Workup Of Disease Research Articles

Metastatic Melanoma of Unknown Primary with Plasmacytoid Morphology Presenting as Acute Liver Failure

Abstract Introduction/Objective Viral hepatitis, drug toxicity, and autoimmune disorders are common etiologies of acute liver failure (ALF). Very rarely, a cause like metastatic melanoma may present as a primary driver of ALF. Malignant melanoma is histologically diverse and plasmacytoid melanoma is an unusual variant that may present as a solitary tumor or metastatic disease. Methods/Case Report A 48-year-old female presented with 2 weeks of right upper quadrant pain, nausea, coffee ground emesis and bleeding per rectum. She had no history of liver disease or alcohol use. On presentation, AST was 83 U/L, ALT was 29U/L, ALP was 159U/L and total bilirubin was 12.7g/dl. Viral hepatitis panel, HIV and chronic liver disease workup was negative. Esophagogastroduodenoscopy and colonoscopy showed no sources of bleeding. She was diagnosed with decompensated cirrhosis, ALF, and acute kidney injury from hepatorenal syndrome. Cirrhosis and multifocal indeterminate T1 hyper/T2 hypo intense lesions (dysplastic or regenerative nodules) were seen on MRI. Liver biopsy revealed metastatic melanoma. Almost entire liver parenchyma on biopsy was replaced by a population of neoplastic cells with plasmacytoid features. Immunostaining was positive for MART-1, HMB45 and SOX-10. Staining for Pan Cytokeratin and CK-7 highlighted the bile ducts and negative staining was seen for CK20, CD3, CD20, PAX-8, GATA-3, CDX-2 and P63. No primary lesion was found. It was deemed unlikely that she would benefit from therapy before complications occur. She passed away in 16 days. Results (if a Case Study enter NA) NA Conclusion In most cases of ALF associated with malignant melanoma, the liver may have a seemingly normal appearance on imaging studies due to the distinctive histology of leukemoid tumor infiltration within the liver sinusoids, resulting in sinusoidal obstruction and subsequent hepatocellular dysfunction. The rapidity of liver failure in these cases is related to the replacement of liver parenchyma by malignant cells. The plasmacytoid morphology is seen in a variety of malignancies and to avoid a potential misdiagnosis of an aggressive malignant melanoma, it is imperative to perform a thorough histopathological evaluation aided with immunohistochemistry. It is important to keep in mind that the potential involvement of malignant tumor cell infiltration may cause ALF and early histological assessment with a liver biopsy may be of paramount significance and may possibly change the course of the disease.

6588 Insulin Autoimmune Syndrome Presenting with Severe Insulin Resistance and Recurrent Diabetic Ketoacidosis

Abstract Disclosure: E. Looi: None. R. Rosenberg: None. S. Sugar: None. H. Stone: None. A.W. Michels: None. D. Saxon: None. Background: Insulin autoimmune syndrome (IAS) is a rare cause of severe insulin resistance and is typically associated with intermittent hypoglycemia due to insulin antibodies (IA) with high binding capacity and low insulin affinity. However, consideration should be given for atypical presentation of IAS or co-presentation of IAS with type B insulin resistance syndrome (TBIRS) in the absence of hypoglycemia, as described in this case. Case: A 78-year-old African American female (BMI 21 kg/m2) with poorly controlled type 2 diabetes (A1c 11%) experienced recurrent episodes of diabetic ketoacidosis (DKA) despite adherence to escalating insulin doses (310 units daily, 5 u/kg/day). She was referred to endocrinology and continuous glucose monitoring revealed consistently elevated glucose levels (300-400 mg/dL) without hypoglycemia. She had normal renal function, hepatic function, and lipid panel. During a subsequent hospitalization, she required insulin drip rates of 50-70 u/hr. Insulin resistance workup revealed significantly elevated IA level (8.346, normal ≤ 0.010) measured using a fluid-phase radiobinding assay with high insulin binding capacity (1040 U insulin-binding/L blood) and low insulin binding affinity (1.9x107 M), which supported the diagnosis of IAS. Rheumatologic workup for other autoimmune diseases was negative. Due to recurrent DKA episodes, severe insulin resistance without obvious alternative cause, and lack of hypoglycemic events despite low IA binding affinity, co-morbid TBIRS was considered. As there are no commercially available insulin receptor antibody (IRAb) assays, diagnosis could not be confirmed before her condition worsened, and she was admitted for another episode of DKA within a week of being discharged. Due to clinical deterioration and high suspicion for IAS ± TBIRS, treatment with a combination of immunosuppressive agents was initiated in accordance with an NIH protocol (Klubo-Gwiezdzinska J, et al. 2018). Intravenous immune globulin (0.5g/kg/day) was administered over 2 days which resulted in a brief reprieve and followed by significant relapse. Two doses of rituximab (750 mg/m2) and 2 steroid pulses (dexamethasone 40 mg PO daily for 4 days) were then administered 2 weeks apart. Cyclophosphamide 100 mg daily was also started. Her hyperglycemia and insulin requirements subsequently improved, and she was eventually discharged with good glycemic control on a total daily dose of 40 units of insulin (0.5 u/kg/day), an 87.1% reduction in daily insulin requirement. Conclusion: This case demonstrates that IAS - although classically associated with hypoglycemic episodes - may also present with severe insulin resistance and recurrent DKA without hypoglycemia. Whether characterized by high IA binding capacity and affinity or coexisting with IRAb, a combination of immunosuppressants proved effective in treating both TBIRS and IAS in this instance. Presentation: 6/3/2024

6472 Methimazole Induced Agranulocytosis: Uncommon Complication of a Common Medication

Abstract Disclosure: R. Kaur: None. L. Kaur: None. A. Sridhar: None. T. Chaudhary: None. N. Patel: None. Methimazole (MMI) induced agranulocytosis is a rare and life threatening adverse effect that usually occurs within 3 months of drug initiation and can rapidly lead to overwhelming infection. It is reported in 0.1 to 0.5 % of patients on treatment with methimazole. MMI is a standard drug used in graves disease and toxic multinodular goiter. We report a case of MMI induced agranulocytosis in an elderly female with recently diagnosed toxic multinodular goiter. A 66 year old female with past medical history of recently diagnosed toxic multinodular goiter for which she was started on methimazole 80mg/day two months ago presented to the emergency department with chief complaint of severe sore throat associated with rapidly increasing pharyngeal pain and fever over the past 24 hours. She was lethargic, febrile with temperature of 102 F, tachycardic with heart rate of 115/minute and hypotensive with blood pressure of 108/64 mm Hg. Physical examination revealed diffuse pharyngeal and tonsillar erythema with bilateral purulent exudate with tender anterior cervical lymphadenopathy. Thyroid was enlarged, firm, irregular and nontender. Pulmonary, cardiac and abdominal exam was unremarkable. Lab work showed severe leukopenia with WBC count of 1,600/mm3, neutropenia with absolute neutrophil count of 0.0 x 1000/ul (normal range 1.8-7.3 x 1000/ul) and erythrocyte sedimentation rate and C reactive protein were both elevated. Blood cultures and fungal cultures showed no growth. Urinalysis and urine culture were both unremarkable. She had an extensive haematological, rheumatological and infectious disease workup for neutropenia, which was largely unrevealing. Rapid streptococcal testing was negative but throat cultures grew beta haemolytic streptococci. Treatment included suspending methimazole, administering antimicrobial therapy with piperacillin - tazobactam, acyclovir and fluconazole. She was also started on a granulocyte colony stimulating factor. Patient presented satisfactory evolution with progressive increase in leukocyte count and remission of symptoms by day 5 of treatment, rendering further bone marrow testing unnecessary. Antibiotics were changed to oral amoxicillin-clavulanic acid after throat culture results were available and the patient was discharged in stable condition. One month after discharge she underwent total thyroidectomy for definitive cure and is currently followed up as an outpatient by endocrinology. The objective of this case report is to present an uncommon case of agranulocytosis secondary to use of methimazole and to increase awareness among the physicians about the need to consider this diagnosis in patients on this medication. It is also advised that these patients be educated about the drugs side effects, a practice that may avert suffering and unnecessary costs. Presentation: 6/3/2024

14-month-old female with anti-MDA5 juvenile dermatomyositis complicated by liver disease: a case report

BackgroundJuvenile Dermatomyositis (JDM) is a rare disorder with subtypes associated with different myositis-specific antibodies (MSAs) including anti-MDA5. Hepatic involvement in JDM is rare and has not previously been documented in anti-MDA5 JDM. There is a lack of formal research on treatment protocols for anti-MDA5 JDM, though tofacitinib is a highly regarded emerging therapy.Case presentationA previously healthy 14-month-old Hispanic female presented to a pediatric rheumatology clinic with eight months of worsening rash, weakness, periorbital edema, intermittent fevers, and weight loss. Her physical exam was notable for fever, thinning of hair, heliotrope rash, periorbital edema, violaceous macules on her bilateral elbows, forearms, arms, and knees, arthritis, Gottron’s sign, and hepatomegaly. The patient was admitted, and symptoms progressed to include hypoxemia. Subsequent workup was notable for ground glass opacities of bilateral lung fields on chest CT, myositis visualized on MRI and confirmed with muscle biopsy, and liver biopsy showing nonspecific signs of liver injury. After a thorough infectious disease workup to rule out concomitant infection, the patient was started on high-dose steroids and induction with cyclophosphamide. She responded well with disease remission maintained with tofacitinib in the outpatient setting.Discussion and conclusionsOur patient is notable due to her young age at presentation, histopathologically confirmed liver injury, and response to treatment. The case adds to the growing body of literature supporting tofacitinib for anti-MDA5 JDM in the pediatric population. Future research can better standardize effective treatment protocols and define the mechanism of liver involvement. For patients with nonspecific liver injury, muscular, and cutaneous disease, anti-MDA5 JDM should be considered in the differential diagnosis with treatment options including tofacitinib for confirmed cases.

Cerebral abscess in Down syndrome: a systematic review on treatment and prognosis. Illustrative case.

No universal protocol exists for treating cerebral abscesses in Down syndrome. An illustrative case supplemented with a systematic literature review on brain abscesses in Down syndrome is presented, comprising a total of 16 cases. Preoperative infectious disease workups, cardiac examinations including echocardiography, as well as reported surgical and antibiotic treatments were correlated in the reported cohorts. Overall, 18.8% of cases (n = 3) had no reported cardiac evaluation. The majority of cases were treated surgically (n = 8), with aspiration (n = 3), drainage (n = 2), or other operations (n = 3); 25% (n = 4) were treated with antibiotics only. Strikingly, 25% of cases (n = 4) reported neither surgical nor antibiotic therapy, a significantly higher rate compared to 0%-3% of patients with brain abscess in other reported cohorts. Half of the patients (n = 8) who died either lacked a cardiac evaluation or had existing heart conditions. This mortality rate was about 4 times higher than the rates observed in other studies. Down syndrome patients with cerebral abscess have a high morbidity rate, mainly due to cardiac disease. Therefore, early diagnostic workup, including echocardiography, allows proactive management with an improved outcome. https://thejns.org/doi/10.3171/CASE23394.

Discriminative performance of ocular surface staining and lid wiper epitheliopathy in dry eye disease: An investigator-masked, prospective registry-based, diagnostic accuracy study

PurposeTo evaluate the diagnostic performance of corneal and conjunctival staining, and lid wiper epitheliopathy (LWE) in detecting dry eye disease, as defined by the global consensus Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) criteria. MethodsA total of 2066 community residents (1285 females; mean ± SD age, 40 ± 19 years) were recruited in an investigator-masked, prospective registry-based, diagnostic accuracy study. Dry eye symptomology and ocular surface parameters were assessed in a single clinical session. The Sjögren's International Collaborative Clinical Alliance (SICCA) corneal and conjunctival staining scoring and Korb lid wiper epitheliopathy (LWE) grading were evaluated by an independent masked assessor. ResultsOverall, 807 (39 %) participants fulfilled the TFOS DEWS II criteria for dry eye disease, of which 178 (9 %) participants were classified as moderate-to-severe disease. The discriminative abilities of superior and inferior LWE (C-statistics, 0.724 and 0.712, respectively) were greater than corneal and conjunctival staining (C-statistics, 0.573 and 0.627, respectively). The Youden-optimal diagnostic cut-offs for the SICCA corneal and conjunctival staining scores were both ≥1, and the optimal thresholds for the Korb superior and inferior LWE grades were both ≥1. LWE was more commonly detected in both mild-to-moderate and moderate-to-severe dry eye disease, and demonstrated more consistent correlation with other ocular surface parameters across a broader range of disease severity. ConclusionsLWE demonstrates superior diagnostic performance relative to corneal and conjunctival staining. These findings would support the routine incorporation of LWE evaluation as part of the diagnostic workup of dry eye disease.

Unmasking an unusual presentation of Hodgkin’s lymphoma masquerading as ocular inflammation: a case report

BackgroundHodgkin’s lymphoma (HL) is an extremely rare cause of ocular inflammation that is usually not considered in the typical workup of uveitis and other eye diseases. A few cases of ocular inflammation were reported previously showcasing HL with absence of typical symptoms of HL at presentation. Acknowledging the potential ocular inflammation associated with HL can prompt ophthalmologists to broaden their diagnostic approach and collaborate with internal medicine departments to investigate this rare yet significant etiology.Case presentationA 17-year-old Caucasian woman presenting unilateral panuveitis was later diagnosed with HL. The ocular findings were non-necrotizing scleritis, anterior uveitis, vitritis, white/yellowish chorioretinal lesions, papillitis and vasculitis. A left supra-clavicular lymph node biopsy confirmed the diagnosis of nodular sclerosing Hodgkin’s lymphoma stage IIB. Other causes of uveitis were excluded. Chemotherapy led to remission of the disease and the ocular lesions became quiescent with persistent pigmented chorioretinal scars.ConclusionsHodgkin's lymphoma should be considered in the differential diagnosis of diseases that can occasionally be revealed by unilateral ocular inflammation. A comprehensive, multidisciplinary approach is key to properly assessing such cases.

Transabdominal ultrasound for the diagnostic workup of parenchymal pancreatic diseases.

This continuing medical education article highlights the central role of transcutaneous sonography in diagnosing parenchymal pancreatic diseases. It emphasizes the importance of in-depth knowledge of sonographic imaging of organ anatomy and a structured examination methodology, particularly for identifying acute and chronic pancreatitis and related complications. The article provides detailed guidance for optimized examination techniques and equipment settings, even under challenging conditions, and discusses the application of ultrasound in various scenarios of pancreatic diseases. Moreover, the relevance of advanced sonographic techniques such as high-frequency sonography, elastography, and contrast-enhanced sonography is illuminated in the context of expanded diagnostic workup.

Combined Cesarean Section and Splenectomy in a Patient with Massive Splenomegaly

Background To date, there is limited knowledge of patients with idiopathic splenomegaly in pregnancy, and the literature lacks cases of a combined cesarean section with splenectomy. The documented cases of splenomegaly in pregnancy often have infectious etiology such as that of malarial infection or an autoimmune component such as idiopathic thrombocytopenic purpura. This condition is life-threatening and complicates medical management, but its rarity has led to a paucity of management guidelines for patients with idiopathic splenomegaly in pregnancy. Objective The aim of this case is to provide novel insight into the management and outcomes of patients with idiopathic massive splenomegaly in pregnancy. Study Design This study is a case report with a review of the current literature on the reported cases of splenomegaly in pregnancy, splenectomy in pregnancy, and cesarean section with splenectomy. This case describes a history of pancytopenia and massive splenomegaly in a pregnant patient who underwent extensive workup with no clear etiology. This case additionally describes the course of care for this patient, including a combined cesarean section with splenectomy. We searched PubMed for all English language articles from 2000 to 2023, with search terms including “splenomegaly in pregnancy,” “splenectomy in pregnancy,” and “cesarean section and splenectomy.” Results In this patient’s case, despite an exhaustive infectious disease workup and evaluation for hematologic, inflammatory, and neoplastic causes, no clear etiology was identified. Delivery was deemed necessary at 34 weeks and 2 days gestation due to the patient’s severe, persistent pain, her worsening pancytopenia, and the risk of spontaneous splenic rupture during labor and delivery; our multidisciplinary team concluded that it was safer for both mother and baby to proceed with cesarean delivery and splenectomy in the early pre-term period. This patient’s pancytopenia improved within hours of spleen removal and has remained stable to date in outpatient follow-up. Baby Boy completed a NICU course of 22 days after requiring surfactant and respiratory support due to prematurity as well as monitoring due to maternal splenomegaly and thrombocytopenia. Conclusion This case offers valuable insights into managing patients with idiopathic splenomegaly during pregnancy and underscores the need for further investigation. Establishing clear delivery indications for these patients remains crucial, and prospective studies should evaluate the long-term impacts on both mother and child following combined splenectomy and cesarean delivery in the context of pancytopenia.

Accelerated musculoskeletal magnetic resonance imaging with deep learning-based image reconstruction at 0.55 T-3 T

Magnetic resonance imaging (MRI) is acentral component of musculoskeletal imaging. However, long image acquisition times can pose practical barriers in clinical practice. MRI is the established modality of choice in the diagnostic workup of injuries and diseases of the musculoskeletal system due to its high spatial resolution, excellent signal-to-noise ratio (SNR), and unparalleled soft tissue contrast. Continuous advances in hardware and software technology over the last few decades have enabled four-fold acceleration of 2D turbo-spin-echo (TSE) without compromising image quality or diagnostic performance. The recent clinical introduction of deep learning (DL)-based image reconstruction algorithms helps to minimize further the interdependency between SNR, spatial resolution and image acquisition time and allows the use of higher acceleration factors. The combined use of advanced acceleration techniques and DL-based image reconstruction holds enormous potential to maximize efficiency, patient comfort, access, and value of musculoskeletal MRI while maintaining excellent diagnostic accuracy. Accelerated MRI with DL-based image reconstruction has rapidly found its way into clinical practice and proven to be of added value. Furthermore, recent investigations suggest that the potential of this technology does not yet appear to be fully harvested. Deep learning-reconstructed fast musculoskeletal MRI examinations can be reliably used for diagnostic work-up and follow-up of musculoskeletal pathologies in clinical practice.

#281 AVF formation is a common complication of percutaneous ultrasound-guided renal biopsy: a single-center analysis of risk factors and clinical outcome

Abstract Background and Aims Percutaneous renal biopsy is a key procedure for the work-up of renal diseases. Among the possible complications of such procedure, prevalence, risk factors and clinical outcome of arterio-venous fistula (AVF) formation is unclear. We present here a single-center experience on renal biopsy-related complications with a focus on risk factors for AVFs formation and their management. Method We retrospectively analyzed all the kidney biopsies performed in our center between January 2012 and December 2022. All biopsies were conducted under real-time ultrasound (US) guidance by trained nephrologists. Kidney US and doppler mapping were performed routinely 6 and 24 hours post-procedure. In accordance with the description provided in the US report, AVFs were categorized into small, moderate, and high-flow rates. Patients’ comorbidities, histologic sample characteristics, blood tests results and the clinical course were recorded. Logistic regression was employed to investigate potential risk factors for complications. Results 1016 adult native renal biopsies were performed. The average age of patients was 55 ± 17 years, and 677/1016 (66.6%) were males. The histological sample was unsuitable in 29/1016 (2.9%) of the cases; moreover, prevalence of renal medulla and presence of large-caliber arteriole were observed in 88/1016 (8.7%) and 38/1016 (3.7%) of the samples, respectively. The most common complication was hematoma, detected by US in 175/1016 (17.2%), which was considered “complicated” in 21/1016 (2.1%) due to the association with macroscopic hematuria (n = 10), blood transfusion requirement (n = 8), or signs of active bleeding (n = 8), requiring embolization in 6/1016 patients (0.6%). AVFs were identified in 119/1016 (11.7%) biopsies; of these 20/119 (16.8%) required embolization after a median time of 16 days (IQR 5-65). Spontaneous resolution was documented in 65/119 (55%) of cases and occurred after a median of 27 days (IQR 15-49), with 50/55 (90.9%) of cases spontaneously resolving within the first month and the remaining cases no later than the fourth month (Fig. 1). High-flow AVFs more frequently necessitated angiographic intervention compared to moderate and small AVFs (75% vs 25% vs 7%), with a prolonged spontaneous resolution time (median 78 days; IQR 51-106) (Table 1). In the cases requiring embolization, the median creatinine level before and 6 months after procedure was respectively 1.7 mg/dL and 1.9 mg/dL (paired Wilcoxon signed-rank test: p = 0.908). In three cases post-embolization, a loss of renal vascularization at angiography higher than 30% was reported; however, even in these cases no differences in terms of renal function were observed at 6 months compared to the baseline. At multivariate logistic regression, hypertension (OR = 2,2; p = 0.003; 95% CI [1.3-3.7]), renal medulla prevalence (OR = 2,8; p = 0,001; 95% CI [1.6-4.8]), and large-caliber arteriole presence (OR = 2,9; p = 0,008; 95% CI [1.3-6.3]) were associated with a higher risk of AVFs, while obesity emerged as a protective factor (OR = 0,27; p = 0,013; 95% CI [0.1-0.8]). Conclusion AVF is a common complication following renal biopsy but therapeutic intervention is rarely required, as spontaneous resolution is typically observed within one month. In case of symptomatic or persistent AVFs, embolization may be required without an apparent impact on the renal function, at least in the short term. Hypertension and surrogate factors associated with a deeper penetration of the needle into the renal parenchyma are associated with an increased risk of AVF. Conversely, obesity was protective toward the risk of AVF development.

Neurosarcoidosis-Induced Winging Scapula: Efficacy of Infliximab Treatment in Addressing Multifaceted Challenges.

Sarcoidosis, a systemic granulomatous disease primarily affecting the respiratory and lymphatic systems, can rarely manifest as neurosarcoidosis either in isolation or alongside other systemic symptoms. Here, we describe the case of a 45-year-old male with a history of recurrent sinusitis refractory to antibiotics, who presented to the emergency department with sinus congestion and dysphagia. Clinical examination revealed left lower motor neuron facial palsy and enlarged submandibular salivary glands. Despite obtaining negative results from various antibody panels, the patient exhibited elevated Angiotensin Converting Enzyme levels of 83 nmol/kg/min. Additionally, computed tomography chest scans revealed bilateral hilar and mediastinal lymph node enlargement, findings consistent with sarcoidosis. Otorhinolaryngology evaluation for dysphagia confirmed left vocal cord palsy. Following a negative infectious disease workup, submandibular salivary gland biopsy confirmed sarcoidosis. Treatment with mycophenolate mofetil and oral steroids led to gradual improvement in salivary gland swelling, dysphagia, and facial palsy. However, worsening left shoulder pain prompted further investigation, revealing winging of the left scapula on repeat examination. Magnetic resonance imaging (MRI) of the cervical spine revealed a six mm hyperintensity in the left dorsal cord at the C5 level, suggesting possible neurosarcoidosis vs. demyelinating disease. Subsequently, the patient was prescribed anti-tumor necrosis factor alpha inhibitor infliximab. Subsequent MRI of the cervical spine, conducted six months after initiating Infliximab therapy, indicated resolution of the lesions. This positive outcome was supported by the patient's report of symptom improvement, notably reduced shoulder pain and improvement in left scapular winging. This case underscores the unusual co-occurrence of Bell's palsy and vocal cord palsy in the same patient, along with the potential contribution of neurosarcoidosis to the winged scapula. Additionally, it sheds light on the positive response of neurosarcoidosis to Infliximab therapy.

Nerve cross-sectional area in advanced uremic neuropathy: A nerve ultrasound pilot study.

Uremic neuropathy (UN) is a disabling neuropathy in end-stage kidney disease (ESKD) affecting the majority of patients receiving long-term hemodialysis (HD). One previous nerve ultrasound study reported an increased cross-sectional area (CSA) of the median nerve in moderate UN, while another study found enlarged sural nerves in small-fiber polyneuropathy associated with ESKD. The present cohort study aims to analyze bilateral CSA of multiple nerves in UN. Ten nondiabetic ESKD patients with UN on HD for at least 2years and 10 healthy age-matched controls underwent bilateral ultrasound examinations with CSA measurements in 13 arm and leg nerve sites. Nerve conduction studies (NCS) and the total neuropathy score (TNS) were recorded. Pearson's coefficient and the Mann-Whitney U-test were used to analyze correlations and compare groups. ESKD patients presented advanced neuropathic symptoms (mean TNS 15.9). NCS showed significantly reduced motor and sensory amplitudes in the UN group compared to the control group, and a slightly reduced nerve CSA was observed in 5 of 13 nerve sites (p<.05); the other nerve sites were not enlarged. Sural nerve CSA (p<.05) and sensory amplitude (p<.01) were negatively correlated with the TNS. Nerve enlargement was not observed in the present study in advanced UN. A reduced nerve CSA observed in the sural nerve suggests an axonal loss associated with long-term HD in ESKD. During clinical workup of an acute disease of the peripheral nervous system in ESKD patients, nerve enlargement might be attributable to other causes than chronic UN.

Abstract A009: Integrative drug screening and multi-omic characterization of patient-derived bladder cancer organoids reveals novel molecular correlates of chemotherapy response

Abstract Introduction: Predicting response to therapy for each patient’s tumor is critical to improving long-term outcomes for muscle-invasive bladder cancer (MIBC). Our objective is to establish ex vivo bladder cancer patient-derived organoid (PDO) models that are representative of patients’ tumors and determine potential efficacy of standard-of-care and curated experimental therapies. Methods: Tumor material was prospectively collected from consented patients with bladder cancer to generate short-term PDO models, which were screened against a panel of clinically relevant drugs in ex vivo 3D culture. Drugs were tested at the maximum plasma concentration (Cmax) in human trials, so as to provide physiologic relevance. When material was sufficient, cells were additionally tested using full dose response. The number of drugs screened was dependent upon amount of tissue available, with up to 34 drugs screened at Cmax and 9 drugs screened in dose response format. Multiomic profiling was utilized to validate the PDO models, establish the molecular characteristics of each tumor, assess gene expression (GEX) patterns between paired primary tissue and PDOs, and identify potential biomarkers of drug response using Pearson correlation coefficients and Kruskal-Wallis tests with Dunn’s post-hoc pairwise comparison testing. Results: 106 tumors were collected from 97 patients, with 65 samples yielding sufficient material for complete multiomic molecular characterization and PDO screening with 6 to 32 drugs/combinations. RNA sequencing and GSEA enriched pathways across organoids were compared to other published datasets, noting high levels of correlation between our organoid models and in particular the Cancer Cell Line Encyclopedia urethral lines. Moreover, analysis of subtype and mutation/copy number data further indicate that our organoid dataset is representative of the full spectrum of disease. RNA sequencing and subtyping of cultured organoids compared to patient tissue indicate that organoid models are representative of patient tissue and do not undergo subtype shifts in our short-term 3D cultures. Our drug screening results highlight the large spectrum of response to chemotherapies that in fact, clinically benefit only a small proportion of patients in the neoadjuvant setting. Utilizing an integrative approach, novel correlations between ex vivo drug responses and genomic alterations, GEX, and protein expression were identified, including a multiomic signature of gemcitabine response. Conclusions: Rapid organoid development, characterization, and drug screening allows for the prediction of therapeutic response in ~10 days following sample collection. Use of this technique on tissue provided during disease work-up may further guide selection of effective therapeutic agents in patients with bladder cancer, beyond the typical unranked lists derived from genomic analyses. This work would help maximize the overall benefits of standard of care therapies and could be used to identify alternative therapeutics for patients who progress on standard therapies. Citation Format: Nathan M. Merrill, Samuel D. Kaffenberger, Liwei Bao, Nathalie Vandecan, Laura E. Goo, Athena Apfel, Xu Cheng, Zhaoping Qin, Chia-Jen Liu, Armand Bankhead, Yin Wang, Varun Kathawate, Lila Tudrick, Habib Serhan, Zackariah Farah, Chad Ellimoottil, Khaled S. Hafez, Lindsey A. Herrel, Jeffrey S. Montgomery, Todd M. Morgan, Simpa S. Salami, Alon Z. Weizer, Peter J. Ulintz, Mark L. Day, Matthew B. Soellner, Phillip L. Palmbos, Sofia D. Merajver, Aaron M. Udager. Integrative drug screening and multi-omic characterization of patient-derived bladder cancer organoids reveals novel molecular correlates of chemotherapy response [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A009.

Neuromuscular Ultrasound: Diagnosis and Evaluation in Neuromuscular Diseases

Neuromuscular ultrasound has become an integral part of the diagnostic workup of neuromuscular diseases in neurology. Neuromuscular ultrasound can detect nerve enlargement, selective muscle damage, and fasciculation easily and non-invasively, which allows differentiation between auto-immune/inflammatory and degenerative/hereditary diseases. It is significant and essential for all neurologists to master the neuromuscular ultrasound technique.

E033 Beyond the surface: artful imitation of Hodgkin’s lymphoma as axial spondyloarthritis

Abstract Background/Aims Rheumatic conditions may be associated with different neoplastic-diseases. Sacroiliitis is not defined as a paraneoplastic syndrome in the literature and considered as the direct involvement of the sacral/iliac bones or sacroiliac joints. There are only few reported cases of back pain and sacroiliac bones/joint involvement as an initial presentation of Hodgkin’s lymphoma. Methods An 18 year boy presented with low back pain of 18 months duration. He had significant morning stiffness and reported good response with non-steroidal anti-inflammatory drugs. He also complained of intermittent fever, insignificant weight loss and occasional dry cough. He denied peripheral joint pain, skin lesions, urethritis, conjunctivitis, uveitis and gastrointestinal disease. The family history was negative for spondyloarthritis (SpA) and neoplastic diseases. He was given empirical anti-tubercular drugs for 6 months with no significant improvement. He was evaluated by physician and rheumatologist elsewhere and treated as SpA in view of inflammatory low back pain, very high inflammatory markers and sacroiliac bones/joint involvement on MRI. The patient tested negative for HLA-B27 (PCR). He was initially started on sulfasalazine, however there was no induction of remission and later switched to tofacitinib since last 4 months. General examination was unremarkable. Bilateral sacroiliac compression and FABER tests were the only positive findings on systemic examination. Results There was leukocytosis (14,100/mm3) with predominant polymorphs, hemoglobin was 9.8g/dl, thrombocytosis (5.4 lakhs/mm3), serum CRP was markedly raised (123mg/L) and ESR was 57mm/hr. His workup for infectious diseases and rheumatic diseases were unremarkable. Repeat MRI according to SpA protocol showed altered marrow signal intensity in lumbar and sacral vertebral bodies and enhancing lytic lesion in right iliac bone till sacroiliac joint. PET-CT revealed multifocal FDG avid mixed lytic sclerotic lesions disseminated in the axial as well as appendicular skeleton with FDG avid sub-centimetric bilateral neck, supraclavicular, axillary, mediastinal and bilateral external/internal iliac and inguinal lymph nodes. Excision biopsy of right supra-clavicular node showed classical Hodgkin lymphoma (CD15 and CD30+ve). He was referred to the haematology clinic for further management. Bone marrow examination was suggestive of tumour infiltration. He received chemotherapy according to the protocol. He is under haematologist care and on a regular follow up with significant improvement in symptoms along with normal inflammatory markers. Conclusion There may be involvement of sacral/ iliac bones and sacroiliac joints by various malignancies including Hodgkin’s lymphoma. Morning stiffness, good response to NSAIDs and MRI findings may delay the diagnosis of primary malignancy, however we should keep a differential of lymphoproliferative disorders as in the aforementioned case and perform other diagnostic modalities. When the expected clinical response is not achieved, the physician must think of a malignancy in cases with persistently high inflammatory markers and marked constitutional symptoms. Disclosure P. Khatri: None. J. Yadavalli: None. K. Shivam: None. R. Gupta: None.

Punctal Atresia As a Clinical Indicator of Systemic Genetic Anomalies

ABSTRACT Background Punctal atresia or agenesis (PA) is a rare congenital anomaly characterized by the absence or closure of the tear duct puncta, potentially linked to systemic genetic anomalies. The necessity of a genetic workup based solely on the presence of PA remains uncertain. This study investigates a cohort of PA patients, examining the prevalence and types of associated syndromes. Methods A retrospective medical records review of all patients diagnosed with PA at the Children’s Hospital of Philadelphia between 2009–2023 was conducted, analyzing medical histories and genetic testing results. Primary outcomes included the prevalence of systemic syndromes, while secondary outcomes focused on the variety of associated syndromes. Results Forty-four patients were included, of which 31 were male (70%) with a mean ± SD age 3.3 ± 3.3 years. Overall, 87 puncta in the study cohort were affected, and 26 cases (59%) were bilateral. Systemic abnormalities or genetic syndromes were identified in 19 patients (43%), with the most common being Ectodermal Dysplasia and Down syndrome. Additional rare syndromes were demonstrated. No significant association was found between systemic abnormalities and gender, bilaterality, or the number of puncta involved. Conclusions A high incidence of systemic syndromes (43%) was observed in the study cohort. In individuals with PA who also exhibit extraocular disease, systemic evaluation and genetic workup should be considered. Syndromic diagnoses identified in our cohort also include: Branchio-oto-renal syndrome, 22q11.2 deletion syndrome, 1q21.1 microdeletion syndrome, NF1, monosomy 4q and trisomy 6q, which represent novel associations. The lack of correlation between PA’s phenotypic severity and systemic abnormalities highlights the need to obtain a comprehensive medical history and consider a systemic workup in PA patients.

A Machine Learning System to Indicate Diagnosis of Idiopathic Pulmonary Fibrosis Non-Invasively in Challenging Cases.

Radiologic usual interstitial pneumonia (UIP) patterns and concordant clinical characteristics define a diagnosis of idiopathic pulmonary fibrosis (IPF). However, limited expert access and high inter-clinician variability challenge early and pre-invasive diagnostic sensitivity and differentiation of IPF from other interstitial lung diseases (ILDs). We investigated a machine learning-driven software system, Fibresolve, to indicate IPF diagnosis in a heterogeneous group of 300 patients with interstitial lung disease work-up in a retrospective analysis of previously and prospectively collected registry data from two US clinical sites. Fibresolve analyzed cases at the initial pre-invasive assessment. An Expert Clinical Panel (ECP) and three panels of clinicians with varying experience analyzed the cases for comparison. Ground Truth was defined by separate multi-disciplinary discussion (MDD) with the benefit of surgical pathology results and follow-up. Fibresolve met both pre-specified co-primary endpoints of sensitivity superior to ECP and significantly greater specificity (p = 0.0007) than the non-inferior boundary of 80.0%. In the key subgroup of cases with thin-slice CT and atypical UIP patterns (n = 124), Fibresolve's diagnostic yield was 53.1% [CI: 41.3-64.9] (versus 0% pre-invasive clinician diagnostic yield in this group), and its specificity was 85.9% [CI: 76.7-92.6%]. Overall, Fibresolve was found to increase the sensitivity and diagnostic yield for IPF among cases of patients undergoing ILD work-up. These results demonstrate that in combination with standard clinical assessment, Fibresolve may serve as an adjunct in the diagnosis of IPF in a pre-invasive setting.

Photon counting computed tomography of in-stent-stenosis in a phantom: Optimal virtual monoenergetic imaging in ultra high resolution

Coronary computed tomography angiography (CCTA) is becoming increasingly important for the diagnostic workup of coronary artery disease, nevertheless, imaging of in-stent stenosis remains challenging. For the first time, spectral imaging in Ultra High Resolution (UHR) is now possible in clinically available photon counting CT. The aim of this work is to determine the optimal virtual monoenergetic image (VMI) for imaging in-stent stenoses in cardiac stents. 6 stents with inserted hypodense stenoses were scanned in an established phantom in UHR mode. Images were reconstructed with 3 different kernels for spectral data (Qr56, Qr64, Qr72) with varying levels of sharpness. Based on region of interest (ROI) measurements image quality parameters including contrast-to-noise ratio (CNR) were analyzed for all available VMI (40keV-190keV). Finally, based on quantitative results and VMI used in clinical routine, a set of VMI was included in a qualitative reading. CNR showed significant variations across different keV levels (p<0.001). Due to reduced noise there was a focal maximum in the VMI around 65keV. The peak values were observed for kernel Qr56 at 116keV with 19.47±8.67, for kernel Qr64 at 114keV with 13.56±6.58, and for kernel Qr72 at 106keV with 12.19±3.25. However, in the qualitative evaluation the VMI with lower keV (55keV) performed best. Based on these experimental results, a photon counting CCTA in UHR with stents should be reconstructed with the Qr72 kernel for the assessment of in-stent stenoses, and a VMI 55keV should be computed for the evaluation.

Introduction of European diagnostic workup of childhood interstitial lung disease

Introduction of European diagnostic workup of childhood interstitial lung disease