transport, handling, anesthesia) with few-to-no premonitory clinical signs. Infection was the cause of death in 2 cases: 1 had bacterial pyogranulomatous dermatitis, cellulitis, and lymphadenitis with sepsis; the other case had oomycete-induced necrotizing colitis. Incidental parasitic infections included sarcocystosis, nematodosis (oxyurids), and ectoparasitism. Most animals with adequate nutritional status had periportal hepatic lipidosis; this finding was absent in all animals with adipose atrophy, and it is possible that periportal hepatic lipidosis is non-pathologic in American pikas. Three cases had myocardial necrosis that was considered the cause of death; the cause of necrosis was not determined, but it may have been caused by stress or vitamin E-selenium deficiency. Esophageal hyperkeratosis was noted in animals with a history of anorexia and negative energy balance; accumulation of esophageal keratin can result from lack of mucosal abrasion by ingesta. Several histologic findings that are likely normal in American pikas include splenic extramedullary hematopoiesis, thymic tissue in adults, and Clostridium sp. in the enteric lumen.

An overview of mycotoxicoses in rabbits.

Mycotoxicoses are usually a consideration in large animal species but can affect companion animals as well. Due to increasing interest and the ease of using rabbits as laboratory models, a growing number of published experimental studies discuss the effects of various mycotoxins on this species. However, the available evidence is fragmented and heterogeneous, and has not recently been collated in a review, to my knowledge. Although mycotoxicoses in rabbits are typically subclinical, clinical signs can include weight loss, anorexia, gastrointestinal disorders, stunted growth, reproductive abnormalities, and susceptibility to infections. An antemortem diagnosis typically relies on a comprehensive clinical history, and assessment of clinical signs and relevant laboratory findings, with confirmation of exposure achieved through the measurement of mycotoxin concentrations in feed or target organs. My review focuses on the clinicopathologic and histopathologic effects of the mycotoxins most important in rabbits, including fumonisins, ochratoxins, aflatoxins, trichothecenes, and zearalenone. This review offers a thorough overview of the effects of mycotoxins in rabbits, serving as a one-stop resource for veterinary practitioners, diagnosticians, and researchers.

Myoclonus: an update.

Myoclonus, a common hyperkinetic movement disorder, can be disabling for patients. It is important to identify and classify myoclonus correctly to ensure appropriate workup and treatment. While the clinical history, examination, and process of classifying myoclonus remain largely unchanged, new causes and triggers for myoclonus are being elucidated, and new genetic causes have been found. Treatment can be challenging, though preliminary data about new options has been promising. In this article, we will briefly outline the process of classifying and treating myoclonus. We will then discuss three specific scenarios where myoclonus has been identified: myoclonus associated with SARS-CoV-2 infections, spinal myoclonus following surgery or anesthesia of the spine, and auricular myoclonus. We will also discuss new genetic findings associated with myoclonus-dystonia, and promising results regarding the use of perampanel in treating myoclonus. The process of describing unique scenarios associated with myoclonus has helped us build our understanding of the causes, genetic background, expected prognosis, and effective treatment of specific types of myoclonus. We hope that further studies on this topic will help tailor treatment.

A study to investigate the prevalence of headache disorders and migraine conducted using medical claims data and linked results from online surveys: post-hoc analysis of other headache disorders

BackgroundSurveys using questionnaires to collect epidemiologic data may be subject to misclassification. Here, we analyzed a headache questionnaire to evaluate which questions led to a classification other than migraine.MethodsAnonymized surveys coupled with medical claims data from individuals 19–74 years old were obtained from DeSC Healthcare Inc. to examine proportions of patients with primary headache disorders (i.e.; migraine, tension-type headache, cluster headache, and “other headache disorders”). Six criteria that determined migraine were used to explore how people with other headache disorders responded to these questions.ResultsAmong the 21480 respondents, 7331 (34.0%) reported having headaches. 691 (3.2%) respondents reported migraine, 1441 (6.7%) had tension-type headache, 21 (0.1%) had cluster headache, and 5208 (24.2%) reported other headache disorders. Responses of participants with other headache disorders were analyzed, and the top 3 criteria combined with “Symptoms associated with headache” were “Site of pain” (7.3%), “Headache changes in severity during daily activities” (6.4%), and the 3 criteria combined (8.8%). The symptoms associated with headache were “Stiff shoulders” (13.6%), “Stiff neck” (9.4%), or “Nausea or vomiting” (8.7%), Photophobia” (3.3%) and “Phonophobia” (2.5%).ConclusionsPrevalence of migraine as diagnosed by questionnaire was much lower than expected while the prevalence of “other headache” was higher than expected. We believe the reason for this observation was due to misclassification, and resulted from the failure of the questionnaire to identify some features of migraine that would have been revealed by clinical history taking. Questionnaires should, therefore, be carefully designed, and doctors should be educated, on how to ask questions and record information when conducting semi-structured interviews with patients, to obtain more precise information about their symptoms, including photophobia and phonophobia.

Risk factors and prediction of hypoglycaemia using the Hypo-RESOLVE cohort: a secondary analysis of pooled data from insulin clinical trials.

The objective of the Hypoglycaemia REdefining SOLutions for better liVES (Hypo-RESOLVE) project is to use a dataset of pooled clinical trials across pharmaceutical and device companies in people with type 1 or type 2 diabetes to examine factors associated with incident hypoglycaemia events and to quantify the prediction of these events. Data from 90 trials with 46,254 participants were pooled. Analyses were done for type 1 and type 2 diabetes separately. Poisson mixed models, adjusted for age, sex, diabetes duration and trial identifier were fitted to assess the association of clinical variables with hypoglycaemia event counts. Tree-based gradient-boosting algorithms (XGBoost) were fitted using training data and their predictive performance in terms of area under the receiver operating characteristic curve (AUC) evaluated on test data. Baseline models including age, sex and diabetes duration were compared with models that further included a score of hypoglycaemia in the first 6 weeks from study entry, and full models that included further clinical variables. The relative predictive importance of each covariate was assessed using XGBoost's importance procedure. Prediction across the entire trial duration for each trial (mean of 34.8 weeks for type 1 diabetes and 25.3 weeks for type 2 diabetes) was assessed. For both type 1 and type 2 diabetes, variables associated with more frequent hypoglycaemia included female sex, white ethnicity, longer diabetes duration, treatment with human as opposed to analogue-only insulin, higher glucose variability, higher score for hypoglycaemia across the 6 week baseline period, lower BP, lower lipid levels and treatment with psychoactive drugs. Prediction of any hypoglycaemia event of any severity was greater than prediction of hypoglycaemia requiring assistance (level 3 hypoglycaemia), for which events were sparser. For prediction of level 1 or worse hypoglycaemia during the whole follow-up period, the AUC was 0.835 (95% CI 0.826, 0.844) in type 1 diabetes and 0.840 (95% CI 0.831, 0.848) in type 2 diabetes. For level 3 hypoglycaemia, the AUC was lower at 0.689 (95% CI 0.667, 0.712) for type 1 diabetes and 0.705 (95% CI 0.662, 0.748) for type 2 diabetes. Compared with the baseline models, almost all the improvement in prediction could be captured by the individual's hypoglycaemia history, glucose variability and blood glucose over a 6 week baseline period. Although hypoglycaemia rates show large variation according to sociodemographic and clinical characteristics and treatment history, looking at a 6 week period of hypoglycaemia events and glucose measurements predicts future hypoglycaemia risk.

Triaging and Evaluation of Products of Conception in Abortions and Post-Partum Hemorrhage.

The proper evaluation of abortion specimens and placentas from stillbirth and post-partum cases is important for adequate clinical care of post-abortion and post-partum patients. The following topics will be reviewed: (1) the importance of evaluation of both fetal and placental tissue in first trimester abortions to confirm an intrauterine pregnancy versus an ectopic pregnancy; (2) the clinical history associated with an abortion specimen or retained products of conception (POC) influences how the pathologist should triage the specimen; (3) the criteria for diagnosis of a molar pregnancy, which is critical for clinicians to know which patients need follow-up; (4) the utility of genetic studies for both diagnosis and appropriate follow-up of the patient; and (5) the pathologic evaluation of specimens from patients with post-partum hemorrhage for placenta accreta spectrum and subinvolution of maternal vessels.

P.035 Cardiac screening in children with genetic epilepsy at risk for sudden unexpected death in epilepsy

Background: People with epilepsy experience higher rates of cardiac arrhythmia and sudden death than the general population, with the highest risk in genetic epilepsies. Despite growing evidence of a possible cardiac contribution, routine cardiac screening for epilepsy patients is rarely performed. Methods: We performed a single center, retrospective review of patients with developmental epileptic encephalopathies caused by genetic variants expressed in the heart and brain. Clinical history, medications, age, and cardiac evaluation data were extracted. Results: Among 67 patients (56% female), 54 (81%) had at least one ECG. Twenty (37%) had an abnormal ECG. Forty-one had a repeat ECG: 8 showed persistent abnormalities, 7 resolution of abnormalities, and 7 a new abnormality. Five patients with an abnormality did not receive a follow up ECG. Two patients each had histories of cardiac arrest, syncope, and sudden death in a family member. Cardiac phenotypes differed in patients who experienced generalized tonic-clonic seizures and patients with epilepsy for 3+ years. Conclusions: Almost 1/3 of our high-risk epilepsy cohort had history of cardiac events or abnormalities on cardiac testing. Seizure type and epilepsy duration were associated with altered cardiac phenotypes. Since some findings were potentially clinically significant, routine cardiac screening of high-risk epilepsy patients may be warranted.

Indications and Outcomes of Intraocular Lens Explantation in a Tertiary Eyecare Center in Hungary between 2006 and 2020

Purpose. Our study aimed to evaluate the indications and outcomes of intraocular lens (IOL) explantation surgeries in a tertiary eyecare center in Hungary. Materials and Methods. This retrospective study included all IOL explantation surgeries performed between 2006 and 2020 at the Department of Ophthalmology of Semmelweis University, Budapest, Hungary. There were no exclusion criteria for this study. For each patient, the demographics, clinical history, preoperative status, indications for IOL explantation, and operative and postoperative details were reviewed. Primary outcomes included explantation indications and the type of secondary implanted IOL. Results. A total of 161 eyes from 153 patients were included (96 males; 62.7%); age at the time of the IOL explantation was 65.0 ± 17.4 years. The mean time between primary cataract surgery and IOL explantation was 8.5 ± 7.7 years. In total, 139 (86.3%) PCIOLs and 22 (13.7%) ACIOLs were explanted. The main indications for IOL explantation were dislocation (n = 133; 95.7%) and refractive cause (n = 2; 1.4%) in the PCIOL group. Among ACIOL explantations, the main reasons were pseudophakic bullous keratopathy (n = 14; 63.6%), dislocation (n = 4; 18.2%), and refractive cause (n = 2; 9.1%). In the PCIOL group, 115 (82.7%) primary IOLs were implanted in the capsular bag, 16 (11.5%) were sulcus fixated, and 8 (5.8%) were scleral fixated. The most frequent ocular comorbidities were previous vitrectomy (n = 50, 31.1%), previous ocular trauma (n = 45, 28.0%), glaucoma (n = 16, 9.9%), pseudoexfoliation syndrome (n = 15, 9.3%), and high axial myopia (n = 14, 8.7%). The most commonly used secondary IOL implant was the prepupillary iris-claw IOL (n = 115, 73.7%), followed by the retropupillary iris-claw IOL (n = 32, 20.5%). Uncorrected visual acuity (UCVA) was significantly better following IOL exchange in the entire sample (1.57 ± 0.61 (range: 2.40–0.05) vs. 0.77 ± 0.56 (range: 2.40–0.00); p&lt;0.001). Best-corrected visual acuity (BCVA) was maintained or improved in 80.7% of cases after IOL explantation. Conclusions. The most common indication for IOL explantation at a tertiary eyecare center in Hungary is IOL dislocation, followed by pseudophakic bullous keratopathy. Prepupillary and retropupillary iris-claw IOL are the most frequently used secondary implants and their use resulted in a significant UCVA improvement following IOL exchange.

Recognition of Brugada type 1 pattern on ECG by Echo State Networks

Abstract Background/Introduction The development of artificial intelligence (AI) and machine learning (ML) techniques, which can identify data patterns in electrocardiography, has led to the development of automated analysis tools for standard 12-lead ECGs. These tools are able to identify specific features associated with different cardiac diseases, which may be helpful in clinical practice [1]. One field of application is represented by Brugada Syndrome (BrS) diagnosis, which, despite characteristic ECG features, can be challenging to diagnose and correctly distinguish from other diseases. Purpose Within the Brugada Syndrome and Artificial Intelligence Applications to Diagnosis system study, we are developing an innovative model for diagnosing Type 1 BrS based on electrocardiographic pattern recognition through the Echo State Networks (ESN), a Recurrent Neural Network (RNN) type of architecture. Methods From patients enrolled in 5 Centers, 306 12-lead ECGs were obtained. The datasets were composed of spontaneous Type 1 pattern (coved) (group A, 98 patients); patients undergoing ajmaline test, classified as positive (group B, 47 patients) or negative (group C, 35 patients) according to test results; 220 controls with no clinical and familial history of arrhythmias (group D). ESN analyzed, as input, data collected from 1 beat of the ECG V2 lead. The datasets were used for the ESN model training and were assessed through a double cross-validation approach. The ESN performance was compared with the evaluation of 4 independent cardiologists, and sensitivity, specificity and accuracy were determined. Results The ESN model correctly classified 280/306 ECGs (91.5%), with a performance of 3.6 points superior to clinicians (269/306, 88.0%). ESN sensitivity (87.0% vs. 86.9%) and specificity (94.5% vs. 89.1%) are described in Table 1; accuracy in each group of the dataset (groups A, B, C, and D), represented in Table 2, were comparable to or greater than those of clinicians. Conclusion(s) In this work, an ESN-based system for diagnosing Type 1 BrS pattern on ECG was developed. Our results show that this ML model can detect ECG patterns associated with Type 1 BrS with accuracy, sensitivity and specificity comparable or superior to clinicians. In the future, we will use a larger dataset to increase the model performance further, with the real possibility of becoming a tool for everyday clinical practice.ESN and clinicians' diagnostic accuracyECG accuracy in each dataset group

Systematic right ventricular electrophysiologic evaluation in patients with repaired tetralogy of Fallot before pulmonary valve replacement

Abstract Introduction Adults with repaired tetralogy of Fallot (rToF) are prone to develop ventricular tachycardia (VT) in adulthood, due to reentry related to slowly conducting anatomical isthmuses (SCAI). Pulmonary valve replacement (PVR) in patients without history of VT, may lead to obliteration of unrecognized SCAI with subsequent catheter ablation failure; electrophysiologic study is thus recommended before PVR. A systematic evaluation of the topology of SCAI in this population is, however, scant. Methods Consecutive rToF patients undergoing PVR with native right ventricular outflow tract were studied with pre-PVR EPS. Electroanatomical mapping with systematic evaluation of all possible anatomical isthmuses (AI) with pacemapping, activation mapping in sinus/paced rhythm and bipolar voltage mapping was performed (AI1: anterior scar/patch to tricuspid annulus; AI2: anterior scar to pulmonary annulus; AI3: pulmonary annulus to ventricular septal defect – VSD- patch; AI4: VSD to tricuspid annulus). Conduction velocity (CV) across all documented AI was calculated (ratio between the distance among the nearest point with bipolar voltage &amp;gt;1.5 mV and their difference in activation timing). Ventricular programmed stimulation was performed at 2 sites (apex and outflow tract) with drive train ad 600/400 ms, up to three extrastimuli until refractoriness or induction, during baseline and isoproterenol infusion. Radiofrequency catheter ablation (RFCA) was performed in all patients with inducible VT and/or SCAI, aiming at conduction block across the SCAI validated with differential pacing. Results Between May 2023 and November 2023, 10 patients with rToF and 1 double outlet right ventricle were studied (73% males, age 46±10 years; 54% with a previous shunt, 46% with a previous transannular patch, 27% pulmonary valvotomy and infundibular boring; median age at surgery 4 years, interquartile range 3-6). EPS was positive for inducible VT in 4 patients (mean cycle length 297 ms, 3 with left bundle branch morphology and 1 right bundle branch morphology, all inferior axis) and polymorphic VT in 1. AI1 was present in 5 patients, AI2 in 5, AI3 in 7, AI 4 in 2. At least 1 SCAI was present in 7 patients (64%), 2 SCAI in 3 patients (43% of patients with SCAI; in every patient SCAI3+SCAI2 in 2 and SCAI 4 in 1 patient). There were no SCAI1; there were 3 SCAI 2 (mean CV 0.43 m/s), 4 SCAI 3 (mean CV 0.3 m/s), 1 SCAI 4 (CV 0.4 m/s). RFCA was performed in 8 patients; acute success was achieved in all patients, achieving bidirectional conduction block across treated SCAI and non-inducibility of VT. Conclusions SCAI are often present in rToF candidate to PVR and without clinical history of spontaneous VT, involving prevalently SCAI3 and SCAI2. Inducible VT is not sufficient as a marker of arrhythmic risk and SCAI should be better sought for. RFCA of SCAI with bidirectional conduction block is acutely highly efficacious.

Wernicke Encephalopathy Caused by Avoidance-Restrictive Food Intake Disorder in a Child: A Case-Based Review

Background: Wernicke encephalopathy (WE) is an acute and potentially fatal neuropsychiatric disorder resulting from thiamine deficiency: its etiology and clinical presentation can be heterogeneous and arduously recognized, especially in children and adolescents. Case presentation: An 8-year-old girl arrived to the emergency room with ataxic gait, nystagmus, and mental confusion after a 10-day history of repeated severe vomiting; her recent clinical history was characterized by restricted nutrition due to a choking phobia, which caused substantial weight loss. Brain magnetic resonance imaging revealed a bilaterally increased T2 signal in the medial areas of the thalami and cerebral periaqueductal region. Diagnosis of WE based on clinical and neuroradiological findings was established and confirmed after labwork showing low serum thiamine. Following psychiatric evaluation, the patient was also diagnosed with avoidance-restrictive food intake disorder (ARFID), which required starting cognitive behavioral therapy and introducing aripiprazole. The patient displayed improvement of the radiological findings after one month and complete resolution of her neurological symptoms and signs. Conclusions: Eating disorders like ARFID might forerun acute signs of WE; this possibility should be considered even in pediatric patients, especially when atypical neurological pictures or feeding issues come out.

#2774 Association of serum CA-125 and lung ultrasound with other markers of volumen status in peritoneal dialysis patients

Abstract Background and Aims Volume overload (VO) represents the main risk factor for cardiovascular death in peritoneal dialysis (PD) patients. The lack of objective methods and validated markers constitutes the basis for the high prevalence, which is one of the main causes of technique failure. The use of lung ultrasound, VExUS score and serum CA-125 (SeCA-135), has emerged to assess volume in heart failure patients. In this pilot study, we explored the association of these novel approaches with classical markers of VO Method A cross-sectional cohort study was conducted on fourteen PD outpatients, in which volume status was simultaneously assessed through SeCA-125 levels along with standardized 28-site lung ultrasound, VExUS Score (excluding renal Doppler), NT-proBNP levels, and bioimpedance spectroscopy (BIS). Clinical and physical examination parameters were collected simultaneously, and echocardiographic measures were collected from the clinical history in the previous 6 months. The inclusion criteria were: patients over 18 years old, in a PD program for at least 6 months, with good adherence to the technique. The exclusion criteria were: cardiovascular event in the three months prior to the study initiation, active uncontrolled neoplastic disease, or active infection or intercurrent illness in the 2 months prior to evaluation. Because NT-ProBNP does not follow the normal distribution, we used the Ig transformation (LgNT-proBNP) in the statistical process. Results The mean age was 68.9 ± 14.9 years, with an average of 29.9 ± 19.61 months on dialysis, a mean residual diuresis of 1.22 ± 0.88 liters, and the mean weekly KT/V was 2.10 ± 0.63. 28.6% of the patients have Congestive Heart Failure, 57.1% have Diabetes Mellitus and 100% have hypertension. The patients had a mean Charlson Index of 5.7 ± 2.1 and were using an average of 2.4 ± 1.1 antihypertensive drugs. 28.6% of the patients presented dyspnea, 14.3% had pulmonary crackles, and 35.7% had peripheral edema. Mean ECW/TBW was 0.48 ± 0.02, and overhydration by BIS was 1.18 ± 1.46 L. The mean number of B-lines was 8.79 ± 6.43, Se-CA-125 was 20.42 ± 8.66 IU/mL, and NT-proBNP was 3950 (172-35,000) ng/L. SeCA125 was positively associated with left atrial volume (r = 0.823, p = 0.01), estimated PASP (r = 0.787, p = 0.03), LogNT-proBNP (r = 0.614, p = 0.02) and negatively correlated with TAPSE (r = −0.77, p = 0.05). Likewise, LogNT-proBNP was positively associated with CRP (r = 0.54, p = 0.05), and ECW/TBW ratio (r = 0.57, p = 0.03) and negatively correlated with albumin (r = −0.66, p = 0.01). There was no correlation between the number of B-lines and Se-CA-125 with the diameter or collapsibility of the IVC, pulsatility portal vein, or analysis of Doppler hepatic vein, VExUs grade, ECW/TBW ratio, NT-proBNP levels, renal residual function or the presence of edema or pulmonary crackles. Patients with overhydration by BIS (&amp;gt;7.5% OH/TBW) showed more B-lines (13 ± 6.32 vs. 5.57 ± 5.028 p = 0.04). Patients diagnosed as overloaded by B-lines (&amp;gt;5 lines) did not show a higher level of SeCA-125 (22.2 ± 9.50 vs 16 ± 4.16; p &amp;gt; 0.05), VCI diameter (1.6 ± 9.43 vs 2 ± 0.27; p &amp;gt; 0.05), OH/TBW ratio (8.4 ± 8.55 vs 2.55 ± 4.13; p &amp;gt; 0.05) or Log NT-proBNP (0.91 ± 0.76 vs 3.19 ± 0.91; p &amp;gt; 0.05). Conclusion The number of B-lines in lung ultrasound can detect patients with VO earlier compared to BIS. SeCA-125 levels are sensitive to changes in the echocardiogram. The use of both methods can help us detect early signs of volume overload in peritoneal dialysis patients.

Complications and the impact of hematological parameters in donors involved in allogenic peripheral blood stem cell transplantation for hematological malignancies

Hematopoietic stem cell transplantation (HSCT) is a vital treatment option for many hematological malignancies, offering a more convenient alternative to bone marrow transplantation. In allogeneic HSCT, donors provide hematopoietic stem cells for transplantation into patients, necessitating careful consideration of the donor's health and hematological parameters to ensure successful engraftment and treatment outcomes. In a study involving 20 adult donors at Apeksha Hospital, Sri Lanka key hematological parameters, comorbidities, clinical histories, and medications were analyzed. Diabetes mellitus and hypertension were the most prevalent comorbidities among donors, while anemia, primarily linked to iron and vitamin B12 deficiencies, was common. Although baseline coagulation abnormalities were rare and no significant complications occurred during transplantation, early clinical issues such as pain and paresthesia correlated with abnormal peripheral blood smear findings. Notably, a 4-day single daily G-CSF dosing schedule was favored over a 5-day twice daily regimen due to fewer reported problems. While anemia and thrombocytopenia were infrequent, these findings underscore the critical importance of meticulous donor selection and vigilant monitoring throughout the transplantation process to optimize outcomes.

#3092 Case report: Renal cystic disease caused to heterozygous NEK8 variant in pediatric patient

Abstract Background and Aims Polycystic kidney diseases (PKDs) are the most prevalent inherited kidney disease [1]. They are caused by pathogenic variants in genes encoding for proteins with roles in the functioning of primary cilium, a sensory organelle at the cell surface of almost all cells regulating key signaling pathways. Therefore, they are also classified as Ciliopathy and can occur with isolated renal involvement with/without systemic manifestations. As 1 of the family of “Never in Mitosis A–related kinases” (NEK), NEK8 is a regulator of Hippo pathway that controls cell growth, regulate the renal tubule epithelial cell cytoskeletal structure, and is involved in ciliary biogenesis/function. Biallelic NEK8 mutations are reported as causing a syndromic ciliopathy with multiorgan developmental defects, referred to as renal-hepatic-pancreatic dysplasia [1]. A recent paper [1] analyzed a total of 21 patients from 12 families with heterozygous NEK8 variants and cystic kidney disease and proposed a dominant negative effect for specific heterozygous variants in the NEK8 kinase domain as a new cause of PKD. Method We describe a case report of PKD associated with NEK8 heterozygous mutation. Results 8 years old female patient accessed to Emergency Department with first evidence of isolated macro-hematuria. Previous medical history was unremarkable. The girl was afebrile, in good clinical condition, with elevated blood pressure values (120/82 mmHg) at the physical examination. The laboratory tests showed normal blood count with hemoglobin 11.7 g/dl, serum creatinine 0.42 mg/dl, no inflammatory markers. Urinalysis revealed proteinuria (100 mg/dL), hemoglobinuria, active urinary sediment with microhematuria (3557 red blood cell/microliter) and leukocyturia (535 white blood cells/microliter). An abdominal ultrasound study observed kidneys of increased size (longitudinal diameter of approximately 14 cm) with presence of multiple cystic formations with a maximum diameter of 2 cm and lost cortico-medullary differentiation; other organs were normal. Ultrasound findings were confirmed with MRI. The macrohematuria resolved quickly, however we recorded the persistence of positive urinary sediment. No other concomitant clinical manifestations were recorded and the cardiological evaluation was normal. Suspecting a cystic renal disease, we proposed a genetic analysis by whole exome sequencing (WES): an heterozygous NEK8 variant (c.133C&amp;gt;T, p. Arg45Trp) was found. Due to persistent proteinuria and hypertension we suggested to initiate RAAS inhibitor treatment. Conclusion The patient's clinical history and onset of disease agree with the data described in the literature for the NEK8 variant c.133C&amp;gt;T, p. Arg45Trp. In literature all patients had an early onset of PKD. Enlarged kidney were present in 79%, followed by hypertension in 67% of cases; no patients had liver involvement, as in our patient. Kidney failure occurred before adulthood in non-mosaic case. The absence of a phenotype with systemic involvement, doesn't exclude the possible subsequent appearance of extra-renal manifestations. Therefore, it is necessary to set up a multidisciplinary follow-up, including cardiological evaluation and radiological study of brain structure. An early nephroprotective therapy and behavioral strategy must be established to prevent disease progression. Thus, it is suggested to include NEK8 in the genetic analysis when PKD is suspected.