Idelalisib-Induced Pneumonitis in Chronic Lymphocytic Leukemia.

Idelalisib, a phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, effectively treats relapsed chronic lymphocytic leukemia (CLL). While this targeted approach offers a therapeutic edge, particularly in B-cell malignancies, it is associated with complications such as pneumonitis. This report details idelalisib-induced pneumonitis, highlighting the importance of early diagnosis and tailored treatment in achieving a favorable patient outcome.

Delayed Presentation of Malignancy-Associated Pseudoachalasia of the Gastric Cardia.

Pseudoachalasia is a condition in which symptoms, manometry, and imaging findings highly resemble primary achalasia but has a secondary etiology. The majority of patients with pseudoachalasia have the condition as the result of a malignancy, most often at the gastroesophageal junction. There may be issues with timely identification of this malignancy as symptoms are often obscure with diagnostic testing yielding nonspecific results. We describe a case of a 65-year-old diabetic female smoker with a four-month history of intractable vomiting, abdominal pain, and weight loss who was belatedly found to have an adenocarcinoma at the gastric cardia necessitating a total gastrectomy and chemotherapy administration. The case educates clinicians on the clinical alarm symptoms related to malignant pseudoachalasia and stresses the paramount importance of performing a timely esophagogastroduodenoscopy in all cases of achalasia, even with seemingly normal imaging, to rule out pseudoachalasia related to malignancy.

Mycophenolate Mofetil-Induced Colonic Injury Manifesting Endoscopically As Ischemic Colitis.

Mycophenolate mofetil (MMOF) is a commonly used immunosuppressive prodrug in kidney transplant patients. However, it is not without side effects. The most common of these is diarrhea which inadvertently leads to colonoscopic and endoscopic evaluation when all other workup returns negative. Colonoscopies often show diffuse ulcers and colitis changes depending on the degree of diarrhea. In rare situations, MMOF-induced ischemic colitis may occur on gross endoscopy. We describe an unusual phenomenon of an adult male status post renal transplant with histopathologically diagnosed MMOF-induced colitis who developed gross endoscopic findings concerning ischemic colitis. Our case highlights the importance of recognizing that MMOF-induced colonic changes can rarely mimic ischemic colitis. With this in mind, we aim for gastroenterologists to better understand the varying endoscopic colonic findings of this immunosuppressive drug.

Eculizumab in the Treatment of Gemcitabine-Induced Atypical Hemolytic Uremic Syndrome.

Gemcitabine-induced hemolytic uremic syndrome is an often-missed condition. We present a case outlining the successful management of a patient with metastatic cholangiocarcinoma treated with gemcitabine who subsequently developed hemolytic uremic syndrome. Early recognition and stopping gemcitabine are essential in this patient population. Complement inhibitors have been used, and our patient improved on eculizumab therapy.

Diagnostic Obscurity of Gastrointestinal Subepithelial Tumors: An Organizing Gastric Hematoma Requiring En Bloc Resection.

Gastric subepithelial tumors (SETs) are often incidentally found during examinations of the gastrointestinal tract. Able to arise from any layer of the stomach, these tumors are predominantly asymptomatic and are classified as either benign or malignant based on size, consistency, shape, and mobility as determined by endoscopic evaluation. We present the first reported case of a gastric SET presenting as a chronic organizing hematoma. In doing so, we discuss the necessity of multimodal imaging techniques and multidisciplinary management in identifying often obscure gastric SETs to intervene on potentially malignant masses early.

Early orbital involvement in a rare diagnosis of Burkitt-like lymphoma with 11q aberration.

Burkitt-like lymphoma with 11q aberration is a rare condition that poses a diagnostic challenge due to similarities with Burkitt's lymphoma. Due to the rarity of cases, no specific guidelines exist for therapy, and it is treated the same way as Burkitt's lymphoma. We present such a case with initial orbital involvement, an unusual manifestation. Our patient achieved remission with induction chemotherapy, although he will need regular follow-up given the paucity of information on long-term monitoring in these patients.

Diffuse Large B-Cell Lymphoma of the Cecum.

Lymphoma when arising from sites other than lymph nodes is termed extranodal lymphoma, commonly affecting the gastrointestinal tract. Primary colorectal lymphoma is a rare phenomenon among malignancies affecting the colon. We report a case of a patient with a history of Burkitt lymphoma in remission, presenting with a large cecal mass and a new diagnosis of diffuse large B-cell lymphoma treated with chemotherapy.

Carfilzomib-Induced Tumor Lysis Syndrome and Biventricular Heart Failure in a Patient With Multiple Myeloma.

Carfilzomib is a proteasome inhibitor (PI) used in multiple myeloma (MM) that is resistant to other therapies. Despite its efficacy and potency, carfilzomib has been associated with kidney injuries, cardiovascular toxic effects, and hematological adverse events. Tumor lysis syndrome (TLS) following the use of PIs in MM, a malignancy not known to cause TLS, has seldom been reported. We present a case of a patient with a known diagnosis of MM who received prior therapy including bortezomib, a first-generation PI, developing worsening heart failure and new onset TLS days after the administration of carfilzomib.

An Obscure Presence of Gastroduodenal Involvement in a Newly Diagnosed Ileocolonic Crohn's Disease Patient.

Whereas typical Crohn's disease is confined to the terminal ileum and presents with abdominal pain and diarrhea, gastroduodenal manifestations of Crohn's disease are rare, with often asymptomatic patient presentations and inconclusive diagnostic testing. It is, however, a more severe form of Crohn's disease and thus warrants treatment with steroids and biologics much earlier than its ileocolonic counterpart. We present the case of a young, otherwise healthy, male with newly diagnosed ileocolonic Crohn's disease with concurrent gastroduodenal involvement that initially failed management with biologic agents. We discuss the clinical manifestations and often obscure pathology of gastroduodenal Crohn's disease and highlight the necessity of performing a concurrent esophagogastroduodenoscopic evaluation on newly diagnosed ileocolonic Crohn's disease to assess the presence of upper gastrointestinal involvement.

Venetoclax and Azacitidine in the Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm Refractory to Conventional Therapy.

Blastic plasmacytoid dendritic cell neoplasm is a rare and aggressive hematological malignancy associated with poor prognosis and limited treatment options. No guideline-directed therapy existed until the approval of tagraxofusp in 2018 by the Food and Drug Administration. Multiple clinical trials are undergoing as treatment options continue to evolve. We report a case refractory to tagraxofusp and pivekimab sunirine with subsequent remission achieved on venetoclax and azacitidine therapy.

Severe Cholestatic Drug-Induced Liver Injury With Cephalosporin Use.

Drug-induced liver injury (DILI) is a phenomenon that occurs with nearly all classes of medications. Cholestatic DILI represents a fraction of these cases and can present as bland cholestasis, cholestatic hepatitis, secondary sclerosis cholangitis, and vanishing bile duct syndrome. Risk factors have been identified for cholestatic DILI, including older age, genetic determinants, and certain medications such as amoxicillin-clavulanate. Here, we describe a complicated case of severe cholestatic DILI secondary to cephalosporin use. A 27-year-old female presented to the hospital initially with fever and abdominal pain for four weeks after an emergency C-section for pre-eclampsia and hemolysis, elevated liver enzymes, lowered platelets (HELLP) syndrome. She was found to have a retroperitoneal abscess and underwent bilateral drain placement. She was initially started on cefazolin, and then coverage was broadened to cefepime. Shortly after, alkaline phosphatase (ALP) rose and peaked at 3498 IU/L, with aspartate aminotransferase (AST) and alanine transaminase (ALT) elevated at 274 IU/L and 122 IU/L, respectively. Extensive testing for secondary causes and a liver biopsy were consistent with DILI. Liver enzymes down-trended with the cessation of cefepime. This case report highlights that prompt recognition of the culprit medication is paramount to recovering normal liver function.

Pulmonary Arteriovenous Malformation in a Rare Case of Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia is a rare condition presenting with anemia requiring transfusion and nosebleeds often refractory to supportive therapy. We discuss a case of a male in his 60s with a history of epistaxis, anemia requiring transfusions, and acute on chronic worsening shortness of breath presenting for evaluation. He was diagnosed with hereditary hemorrhagic telangiectasia. In addition, he was found to have pulmonary arteriovenous malformations and nonbleeding gastric telangiectasias. The patient underwent coil embolization of pulmonary arteriovenous malformations with a resolution of his shortness of breath and his anemia improved with iron supplementation.

Ponatinib-Induced Cerebrovascular Accident (CVA).

Ponatinib is a highly potent tyrosine kinase inhibitor shown to have excellent outcomes in the treatment of acute and chronic leukemias. Despite its high efficacy, ponatinib has been shown to carry an increased risk for cardiovascular adverse events, not attributable to a known mechanism. We present a case of a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) who developed a cerebrovascular condition while receiving maintenance therapy with the lowest treatment dose of ponatinib for a prolonged duration.

Inhibition of transient potential receptor vanilloid type 1 suppresses seizure susceptibility in the genetically epilepsy-prone rat.

AIMS: Intracellular calcium plays an important role in neuronal hyperexcitability that leads to seizures. One calcium influx route of interest is the transient receptor potential vanilloid type 1 (TRPV1) channel. Here, we evaluated the effects of capsazepine (CPZ), a potent blocker of TRPV1 channels on acoustically evoked seizures (audiogenic seizures, AGS) in the genetically epilepsy-prone rat (GEPR-3), a model of inherited epilepsy. METHODS: Male and female GEPR-3s were used. For the acute CPZ treatment study, GEPR-3s were tested for AGS susceptibility before and after treatment with various doses of CPZ (0, 1, 3, and 10 mg/kg; ip). For semichronic CPZ treatment study, GEPR-3s were tested for AGS susceptibility before and after 5-day CPZ treatment at the dose of 1 mg/kg (ip). The prevalence, latency, and severity of AGS were recorded and analyzed. RESULTS: We found that acute CPZ pretreatment reduced the seizure severity in male GEPR-3s; the effect was dose-dependent. In female GEPR-3s, however, CPZ treatment completely suppressed the seizure susceptibility. Furthermore, semichronic CPZ treatment suppressed seizure susceptibility in female GEPR-3s, but only reduced the seizure severity in male GEPR-3s. CONCLUSIONS: These findings suggest that the TRPV1 channel is a promising molecular target for seizure suppression, with female GEPR-3s exhibiting higher sensitivity than male GEPR-3s.

Alcohol Withdrawal Increases Protein Kinase A Activity in the Rat Inferior Colliculus.

BACKGROUND: Cyclic AMP-dependent protein kinase A (PKA) signaling is a key target for the action of alcohol and may therefore play a role in the pathophysiology of alcohol withdrawal seizures (AWSs). Here, we investigated the role of PKA activity with respect to increased seizure susceptibility in rats that were subjected to alcohol withdrawal. METHODS: Adult male Sprague Dawley rats received 3 daily doses of ethanol (EtOH) (or vehicle) for 4 consecutive days. Rats were then tested for susceptibility to acoustically evoked AWSs 3, 24, and 48 hours after the last alcohol dose. In separate experiments, the inferior colliculus (IC) was collected at these same time points from rats subjected to alcohol withdrawal and control rats following alcohol withdrawal. PKA activity, catalytic Cα (PKACα ) protein, regulatory RIIα (PKARIIα ) protein, and RIIß (PKARIIß ) protein were measured in the IC. Lastly, in situ pharmacological studies were performed to evaluate whether inhibiting PKA activity in the IC suppressed AWSs. RESULTS: In the EtOH-treated group, AWSs were observed at the 24-hour time point, but not at the 3-hour or 48-hour time points. In the IC, PKA activity was significantly higher both 3 hours (i.e., before AWS susceptibility) and 24 hours after the last alcohol dose (when AWS susceptibility peaked) than in control rats. Consistent with these findings, protein levels of the PKACα subunit were significantly increased in the IC both 3 and 24 hours after the last alcohol dose. Lastly, in situ inhibition of PKA activity within the IC suppressed AWSs. CONCLUSIONS: The increase in PKA activity and PKACα protein expression in the IC preceded the occurrence of AWSs, and inhibiting PKA activity within the IC suppressed acoustically evoked AWSs. Together, these findings suggest that altered PKA activity plays a key role in the pathogenesis of AWSs.

Conditional deletion of the glutamate transporter GLT-1 reveals that astrocytic GLT-1 protects against fatal epilepsy while neuronal GLT-1 contributes significantly to glutamate uptake into synaptosomes.

GLT-1 (EAAT2; slc1a2) is the major glutamate transporter in the brain, and is predominantly expressed in astrocytes, but at lower levels also in excitatory terminals. We generated a conditional GLT-1 knock-out mouse to uncover cell-type-specific functional roles of GLT-1. Inactivation of the GLT-1 gene was achieved in either neurons or astrocytes by expression of synapsin-Cre or inducible human GFAP-CreERT2. Elimination of GLT-1 from astrocytes resulted in loss of ∼80% of GLT-1 protein and of glutamate uptake activity that could be solubilized and reconstituted in liposomes. This loss was accompanied by excess mortality, lower body weight, and seizures suggesting that astrocytic GLT-1 is of major importance. However, there was only a small (15%) reduction that did not reach significance of glutamate uptake into crude forebrain synaptosomes. In contrast, when GLT-1 was deleted in neurons, both the GLT-1 protein and glutamate uptake activity that could be solubilized and reconstituted in liposomes were virtually unaffected. These mice showed normal survival, weight gain, and no seizures. However, the synaptosomal glutamate uptake capacity (Vmax) was reduced significantly (40%). In conclusion, astrocytic GLT-1 performs critical functions required for normal weight gain, resistance to epilepsy, and survival. However, the contribution of astrocytic GLT-1 to glutamate uptake into synaptosomes is less than expected, and the contribution of neuronal GLT-1 to synaptosomal glutamate uptake is greater than expected based on their relative protein expression. These results have important implications for the interpretation of the many previous studies assessing glutamate uptake capacity by measuring synaptosomal uptake.