United States


As clopidogrel demonstrates both long-term and short-term situational benefits for morbidity and mortality, it has become one most prescribed medications in the medical field. The mechanism of clopidogrel hepatotoxicity is not known, is difficult to reproduce, and may be due to the complex hepatic metabolism of the clopidogrel molecule. Immunologic features are usually not prominent, but hypersensitivity reactions to clopidogrel have been described. We describe the case of a patient who experienced clopidogrel-induced liver injury. The patient was an elderly woman who presented to the emergency department with nausea and generalized weakness. She had 1 prehospital episode of nonbilious, non-bloody vomiting, along with hyperchromic urine and constipation for 3 days pre-hospitalization. 13 days prior to this admission she was hospitalized for a transient ischemic attack (TIA) and discharged with clopidogrel and aspirin for 21 days. She had an uncomplicated posthospital course until the onset of these new symptoms. On admission, patients showed a new-onset dramatic elevation in liver markers. Abdominal MRI revealed moderate edema along the portal triad and a HIDA scan came back normal. Acetaminophen level and hepatitis screen were noncontributory. Her liver enzymes steadily elevated to the several thousands without reasonable explanation until Clopidogrel was isolated as the cause of the patient’s liver injury, and was discontinued with success. Her liver enzymes steadily down trended with discontinuation of clopidogrel and she improved dramatically. As more tests came back inconclusive for the underlying etiology of this patient’s liver injury, and her clinical condition remained undefined. A reasonable explanation for this patient’s condition was a diagnostic challenge. This was until her relatively recent initiation of Clopidogrel was considered. Clopidogrel was the only new medication this patient began taking between her two hospitalizations, and its discontinuation was followed by dramatic success. As these medications have become a mainstay of primary care in medicine, Clopidogrel side effects are critical for providers to be aware of and to understand thoroughly as they prescribe this incredibly beneficial class of medications.



AMA Research Challenge 2022

Clopidogrel: A Case Report of Suspected Drug Induced Liver Injury

# Welcome everyone to ACL 2022!

The 60th Annual Meeting of the Association for Computational Linguistics is taking place May 22-27, 2022 as a hybrid event, in Dublin and online. We are happy to welcome all of you to this anniversary edition with an almost 50-50 in-person and virtual participation. 
The main conference program features oral presentations, in-person and virtual posters and demo sessions, a plenary session for our best paper presentations and awards, three amazing keynote events and two new initiatives of invited talks: Spotlight Talks for Young Rising Stars (STIRS) and The Next Big Idea Talks. Posters (including Findings of ACL 2022) and demos are grouped by areas for both the in-person and the virtual sessions. For the virtual component, the talks will be on Zoom and the posters and the demos will be in GatherTown. The Student Research Workshop will have an oral session and a poster session as part of Poster Session 1. The program also features eight Tutorials and 28 Workshops. 

 
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ACL 2022

The Association for Computational Linguistics (ACL) is the premier international scientific and professional society for people working on computational problems involving human language, a field often referred to as either computational linguistics or natural language processing (NLP). 

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Ricardo Correa, MD, EdD
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Charles Lopresto, DO

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Welcome to the largest national, multi-specialty research event featuring research from 750 medical students, residents and fellows, and international medical graduates.


Background:
A rare consequence of DRESS syndrome is eosinophilic myocarditis. Our case discusses this condition in conjunction with utilization of the lifesaving modality Extra-Corporeal Membrane Oxygenation, and treatment options.

Case Presentation:
A 30-year-old female patient with a PMHx of DM1, adrenal insufficiency, vitiligo and seizure disorder, which all developed following DRESS syndrome from lamotrigine exposure presented for chest pain. She had no prior cardiac history. EKG showed low voltage QRS. Echocardiogram revealed a small pericardial effusion, pericardial thickening, EF of 55 to 60%, and no tamponade physiology. Labs showed: BNP 4194, CRP 1.48, ESR 7, and a troponin peak of 3121. The patient was treated for acute pericarditis with colchicine and prednisone with resolution of her symptoms.
Sixteen days later, she presented back with recurrent chest pain and hypotension. Labs showed: BNP 14,981 CRP 2.94, troponin peak of 24,097. TTE showed EF 30-35%. EKG showed new RBBB and inferior q waves. Repeat TTE showed EF 10-15%. Left heart catherization revealed normal coronary arteries. Following LHC, multiple episodes of ventricular tachycardia were noted, requiring defibrillated and intubation. Following intubation, she became pulseless requiring CPR and placed on VA ECMO. The patient remained on ECMO support and was started on immunosuppressive modalities following endocardial biopsy confirming eosinophilic myocarditis. Four days after discontinuing ECMO, TTE showed EF 45% with normal RSVP.

Discussion:
DRESS is a rare and potentially life-threatening condition caused by delayed hypersensitivity reaction. Although many cardiac imaging tests assist in the diagnosis, the most definitive remains endomyocardial biopsy. This case report is unique in that there is no other case report that emphasizes the importance of early ECMO support and an anti-IL- 5 antibody in the treatment of eosinophilic myocarditis. In this case, the role of ECMO was significant in the bridge to recovery.
Typical, long-term treatments of eosinophilic myocarditis include steroids in adjunct with immunosuppressive strategies. Our patient’s regimen included prednisone daily, mycophenolate twice a day, and mepolizumab injections monthly. Eosinophils acquire IL-5 receptor on their surface during the early stages of differentiation, and maturation. Mepolizumab, is an anti-IL-5 recombinant humanized monoclonal antibody, which stops the interaction between IL-5 and its receptor on eosinophils.

DRESS Syndrome Associated Eosinophilic Myocarditis: A Rare Condition Leading to Life Saving Measures on ECMO

Background:
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is typically characterized by extensive skin rash with associated visceral organ involvement, fever, lymphadenopathy, and eosinophilia. The condition typically has a two-to-eight-week latency period in symptom development following initiation of offending drug. Additionally, hepatic injury is the most common visceral organ involved with separate long-term sequelae of DRESS including autoimmune conditions such as autoimmune thyroid disease, vitiligo, and lupus erythematosus. 

Case Presentation: 
An 18-year-old, college-attending male, with a two-month history of Bactrim use for acne treatment, presented with an eight-day history of diffuse rash without mucosal involvement. Patient initially developed a pruritic rash that responded to Zyrtec and the discontinuation of Bactrim. Patient later became febrile and the rash returned. The rash was described to start as a pink, maculopapular rash that coalesced to become more diffuse, violaceous plaques. 
The patient presented to campus health services where he was received a dose of epinephrine and methylprednisolone due to anaphylaxis concerns along with ceftriaxone for meningitis concerns, and referred to the hospital for further evaluation. His hospital workup was significant for leukocytosis without eosinophilia with accompanying transaminitis, hyperbilirubinemia, elevated lactate, and abnormal coagulation studies. Rickettsia labs and blood cultures were negative, ruling out rocky mountain spotted fever and meningococcemia. Patient also had a normal EKG and low TSH with a normal free T4. 
Given these findings and patient’s recent Bactrim use, the patient was diagnosed with DRESS and started on prednisone. Over the next few days, the transaminitis and hyperbilirubinemia improved. Given the improvement in symptoms and no new presentation of organ involvement, patient was discharged with dermatology follow-up for a steroid taper and endocrinology assessment for thyroid abnormalities secondary to or independent from DRESS. 

Discussion: 
Despite its name, DRESS can present without eosinophilia. Early recognition despite the condition’s heterogenous presentation is imperative for triaging severity of disease and treatment initiation with glucocorticoids, discontinuation of offending drug, and appropriate supportive care. Additionally, the use of Bactrim for the acne treatment should be used with caution given its association with this severe drug reaction.

DRESS vs. DRSS: The Heterogenous Presentation of Drug Reaction with Eosinophilia and Systemic Symptoms

Background:
Invasive fungal sinusitis is a rare but possibly fatal complication of Covid-19 infection. We report an extremely rare case of invasive fungal sinusitis due to an uncommon pathogen, Alternaria.

Case Presentation:
Patient is a 49-year-old female with a history of poorly controlled diabetes presenting with right maxillary fungal sinusitis with abscess. One month prior, after recovering from COVID-19 pneumonia, she developed right facial swelling, diplopia, blurry vision, and pain with extraocular movements. She was admitted at an outside hospital for diabetic ketoacidosis and facial cellulitis with right maxillary sinusitis, which was treated with piperacillin-tazobactam and vancomycin. She also received micafungin for possible fungal infection, which was discontinued after culture showed no growth at 1 week. Later, the patient had progressive facial symptoms prompting her to return to the emergency room. MRI of the orbit showed acute abscess with concerns for meningeal involvement in her right orbital structures and she was restarted on antibiotics. Fungal culture from prior admission was noted to have grown Alternaria species. She was transferred to our hospital and was treated with multiple surgical debridements and 2 weeks of voriconazole, amphotericin B, and daptomycin with improvement in her symptoms. She was discharged to a SNF to continue receiving treatment.

Discussion:
While studies on fungal sinusitis in association with COVID-19 have been limited, Mucor and Aspergillus appear to be the most common pathogens. Possible risk factors for COVID-19 associated fungal sinusitis include steroid use, diabetes, renal failure, and hypertension. 

Alternaria is a dematiaceous hyphomycete commonly involved in human infection. The most frequent clinical manifestations are cutaneous and subcutaneous infections, followed by oculomycosis, rhinosinusitis, and onychomycosis. Important risk factors include solid organ transplantation, Cushing’s syndrome, and bone marrow transplants. 

A noted complication in the care of our patient was the delayed recognition of fungal sinusitis; her fungal culture did not show growth until after discharge. Many species involved in fungal sinusitis, including Alternaria, are detected after 1 week of culture; however, fungi can be detected after longer incubation periods. In patients with multiple risk factors and COVID-19 infection, it may be important to continue monitoring for fungal isolates, even if patients are improving clinically.

Fungal Sinusitis with COVID-19: Not Always Mucor!

Haemophilus parainfluenzae is a gram-negative coccobacillus commonly found in the normal flora of the mucosal membranes of the upper respiratory tract. It has been rarely reported to cause invasive infection including meningitis, endocarditis, urinary tract infections, soft tissue infections, hepatic abscess, and epidural abscess. Osteomyelitis and septic arthritis caused by Haemophilus parainfluenzae are a rare entity with just a few cases described in the literature. 

Case Presentation
A 72-year-old man presented with a two-days of lower back pain. The pain was constant, non-radiating and worse with movement. He had a history of recurrent low back pain due to a previous L3 compression fracture and recurrent acute sinusitisepisodes. Physical exam was remarkable for tenderness to palpation of paraspinous muscle bilaterally at L3-L5 level, and limited flexion of the back due to pain. CT of the lumbar spine showed chronic changes including compression fracture and retropulsion of L3 vertebral body with moderate to severe narrowing of spinal canal. Despite been sent home with anti-inflammatories and muscle-relaxants, he continued with intractable back pain for the next two months. At this time, erythrocyte sedimentation rate was noted to be 36 mm/h and C-reactive protein 3.8 mg/dL. MRI showed concerning findings for osteomyelitis and discitis. CT guided- aspiration bone biopsy cultures grew Haemophilus parainfluenzae. He was treated with ceftriaxone for 6 weeks with improvement of symptoms. 

Discussion
Bone and joint infections caused by H. Parainfluenzae have rarely been reported in literature. From our review of the literature, most of the cases mentioned in the literature about bone and joint infections cause by H. parainfluenzae were on patients with underlying chronic conditions, bone structural abnormalities, or recent procedure. From these cases hematogenous spread or close contaminated source seems to be the most common routes of infection for Haemophilus parainfluenzae given patients history. In our case, the patient had a recent history of recurrent upper respiratory infections with an underlying bone abnormality that could have served as a reservoir for infection. Although H. parainfluenzae is a rare cause of bone infection, careful evaluation of patient’s history and possible preceding factors for infection should be considered in every patient.

Haemophilus parainfluenzae ostemyelitis: A case report and literature review

Background
Hemosuccus pancreaticus is a rare form of upper gastrointestinal bleed with an incidence of 1 in 1500 cases that is defined as hemorrhage of the pancreatic duct, typically in the setting of a patient with chronic pancreatitis, vascular diseases, or pancreatic tumors. A common presentation occurs from pseudoaneurysm formation in the pancreatic circulation, which becomes prone to rupture, causing hemorrhage. Symptoms of epigastric abdominal pain radiating to the back that spontaneously resolve and are followed by melena are highly indicative of hemosuccus pancreaticus. CT angiography is the gold standard for identifying active hemorrhage, and coil embolization is a common and effective treatment once patients are hemodynamically stable.

Case Presentation
Here we present a case report of a 64 year-old male with a past medical history of a
mechanical mitral valve replacement, on warfarin, and without a history of acute or chronic pancreatitis, who presented to the E.D. with a chief complaint of 3 days of melena followed by an episode of a massive bright red bloody bowel movement causing persistent lightheadedness. He had a similar episode of bleeding months ago for which he underwent a push enteroscopy that revealed no abnormalities. He also endorsed a significant history of alcohol use, consuming 5-6 drinks a day. He was hypotensive to the 60s/40s with a hemoglobin (Hgb) of 5.0 and an INR of 12. He was volume resuscitated with fluids, packed red blood cells (pRBCs), vitamin K, and fresh frozen plasma, after which he became hemodynamically stable. An upper endoscopy revealed frank blood at the Ampulla of Vater. Subsequent CT angiogram revealed active contrast extravasation into the second portion of the duodenum from a gastroduodenal artery (GDA) segment, and he successfully underwent a GDA coil embolization with no further bleeding. He remained hemodynamically stable and was started on a Lovenox bridge to warfarin before discharge with a plan for outpatient follow-up.

Discussion
This case illustrates the point that hemosuccus pancreaticus should be considered in
patients with a history of alcohol abuse who present with a history of melena and a
significant acute gastrointestinal bleed, even in the absence of a history of chronic
pancreatitis.

Hemosuccus Pancreaticus in the setting of a supra-therapeutic INR

Hypercalcemia Secondary to B Cell Lymphoma – A Case Report

Background
Blastoschizomyces capitatus is an emerging opportunistic pathogen that can be found on the flora of the skin, gastrointestinal tract and upper respiratory tract. Invasive B. capitatus infection is more commonly seen in neutropenic patients, but can also be seen in immunocompetent hosts with COPD, in prolonged use of corticosteroids and/or broad-spectrum antibiotics and antifungals, intensive care unit patients, especially those on total parenteral nutrition or with central venous catheters in place. 


Case Presentation
38-year-old male with no past medical history who was admitted to the intensive care unit (ICU) for the management of diabetic ketoacidosis. Initial chest Xray, urinalysis, urine culture and blood cultures were all negative. On hospital day 2, he developed a fever with maximum temperature of 105°F and had leukocytosis with neutrophilia. He received 1 dose of piperacillin-tazobactam 2.25 g and was continued on cefepime 1 g twice daily for 9 days. Later, his blood cultures indicated Staphylococcus epidermidis and he was treated with 8 doses IV vancomycin. Due to persistent fever and leukocytosis, he was started on meropenem 500 mg daily and micafungin 100 mg daily, both for 7 days. He was placed on total parenteral nutrition for ileus and was given steroids for the treatment of thrombotic thrombocytopenic purpura. He also required the placement of a subclavian triple lumen catheter and a dialysis catheter. On day 29, his blood cultures were positive for blastoschizomyces capitatus. He completed treatment with Amphotericin B liposomal 500 mg daily for 8 days, Voriconazole 700 mg x 1 dose, then 400 mg twice daily x 13 days. His central triple lumen catheter and dialysis catheter were replaced. Repeated blood culture showed resolution of his bacteremia. 

Discussion
ICU patients have many of the risk factors for developing this opportunistic infection. Limiting the use of corticosteroids and broad-spectrum antibiotics, starting the patient on enteral nutrition early and removing central venous catheters when appropriate is critical in preventing invasive B. capitatus infection. Detection of capitatus in blood is associated with high mortality and early treatment with liposomal amphotericin B and voriconazole is paramount.

Isolated blastoschizomyces capitatus in an immunocompetent host

Lethal And Rare Side Effect Of Cyclosporin That Is Reversible If
Diagnosed Timely.
Introduction: Posterior Reversible Encephalopathy Syndrome-PRES, is a lethal but reversible condition that is caused due to impairment of cerebral perfusion autoregulatory mechanism. There are limited number PRES cases reported from Cyclosporine and hence wanted to alert the physician community to be more vigilant about closed surveillance of this population who presents with acute neurological changes.
Case Description: 22-year-old male with history of Cystic Fibrosis status post double lung and liver transplant, on cyclosporin presented to the ED after having a witnessed seizure. Patient reports of having severe headache upon waking up that morning, radiating from neck to his occipital area followed by nausea and vomiting which culminated in seizure. Patient also had another episode of seizure in the ED. Patient received Ativan and Keppra. Patient had fatigue but denies any other complains in ED. Vitals were BP-180/121, RR-20, HR-98, T-97.5F and SPO2 98% on 2L NC. On Physical Examination Patient appeared lethargic and had decreased breath sound bilaterally on auscultation of lungs. After the seizure at the hospital patient’s BP normalized. Neurologist and transplant team was contacted, and MRI was recommended along with continuation of Keppra and holding of cyclosporin.
Cyclosporine levels were checked and found to be normal. MRI showed hyperintense FLAIR and T2 signal within cortical/subcortical region of the bilateral occipital, frontal lobes and left cerebellum. The diagnosis of PRES was established. Due to lack of neurology service at our hospital, patient was transferred to another facility for further management. On further investigation it was found out that Patient had once developed PRES syndrome when he was initially on tacrolimus and was later changed to Cyclosporine 2 years back.
Discussion: PRES occurs when cerebral perfusion autoregulation is impaired
resulting in radiographic evidence of vasogenic edema. Presentation includes
neurological symptoms ranging from headache to seizures. Due to its vague
symptoms, PRES is occasionally missed. It is also commonly associated with
Tacrolimus, but we should be aware that any immunosuppressive or
cytotoxic medications can cause this. It is also to be noted that these patients
present with HTN emergency or labile BP but nitroglycerine should never be
used as it can aggravate cerebral edema. PRES is reversible and patients can
recover within weeks if diagnosed timely by rapid control of BP or withdrawal
of offending drug. If diagnosis is delayed or missed Patients can have
permanent neurological injury or even death due to high intracranial
pressure. Recognition of this syndrome is critical to institution of appropriate
therapy and prevention of this lethal outcome. This case illustrates that If a
patient presents with neurologic symptoms as mentioned above, and is
either in hypertensive emergency, has labile blood pressures and is on
cytotoxic agents or immunomodulators PRES should be in the differential
diagnosis.

Lethal And Rare Side Effect Of Cyclosporine That Is Reversible If Diagnosed Timely.

Mycobacterium abscessus complex (MABc) is part of the rapid-growing non-tuberculous mycobacteria group that usually resides in natural water sources. When it affects humans, it can be highly resistant and difficult to manage. The most common presentation is localized, mainly in the lungs and soft tissue, but can be generalized in immunocompromised patients. Here we present a case report of a 40-year-old female with a chronic infection of the abdominal wall after abdominoplasty.

A Rare Insidious Case Of Skin And Soft Tissue Infection Due To Mycobacterium Abscessus: A Case Report

Gastrointestinal stromal tumors (GIST) are the most common type of gastrointestinal tract mesenchymal tumors. They are typically characterized by activating mutations in the KIT or PDGFRA oncogenes. They usually present incidentally or with chronic and nonspecific symptoms like bloating, early satiety, fatigue, or anemia in patients over the age of 60 years. Approximately 5% of cases will present with an abdominal mass. Up to 10% of GISTs will present with advanced disease where the primary tumor is difficult to establish. We present a case here of a metastatic GIST with an unusual and late presentation, with a palpable abdominal mass, and without an obvious primary tumor on initial CT/ MRI imaging. 


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