bluuebunny/crossref_metadata_2025_split huggingface dataset:
1545 Drug-Induced Colitis With Nintedanib Therapy
Authors: Penmetsa Amulya , Santa Stephanie , Abu-Farsakh Sohaib , Drage Michael , Ettel Mark , DeCross Arthur , Marino Danielle E. 
Published: October 2019

INTRODUCTION:
Nintedanib has emerged as an important treatment agent for Idiopathic Pulmonary Fibrosis (IPF). Gastrointestinal side effects, such as diarrhea and nausea, have been reported. However, Nintedanib-Induced Colitis, as described in the following cases, is a rare finding.

CASE DESCRIPTION/METHODS:
Case 1: 65 year-old man with a history of IPF on Nintedanib for three years presented with diarrhea. He reported two watery, non-bloody bowel movements daily with urgency, despite taking four tablets of loperamide daily. He had lower abdominal pain and an eighty-pound weight loss. A colonoscopy revealed mild edema, loss of vascular markings throughout the colon, and significant patches of submucosal hemorrhage/petechiae in the right colon. Biopsies revealed subepithelial deposition of amorphous eosinophilic material, prominently filling the subepithelial capillaries (Figure 1). Masson trichrome stain highlights dense blue staining, indicating collagen. The patient's symptoms resolved within a few days of discontinuing Nintedanib, and returned with rechallenge. Case 2: 76 year-old man with IPF on Nintedanib for three years presented with four loose, non-bloody bowel movements daily. He had bowel urgency, abdominal pain, and ten-pound weight loss despite loperamide use. Colonoscopy showed diffuse villous clubbing and erythema in the ileum. The entire colon revealed erythema and loss of vascular markings without ulcers (Figure 2). Histopathology revealed a paucicellular area of eosinophilic change in the lamina propria of the colon (Figure 3). There was no definite collagen deposition in this case. Nintedanib was discontinued and the patient's diarrhea resolved within two days; it returned with rechallenge.

DISCUSSION:
Nintedanib is a tyrosine kinase inhibitor, which is associated with diarrhea in about half of patients. Diarrhea is usually reported in the first three months of treatment and is generally adequately treated with anti-diarrheal medications. However, the specific entity of Nintedanib-induced colitis is a rare finding. There have only been two cases reported in the literature, neither of which described any particular pathologic findings. Our two cases demonstrate that symptoms resolve rapidly with drug withdrawal, recur rapidly upon rechallenge, and resolve again on withdrawal, suggesting a hypersensitivity reaction. Both cases demonstrate deposition of subepithelial eosinophilic material, which may offer a diagnostic clue to this drug induced diarrhea.
1724 Acquired Broncho-Esophageal Fistula After 10 Years of Esophageal Stent Placement
Authors: Elkhouly Mohamed A. , Attar Bashar M. , Elkafrawy Ahmed A. , Haque Zohaib , Salazar Miguel , Vohra Ishaan 
Published: October 2019

INTRODUCTION:
Acquired benign Broncho-esophageal fistulas (BEF) are uncommon and develops as a complication of inflammatory processes, malignant neoplasm and traumas of the chest but it has been rarely reported with esophageal or tracheal stents. We are reporting a case of Lt BEF after 10 years of esophageal stent placement for recurrent benign esophageal stricture.

CASE DESCRIPTION/METHODS:
A 52 years-old-female with history of HIV-1 infection was admitted with dysphagia to solid food. Her condition started 10 years ago after she presented with progressive odynophagia and dysphagia to solids and liquids. EGD at that time showed giant aphthous esophageal ulcer, 25 to 34 cm from the incisors, involving entire esophageal circumference. Biopsy showed ulcerated squamous mucosa with diffuse acute and chronic inflammation, negative stains for acid fast bacilli, fungal infection, CMV and HSV. She was treated with pantoprazole, hydrocortisone and thalidomide without improvement of her symptoms. Repeated EGD showed formation of benign esophageal stricture with negative repeated biopsy results. Over 6 months, she underwent multiple balloon dilatation of the stricture until 16 to 20 mm × 120 mm in length, Polyflex stent was placed with improvement of her symptoms She was lost for follow up before presenting again with progressive dysphagia to solids of 3 months duration associated with progressive weight loss. Esophagogram showed stable position of the stent in the mid esophagus with stable dilated proximal esophagus and no esophageal stricture. Due to concern of stent malfunction, the stent was removed but the patient continued to have dysphagia. Repeated esophagogram four days later, showed contrast media in the Left main bronchus tracking to the left lower lung lobe. Bronchoscopy and upper endoscopy showed chronic acquired Broncho-esophageal fistula extending from the lateral edge of membranous left main bronchus to the esophagus, 25 cm from incisors. PEG tube was placed for nutrition and she is planned for fistula repair in two weeks.

DISCUSSION:
BEF is a serious condition and treatment is mandatory to avoid continuous aspiration, chronic sepsis, and pulmonary failure, mainly in immunocompromised patients. There are no studies on the incidence of such fistulas after esophageal stent placements. On the other hand, some studies favored tracheal or esophageal stents as a corrective measure, although neither are free from complications, and they are palliative measures, making surgical repair the best option.
1824 Acute Esophageal Necrosis Secondary to Intrathoracic Gastric Volvulus Without Deadly Outcome
Authors: Chowdhury Nazif , Alom Md S. , Saleem Atif 
Published: October 2019

INTRODUCTION:
Esophageal necrosis is one of the rarely seen conditions of the esophagus. It usually happens in elderly patients and occurs secondary to impaired blood flow in combination with gastric outlet obstruction or gastroesophageal reflux disease. Gastric volvulus is also a rare condition for adults after the age of 50 and is a surgical emergency. Esophageal necrosis and gastric volvulus carry a very high mortality and morbidity if not treated quickly.

CASE DESCRIPTION/METHODS:
This is an 85-year-old female with past medical history of hypertension and hyperlipidemia. She presented to the hospital with dysphagia to solid food for one week. She complained of abdominal pain, nausea, vomiting, and chest discomfort. Physical examination revealed abdominal distention, mild epigastric tenderness and normal bowel sounds. CT scan of the abdomen and pelvis showed a very large hiatal hernia with the entire stomach herniated into the chest. There was a high clinical suspicion for esophageal necrosis and gastric volvulus given her continued symptoms and thus the decision was made to do an emergent upper GI endoscopy. The upper GI endoscopy showed necrosis of the mid and distal esophagus with a sharp demarcation at the mid esophagus. There was blackish discoloration with severe ulcerative esophagitis in the lower third of the esophagus. There was also a large 7 to 8 cm hiatal hernia with a large para-esophageal component. There was evidence of gastric volvulus. A nasogastric tube was placed endoscopically past the volvulus to decompress the stomach.The patient was taken for emergent laparoscopic surgery. Surgery revealed a large hiatal hernia with intrathoracic stomach, and lower esophageal necrotic ulcerations with perforation. This was evidenced by a 7 mm sized opening at the left lateral distal esophagus with leakage of saliva and gastric contents. The perforation and hiatal hernia were repaired and a G tube was placed. Patient did very well and was discharged home two weeks after surgery.

DISCUSSION:
Diagnosis of acute esophageal necrosis is often incidental during upper GI endoscopy for evaluation of upper GI bleeding. There are no laboratory or imaging findings specific for acute esophageal necrosis. A high clinical suspicion and urgent upper GI endoscopy are needed to make the diagnosis. This case demonstrates that emergent upper GI endoscopy followed by surgical repair can lead to a favorable outcome.
2053 Mesalamine-Induced Myocarditis in a Patient With Newly Diagnosed IBD
Authors: Ricci Michelle A. , Epstein Ian 
Published: October 2019

INTRODUCTION:
Mesalamine, a 5-ASA agent, is used as first line treatment in mild to moderate IBD. Adverse reactions include GI symptoms and often do not require discontinuation of therapy. Inflammation of the myocardium (myocarditis) is a rare but potentially lethal complication of mesalamine treatment. Early recognition and intervention is vital to prevent progression of inflammation and adverse patient outcomes.

CASE DESCRIPTION/METHODS:
A 62-year-old woman presented with an 8 month history of GI symptoms. Colonoscopy demonstrated patchy colonic inflammation which was biopsy confirmed. She was treated with mesalamine 500 mg PO OD. At a 6-week follow up visit, she had mild dyspnea and chest discomfort, but a direct causal relationship with mesalamine was not delineated. Due to persistent GI symptoms, her mesalamine dose was increased to 2 g PO BID. After 9 days her cardiorespiratory symptoms worsened. She was advised to discontinue mesalamine and seek emergency care. She was admitted to the CCU where an echocardiogram demonstrated an EF of 15%. Ischemic heart disease was ruled out with cardiac catheterization. Cardiac MRI was consistent with myocarditis. She was started on prednisone 20 mg OD. Following discontinuation of mesalamine with prednisone treatment, her cardiorespiratory symptoms improved. Follow-up echocardiogram showed minimal improvement (EF 20%).

DISCUSSION:
Mesalamine associated myocarditis is a rare phenomenon that presents 2-4 weeks after initiation of therapy. It is associated with severe clinical sequelae including myocardial dysfunction and death. Early case reports suspected the cause was the sulfapyridine group of sulfasalazine. There have been subsequent case reports of myocarditis from 5-ASA alone. The mechanism is believed to be a hypersensitivity reaction rather than direct cardiotoxicity. Supporting this theory are reports of return of symptoms when a 5-ASA agent is reintroduced. Clinical presentation is variable, and patients may present with normal laboratory and imaging studies. Myocarditis can rarely represent an extra intestinal manifestation of IBD. The improvement of this patient’s symptoms with discontinuation of mesalamine, and the temporal relationship between symptom onset and initiation of mesalamine favors mesalamine induced myocarditis. Given the significant consequences of this rare adverse reaction, dyspnea and chest discomfort in a patient on mesalamine should evoke prompt and permanent discontinuation of the drug. Delayed recognition can lead to patient morbidity.
2127 Splenic Abscess Management With a Lumen Apposing Metal Stent: Case Report
Authors: Nieto Jose , Nguyen Anthony , Dawood Enad 
Published: October 2019

INTRODUCTION:
Splenic abscess is an uncommon infection (incidence 0.5%) that if left untreated, could be fatal. The most common source of splenic abscesses is usually hematogenous spread from an infected source from another part of the body. The patient typically presents with fever, left upper quadrant pain, and/or splenomegaly. CT scan is the imaging modality of choice for diagnosing splenic abscess. Management of splenic abscess consists of antibiotic treatment and splenectomy. The use of percutaneous CT-guided drainage is a safer spleen-conserving alternative to surgery. In this case report , we describe novel approach, to treat splenic abscess via endoscopic ultrasound-guided (EUS) placement of a lumen apposing metal stent (AXIOS).

CASE DESCRIPTION/METHODS:
This is a 44 year old male with a past medical history significant for necrotizing pancreatitis and gastric varicies who presented to our center with fever and weakness. He was previously admitted 3 months prior with post ERCP necrotizing pancreatitis which was managed successfully with endoscopic therapy. The patient reported that on the day of admission, he developed a low-grade fever and lethargy. The abdomen was soft, mildly distended, with tenderness to palpation in the left and right lower quadrants. CT of the abdomen revealed a formation of a splenic abscess measuring 5 cm × 6.5 cm. Blood cultures were positive for ESBL and the patient was started on antibiotics. An EUS was performed that showed a splenic abscess and an abscessgastrostomy was successfully performed using a 10 × 10 mm lumen-apposing metal stent (LAMS). One week later a repeat EGD with debrivement and lavage of the abscess cavity was performed and a 10 F × 5 cm double pigtail stent was exchanged for the LAMS. On month later, a CT scan showed complete splenic abscess resolution and the double pigtail was removed. Six month CT scan showed no abscess recurrence.

DISCUSSION:
EUS has been described in the drainage of pelvic, mediastinal and intrabdominal abcess. In this report we describe the first use of lumen apposing metal stent for endoscopic management of a splenic abscesses. Lee et al first reported the use of EUS guided splenic abscess drainage with the use of a double pigtail stent. This approach showed to be safe and less invasive alternative to the standard of care. In cases of worsening clinical status and reported morbidities as high as 79% with surgical and percutaneous drainage procedures, endoscopic therapies should be considered in the management of splenic abscess.
2235 Nivolumab-Induced Severe Allograft Rejection in Recurrent Post-Transplant Hepatocellular Carcinoma
Authors: Kumar Shiva 
Published: October 2019

INTRODUCTION:
Hepatocellular carcinoma (HCC) is an established indication for liver transplantation (LT), but recurrent HCC post LT presents a unique therapeutic challenge. Nivolumab is an immune checkpoint inhibitor (ICPI) approved for treatment of HCC, but data on its safety following LT is limited. We present a case of Nivolumab-induced severe, steroid-resistant acute cellular rejection (ACR) in a patient with recurrent HCC post LT, treated successfully with thymoglobulin and plasmapheresis.

CASE DESCRIPTION/METHODS:
A 64-year-old male was noted to have evidence of locally advanced recurrent HCC on surveillance imaging two years post-LT. Systemic therapy using Sorafenib had to be discontinued due to severe proteinuria. Given limited therapeutic options and evidence of progressive disease, a decision was made to initiate Nivolumab. A week later, liver tests were elevated and continued to worsen significantly (peak values 3 weeks post infusion: ALT 424 U/L, AST 215 U/L, ALP 1074 IU/L, Br 16 mg/dL). Further infusions were discontinued. Liver biopsy revealed features of ACR with moderate portal inflammation, patchy bile duct injury and endotheliitis. Since ACR was resistant to high dose steroids, thymoglobulin was administered with some improvement. However, given persistent liver test elevation, we proceeded with plasmapheresis and after 5 sessions, marked improvement was noted and repeat biopsy showed resolution of ACR (Figure 1).

DISCUSSION:
Nivolumab, a monoclonal antibody that targets programmed cell death protein 1, was FDA approved in 2017 for the treatment of HCC in patients previously treated with Sorafenib. However, there is limited experience with its use in solid organ transplant recipients. The immunological mechanism of nivolumab induced ACR is unclear and there is no consensus on management. As with our patient, none of the reported cases responded to high-dose steroid therapy. Use of thymoglobulin and plasmapheresis has not been reported in this setting previously. Even though plasmapheresis would likely not impact nivolumab-induced T cell–mediated immune rejection, given its long half- life, we hypothesized that plasmapheresis could help by removing the medication from the circulation. Severe ACR with ICPI therapy could result in allograft failure, with limited therapeutic options. Factors that contribute to ACR and whether this may be impacted by length of time after LT remain unclear. There is a critical need for safe and effective systemic options for treatment of recurrent HCC post-LT.
2397 Successful Reversal of Sickle Cell Intrahepatic Cholestasis Associated Acute Liver Failure With Combined pRBC and Plasma Exchange Transfusion: A Case Report
Authors: Galappaththy Suguni Loku , Kaddourah Osama , Dandekar Monisha , Likhitsup Alisa 
Published: October 2019

INTRODUCTION:
Sickle cell intrahepatic cholestasis (SCIC) with acute liver failure (ALF) is a severe variant of Sickle cell hepatopathy that has significant mortality despite aggressive supportive therapy. Even though packed red blood cells (pRBCs) exchange has vastly improved outcomes, there is little evidence on alternative therapies to treat those who show inadequate response to pRBC exchange transfusion (ET).

CASE DESCRIPTION/METHODS:
A 37-year-old African American male with Hemoglobin SS disease complicated by chronic pain and nephropathy ESRD on dialysis, who was referred to our liver transplant program for ALF. Patient presented with lethargy and fever. Upon arrival he was somnolent, jaundiced, cardiopulmonary and abdominal exam was unremarkable, no focal neurological deficits but presence of asterixis was noted. Hb 6 g/dL, WBC 13,000/µL, Platelet 147,000/µL, corrected reticulocyte count 5.9%, LDH 1816 IU/L, Total bilirubin 49 mg/dl, direct bilirubin 37 mg/dL, ALT 112 IU/L, AST 259 IU/L, ALP 296 IU/L, albumin 3.5 g/dL and INR 1.9. CT head was unremarkable. MRCP revealed hepatomegaly, cholecystectomy without evidence of biliary obstruction. Ultrasound duplex liver showed patent hepatic vessels. Other causes of ALF including drugs, alcohol, acetaminophen, and viral hepatitis etiology were excluded. N-acetylcysteine infusion protocol was initiated. Patient received 10 units pRBC ET. Despite successful reduction of HbS fraction from 79.5% to 16%, the patient remained encephalopathic with asterixis and developed severe headache. Furthermore, bilirubin and INR continued to rise (Figure 1). Transjugular liver biopsy revealed portosystemic gradient of 20 mmHg. Liver pathology showed sinusoidal distension by sickled erythrocytes, zone 3 predominant intracanalicular cholestasis with ballooned hepatocytes and hepatocyte siderosis (Figure 2). Total 9L of plasma ET was performed on 2 consecutive days with successful reversal of headache, encephalopathy, and coagulopathy. His bilirubin levels continue to decline. He did not require a liver transplant and was discharged home with prophylaxis pRBC ET to maintain HbS fraction < 30%.

DISCUSSION:
SCIC with ALF is rare with significant mortality. Plasma ET was used in our patient whom ALF was refractory despite adequate pRBC ET (HbS < 30%). Larger studies are needed to evaluate plasma ET benefit in sickle cell disease patients with end organ damage, regarding treatment outcome as well as transplant-free survival.
2434 Cholestatic Jaundice: A Rare Presentation of Coxiella burnetii
Authors: Zaibaq-Krill Jenine , Weber Frederick H. 
Published: October 2019

INTRODUCTION:
Q fever, caused by Coxiella burnetti, is a zoonotic infection which naturally infects animals. Humans can contract it by inhalation of contaminated feces, ingestion of contaminated milk, and very rarely by ingestion of contaminated organs. Q fever can have varying clinical presentations including flu-like illness, pneumonia, or endocarditis, but hepatitis is the most common amongst young, healthy patients. We present a striking case of cholestatic jaundice secondary to Q fever.

CASE DESCRIPTION/METHODS:
A 43 year old male presented with a two week history of severe myalgias, headache, jaundice, fever, and abdominal pain which began after returning to the US from his 7th military tour in Afghanistan. He denied exposure to contaminated water or ticks but had eaten local cuisine including goat liver. He was febrile to 102.5 F, had scleral icterus, conjunctival suffusion, was jaundice, and had hepatosplenomegaly. Pertinent labs: platelets 59,500, total bilirubin 12.4 mg/dL, direct bilirubin 8 mg/dL, AST 41 units/L, ALT 56 units/L, and alkaline phosphatase 138 units/L. Pipercillicin/tazobactam and doxycycline were started empirically. There was no biliary obstruction on MRCP. Testing for CMV, EBV, HIV, syphilis, malaria, Rocky Mountain Spotted Fever, tularemia, ehrlichiosis, chikungunya, leptospirosis, histoplasmosis, tuberculosis, Q fever, and dengue were obtained. Ten days into his hospital stay the Coxiella burnetii DNA PCR returned positive. Despite optimum therapy on doxycyline, he did not defervesce for 14 days, 24 hours after hydroxychloroquine was added. At follow up, he remained afebrile and his total bilirubin had normalized to 0.9 mg/dL (peak of 13.7 mg/dL).

DISCUSSION:
This is a rare presentation of a rare disease given the degree of hyperbilirubinemia as Q fever typically causes a hepatocellular pattern of injury. It is unusual for Q fever to cause a bilirubin greater than 5 mg/dL. Also, febrile duration despite appropriate pharmacologic therapy has been found to be prolonged in patients with hyperbilirubinemia as opposed to those without, as was the case with our patient. Thrombocytopenia has also been described as a rare feature of Coxiella burnettii infection. Given this clinical picture, it is important to consider Q fever for a direct hyperbilirubinemia, prolonged fever, and thrombocytopenia in patients with a potential exposure history. It is also essential to consider oral transmission of Coxiella burnetti as a potential rare mode of transmission.
2734 Immunotherapy-Mediated Hemorrhagic Gastritis After Ipilimumab and Nivolumab Therapy
Authors: Earasi Athidi G. , Figueroa Esteban J. , Mehra Pooja , Baray Merwise , Crawford Michael P. , Hall Richard D. , Behm Brian 
Published: October 2019

INTRODUCTION:
Combined checkpoint inhibitor immunotherapy with ipilimumab (anti-cytotoxic T-lymphocyte antigen 4 antibody) and nivolumab (anti-programmed cell death receptor 1 antibody) has greatly advanced the treatment of multiple malignancies but is associated with increased immune-related toxicities. Gastrointestinal toxicity is one of the most frequent adverse effects, and while lower GI tract toxicity, such as anti-CTLA-4-mediated colitis, is well known, severe toxicity of the upper GI tract is rare and not well described. We report a case of severe hemorrhagic gastritis in a patient after initiation of ipilimumab and nivolumab therapy for metastatic renal cell carcinoma.

CASE DESCRIPTION/METHODS:
A 70-year-old man with history of metastatic renal cell carcinoma and recent immune-related myocarditis initially presented with myasthenic weakness after receiving single doses of ipilimumab and nivolumab 5 weeks prior. His presentation was most consistent with seronegative, immune-mediated myasthenia gravis-like syndrome. He was treated with intravenous steroids and plasmapheresis. After 9 days of steroid therapy, he developed large volume melena requiring 4 units of blood despite twice-daily proton pump inhibitor therapy. Endoscopic evaluation revealed diffuse, severe inflammation with hemorrhage characterized by adherent blood and erythematous, friable gastric mucosa in the body, antrum, and prepyloric regions. Hemostatic spray was applied as a temporizing measure to control bleeding. Biopsy specimens demonstrated neutrophilic microabscesses with intraglandular apoptotic bodies, increased lymphocytes and scattered neutrophils in lamina propria, and reactive mucosal features. These findings were compatible with checkpoint inhibitor-induced acute gastritis. Immunohistochemical stains for H. pylori and cytomegalovirus were negative. Despite immunosuppressive therapy with high dose steroids, mycophenalate mofetil, and trial of infliximab, he continued to decline with ongoing anemia and progressive weakness. He was transitioned to comfort measures and died soon afterward.

DISCUSSION:
To our knowledge, this is the first reported case of severe hemorrhagic, non-infectious gastritis as a rare complication of immunotherapy with ipilimumab and nivolumab. Physicians should be aware that checkpoint inhibitor-induced toxicity of the upper GI tract can occur early after initiation of therapy and have a severe, refractory course. Management includes exclusion of infectious process and immunosuppressive therapy.