Comprehensive Workup Research Articles

Clinical risk factors and prediction model for infective endocarditis in patients with gram-positive bacteremia

Abstract Introduction Gram-positive bacteremia (GPB) is a common condition in clinical practice that potentially leads to infective endocarditis (IE), a high morbidity and mortality disease. Clinicians still encounter challenges in determining the likelihood of developing IE in GPB patients. Comprehensive and invasive cardiac investigations in every patient with GPB for IE could be unnecessary and potentially harmful while missing proper investigations might result in the delay or misdiagnosis of this fatal condition. Objective We aimed to determine the significant clinical risk factors and develop the prediction model for IE in patients with GPB. Methods Data were obtained from medical records of hospitalized adult patients with GPB in our hospital from January 2016 to December 2020. IE was defined by the ‘definite’ group according to modified Duke criteria. The cohort was divided into training (80%) and test (20%) sets. We identified the association between clinical risk factors and the development of IE by logistic regression analyses. Significantly associated clinical risk factors in multivariate analysis were used in the prediction model. The area under the receiver operating characteristic curve (AUROC) was utilized to evaluate model performances. Results A total of 794 patients with GPB were included in the study. IE was diagnosed in 89 patients (11.2%). Among 21 selected clinical risk factors from univariate analysis, 10 variables, including the unknown origin of bacteremia, mechanical and bioprosthetic heart valve, duration of symptoms more than 7 days, presence of Roth spot, neurological symptoms, murmur, heart failure, number of positive hemoculture more than 2 specimens, and Staphylococcus aureus septicemia, were significantly associated with IE in multivariate analysis (Figure 1) and were utilized in the prediction model. The AUROC of prediction models were 0.943 and 0.865 in training and test sets, respectively. Conclusions Our prediction model based on clinical risk factors can precisely predict IE in patients with GPB. Using this model allows clinicians to address patients at risk and guide decision-making in which cases need an urgent and comprehensive workup for IE or a wait-and-see strategy.Figure 1

Cardiac papillary fibroelastoma: a rare cause of ST-segment elevation myocardial infarction: a case report

Introduction and importance: Primary tumors of the heart are extremely rare occurrences. Among them, cardiac papillary fibroelastoma (CPF) is the second most common type. Although these tumors are usually benign, they can pose a risk of embolization, which may lead to severe complications like sudden death or embolization affecting the neurological, systemic, or coronary vasculature. Such complications can be life-threatening. Case presentation: In this report, the authors present the case of a 68-year-old woman who experienced ST-segment elevation myocardial infarction due to embolization from a large papillary fibroelastoma. To address the issue, the authors performed a minimally invasive surgical removal and resection of the aortic valve, followed by a histological examination to confirm the diagnosis. Clinical discussion: This case report discusses a rare occurrence of myocardial infarction caused by tumor embolization from a CPF. The patient presented with complete blockage of a coronary artery in the absence of atherosclerotic disease. Through a comprehensive workup, including transesophageal echocardiography, the CPF was identified as the source of embolization. Surgical resection of CPFs is curative, and recurrence has not been documented. Clinicians should consider CPFs in cases of coronary artery occlusion without atherosclerotic disease and employ transesophageal echocardiography for diagnosis. Prompt surgical intervention leads to an excellent prognosis and prevents recurrent embolization. Conclusion: This report emphasizes the importance of recognizing the potential complications associated with papillary fibroelastoma-induced embolization to the coronary arteries and highlights the need to mitigate the risk of such complications occurring.

Trigeminal Nerve Involvement in Bulbar-Onset Anti-IgLON5 Disease.

Anti-IgLON5 disease (IgLON5-D) may present with a bulbar-onset motor neuron disease-like phenotype, mimicking bulbar-onset amyotrophic lateral sclerosis. Recognition of their distinctive clinical and paraclinical features may help for differential diagnosis. We report 2 cases of atypical trigeminal neuropathy in bulbar-onset IgLON5-D. Trigeminal nerve involvement was assessed using comprehensive clinical, laboratory, electrophysiologic, and MRI workup. Both patients were referred for progressive dysphagia, sialorrhea, and hoarseness. They were treated with bilevel positive airway pressure for nocturnal hypoventilation. Patient 1 complained of continuous facial burning pain with allodynia, exacerbated by mastication and prolonged speech. Patient 2 reported no facial pain. Anti-IgLON5 autoantibodies (IgLON5-Abs) were positive in serum for both patients and CSF for patient 1. Cerebral MRI revealed bilateral T2 fluid-attenuated inversion recovery (FLAIR) hyperintensity and enlargement of trigeminal nerves without gadolinium enhancement in both patients. Needle myography showed fasciculations in masseter muscles. Blink-reflex study confirmed bilateral trigeminal neuropathy only in patient 2. Cortical laser-evoked potentials showed a bilateral small-fiber dysfunction in the trigeminal nerve ophthalmic branch in patient 1. In case of progressive atypical bulbar symptoms, the presence of a trigeminal neuropathy or trigeminal nerve abnormalities on MRI should encourage the testing of IgLON5-Abs in serum and CSF.

Myocardial bridge in a child with cardiac arrest and ventricular fibrillation: a bridge over troubled water?

Resuscitated cardiac arrest in a child triggers a comprehensive workup to identify an aetiology and direct management. The presence of a myocardial bridge does not automatically imply causation. Careful determination of the haemodynamic significance of the myocardial bridge is critical to avoid an unnecessary sternotomy and to provide appropriate treatment.

H - 26 Cognitive Functioning Following Bariatric Surgery in a Bilingual, Spanish, and English - Speaking, Patient: a Case Study.

Overall, 256,000 bariatric surgeries were completed in the United States in 2019 (ASMBS, 2023). Bariatric surgeries are effective in reducing morbidity, prolonging life, and improving cognition, particularly among patients with BMI >40 and those with BMI >35 and obesity-related complications (Handley et al., 2016; Cornejo-Pareja et al., 2021). Nevertheless, up to 16% of patients undergoing bariatric procedures experience neurological sequelae (Thaisetthawatku et al., 2004) that is likely secondary to surgery-related nutritional deficiencies (Gasmi et al., 2022). Although neuropsychological assessments may help to identify postsurgical cognitive changes, cultural and linguistic differences may preclude reliable and valid assessment of non-native English-speaking persons. A Spanish-dominant 38-year-old, right-handed, female reported diminished attention, reduced thinking speed, and memory difficulties that were interfering with her daily functioning. She completed a thorough Clinical Interview (both individually and with collaterals), Record Review, and a comprehensive neuropsychological workup. She demonstrated multi-domain impairment (>1.5S.D. below the normative mean), suggesting a possible dementia or encephalopathy. When her cognitive profile was interpreted in the context of her medical history, further testing was recommended to rule out reversible etiologies. Interdisciplinary collaborations with primary care and gastroenterology revealed nutritional deficiencies that had persisted for over 18months after bariatric surgery and that were not fully resolved with regular oral vitamin consumption. Cultural and linguistic differences were relevant when assessing cognitive changes in non-native English-speaking persons, and in helping to determine whether pharmacological and behavioral interventions are ameliorating these complications. Practical considerations of these high-stakes assessments will be discussed from neuropsychological, psychosocial, and ethical perspectives.

Unmasking Hypoglossal Nerve Schwannomas Mimicking Submandibular Salivary Gland Tumors: Case Report of a Rare Presentation and Surgical Management

Background: Schwannomas are solitary neurogenic tumors originating from the myelin-producing cells of the neural sheath. Hypoglossal nerve schwannomas are exceedingly rare, particularly those extracranially originating and mimicking a submandibular salivary gland tumor. Methods: We report the case of a 31-year-old female who presented to our ENT department with a painless swelling in her left submandibular region that has persisted for approximately five months. Discussion: Due to the rarity of these tumors and their unique nature, a comprehensive diagnostic workup is imperative for accurate diagnosis. Surgical excision remains the gold standard treatment. Conclusions: Extracranial hypoglossal nerve schwannomas represent a rare clinical entity requiring a thorough diagnostic process for precise identification. The preferred treatment strategy for managing hypoglossal gland schwannomas involves complete tumor excision while preserving the facial nerve.

SAT172 Unmasking A Pediatric Disease In Adult, A Belated Diagnosis

Abstract Disclosure: H. Syed: None. P. Au: None. M.J. Gardner: None. Background: Glycogen storage diseases (GSD) are a rare group of diseases that change the way the body uses and stores glycogen. They are usually diagnosed in the pediatric population. Hypoglycemia can be a sign. Clinical Case: A 32 year old female presented with worsening and more frequent episodes of hypoglycemia. She had no history of diabetes and was not on any hypoglycemic agents. She had been having episodes of spontaneous hypoglycemia since childhood and would get symptomatic as well. No comprehensive workup had been done prior. The episodes were becoming more frequent. A blinded continuous glucose monitor was placed on the patient to monitor her glucose levels. Results indeed showed few episodes of hypoglycemia with glucose levels in the 40s. Interestingly, she also had postprandial hyperglycemia with glucose level above 180 following an episode of hypoglycemia. She underwent a 72 hour fast in the hospital and became hypoglycemic within 24 hours with a low blood glucose of 55, consistent with hypoglycemia, and she was also symptomatic as well. At the same time, her beta hydroxybutyrate increased to 3.91 mmol/L, consistent with ketosis. Her insulin level and C-peptide level at the time of hypoglycemia were 4.35 mcunit/mL and 0.239 nmol/L, respectively, and thus insulinoma was ruled out. She next underwent a mixed meal study during which her postprandial blood glucose increased to at least 198 indicating postprandial hyperglycemia. At the same time, patient's postprandial lactate also elevated to 4 mmol/L, consistent with lactic acidosis. Her symptoms of hypoglycemia resolved once her blood sugar (BG) improved. She met criteria for Whipple’s triad. She also had had an 8 am cortisol of 13.06 mcg/dL and had an appropriate response to the ACTH stimulation test with a 60 minute post cortisol above 20 mcg/dL, thus ruling out adrenal insufficiency as a cause of hypoglycemia. These findings of the 72 hour fast that resulted in hypoglycemia, followed by postprandial hyperglycemia with lactic acidosis are consistent with Glycogen Storage Disorder Type 0. Treatment involves intake of uncooked cornstarch with protein. Patient incorporated both uncooked cornstarch along with increasing amount of protein in her diet and started using a continuous glucose monitor with alarm to monitor her BGs. As a result her episodes of frequent hypoglycemia improved. Conclusion: This case illustrates a rare case of hypoglycemia in an adult that was not thoroughly investigated when she was in her childhood and adolescence. This case teaches the importance of being familiar with pediatric conditions since it is possible that pediatric conditions, especially if they are missed by providers and not appropriately diagnosed. Presentation: Saturday, June 17, 2023

FRI459 Sperm-Carried IGF2: Towards The Discovery Of The Spark That Gives Rise To Life

Abstract Disclosure: R. Cannarella: None. O.J. Rando: None. S. Chamayou: None. S. La Vignera: None. R.A. Condorelli: None. A.E. Calogero: None. Background. Infertility is a public health problem affecting 15% of couples of childbearing age. In half of the cases, the male factor is a primary or contributing cause. Unfortunately, despite a comprehensive diagnostic workup, the causes of male infertility remain unclear in a large percentage of cases, thus suggesting the urgent need for further research. Spermatozoa have now been shown to carry key RNAs that may play critical roles in the development of the embryo. In this contest, a potential key growth regulator is insulin-like growth factor 2 (IGF2) whose gene is highly conserved and paternally imprinted. The gene encoding for IGF2 is involved in growth and proliferation and we have already demonstrated that it is expressed in human spermatozoa (DOI: 10.3389/fendo.2022.1010796). Aim. To evaluate the impact of sperm-carried IGF2 on early embryo growth kinetics and gene expression. Materials and methods. Patients undergoing intracytoplasmic sperm injection (ICSI) for idiopathic or male factor infertility were enrolled. Couples with female factor infertility were excluded. Following clinical practice, an aliquot of the left-over semen samples used for ICSI was used to analyze the IGF2 mRNA levels. The kinetic parameters of each embryo development were recorded and correlated with the amount of IGF2 mRNA measured in the same swim-up spermatozoa used for ICSI. Transcriptome analysis of blastocyst obtained from parthenotes collected from twelve-week-old superovulated mice was performed after incubation with recombinant human IGF2 (rhIGF2) protein (Group 1, n=40) or vehicle (Group 2, n=40) or injection with Igf2 plus Gfp (encoding for a fluorescent protein) mRNAs (Group 3, n=20) or Gfp mRNA only (Group 4, n=20). Results. In total, 16 patients were enrolled and 131 embryos were collected. We found a significant negative correlation between sperm IGF2 mRNA levels and pronucleus fading time (tPN) (r= -0.2572, p= 0.0078, n=106 embryos) and between sperm IGF2 mRNA and time of 2-cell embryo (t2) (r= -0.2368, p= 0.0145, n=106 embryos). In contrast, sperm IGF2 mRNA levels did not correlate with t3, t4, t5, t6, t7, t8, t9, t morula (tM), t blastocyst (tB), and time of expanded blastocyst (tEB). On transcriptome analysis, 501 and 101 genes were differentially expressed between Group 1 and Group 2, and between Group 3 and Group 4, respectively. Pathway enrichment analysis revealed several differentially expressed genes that trigger embryo growth and development, endoderm and mesoderm differentiation, angiogenesis, and sustaining proliferative signaling. Conclusions. Sperm-carried IGF2 triggers the expression of genes involved in early embryo development and improves embryo kinetics. This evidence may shed light on the etiology of apparently idiopathic couple infertility, since low sperm-carried IGF2 levels may be responsible for the impairment of early embryo growth and development. Presentation Date: Friday, June 16, 2023

SAT156 Two Cases Of Hypoglycemia From Inhalation Of Heroin Adulterated With A Sulfonylurea

Abstract Disclosure: K. Kim: None. J. Hwang: None. S. Sam: None. Context: Hypoglycemic disorders in non-diabetic patients are rare. In the setting of concomitant illicit opioid abuse, hypoglycemia is highly unusual and an underlying cause should be systematically investigated. Objective: We report two separate cases of non-diabetic women both admitted to our intensive care unit for critical hypoglycemia secondary to inhaled heroin containing sulfonylureas. Case 1—A 51 year old female with a history of heroin addiction (on methadone) was brought to the emergency department with altered mental status. She was found to have refractory hypoglycemia and was transferred to the medical intensive care unit (MICU) for monitoring. She reported poor appetite and food intake in the past week and endorsed consuming one alcoholic beverage the night before. Case 2—A 61 year old female with a history of heroin and cocaine abuse was found by the paramedics at home with a decreased level of responsiveness and blood sugar of <30 mg/dL who also required MICU admission. She endorsed using heroin, cocaine and substantial alcohol 2 days prior to admission at a party. She reported 2 episodes of hypoglycemia in the past requiring hospitalization, with no known cause. Kidney and liver disease were ruled out in both subjects. A thorough history including illicit drug use and critical blood samples at the time of hypoglycemia including drug toxicity screen, sulfonylurea screen were obtained. Labs demonstrated an insulin-mediated hypoglycemia and positive sulfonylurea screen for glipizide in both patients. Results: Because of their non-diabetic status, their compelling history and the results of their comprehensive laboratory work-up, we conclude that these subjects had a common exposure- insufflation of heroin contaminated with an oral hypoglycemic agent shortly before their admissions with critical hypoglycemia and clinical instability. Conclusions: This is the first report of hypoglycemia related to inhalation of heroin adulterated with the sulfonylurea glipizide. Frequently heroin is intentionally mixed with other agents (diphenhydramine) to increase the volume for sale, optimize the drug uptake or to ease the side effects. These cases highlight the importance of obtaining a thorough clinical history including potential illicit drug use, acquiring timely and appropriate laboratory samples for toxicologic analysis, and interpreting the findings to curb a potentially deadly epidemic. Presentation: Saturday, June 17, 2023

Oncocytoma: A Mystifying Parotid Gland Tumour

Oncocytoma is a rare salivary gland tumor consisting of oncocytes with many hyperplastic mitochondria. It usually occurs in the parotid gland. Very few cases of parotid oncocytoma have been reported in literature. Because of its rarity (<1-2% of salivary gland tumors) and clinical presentation of the tumor. Clinical diagnosis is often challenging due to the likeness of oncocytoma to other benign and low-grade malignant salivary gland tumors there is a tendency among the clinicians to misdiagnose it as pleomorphic adenoma, hemangioma, or other forms of oncocytosis. Previously published articles had all agreed on the reality of this lesion occurring over the parotid gland. The paper aims to review previously published cases of oncoytoma to provide a better insight regarding demographic, clinicopathological, radiological and histological features of this rare tumor of parotid gland. A systemic review of English literature was performed after using a sensitive search strategy involving two different databases: google scholar and PubMed. A total number of 9 cases were included. The tumour is mostly presented in old age as a slowly growing tumour (mean duration 3.17 years) and showed a slightly higher female predominance (Female:Male=1.25:1). They were mostly located over superficial lobe,100%. Conventional histological variant has only been reported. Complete surgical excision was performed for all the cases without any reports of recurrence or malignant transformation. Imaging studies diagnosed the lesion as a benign tumor. Only histopathological examination can confirm it. Definitive histology examination concludes to oncocytoma. Furthermore, our aim is to bring to the forefront how these lesions require a comprehensive workup and how to choose the best treatment strategy. Mugda Med Coll J. 2023; 6(1): 30-36

A-318 Pseudo-hypertriglyceridemia in a 2-year-old Male with Global Developmental Delay, Myopathy and Adrenal Hypoplasia

Abstract Background Pseudo-hypertriglyceridemia is an overestimation of serum triglyceride levels due to laboratory assays that measure free glycerol concentrations instead of triglycerides directly. Consequently, conditions presenting with elevated levels of endogenous or exogenous free glycerol, such as glycerol kinase deficiency, result in an overestimation of serum triglycerides. Glycerol kinase deficiency (GKD) is caused by pathogenic variants of the GK gene on chromosome Xp21. Three forms of GKD are recognized, characterized as infantile, juvenile, and adult forms. While the juvenile and adult forms are recognized as isolated GKD, the infantile form manifests itself as part of the Xp21.3 contiguous gene deletion syndrome, also known as complex GKD. This syndrome is composed of genes associated with Duchenne muscular dystrophy (DMD), X-linked congenital adrenal hypoplasia (NR0B1), and intellectual disability (IL1RAPL1). GKD is characterized biochemically by hyperglycerolaemia and glyceroluria. Case Description A 2-year-old male presented to the genetics clinic with a history of global developmental delay (gross motor and speech), axial hypotonia, poor head control and inability to sit unassisted or walk. Significant findings on examination included a startled appearance, absent eyebrows and temporal thinning, high forehead, frontal bossing, axial hypotonia and peripheral hypertonia. Laboratory findings included elevated creatine kinase (CK) of 14809 units/L (normal 27–160 units/L), aspartate aminotransferase (AST) of 307 (normal 20–60 units/L), alanine aminotransferase (ALT) 265 (normal 15–45 units/L), Adrenocorticotropic Hormone (ACTH) 156 (normal 6–48 pg/mL), and elevated triglycerides at 683 (normal 44–157 mg/dL). There was also a family history of developmental delay and intellectual disability in patient's mother and younger sister. Method Triglycerides are commonly measured indirectly with different enzyme reagents. The Triglycerides in this boy were measured by an automated chemistry analyzer based on a colorimetric serial enzymatic reaction including lipase, glycerol kinase and L-α-glycerol-phosphate oxidase1. Urinary organic acids profile including glycerol was extracted from acidified urine (pH 1-2) using diethyl ether. Organic extracts are then evaporated to dryness under nitrogen and trimethysilyl derivatized by the addition of N, O-bis (trimethylsilyl) trifluoroacetamide with 1% trimethylchorosilane (BSTFA/TMCS) and analyzed by gas chromatography-mass spectrometry (GC-MS). Results A comprehensive work-up including qualitative urinary organic acid analysis and chromosomal microarray was carried out. Urinary organic acids analysis revealed very abnormal accumulation of glycerol. Chromosomal microarray results showed a 4.2 Mb deletion of Xp21.3p21.1 (29296579-33551038) including complete copies of GK, DMD, and NR0B1 genes as well as multiple exons of IL1RAPL1. This confirmed his GKD as part of the Xp21 continuous gene deletion syndrome. Elevated triglycerides were then recognized as pseudo-hypertriglyceridemia after the diagnosis. Mild glyceroluria is also observed in the younger sister of this patient. Discussion and Conclusion This case highlights the importance recognizing pseudo-hypertriglyceridemia and diagnostic challenges. Earlier identification through urine organic acid analysis could have been made. The combination of clinical presentations and increased glycerol should cause suspicion for GKD. Female carriers of this X-linked disorder need to be evaluated for intellectual disability, as seen in this patient's mother and younger sister.

A unique case of a fulminant clonal CD8-positive T-cell lymphoproliferative disorder with CNS involvement

BackgroundThis is a unique case that describes the presentation, investigations, and disease trajectory of a fatal, clonal CD8-positive T-cell lymphoproliferative disorder in an otherwise healthy and immunocompetent patient with Epstein-Barr virus seronegative status. Central nervous system involving T-cell lymphoproliferative disorders are rare and typically encountered in the setting of immunocompromise. These disorders are often associated with aggressive cytomorphological features and characteristic magnetic resonance imaging patterns, which were not seen in this case.Case presentationHere we describe a case of a 65 year-old male presenting with neuropsychiatric symptoms, truncal ataxia, and falls who’s bone marrow, cerebrospinal fluid, and brain biopsy were consistent with a clonal CD8-positive T-cell lymphoproliferative disorder that did not meet existing World Health Organization criteria for classification as T-cell lymphoma. The patient was treated with intrathecal methotrexate resulting in transient improvement of his symptoms followed by disease progression and death related to aspiration.ConclusionsThis case highlights the importance of urgent and comprehensive work-up in patients with clinical features suggestive of lymphoma with central nervous system involvement, despite atypical imaging features and lack of cytomorphological features satisfying current World Health Organization classification criteria.

Orthosurgical synergism in the management of severe skeletal Class-III malocclusion- A case report

: What is now known as a Class-III malocclusion was initially recognized by Pierre Fauchard. True Class-III malocclusion is a genetically based condition that manifests in childhood. As the youngster reaches the teenage growth spurt, it becomes more obvious. Typically, we will discover a parent or grandparent who is dealing with the same issue. Class-III malocclusion, however, is not a disease. The abnormality itself is a compensatory mechanism to make up for variation that has happened at some point during the course of the individual's development.The case presented here demonstrates the importance of presurgical decompensation, surgical planning, including cephalometric predictions, and mock surgery in the management of severe skeletal Class-III malocclusion. The treatment included comprehensive orthodontic and surgical workup that included bilateral sagittal split osteotomy for mandibular setback of 3mm and LeFort-I osteotomy for maxillary advancement of 3mm. Class-I jaw relationships with a pleasing profile and correctly aligned arches were attained after 2 years of detailed treatment. This led to an aesthetic improvement and a significant increase in the patient's confidence. Class-III skeletal malocclusions can be corrected surgically or through camouflage. However, an ortho-surgical approach may be necessary if the issue cannot be resolved with orthodontics alone. When done correctly, bi-jaw surgery has repeatedly been shown to be quite successful.

DNA methylation profiling to determine the primary sites of metastatic cancers using formalin-fixed paraffin-embedded tissues

Identifying the primary site of metastatic cancer is critical to guiding the subsequent treatment. Approximately 3–9% of metastatic patients are diagnosed with cancer of unknown primary sites (CUP) even after a comprehensive diagnostic workup. However, a widely accepted molecular test is still not available. Here, we report a method that applies formalin-fixed, paraffin-embedded tissues to construct reduced representation bisulfite sequencing libraries (FFPE-RRBS). We then generate and systematically evaluate 28 molecular classifiers, built on four DNA methylation scoring methods and seven machine learning approaches, using the RRBS library dataset of 498 fresh-frozen tumor tissues from primary cancer patients. Among these classifiers, the beta value-based linear support vector (BELIVE) performs the best, achieving overall accuracies of 81-93% for identifying the primary sites in 215 metastatic patients using top-k predictions (k = 1, 2, 3). Coincidentally, BELIVE also successfully predicts the tissue of origin in 81-93% of CUP patients (n = 68).

Novel peeling skin condition in neonatal Pacific walruses, Saint Lawrence Island, Alaska, USA.

We describe here a novel peeling skin condition (PSC) in 2 neonatal Pacific walruses (Odobenus rosmarus subsp. divergens). Macroscopically, calves had various degrees of peeling skin exacerbated by mechanical trauma. Lesions occurred in areas subject to friction: ventrum, fore- and hindflippers, and associated joints. Histopathologic features included pseudocarcinomatous epithelial hyperplasia with orthokeratotic hyperkeratosis. Bacterial cocci were present within the stratum corneum. A few intraepidermal clefts were present. Inflammation, epidermolysis, and vasculopathies were not observed. PCR assays were negative for vesivirus and for Staphylococcus aureus exfoliative and toxic shock syndrome toxins. Tissue samples were cultured and bacteria isolated and identified by MALDI-TOF MS as Carnobacterium maltaromaticum, Psychrobacter phenylpyruvicus, Globicatella sanguinis, Streptococcus phocae, Pseudomonas spp., Rahnella aquatilis, and Escherichia coli. Given the young age of the calves and their clinical presentation, congenital ichthyosis was suspected. No genetic differences were detected for sequenced portions of keratin genes (keratin gene K10) between diseased and normal walrus skin. This rare PSC in neonatal Pacific walruses is recognized as novel by indigenous Alaskan marine mammal hunters of the Bering Strait region. A comprehensive diagnostic work-up of future case materials is needed to characterize the underlying biochemical defect(s).

Time to TAVI: streamlining the pathway to treatment

IntroductionSevere aortic stenosis is a major cause of morbidity and mortality. The existing treatment pathway for transcatheter aortic valve implantation (TAVI) traditionally relies on tertiary Heart Valve Centre workup. However,...

Multidisciplinary management of inducible laryngeal obstruction and breathing pattern disorder.

Inducible laryngeal obstruction and breathing pattern disorder are common causes of breathlessness.Inducible laryngeal obstruction is an inappropriate, transient, reversible narrowing of the laryngeal area that causes breathlessness and laryngeal symptoms.Breathing pattern disorder is an alteration in the normal biomechanical patterns of breathing that results in intermittent or chronic symptoms, which may be respiratory and/or non-respiratory.People with inducible laryngeal obstruction or breathing pattern disorder often have other comorbidities that will also need addressing.Multidisciplinary assessment and treatment is essential for comprehensive workup and holistic care.Timely assessment and diagnosis can prevent unnecessary medication use and hospital admissions and facilitate effective management of the condition using reassurance, advice, education, breathing retraining and vocal exercises.

Advancing diagnosis and management of liver disease in adults through exome sequencing

Whole-exome sequencing (WES) is an effective tool for diagnosis in patients who remain undiagnosed despite a comprehensive clinical work-up. While WES is being used increasingly in pediatrics and oncology, it remains underutilized in non-oncological adult medicine, including in patients with liver disease, in part based on the faulty premise that adults are unlikely to harbor rare genetic variants with large effect size. Here, we aim to assess the burden of rare genetic variants underlying liver disease in adults at two major tertiary referral academic medical centers. WES analysis paired with comprehensive clinical evaluation was performed in fifty-two adult patients with liver disease of unknown etiology evaluated at two US tertiary academic health care centers. Exome analysis uncovered a definitive or presumed diagnosis in 33% of patients (17/52) providing insight into their disease pathogenesis, with most of these patients (12/17) not having a known family history of liver disease. Our data shows that over two-thirds of undiagnosed liver disease patients attaining a genetic diagnosis were being evaluated for cholestasis or hepatic steatosis of unknown etiology. This study reveals an underappreciated incidence and spectrum of genetic diseases presenting in adulthood and underscores the clinical value of incorporating exome sequencing in the evaluation and management of adults with liver disease of unknown etiology. S.V. is supported by the NIH/NIDDK (K08 DK113109 and R01 DK131033-01A1) and the Doris Duke Charitable Foundation Grant #2019081. This work was supported in part by NIH-funded Yale Liver Center, P30 DK34989.

SDPS-47 CIRCULATING TUMOR CELL ANALYSIS FROM THE CEREBROSPINAL FLUID INFORMS EARLY DIAGNOSIS, TREATMENT AND PROGNOSIS IN LEPTOMENINGEAL CARCINOMATOSIS

Abstract INTRODUCTION Leptomeningeal carcinomatosis (LMC) is an aggressive pattern of recurrence with limited survival. Early detection by traditional CSF (cerebrospinal fluid) cytology is poor. We evaluated CSF circulating tumor cells (CTCs) with a commercially available assay (CNSideTM) and subsequent molecular profiling on captured CTCs, to determine if CTC analysis would lead to early detection, identification of therapeutic targets, and improved treatment outcomes. METHODS We analyzed 58 patients with carcinoma who were referred to Neuro-oncology clinic for evaluation for LMC, and underwent comprehensive work-up with CSF sampling (traditional cytology and CTCs), brain and spine MRI, and neurologic examination, and were followed for survival. RESULTS 28/58 were diagnosed with LMC (breast n=16, Lung n=9, other n=3). 24/28 were female. Median KPS was 80. 15/16 breast cancer patients were HER2- on initial systemic cancer diagnosis. The mean time to LMC from cancer diagnosis was 70 months. In the patients with LMC, CTCs were positive in 96%, compared to traditional cytology, which was positive in 64%. Molecular analysis of the CTCs in 15 patients with HER2- primary tumors detected HER2+ amplification in 3/15 patients. 14/28 patients received first line therapy for LMC with radiation + systemic chemotherapy + intrathecal chemotherapy, and 8/28 received systemic chemotherapy + intrathecal chemotherapy. 6/28 received other combinations. The overall median progression-free survival (PFS) was 5.3 months and the overall survival (OS) was 7.7 months from LMC diagnosis (breast PFS 4.5 months, OS 6.3 months; Lung PFS 5.3 months, OS 23.5 months). CONCLUSION CTC detection had superior sensitivity compared to traditional cytology, allowing for earlier detection of LMC and consequently earlier treatment. Molecular analysis of CTCs can allow for identification of therapeutic targets specific to the CSF, such as intrathecal trastuzumab for HER2+ LMC. PFS and OS in our cohort with this approach suggested improved survival compared to historical controls.

Adrenal and periadrenal schwannoma: histological, molecular and clinical characterization of an institutional case series.

Adrenal schwannoma (AS) and periadrenal schwannoma (PAS) are exceedingly rare Schwann cell tumors that develop from the adrenal medulla and periadrenal peripheral nerves respectively. The underlying genetic events are elusive. We searched our institutional database for AS/PAS cases and reviewed the histology and clinical outcome. Comprehensive molecular work-up was performed. We found reports of 4 AS/PAS cases diagnosed between 1992 and 2022 among the 1248 adrenal lesions submitted for histopathology during the same time period (0.32%). Two patients were male, two were female, and the age span was 59-80 years. Median size was 70 mm (range 50-100 mm), and from a radiology perspective, the lesions were initially suspected of malignant lesions originating from either adrenals or kidneys. Hormonal analyses were normal in all cases. Histologically, three cases were annotated as cellular AS or PAS, and one case was annotated as microcystic AS. Molecular characterization using focused next-generation sequencing did not identify SMARCB1 or NF2 mutations, alterations previously associated to schwannoma at other anatomical sites. The postoperative period was without complications for all patients, and follow-up did not show any signs of relapse or metastatic disease. AS/PAS are rare neoplasms that are most often benign, and the molecular etiology is most likely not related to mutations in established schwannoma-related genes. Since these tumors may be misinterpreted as malignant, knowledge of this entity is essential for radiologists, endocrinologists, surgeons and pathologists.