International multicenter validation of GES score for HCC risk stratification in chronic hepatitis C patients.

We have recently demonstrated the ability of a simple predictive model (GES) score to determine the risk of hepatocellular carcinoma (HCC) after using direct-acting antivirals. However, our results were restricted to Egyptian patients with hepatitis C virus (HCV) genotype 4. Therefore, we studied a large, independent cohort of multiethnic populations through our international collaborative activity. Depending on their GES scores, patients are stratified into low risk (≤ 6/12.5), intermediate risk (> 6-7.5/12.5), and high risk (> 7.5/12.5) for HCC. A total of 12,038 patients with chronic HCV were analyzed in this study, of whom 11,202 were recruited from 54 centers in France, Japan, India, the U.S., and Spain, and the remaining 836 were selected from the Gilead-sponsored randomized controlled trial conducted across the U.S., Europe, Canada, and Australia. Descriptive statistics and log-rank tests. The performance of the GES score was evaluated using Harrell's C-index (HCI). The GES score proved successful at stratifying all patients into 3 risk groups, namely low-risk, intermediate-risk, and high-risk. It also displayed significant predictive value for HCC development in all participants (p < .0001), with HCI ranging from 0.55 to 0.76 among all cohorts after adjusting for HCV genotypes and patient ethnicities. The GES score can be used to stratify HCV patients into 3 categories of risk for HCC, namely low-risk, intermediate-risk, and high-risk, irrespective of their ethnicities or HCV genotypes. This international multicenter validation may allow the use of GES score in individualized HCC risk-based surveillance programs.

Pitfalls in Urinary Tract Cytopathology.

BACKGROUND: Urine cytopathology is a cost-effective method to diagnose and follow patients with high-grade urothelial carcinoma (UC). However, some benign, reactive, and metaplastic changes may mimic UC and pose a diagnostic challenge for cytopathologists. SUMMARY: Our comprehensive review focuses on summarizing common pitfalls encountered in urine cytopathology, based on the 2nd edition of The Paris System (TPS) for reporting urinary tract cytopathology and other recent published literature. These pitfalls include urothelial tissue fragments, degenerative changes, treatment effects, viral cytopathic changes, iatrogenic and metaplastic changes. Our aim was to provide a clear understanding of these mimics in order to avoid diagnostic errors. KEY MESSAGE: It is crucial for cytopathologists to recognize benign, reactive, or metaplastic lesions that sometimes resemble UC. An awareness of these cytological changes is essential to make an accurate diagnosis.

Primary cerebral lymphoma' characteristics, incidence, survival, and causes of death in the United States.

PURPOSE: This study aimed to provide an updated overview of primary central lymphoma (PCL) using a large cohort of 33 years. That being said, we attempted to examine the patient demographics, management plans and their outcome, causes of death and the time trends in overall incidence and mortality rates of these patients. METHODS: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database between 1983 and 2016. We calculated the frequencies and the average annual age-adjusted rate (AAR) of PCL patients. Uni- and multivariable accelerated failure time regression were used to identify possible prognostic factors affecting the patients' survival. Furthermore, detailed causes of death were extracted and joint point regression analysis was done to examine incidence and mortality trends. RESULTS: We identified 2925 PCL cases. The AAR was 0.148 per 100,000. An increase in age was significantly associated with shorter survival (HR: 1.01, 95%CI = 1.01-1.01, P < .001), while a recent year of diagnosis after 1993-2002 and 2002 was associated with improved survival (HR: 0.76, CI = 0.65-0.89, P = .001), and (HR: 0.48, CI = 0.41-0.56, P < .001), respectively. Overall, the trend of mortality rates in PCL patients has declined over the past years (-1.38% per year). CONCLUSION: Our results support the previous evidence by showing an increase in patients' survival over time. While most PCL-related deaths occur within the first year, subsequent slow progression was observed after the first few years of survival. More attention should be given to the other possible non-PCL causes of death, especially beyond ten years of survival.

Ustekinumab dose escalation improves clinical responses in refractory Crohn's disease.

BACKGROUND: Clinicians often utilize off-label dose escalation of ustekinumab (UST) in Crohn's disease (CD) patients with disease refractory to standard dosing. Previous studies report mixed results with dose escalation of UST. METHODS: A retrospective observational study of 143 adult patients with CD receiving UST over a 33-month time period was conducted. Patients receiving UST at standard dosage for a minimum of 16 weeks were included in the analysis. Primary outcomes collected were clinical response [Physician Global Assessment Score (PGA) by >1] and remission (PGA = 0). Changes in clinical parameters were calculated for dose-escalated patients beginning with the time of dose switch (~42 weeks) and compared with a group of patients who were classified as "failing" standard dosing at 42 weeks who were not dose escalated. RESULTS: Dose escalation improved PGA by 0.47 ± 0.19 compared with patients remaining on every 8 weeks dosing (Q8 week), who worsened by 0.23 ± 0.23 (p < 0.05). Dose escalation decreased CRP 0.33 ± 0.19 mg/L and increased serum albumin 0.23 ± 0.06 g/dL (p < 0.05). Surprisingly, disease duration and prior CD surgeries inversely correlated with the need for dose escalation. CONCLUSION: Our results support UST Q4 week dose escalation for selected CD patients who fail to achieve remission on standard Q8 week dosing. Dose escalation improves clinical outcomes, prevents worsening disease severity, and positively impacts CRP and albumin levels. Together these data indicate that clinicians should attempt Q4 week UST dosing in refractory CD patients before switching to an alternative class of biologic therapy.

Late-Onset Cerebral Toxoplasmosis After Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND Toxoplasmosis is an uncommon but potentially fatal complication following allogeneic hematopoietic stem cell transplantation (HCT). Post-transplant toxoplasmosis is often a reactivation of prior infection and typically occurs within the first 6 months of transplant. Herein, we report that cerebral toxoplasmosis may occur 22 months after allogeneic hematopoietic stem cell transplantation. CASE REPORT We describe a case of cerebral toxoplasmosis that occurred 22 months after an allogeneic HCT while the patient was on aerosolized pentamidine for Pneumocystis jiroveci pneumonia (PCP) prophylaxis. The disease was only diagnosed after brain biopsy because of atypical MRI appearance of the cerebral lesion and negative Toxoplasma gondii IgG antibody test result in the cerebrospinal fluid (CSF). The patient received pyrimethamine and sulfadiazine treatment, with dramatic improvement after several months. The patient is alive 2 years after infection diagnosis, with no evidence of disease and is off Toxoplasma prophylaxis. CONCLUSIONS Cerebral toxoplasmosis can occur late after allogeneic HCT while patients are on immunosuppression therapy, with atypical features on imaging studies and negative Toxoplasma gondii IgG antibody test result in the CSF. Pre-transplant serologic screening for T. gondii antibodies in allogeneic transplant candidates is warranted. Brain biopsy can be a helpful diagnostic tool for cerebral lesions.