Workup Of Disease Research Articles

S2555 Longstanding Hepatosplenomegaly in an Undiagnosed Sarcoidosis Patient

INTRODUCTION: Sarcoidosis, a multisystem granulomatous disease, typically affects the lungs and lymph nodes. Although there is hepatic involvement in approximately 66% of cases, the liver is rarely the cause of symptoms.We present a case of longstanding sarcoidosis in a young patient whose delayed diagnosis likely resulted in worsened portal hypertension and severe pancytopenia. CASE DESCRIPTION/METHODS: In 2015, a 25 year-old Panamanian woman was referred to Hepatology for elevated liver tests. Initial workup ruled out autoimmune hepatitis and viral hepatitis. She was lost to follow-up until 2017 when she saw a different hepatologist for elevated liver tests. As noted in Table 1, she developed significant cholestasis during that interval. Serologic studies for primary cholestatic liver disease were negative. Imaging showed hepatosplenomegaly but she was again lost to follow-up. In 2019, she presented to the Emergency Department with severe abdominal pain. Labs showed pancytopenia and computed tomography (CT) of the abdomen/pelvis showed hepatosplenomegaly. She was referred to Hematology/Oncology. Bone marrow biopsy was negative. She was again referred to Hepatology. She reported a chronic rash on her lower extremities, but was otherwise asymptomatic. Skin biopsy suggested erythema nodosum. Physical exam was notable for massive splenomegaly, confirmed by CT (Figure 1). Labs revealed pancytopenia and persistent cholestasis. An extensive workup for granulomatous diseases and systemic fungal, viral and mycobacterial infections was completed. Angiotensin converting enzyme (ACE) was markedly elevated (Table 1). Ultimately, liver biopsy was performed. Results confirmed granulomatous hepatitis. (Figure 2). After referral to the Sarcoidosis team, she was noted to have significantly elevated interleukin-2 (IL-2) level, consistent with the diagnosis. DISCUSSION: This case nicely illustrates the natural history of hepatic sarcoidosis. Our patient presented with a normal hematologic profile and mildly elevated liver tests, however she progressed to develop significant cholestasis, portal hypertension and pancytopenia. Earlier recognition and treatment may have hindered progression of portal hypertension. Sarcoidosis should be strongly considered in the diagnostic workup of elevated liver tests, especially in young patients who are at highest risk . In addition to ACE, absolute lymphocyte count and IL-2 level are highly sensitive for sarcoidosis and were also abnormal in our patient.Table 1.: Lab values from 2015-2020. Abbreviations: VCA: Viral Capsid Antigen; EBNA: Epstein-Barr Nuclear AntiigenFigure 1.: CT abdomen and Pelvis showing hepatosplenomegaly.Figure 2.: Liver biopsy pathology showing granulomatous hepatitis.

S1529 Occult Portobiliary Fistula Following Percutaneous Liver Biopsy

INTRODUCTION: Percutaneous liver biopsies are commonly performed procedures in the diagnostic workup or staging of liver diseases, and bleeding is the most important complication. Hemobilia is defined as bleeding into the biliary tree, and is a rare complication of liver biopsy that classically presents with a triad of GI bleeding, abdominal pain, and jaundice. CASE DESCRIPTION/METHODS: A 44-year-old male underwent an uneventful liver biopsy for workup of hepatic steatosis. The next day he presented to the ER with RUQ abdominal pain and jaundice. Vital signs were normal and physical examination revealed scleral icterus and epigastric tenderness. Liver function tests showed AST and ALT of 2248 U/L and 2915 U/L, respectively, alkaline phosphatase of 200 U/L, and total bilirubin of 23.3 mg/dL with direct bilirubin of 13.9 mg/dL. CT scan revealed small hemoperitoneum and diffuse hepatic steatosis. Ultrasound with doppler showed normal biliary and intrahepatic ducts and patent portal and hepatic veins with normal blood flow. On the fourth hospital day, MRCP revealed moderate right intrahepatic biliary ductal dilatation with associated hemobilia to the level of the biliary confluence (Figure 1). MRI with contrast revealed completely thrombosed right portal vein and branches, and persistent right intrahepatic biliary ductal dilatation (Figure 2). Oral anticoagulation was considered; however, the gastroenterology team felt the liver biopsy caused an iatrogenic portobiliary fistula, leading to the formation of the portal vein thrombus which may have helped seal the fistula. Therefore, the decision was made to hold anticoagulation and discharge the patient. Liver function tests one month later revealed AST and ALT of 20 U/L and 70 U/L respectively. Repeat MRI showed a reduction of right intrahepatic biliary dilation, and chronic right portal vein thrombus with recanalization and mild cavernous transformation (Figure 3). DISCUSSION: Given the biliary dilation on MRCP, we suspect that a blood clot at the biliary confluence caused an obstruction leading to acute severe rise in AST, ALT and direct hyperbilirubinemia. Due to the risk of further bleeding and possible tamponade effect of clot, anticoagulating the patient may have worsened the situation. Portobiliary fistulas leading to hemobilia are a rare complication of percutaneous liver biopsy. While GI bleeding, jaundice, or abdominal pain post-biopsy should prompt a diagnostic workup, it should also be kept in mind that there could be uncommon presentations of hemobilia.Figure 1.: MRCP showing moderate right intrahepatic biliary ductal dilatation with associated hemobilia.Figure 2.: Contrast enhanced MRI showing thrombosed right portal vein and branches, and right intrahepatic biliary ductal dilatation.Figure 3.: Follow-up MRI showing reduction of right intrahepatic biliary dilation, and chronic right portal vein thrombus.

S2697 Drug Induced Liver Injury From Chronic Allopurinol Therapy Occurring With Onset of Renal Failure

INTRODUCTION: Allopurinol is a rare cause of drug induced liver injury with high fatality rate. When suspected, the medication should be discontinued immediately and subsequent supportive care should be provided. CASE DESCRIPTION/METHODS: A 69-year-old male with history of autosomal dominant polycystic kidney disease, hyperuricemia on chronic allopurinol therapy, systolic heart failure, and atrial fibrillation presented with acute encephalopathy, weakness, and weight loss due to progression of uremia from renal failure. Labs were additionally remarkable for elevated liver enzymes in a cholestatic pattern. Nephrology initiated hemodialysis. Mental status improved, but liver function continued to worsen. Chronic liver disease workup returned negative. Ultrasound revealed cystic liver disease but was otherwise unremarkable. ERCP with EUS showed incomplete pancreas divisum, rarefaction of intrahepatic bile ducts, and slight tapering of the right and left main hepatic ducts. Liver biopsy revealed moderate pericholangitis, ductular reaction, and bland zone 3 cholestasis consistent with drug induced liver injury. Allopurinol was determined to be a “definite” DILI culprit by RUCAM scoring and was stopped. Unfortunately, liver failure progressed. Patient underwent liver transplant workup but was a poor candidate and discharged on hospice. DISCUSSION: Drug induced liver injury (DILI) is the most common cause of acute liver failure in the United States, accounting for up to 50% of fulminant cases. While acetaminophen has been cited most often, DILI can be caused by many medications and supplements with risk dependent on dosing, drug lipophilicity, and hepatic metabolism. In patients on chronic allopurinol therapy, only 2 to 6% will have elevated liver enzymes. In this patient, we suspect that development of acute on chronic renal failure led to toxic injury from allopurinol, which is hepatically converted to its active metabolite but renally excreted. Allopurinol DILI can either be immunoallergenic, presenting with fever, eosinophilia, and arthralgias, or cholestatic with cases of vanishing duct syndrome reported. While rare, allopurinol hepatotoxicity has a high fatality rate. Liver biopsy will show cholestatic or mixed hepatitis, bile duct injury or loss, and sometimes acute granulomatous changes. After discontinuation of the suspected agent, treatment is supportive in nature. Lab values should be monitored to resolution, and in severe cases liver transplant evaluation should be considered.

FAT EMBOLISM SYNDROME AS THE PRESENTING SYNDROME OF UNDIAGNOSED SICKLE CELL DISEASE IN A MIDDLE-AGED ADULT

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Fat embolism syndrome (FES) represents a myriad of clinical signs and symptoms that occur following the release of fat emboli into systemic circulation including hypoxemia, neurologic changes, petechial rash, and multi-organ dysfunction. FES often occurs post-orthopedic trauma but can be a complication of sickle cell disease (SS) [1]. CASE PRESENTATION: An otherwise healthy 44-year-old female presented to our emergency department (ED) with worsening, atraumatic back and knee pain after an ED visit three days prior where x-rays and blood-work were unremarkable. She was short of breath, hypoxic, tachycardic and hypotensive. Her mental and respiratory status deteriorated requiring intubation. Laboratory work was significant for hemoglobin 8.5 g/dL, hematocrit 24.0%, WBC 14.8x10⁹/L, and platelets 59x10⁹/L including 11% bands and 15% nRBCs (baseline CBC had no abnormalities). A chest x-ray revealed bilateral, patchy infiltrates consistent with pulmonary edema. Further blood-work revealed acute renal and liver failure, lactic acidosis, and troponinemia. CT imaging revealed patchy, widespread pulmonary disease/edema and splenomegaly. She underwent resuscitation with fluid, blood products, vasopressor support, and broad spectrum antibiotics. All infectious disease workups were negative. The patient was ultimately transferred elsewhere for whole blood exchange but expired. Autopsy revealed vertebral and long-bone marrow infarction and evidence of FES. She was discovered to be hemoglobin SS post-mortem, and no trigger for this episode, including infectious disease, was identified. DISCUSSION: Sickle cell disease screening is routine in the United States but less standardized in other nations [2]. Most sickle cell disease patients exhibit disease signs by age 4-5 months making her middle-aged presentation uncommon. Our patient, a Haitian immigrant, as well as her husband, adamantly denied prior SS symptoms or crisis. Moreover, according to a recent systematic review, FES is a rare complication of sickle cell disease with a predilection for heterozygous patients [2]. Of all FES cases, only 15% of patients were homozygous SS (n = 13) [3]. It is rare for FES to be the presenting syndrome of a previously undiagnosed, middle-aged, homozygous SS disease patient. CONCLUSIONS: We present a rare case of FES as the presenting syndrome of a previously undiagnosed, middle-aged, SS disease patient. Prompt consideration and treatment of FES should be initiated to avoid complications. Reference #1: Akhtar S. Fat embolism. Anesthesiol. Clin. 2009; 27 (3):533–550. Reference #2: Center for Disease Control Sickle Cell Disease. Oct 2019. Retrieved from https://www.cdc.gov/ncbddd/sicklecell Reference #3: Tsitsikas DA, May JE, Gangaraju R, Abukar J, Amos RJ, Marques MB. Revisiting Fat Embolism in Sickle Syndrome: Diagnostic and Emergency Therapeutic Measures. British Journal of Haematology. 2019 Aug; 186(4), 112-115. DISCLOSURES: No relevant relationships by Osman Abbasi, source=Web Response No relevant relationships by Jamie Allen, source=Web Response No relevant relationships by Jeffrey Gesell, source=Web Response No relevant relationships by Benjamin Lin, source=Web Response No relevant relationships by Louis Morolla, source=Web Response No relevant relationships by Andres Zirlinger, source=Web Response

S2382 COVID-19 and Cholestasis: Potential Role of Interleukin-6

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a pandemic with over 1 million cases in the United States. Pulmonary symptoms are the most common; however, the liver is one of the involved organs. Although elevations in serum (S) activity (A) of transaminases and bilirubin concentration are documented, increased SA of alkaline phosphatase (ALP) is uncommon. Two cases of PCR confirmed Sars-CoV-2 infection and high ALP SA are presented. CASE DESCRIPTION/METHODS: A 49-year-old man was hospitalized with COVID-19 pneumonia. ALP SA was 250 U/L, and that of GGT 322 U/L, suggesting a hepatic origin of the former. SA of ALT and AST was elevated to 295 and 271 U/L, respectively. A liver ultrasound suggested fatty infiltration, and excluded bile duct dilatation and space occupying lesions. The patient improved in association with treatment. SA of AST and ALT trended down; however that of ALP remained elevated, ranging from 187 U/L to 231 U/L on the day of discharge. A 75-year-old man complaining of fever, fatigue and shortness of breath for four days was hospitalized with COVID-19. Initial tests revealed an ALP and GGT SAs of 673 U/L and 949 U/L, respectively, and normal SA of AST, ALT and S bilirubin. An MRCP excluded biliary obstruction. ALP SA remained in the 800 U/L range until discharge, without changes in the rest of the hepatic panel. Both patients had an unrevealing liver disease workup and were given an outpatient follow-up. DISCUSSION: Increased ALP SA has been reported in 1.8 % of patients with COVID-19. SARS-CoV-2 binds to the angiotensin-converting enzyme 2 receptor found on hepatocytes and biliary epithelial cells to enter its target cells; thus, the virus may cause cellular injury or impair the function of the liver transporters leading to cholestasis. Sepsis is also associated with cholestasis by the effect of cytokines including interleukin-6 (IL-6). In this context, IL-6 is a driver of the cytokine storm seen in COVID-19. However, liver failure has not been reported in COVID-19; this may be explained by the reported protective effect that IL-6 exerts on the liver as a mediator of liver regeneration.

A Rare Case of Dysferlinopathy Causing Cardiomyopathy

Introduction We report a case of a 30-year-old man who presented with advanced heart failure secondary to dilated cardiomyopathy. The patient was diagnosed with limb girdle muscular dystrophy type 2B (LGMD2B), a rare autosomal recessive disease. Cardiomyopathy is only rarely described in dysferlinopathies. Case This patient is a 30-year old African American male with medical history of left foot crush injury in 2016. The following year after injury he developed progressive exercise intolerance and palpitations. An electrocardiogram (ECG) showed sinus tachycardia. Echocardiogram revealed a severely dilated left ventricle, with increased wall thickness, apical trabeculations and ejection fraction (EF) of 20%. Right ventricle had normal size and function, and there was no significant valvular disease. His functional capacity and cardiac performance on imaging tests did not improve despite guideline directed medical therapy. He also had persistently elevated transaminases. Chronic liver disease workup was negative with liver biopsy showing mild sinusoidal dilatation without significant fibrosis. Persistently elevated transaminases in the absence of liver disease and significant systemic congestion prompted testing for muscle enzymes, which were severely elevated (CK-16,196; Aldolase 84.3 U/l). Neurologic examined revealed mild proximal muscle weakness. Further evaluation included electromyography (EMG), which was consistent with chronic myopathy. Genetic testing revealed a pathogenic splice site variant (c.2643+1GA), and two variants of uncertain significance (p.Asn367Lys, p.Arg553His) in the dysferlin gene. Muscle biopsy was performed which showed active myopathic features with myofiber necrosis and regeneration (Figure 1A, 1B). No chronic remodeling was present. Immunohistochemical staining showed loss of dysferlin expression (figure 1C; insert normal control). Expression of other sarcolemmal proteins like dystrophin was preserved (figure 1D). The biopsy findings support a diagnosis of a dysferlinopathy in the context of the described genetic variants and argue for the combination of the described variants to be disease causing. Conclusion LGMD2B is a rare limb girdle muscular dystrophy with very few previously reported cases of cardiac muscle involvement. Our case highlights the importance of a comprehensive diagnostic evaluation of idiopathic cardiomyopathy in young patients. Chronically elevated transaminases in young patients should prompt evaluation for myopathy, and genetic evaluation in the appropriate clinical context.

"One stop" liver-focused endoscopy: EUS-guided portal pressure gradient measurement technique.

Referral for abnormal liver chemistry is one of the most frequently encountered reasons for visits to gastroenterologists and hepatologists, particularly given the versatility and vulnerability of the liver.1Kwo P.Y. Cohen S.M. Lim J.K. ACG clinical guideline: evaluation of abnormal liver chemistries.Am J Gastroenterol. 2017; 112: 18-35Crossref PubMed Scopus (395) Google Scholar Here, we present a 40-year-old man with class III obesity, essential hypertension, and hyperlipidemia who was referred for further diagnostic workup of his abnormal liver chemistry. Despite periods of significant weight loss, his liver transaminases had remained elevated over the prior 10 years (alanine aminotransferase 20-93 U/L, aspartate aminotransferase 20-71 U/L). Diagnostic workup included an abdominal ultrasound with evidence of hepatic steatosis and transient elastography (Fibroscan) that demonstrated a liver stiffness of 12.8 kPa, S3 (marked steatosis), and F3 (severe fibrosis). After reviewing the risks, benefits, and alternatives, the decision was made to perform an EGD to evaluate for stigmata of portal hypertension and an EUS to obtain a liver biopsy specimen and portal pressure gradient (PPG) measurements. The patient was intubated and remained in the supine position for the entirety of the procedure (Video 1, available online at www.VideoGIE.org). Initially, an EGD was performed, with no endoscopic evidence of varices or stigmata of portal hypertension. Next, the EUS examination was performed. The left lobe of the liver appeared diffusely hyperechoic, suggestive of steatosis. Real-time elastography was then performed on the left and right lobes of the liver to assess liver stiffness. The region of interest was positioned over the hepatic parenchyma, and an average of 10 measurements was obtained from each lobe of the liver. Mean liver stiffness was 11.5 kPa. The EchoTip Insight Portosystemic Pressure Gradient Measurement System (Cook Medical, Bloomington, Ind, USA) then was set up, involving a 25-gauge FNA needle, noncompressible tubing, a compact digital manometer, and heparinized saline solution. The middle hepatic vein was first identified and punctured using a transgastric approach. Once the needle tip was seen within the vessel, approximately 1 to 2 mL of heparinized saline solution was used to flush the needle. The pressure reading on the manometer was obtained and recorded once stable. This process was repeated a total of 3 times, including repeat flushes of heparinized saline solution to obtain the mean hepatic vein pressure measurement. Next, the umbilical portion of the left portal vein was identified, and using the aforementioned approach, the process was repeated 3 times to obtain the mean portal vein pressure measurement. The PPG was calculated by subtracting the mean hepatic vein pressure (16.4 mm Hg) from the mean portal vein pressure (23.4), which measured 7 mm Hg (consistent with preclinical portal hypertension). Last, EUS-guided liver biopsy was performed. Using a 19-gauge EUS–fine needle biopsy needle primed with heparin, we performed a transgastric puncture to obtain a sample from the left lobe of the liver. This process was then repeated using a transduodenal approach to obtain tissue from the right lobe of the liver. Liver core was then expressed onto a slide and sent to surgical pathology. The patient was discharged home after endoscopy without any adverse events. Surgical pathology from the liver biopsy revealed mild steatohepatitis with stage 0-1/4 fibrosis (Fig. 1). On outpatient follow-up, the patient was started on a stricter diet and exercise regimen for weight loss. EUS-guided applications have been increasing over the past decade; today, both endoscopy and echoendoscopy offer tremendous diagnostic information to help guide management in the workup of liver disease.2Samarasena J. Chang K.J. Endo-hepatology: a new paradigm.Endosc Ultrasound. 2018; 7: 219-222Crossref PubMed Scopus (6) Google Scholar In particular, EUS-guided liver biopsy has emerged as a safe and minimally invasive approach and an alternative to a percutaneous technique and now can be paired with EUS-guided real-time elastography and PPG measurement.3Huang J.Y. Samarasena J.B. Tsujino T. et al.EUS-guided portal pressure gradient measurement with a simple novel device: a human pilot study.Gastrointest Endosc. 2017; 85: 996-1001Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar,4Shah A. Martinez I.C. Valentin N. et al.Efficacy and safety of endoscopic ultrasound-guided liver biopsies in parenchymal liver diseases: a systematic review and meta-analysis.Am J Gastroenterol. 2018; 113: S565-S566Crossref Google Scholar Here, we demonstrate the safety and technique of EUS-guided PPG measurement in the diagnostic workup of abnormal liver tests. Dr Sharaiha is a consultant for Boston Scientific and Apollo Endosurgery (terminated). All other authors disclosed no financial relationships. https://www.videogie.org/cms/asset/91a9cbf3-9569-4652-812c-a82edde33120/mmc1.mp4Loading ... Download .mp4 (65.17 MB) Help with .mp4 files Video 1“One stop” liver-focused endoscopy: EUS-guided portal pressure gradient measurement technique.

Morphometric Analysis of Clavicle and Its Medullary Canal: A Computed Tomographic Study.

Intramedullary fixation is one of the common methods of treating clavicle fractures. Morphometric data of the clavicle and its medullary canal will help design a better device and surgical technique. Morphometric studies on clavicle are sparse; hence, this study. A 3-D reconstruction of 64 clavicles of 32 patients was done from computed tomography (CT) scan data of thorax obtained for the diagnostic workup of unrelated disease. The various dimensions of the clavicle and its medullary canal were measured. The narrowest part, point of change of direction of the medullary canal, curvatures of the clavicle, the position of the coracoid process, and the relation of these features to eight equally divided segments of clavicle were noted. The average length of the clavicle was 142.5mm. The average height and width of the narrowest part of the medullary canal were 2.4mm and 2.5mm, respectively, corresponding to segment 5 (S5) in more than half of the clavicles. The change of direction of the medullary canal and the medial edge of the coracoid process were corresponding to segment 6 (S6) in the majority of the clavicles. This computed tomographic study provides morphometric data of the clavicle applicable to intramedullary fixation of clavicle fractures. In the studied population, the clavicles were shorter, more curved, and had medullary canal dimensions less than 2.5mm at the narrowest part. This may pose difficulties in intramedullary fixation. The coracoid process was a reliable anatomical landmark.

Risk Factors for Major Hemorrhage Following Percutaneous Image-Guided Renal Biopsy: What is the "core" of the Problem? A Retrospective Case-control Study.

Objectives:Percutaneous renal biopsy (PRB) plays a critical role in the work-up of renal parenchymal disease. Although it is considered a low-risk procedure, additional interventions may be required in about 7% of the cases following biopsy. The purpose of this study was to identify risk factors for major hemorrhage by microscopic analysis of the cores obtained following PRB, with an intent to enhance the sensitivity and specificity of the risk stratification process, especially in patients undergoing this procedure in an outpatient setting.Material and Methods:A retrospective review identified 17 of 179 patients (9.50%) with major hemorrhage following PRB between July 2014 and June 2019. Using propensity score matching, 26 controls (without major hemorrhage) were matched to 17 cases (with major hemorrhage). The biopsy cores obtained from the cases and controls were analyzed by a single pathologist for medullary, cortical, total (medullary + cortical) lengths, and the number of arcuate arteries (AAs). Medullary:cortical (M:C), cortical:total (C:T), and medullary:total (M:T) length ratios were then calculated.Results:A stratified version of logistic regression was used to test for an association between each of the variables identified on the cores and the probability of a major hemorrhage. The analysis revealed that there was a statistically significant association between the number of AAs per specimen with the risk of major hemorrhage (P = 0.0006). When 0, 1, or >2 AAs were identified, the frequency of major hemorrhage was 13.04%, 66.67%, and 75.00%, respectively. The odds of major hemorrhage were 6 times higher with one AA and (95% CI, 1.28–32.30) and 15 times higher with >2 AAs (95% CI, 1.41–169.57). No significant association was found between medullary length (P = 0.228), medulla:cortex (M:C) (P = 0.089), medulla:total (M:T) (P = 0.108), or cortex:total (C:T) (P = 0.112) length ratios and major hemorrhage.Conclusion:There was a strong and incremental correlation between major renal hemorrhage following PRB and the number of AAs per core specimen. Identification of AAs by the pathologist, while assessing for sample adequacy, in the US suite can help predict major hemorrhage in patients undergoing PRBs.

Diagnostic value of TBLC in idiopathic pulmonary fibrosis

Over the past 5 years, evidence has been growing for the use of transbronchial lung cryobiopsy (TBLC) in the diagnostic evaluation of interstitial lung disease. 1 Maldonado F Danoff SK Wells AU et al. Transbronchial cryobiopsy for the diagnosis of interstitial lung diseases: CHEST Guideline and Expert Panel Report. Chest. 2020; 157: 1030-1042 Summary Full Text Full Text PDF PubMed Scopus (43) Google Scholar , 2 Lentz RJ Argento AC Colby TV Rickman OB Maldonado F Transbronchial cryobiopsy for diffuse parenchymal lung disease: a state-of-the-art review of procedural techniques, current evidence, and future challenges. J Thorac Dis. 2017; 9: 2186-2203 Crossref PubMed Scopus (72) Google Scholar , 3 Troy LK Grainge C Corte TJ et al. Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study. Lancet Respir Med. 2020; 8: 171-181 Summary Full Text Full Text PDF PubMed Scopus (96) Google Scholar In The Lancet Respiratory Medicine, Sara Tomassetti and colleagues 4 Tomassetti S Ravaglia C Wells AU et al. Prognostic value of transbronchial lung cryobiopsy for the multidisciplinary diagnosis of idiopathic pulmonary fibrosis: a retrospective validation study. Lancet Respir Med. 2020; 8: 786-794 Summary Full Text Full Text PDF PubMed Scopus (5) Google Scholar report the long-term outcomes of patients with interstitial lung disease diagnosed by TBLC or surgical lung biopsy (SLB) and hypothesise that if diagnostic accuracy were similar between the two modalities, prognostic outcome would also be similar, and further would be distinct for idiopathic pulmonary fibrosis versus other interstitial lung diseases. A well-designed, single-centre, retrospective study was done of 426 consecutive patients with interstitial lung disease, of whom 160 had undergone SLB and 266 had undergone TBLC. The primary study conclusion was that idiopathic pulmonary fibrosis cases diagnosed by TBLC had (expectedly) poorer clinical outcomes compared with patients with an alternative diagnosis (transplant-free survival adjusted HR 2·98, 95% CI 1·19–7·47; p=0·02), and therefore TBLC, similarly to SLB, could be relied on to provide accurate histopathological information to multidisciplinary team (MDT) discussions in the work-up of undifferentiated interstitial lung disease. Additionally, the investigators found that adjusted comparative survival in idiopathic pulmonary fibrosis appeared worse for those diagnosed by SLB compared with those diagnosed by TBLC (adjusted HR 4·07, 95% CI 2·01–8·24; p<0·0001). Prognostic value of transbronchial lung cryobiopsy for the multidisciplinary diagnosis of idiopathic pulmonary fibrosis: a retrospective validation studyTBLC makes an important diagnostic contribution in interstitial lung disease, on the basis of the prognostic distinction between idiopathic pulmonary fibrosis and other interstitial lung diseases when TBLC findings are included in multidisciplinary diagnosis. Full-Text PDF

Pre-Liver Transplant Coronary Artery Disease Workup for Low-Risk Patients.

Coronary artery disease (CAD) is a leading cause of mortality following orthotopic liver transplant, yet there is no standardized protocol for pre-liver-transplant coronary artery disease assessment. The main objective of this study was to determine the agreement between 2 methods of cardiac risk assessment: dobutamine stress echocardiogram (DSE) and coronary calcium score (CCS) and to determine which test was best able to predict coronary calcification in low-risk patients. A retrospective study was performed using the medical records of 436 patients who received cardiac clearance for a liver transplant. A total of 152 patients' medical records were included based on the inclusion of patients who had received both DSE and CCS. A kappa coefficient was calculated to determine the agreement between the DSE and CCS results. In addition, the positive predictive values (PPVs) of both the CCS and DSE along with cardiac catheterization indicating abdominal occlusion were analyzed to compare the accuracy of the 2 tests. It was determined that there was a 12% agreement between DSE results and CCS. It was found that the DSE had a PPV of 56% and the CCS had a PPV of 80%. From this data, it was concluded that there was no agreement between the results of the CCS and the DSE. While neither the CCS nor the DSE presents an optimal method of risk assessment, the CCS had a much higher PPV and was therefore determined to be the more accurate test.

Improved HLA-based prediction of coeliac disease identifies two novel genetic interactions.

Human Leucocyte Antigen (HLA) testing is useful in the clinical work-up of coeliac disease (CD) with high negative but low positive predictive value. We construct a genomic risk score (GRS) using HLA risk genotypes to improve CD prediction and guide exclusion criteria. Imputed HLA genotypes for five European CD case-control GWAS (n > 15,000) were used to construct and validate an interpretable HLA-based risk model (HDQ15), which shows statistically significant improvements in predictive performance upon all previous HLA-based risk models. Conditioning on this model, we find two novel associations, HLA-DQ6.2 and HLA-DQ7.3, that interact significantly with HLA-DQ2.5 (p = 2.51 × 10-9, 1.99 × 10-7, respectively). Integrating these novel alleles into a new risk model (HDQ17) leads to predictive performance equivalent or better than the strongest reported GRS (GRS228) using 228 single nucleotide polymorphisms (SNPs). We also demonstrate that our proposed HLA-based models can be implemented using only six HLA tagging SNPs with statistically equivalent predictive performance. Using insights from our model to guide exclusionary criteria, we find the positive predictive value of CD testing in high-risk populations can be increased by 55%, from 17.5 to 27.1%, while maintaining a negative predictive value above 99%. Our results suggest that HLA typing is currently undervalued in CD assessment.

Magnetic resonance imaging biomarkers of cerebrospinal fluid tracer dynamics in idiopathic normal pressure hydrocephalus.

Disturbed clearance of toxic metabolites from the brain via cerebrospinal fluid is emerging as an important mechanism behind dementia and neurodegeneration. To this end, magnetic resonance imaging work-up of dementia diseases is largely focused on anatomical derangements of the brain. This study explores magnetic resonance imaging biomarkers of cerebrospinal fluid tracer dynamics in patients with the dementia subtype idiopathic normal pressure hydrocephalus and a cohort of reference subjects. All study participants underwent multi-phase magnetic resonance imaging up to 48 h after intrathecal administration of the contrast agent gadobutrol (0.5 ml, 1 mmol/ml), serving as cerebrospinal fluid tracer. Imaging biomarkers of cerebrospinal fluid tracer dynamics (i.e. ventricular reflux grades 0–4 and clearance) were compared with anatomical magnetic resonance imaging biomarkers of cerebrospinal fluid space anatomy (Evans’ index, callosal angle and disproportional enlargement of subarachnoid spaces hydrocephalus) and neurodegeneration (Schelten’s medial temporal atrophy scores, Fazeka’s scores and entorhinal cortex thickness). The imaging scores were also related to a pulsatile intracranial pressure score indicative of intracranial compliance. In shunt-responsive idiopathic normal pressure hydrocephalus, the imaging biomarkers demonstrated significantly altered cerebrospinal fluid tracer dynamics (ventricular reflux grades 3–4 and reduced clearance of tracer), deranged cerebrospinal fluid space anatomy and pronounced neurodegeneration. The altered MRI biomarkers were accompanied by pressure indices of impaired intracranial compliance. In conclusion, we present novel magnetic resonance imaging biomarkers characterizing idiopathic normal pressure hydrocephalus pathophysiology, namely measures of cerebrospinal fluid molecular redistribution and clearance, which add information to traditional imaging scores of cerebrospinal fluid space anatomy and neurodegeneration.

Assessment of the Clinical Utility of Plasma Metagenomic Next-Generation Sequencing in a Pediatric Hospital Population.

Metagenomic next-generation sequencing (mNGS) of plasma cell-free DNA (cfDNA) is commercially available, but its role in the workup of infectious diseases is unclear. To understand the clinical utility of plasma mNGS, we retrospectively reviewed patients tested at a pediatric institution over 2 years to evaluate the clinical relevance of the organism(s) identified and the impact on antimicrobial management. We also investigated the effect of pretest antimicrobials and interpretation of molecules of microbial cfDNA per microliter (MPM) of plasma. Twenty-nine of 59 (49%) mNGS tests detected organism(s), and 28/51 (55%) organisms detected were clinically relevant. The median MPM of clinically relevant organisms was 1,533, versus 221 for irrelevant organisms (P = 0.01). mNGS test positive and negative percent agreements were 53% and 79%, respectively, and 50% of negative mNGS tests were true negatives. Fourteen percent of tests impacted clinical management by changing antimicrobial therapy. Immunocompromised status was the only patient characteristic that trended toward a significant clinical impact (P = 0.056). No patients with culture-negative endocarditis had organisms identified by mNGS. There were no significant differences in antimicrobial duration retest between tests with clinically relevant organism(s) and those that returned negative, nor were the MPMs different between pretreated and untreated organisms, suggesting that 10 days of antimicrobial therapy as observed in this cohort did not sterilize testing; however, no pretreated organisms identified resulted in a new diagnosis impacting clinical management. Plasma mNGS demonstrated higher utility for immunocompromised patients, but given the detection of many clinically irrelevant organisms (45%), cautious interpretation and infectious diseases consultation are prudent.

The added value of CT virtual angioscopy to MDCT angiography in the evaluation of aortic diseases.

Incorporation of virtual angioscopy (VA) in the diagnostic work-up of aortic diseases could improve the clinical value and efficiency of multidetector computed tomography angiography (MDCTA). We aim to evaluate the clinical usefulness of virtual aortic navigation by CT angiography in various aortic diseases as a complement to standard MDCTA. We retrospectively selected 211 patients who performed MDCTA for suspected or operated aortic diseases. VA endoluminal images of the aorta were obtained by a fly-through technique. Two senior vascular radiologists independently evaluated all MDCTA images. After 1 month, the same two radiologists independently reviewed the MDCTA images combined with CTVA images. The respective accuracy of CTVA in delineating aortic abnormalities was compared to that of MDCTA using Fisher's exact test. The Fleiss kappa (κ) statistic was used to assess the inter-reader agreement (IRA). We detected 229 abnormalities in 203 patients on MDCTA and 231 abnormalities in 205 patients on CTVA. CTVA provided significant additional findings in 63.8% (146/229) of all abnormalities diagnosed by MDCTA (p < 0.001, odd ratio [OR] = 42). Although CTVA diagnosed two abnormalities overlooked by MDCTA, the value was statistically insignificant (p = 0.787, OR = 1.3). Regarding postoperative abnormalities, the CTVA added significant additional findings over MDCTA (p = 0.006, OR = 87.4). The overall IRA for the performance of CTVA was good (κ = 0.699). CTVA yields extra findings and improves diagnostic efficiency of MDCTA, especially in postoperative patients.

Duodenal bulb biopsy in the diagnostic work-up of coeliac disease.

Coeliac disease (CD) is an autoimmune enteropathy which can present with patchy mucosal lesions. The aim of the present study is to investigate the significance of duodenal bulb biopsy in the diagnostic work-up of CD in both pediatric and adult patients, and to highlight the key points for pathologists. D1 (duodenal bulb) and D2 (distal duodenum) biopsies of 153 newly diagnosed serology-positive CD patients were evaluated for villous/crypt ratio and intraepithelial lymphocyte (IEL) counts on CD3-stained slides and were classified according to Marsh. Mucosal pathology was patchy in 15% (13% only D1 and 2% only D2) of patients, and 85% of patients had diffuse mucosal pathology involving both D1 and D2 biopsies which showed concordant histology in 60% and discordant in 25% of the cases. Though majority of the patients (75%) with only D1 involvement were pediatric cases, no significant difference was found between pediatric and adult patients when all cases were considered (17 vs 14%). Our results clearly indicate that without D1 sampling, diagnosis of CD would have been missed in a significant number of cases (13%), thereby highlighting the importance of taking duodenal biopsies from multiple sites in the diagnostic work-up of CD. We, therefore, conclude that every biopsy piece from both D1 and D2 should be carefully evaluated for the whole spectrum of mucosal changes caused by gluten ingestion and classified using a scheme based on Marsh to allow recognition of mild lesions.

MON-481 Remarkable Euthyroid Hyperthyroxinemia Mistaken for Thyrotoxicosis

CLINICAL CASEA 46 year old caucasian female with past medical history of menorrhagia was referred from primary care for evaluation of thyrotoxicosis. Thyroid function was assessed in the context of menometrorrhagia. She did not have any history of thyroid disorder or abnormal thyroid function tests. Per outside records, recent labs demonstrated TSH 0.88 uIU/mL (0.36-3.74), Free T4 > 8.00 ng/dL (0.76-1.46), Free T3 2.9 pg/mL (2.18-3.98). All other labs were within normal limits. Thyroid ultrasound revealed normal parenchyma and volume. She did not take any medications or supplements including biotin. She denied heat intolerance, anxiety, palpitations, dyspnea, tremors, hyperdefecation, or change in hair, skin, or mood. No epiphora, diplopia, or eye irritation was reported. Her father had been diagnosed with hyperthyroidism, mother with hypothyroidism.Repeat labs at our visit revealed normal TSH of 1.05 uIU/mL (0.358- 3.74), normal Free T3 2.58 pg/mL (2.18- 3.98), normal Total T3 136 ng/dL (80-200), elevated Free T4 >8.00 ng/dL (0.76-1.46) and elevated Total T4 11.6 ug/dL (4.5-10.5). These lab values were not consistent with patient’s euthyroid clinical status, prompting assessment of Free T4 by dialysis, normal at 1.5 ng/dL (0.9-2.2) and T3 uptake, high at 40% (24-39%). This picture was consistent with Familial Dysalbuminemic Hyperthyroxenemia (FDH). The decision was made not to treat the patient with anti-thyroid medications and to perform a confirmatory genetic testing to test for mutations in the ALB (albumin) gene.DISCUSSIONThe free T4 assay used by our institution is performed on the Siemens Dimension Vista platform using a two-step chemiluminescent immunoassay. While in theory two-step assays should not yield abnormal results in FDH, several two-step assays are known to yield falsely high results in patients with FDH (1, 2, 3).Other potential etiologies for discordant Free T4 levels include thyroid hormone autoantibodies, heterophile antibodies, biotin use, and anti-streptavidin antibodies (3).CONCLUSIONRecognition of laboratory error in the workup of thyroid disease is essential. Clinicians must ensure thyroid function labs are consistent with each other and with the patient’s presentation. In such cases misdiagnosis of hyperthyroidism or thyroid hormone resistance may lead to unnecessary testing and inappropriate treatment (3).

The role of imaging in the diagnosis and management of Peyronie's disease.

Several imaging modalities exist for the assessment of Peyronie's disease. However, comprehensive recommendations for using these objective modalities based on large-scale evidence-based studies do not yet exist. Our objective is to evaluate current imaging techniques and provide a model that we follow in our clinic in the workup and management of Peyronie's disease. Computed tomography and radiography excellently visualize penile plaque calcifications, and MRI adeptly identifies plaques in complex locations, such as the corporal septum. Ultrasonography has extensive applications in plaque localization and characterization. Used along with color Doppler ultrasound, it is capable of detecting vascular abnormalities. Sonoelastography is an emerging subtype of ultrasongraphy that utilizes elastic properties of tissue to identify penile plaques that may not be visualized with other modalities. Ultrasonography is the preferred imaging modality in Peyronie's disease and noninvasively characterizes penile plaques and monitors plaque response to various treatments. At our center, we perform ultrasonography with intracavernosal injection in all patients with Peyronie's disease to evaluate the degree of curvature, plaque characteristics, and concomitant erectile dysfunction to better guide management decisions.

Potential utility of targeted Nanopore sequencing for improving etiologic diagnosis of bacterial and fungal respiratory infection

BackgroundDiversified etiology of lower respiratory tract infection renders diagnosis challenging. The mainstay microbial culture is time-consuming and constrained by variable growth requirements. In this study, we explored the use of Nanopore sequencing as a supplementary tool to alleviate this diagnostic bottleneck.MethodsWe developed a targeted Nanopore method based on amplification of bacterial 16S rRNA gene and fungal internal transcribed spacer region. The performance was compared with routine infectious disease workups on 43 respiratory specimens.ResultsNanopore successfully identified majority of microbes (47/54, 87.04%) and 7 possible pathogens not detected by routine workups, which were attributable to the content of microbiological investigations (n = 5) and negative culture (n = 2). The average sequencing time for first target reads was 7 min (1–43 min) plus 5 h of pre-sequencing preparation.ConclusionsThe Nanopore method described here was rapid, economical and hypothesis-free, which might provide valuable hints to further microbiological follow-up for opportunistic pathogens missed or not detectable by conventional tests.

РОЛЬ НИРКОВОЇ ОНКОЦИТОМИ В ПРОГРЕСУЮЧІЙ НИРКОВІЙ НЕДОСТАТНОСТІ. ОГЛЯД НА ОСНОВІ КОНКРЕТНОГО ВИПАДКУ

The presentation of a renal mass presumes a malignancy unless proven otherwise by histologic evaluation. We present a case of 40-year-old man with advance uremia necessitating renal replacement. Radiologic images showed a right renal mass and the patient underwent a nephrectomy. The pathologic diagnosis was a benign renal neoplasm, oncocytoma. This neoplasm is not a cause of renal failure but may be associated with other malignant lesions. Focal segmental glomerulosclerosis was the reason for renal failure. Lesion was discovered incidentally during the workup of chronic kidney disease. Histopathology delineated two separate pathologies designing the management plan. After few months of hemodialysis patient could receive renal transplant, a therapy of choice as oncocytoma is a benign condition which doesn’t preclude transplantation.