Successful Treatment of Central Nervous System Post-Transplant Lymphoproliferative Disease With a Reduced Dose of High-Dose Methotrexate.

Post-transplant lymphoproliferative disease (PTLD) is a complication of solid organ and hematopoietic stem cell transplantation that occurs as a result of immunosuppression. PTLD isolated to the central nervous system (CNS) is a rare disease and it presents with nonspecific signs and symptoms. Optimal therapy guidelines have not yet been established for CNS PTLD. Here, we report a case of successful treatment of CNS PTLD in an adult female following two subsequent kidney transplants. Initial management was with immunosuppression reduction and a trial of rituximab. There were concerns regarding using methotrexate (MTX) given the patient's fragile transplant status. Magnetic resonance imaging of the brain following four cycles of rituximab revealed the progression of the disease. Subsequently, high-dose MTX (HD-MTX) was considered within the constraints of potential kidney toxicities given her transplant status and chronic kidney disease. Potential toxicities from other therapies, such as brain radiation, also factored into the final decision. The patient was treated with one cycle of a combination of rituximab and HD-MTX 1 g/m2. The patient tolerated HD-MTX and did not have evidence of renal toxicity in laboratory studies. Following that, she was started on a reduced dose of HD-MTX at 2 g/m2 every two weeks instead of the higher MTX dose range of 3.5 to 8 g/m2, which was a shared decision with the patient and nephrology after weighing the risk of kidney dysfunction with the possibility of a less than optimal response with regards to her lymphoma. She was followed with a magnetic resonance imaging of the brain, which demonstrated a complete response after four cycles. Further consolidation treatments with HD-MTX 2 g/m2 every four weeks were administered to complete one year of treatment. Following the completion of chemotherapy, the patient was able to achieve and maintain a complete response without affecting her kidney function. She continues to do well one year following treatment. This case highlights the significance of tailoring therapy to each individual based on their comorbidities and clinical response, as well as the possible merit in exploring the use of a reduced dose of HD-MTX in the treatment of CNS PTLD in patients at high risk for renal toxicity.

Using oral anticoagulants among chronic kidney disease patients to prevent recurrent venous thromboembolism: A systematic review and meta-analysis.

INTRODUCTION: Chronic kidney disease (CKD) increases the risk of venous thromboembolism (VTE) among affected patients. Vitamin K antagonists (VKA) and warfarin remains the main stay of its treatment. Due to novelty and unclear risk-to-benefit ratio of direct oral anti-coagulants (DOAC), they remain underutilized in preventing VTE among CKD patients. We aim to assess the efficacy and safety of DOACs and other oral anticoagulants in preventing recurrent VTE among high-risk population. MATERIAL METHODS: We conducted a literature search using PubMed, Embase, Cochrane, Web of Science and Clinicaltrials.gov for randomized controlled trials (RCTs) comparing anti-coagulants like DOAC, LMWH or VKA or any oral anti-coagulant (OAC) (This includes VKAs and DOACs) with either placebo or another anti-coagulant. Two independent reviewers screened the retrieved articles and extracted data using a piloted data extraction sheet. The primary outcome of interest was number of recurrent VTE and other side effects among CKD patients receiving respective treatment. Secondary outcomes were risk of major, non-major and intra-cranial bleed. RESULTS: We retrieved 7244 titles on initial search, reviewed full text of 818 articles, and selected 10 phase III RCTS for quantitative meta-analysis. Out of 36,326 patients in these trials, only 10,840 (29.8%) were evaluable. We stratified patients into four categories based on severity of renal impairment using serum creatinine clearance (SCr) as the marker e.g. mild (>50 - <80) moderate (>30 - ≤50) severe (<30) and any level (from <30 to <80). There was no difference between DOACs vs VKA in decreasing the risk of recurrent VTE among patients with mild (RR:0.86, 95% CI:0.61-1.22, I2 = 25%) moderate/severe (RR:0.72, 95% CI:0.44-1.17, I2 = 0%) or any level of renal impairment (RR:0.83, 95% CI:0.60-1.14, I2 = 34%). No difference in efficacy between LMWH vs VKA among patients with moderate (RR:2.40, 95% CI:0.44-12.96, I2 = 76%) and any level (RR:2.59, 95% CI:0.66-10.16, I2 = 71%) of renal impairment respectively. Similarly, no difference in efficacy between LMWH vs any OAC (This includes VKAs and edoxaban) among patients with (RR:2.16, 95% CI:0.66-7.-06, I2 = 51%) and any level (RR:1.48, 95% CI:0.79-2.78, I2 = 78%) of renal impairment. DOACs compared to VKAs had significantly lower risk of combined major and non-major bleeding (RR: 0.74, 95% CI:0.65-0.84, I2 = 26%), major bleeding (RR: 0.51, 95% CI:0.38-0.69, I2 = 7%) and non-major clinically relevant bleeding (RR: 0.73, 95% CI:0.57-0.94, I2 = 45%) respectively. Risk of intracranial bleeding was comparable (RR: 0.68, 95% CI:0.19-2.44, I2 = 0%). There was no difference in the risk of major bleeding between LMWH vs any OAC (RR: 0.83, 95% CI:0.46-1.51, I2 = 0%). CONCLUSION: DOACS and other anticoagulants (VKA and LMWH) showed no statistical difference in preventing recurrent VTEs among CKD patients but DOACs had significantly lower risk of major and non-major clinically relevant bleeding irrespective of the level of renal impairment compared to VKAs. There was no difference in risk of intra-cranial bleeding between DOACs and VKAs.

Limbic Encephalitis as a Presenting Complication for Small Cell Lung Cancer.

Limbic encephalitis (LE) is a rare neurological paraneoplastic complication that occurs secondary to malignant tumors. It is commonly presented as refractory seizures that are resistant to most anti-epileptics. We are presenting a unique case of small cell lung cancer complicated with LE. The challenging part of our case is that the patient had a history of seizure disorder in the past, and she was treated initially as an anti-epileptic treatment failure. A 68-year-old patient with a history of epilepsy was admitted to the ICU with resistant status epilepticus (SE), and respiratory failure secondary to pneumonia. Further workup revealed that the patient has small cell lung carcinoma. An extensive workup done to investigate resistant seizures revealed that she had a rare type of paraneoplastic autoantibodies (Anti-Hu) in the cerebrospinal fluid, which supported the diagnosis of the paraneoplastic autoimmune LE. High dose steroids helped to decrease the seizures episodes, but the family decided to proceed with palliative measures only at the end. Diagnosing LE requires ruling out other common causes of SE. Treatment options include treating underlying cancer as well as means of immunosuppression or antibody removal by tacrolimus and cyclophosphamide and even intravenous immunoglobulin (IVIG) or plasma exchange. It is important to consider LE in the differential diagnosis when managing patients with resistant SE in the ICU, even if the brain imaging and cerebrospinal fluid (CSF) analysis were within normal limits.

Extraosseous Ewing Sarcoma Presenting with Inferior ST-Elevation Myocardial Infarction and Systemic Emboli due to Tumor Thrombus and Invasion of the Left Atrium.

Extraosseous Ewing sarcoma is an uncommon entity in the adult population. Cardiac metastases or local invasion of a tumor into the heart is a known but also infrequent occurrence for most malignancies. We present a case of a patient with a history of extraosseous Ewing sarcoma who presented to the emergency room with chest pain and was found to have an inferior ST-elevation myocardial infarction and systemic emboli and was found to have recurrence of sarcoma invading the left atrium.

Is It Really SUMP Syndrome? A Case Report.

Sump syndrome is a rare, long-term complication with a prevalence ranging from 0% to 9.6% in patients with a history of side-to-side choledochoduodenostomy. Choledochoduodenostomy was originally performed to achieve drainage of the common bile duct in high-risk patients with low morbidity, which was commonly done in the pre-endoscopic retrograde cholangiopancreatography era. "Sump" comes from the segment of the common bile duct between the anastomosis and the ampulla of Vater, which acts as a stagnant reservoir for debris, stones, and static bile. This predisposes patients to changes in the biliary tree with signs and symptoms in relation to that area. If left untreated, cholangitis, pancreatitis, hepatic abscesses, and secondary biliary cirrhosis can develop. Here, we have a case of a 77-year-old male with a history significant for choledochoduodenostomy, who presented with the clinical signs and symptoms of pancreatitis, choledocholithiasis, and urinary tract infection. Computed tomography (CT) scan findings revealed choledocholithiasis and an enlarged common bile duct with smaller adjacent calculi along with pneumobilia consistent with sump syndrome. The patient's clinical status improved without invasive measures being taken, i.e. endoscopic retrograde cholangiopancreatography. He was subsequently discharged home after improving clinically and no invasive measures were pursued.