The Case of the Young Male with a Longstanding History of Dyspeptic Symptoms: Peritoneal Tuberculosis.

Portal vein thrombosis associated with peritoneal tuberculosis is an uncommon manifestation of extrapulmonary tuberculosis. We report one such case of a 33-year-old male with a one-year history of dyspepsia, having been on proton pump inhibitors all this time with temporary relief. In view of ongoing symptoms, an endoscopy was done, which at first showed duodenal ulcer. On repeat endoscopy after an interval, there was evidence of mucosa-associated lymphoid tissue (MALT) lymphoma, which prompted a host of investigations in the patient. A positron emission tomography (PET) scan revealed extensive omento-peritoneal involvement along with a hypodense lesion in the liver with interval development of portal vein thrombosis on a CT scan of the abdomen. The biopsy of the hepatic lesion showed granulomatous inflammation. Faced with a diagnostic dilemma, finally, a laparoscopic biopsy was done, which confirmed the diagnosis of peritoneal TB with portal vein thrombosis. This case highlights the importance of keeping a high index of suspicion to include tuberculosis as a differential when presented with a case such as this and to conduct appropriate investigations to establish the correct diagnosis.

Real-World Data (RWD) on the 3-Year Follow-Up Outcomes of Different CNS Prophylaxis Strategies Across CNS-IPI Risk Groups in Patients With Diffuse Large B-Cell Non-Hodgkin Lymphoma.

PURPOSE: CNS relapse in patients with diffuse large B-cell lymphoma (DLBCL) is associated with poor prognosis with a median survival of about 2.5 months. Data demonstrating best prophylactic strategy remain controversial and need further definition. PATIENTS AND METHODS: We present data of 110 patients with DLBCL treated with standard systemic therapy divided into four groups based on primary CNS prophylaxis strategy and CNS International Prognostic Index (IPI) risk categories. We compared their 3-year CNS relapse rate and overall survival in each group. RESULTS: The CNS prophylaxis strategy consisted of intrathecal (IT) methotrexate (MTX) in group 1, high-dose (HD) MTX in group 2, combination IT and HD MTX in group 3, and IT and/or HD MTX with intensive chemotherapy in group 4. At 3 years, CNS relapse rate was 8.6% (4/46), 8.3% (1/12), 4.8% (2/42), and 18% (2/11) in groups 1-4 (P = .64), respectively. According to CNS IPI, the CNS relapse rate was 16.6%, 10.1%, and 0% in high-, intermediate-, and low-risk groups, respectively. The 3-year overall survival rate was 69%, 75%, 80%, and 45% in groups 1-4 (P = .71), respectively. CONCLUSION: Our study while did not find statistical significance did indicate a lower incidence of CNS relapse with the addition of systemic HD MTX to IT MTX in the high-risk DLBCL population.

Preliminary observations indicate variable patterns of plasma 5-fluorouracil (5-FU) levels during dose optimization of infusional 5-FU in colorectal cancer patients.

Efforts to improve efficacy and minimize toxicity have led to pharmacokinetic monitoring of plasma 5-Fluorouracil (5-FU) levels in colorectal cancer patients undergoing chemotherapy. We observed variation in basal 5-FU levels in 21 patients and significant variation during subsequent dose optimization. Tumor KRAS, BRAF mutations and TS mRNA levels were determined. Regimens included FOLFOX6 + Avastin (N = 8), FOLFOX6 (N = 11), FOLFIRI (N = 1) and FOLFOX4 (N = 1). Mutations identified in tumors included G12V KRAS (N = 2), G12A KRAS (N = 1), and V600E BRAF (N = 3). Six-of-eleven patients with normalized tumor TS mRNA levels < 4.0 had a 5-FU AUC of 20 mg.h/L or greater, and 80% of patients (4 of 5) with TS levels > 4.0 had a plasma 5-FU AUC of less than or equal to 20 mg.h/L. Approximately 2/3 of patients achieved therapeutic 5-FU AUC levels with 0-2 dose adjustments while a sub-group of ~1/3 of patients slowly achieved therapeutic levels (> 3-4 dose increases leading to supra-therapeutic 5-FU and subsequent reductions to lesser than original doses). Liver metastases and tumor TS levels did not fully account for variable 5-FU AUC optimization patterns. The 5-FU level during continuous infusion was half-therapeutic in one patient who received FOLFOX4. The observed heterogeneous patterns at baseline and during dose optimization of 5-FU levels suggest variations in 5-FU metabolism among treated patients. Physiological and/or genetic differences underlying heterogeneity in 5-FU levels during dose optimization require further study of patient demographics, single nucleotide polymorphisms in Dihydropyrimidine Dehydrogenase (DPD), TS, or other genes that impact 5-FU metabolism and gene expression changes in liver after 5-FU therapy.

Severe hypercapnia in critically ill adult cystic fibrosis patients.

BACKGROUND: Cystic fibrosis (CF) is a monogenetic autosomal recessive multi-organ disease affecting approximately 50,000 patients worldwide. Overall median survival is continually increasing but pulmonary disease remains the most common cause of death. Guidelines have been published in relation to the outpatient maintenance of lung health for CF patients and treatment of acute lung exacerbations but little information exists about the management of the critically ill CF patient. Invasive mechanical ventilation in CF patients with acute respiratory failure is associated with poor outcome and high mortality. METHODS: Retrospective analysis of adult patients with CF who required endotracheal intubation and invasive mechanical ventilation in the Medical Intensive Care Unit (MICU). RESULTS: Between the years 2003 - 2009, 14 adult patients with CF required endotracheal intubation and invasive mechanical ventilation in the Medical Intensive Care Unit (MICU) of the Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. Eleven patients died in the MICU because of progressive respiratory failure and inability to liberate from mechanical ventilation. Seven individuals consistently manifested arterial partial pressures of carbon dioxide (PaCO(2)) greater than 20.00 kPa despite high levels of conventional modes of mechanical ventilation. CONCLUSION: Intubated CF patients with respiratory failure have a high mortality rate. Based on our experience, multiple factors contribute to severe hypercapnia and the effectiveness of conventional modes of mechanical ventilation in many of these patients is limited. KEYWORDS: Cystic fibrosis; Mechanical ventilation; Critical care; Hypercapnia; Respiratory failure.