The precise staging of hepatocellular carcinoma (HCC) based on the size and number of lesions that predict recurrence after orthotopic liver transplantation (OLT) has not been clearly established. We therefore analyzed the outcome of 70 consecutive patients with cirrhosis and HCC who underwent OLT over a 12-year period at our institution. Pathologic tumor staging of the explanted liver was based on the American Tumor Study Group modified Tumor-Node-Metastases (TNM) Staging Classification. Tumor recurrence occurred in 11.4% of patients after OLT. The Kaplan-Meier survival rates at 1 and 5 years were 91.3% and 72.4%, respectively, for patients with pT1 or pT2 HCC; and 82.4% and 74.1%, respectively, for pT3 tumors (P ‫؍‬ .87). Patients with pT4 tumors, however, had a significantly worse 1-year survival of 33.3% (P ‫؍‬ .0001). An ␣-fetoprotein (AFP) level > 1,000 ng/mL, total tumor diameter > 8 cm, age > 55 years and poorly differentiated histologic grade were also significant predictors for reduced survival in univariate analysis. Only pT4 stage and total tumor diameter remained statistically significant in multivariate analysis. Patients with HCC meeting the following criteria: solitary tumor < 6.5 cm, or < 3 nodules with the largest lesion < 4.5 cm and total tumor diameter < 8 cm, had survival rates of 90% and 75.2%, at 1 and 5 years, respectively, after OLT versus a 50% 1-year survival for patients with tumors exceeding these limits (P ‫؍‬ .0005). We conclude that the current criteria for OLT based on tumor size may be modestly expanded while still preserving excellent survival after OLT. (HEPATOLOGY 2001;33:1394-1403.)Orthotopic liver transplantation (OLT) is a rational therapeutic option for patients with hepatocellular carcinoma (HCC), because it addresses the multifocal potential of HCC in many patients that limits the success and applicability of resection, and also treats the underlying liver disease. The early experience of OLT for HCC in unselected patients included those with extensive and bulky tumors, and was associated with a dismal outcome primarily as a result of aggressive tumor recurrence after OLT. 1,2 The observation that small HCC discovered incidentally at the time of pathologic examination of the explanted liver had a much lower recurrence rate after OLT 1,2 provided the impetus for subsequent studies evaluating OLT mainly for patients with small HCC. [3][4][5][6] In a study by Bismuth et al., 3 the subgroup of patients with no more than 3 tumor nodules and none greater than 3 cm in greatest diameter had a 3-year disease-free survival of 83% with OLT, compared with only 18% treated by resection. In a subsequent study by Mazzaferro et al., 5 35 patients with a solitary tumor not exceeding 5 cm or no more than 3 tumors with none greater than 3 cm had excellent overall and recurrence-free survival rates of 85% and 92%, respectively, at 4 years after OLT. In the report by Figueras et al.,6 the 5-year survival rate for OLT in 38 patients with small HCC not exceeding 5 cm in maximal diameter was 7...

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To determine TRALI incidence by prospective, active surveillance and to identify risk factors by a case-control study, 2 academic medical centers enrolled 89 cases and 164 transfused controls. Recipient risk factors identified by multivariate analysis were higher IL-8 levels, liver surgery, chronic alcohol abuse, shock, higher peak airway pressure while being mechanically ventilated,

Chronic kidney disease (CKD) is common among the elderly. However, little is known about how the clinical implications of CKD vary with age. We examined the age-specific incidence of death, treated end-stage renal disease (ESRD), and change in estimated glomerular filtration rate (eGFR) among 209,622 US veterans with CKD stages 3 to 5 followed for a mean of 3.2 years. Patients aged 75 years or older at baseline comprised 47% of the overall cohort and accounted for 28% of the 9227 cases of ESRD that occurred during follow-up. Among patients of all ages, rates of both death and ESRD were inversely related to eGFR at baseline. However, among those with comparable levels of eGFR, older patients had higher rates of death and lower rates of ESRD than younger patients. Consequently, the level of eGFR below which the risk of ESRD exceeded the risk of death varied by age, ranging from 45 ml/min per 1.73 m 2 for 18 to 44 year old patients to 15 ml/min per 1.73 m 2 for 65 to 84 year old patients. Among those 85 years or older, the risk of death always exceeded the risk of ESRD in this cohort. Among patients with eGFR levels Ͻ45 ml/min per 1.73 m 2 at baseline, older patients were less likely than their younger counterparts to experience an annual decline in eGFR of Ͼ3 ml/min per 1.73 m 2 . In conclusion, age is a major effect modifier among patients with an eGFR of Ͻ60 ml/min per 1.73 m 2 , challenging us to move beyond a uniform stage-based approach to managing CKD. 18: 275818: -276518: , 200718: . doi: 10.1681 Chronic kidney disease (CKD) is common in the elderly, 1,2 leading some professional organizations to recommend routine age-based screening for CKD in the primary care setting 3 ; however, relatively little is known about the clinical course of CKD in older individuals. Most previous studies of CKD and current recommendations for its management have not distinguished between patients of different ages, and efforts to identify risk factors for progression of CKD have generally focused on patient characteristics other than age. 4 -17 We hypothesized that the frequency of clinically significant outcomes among patients who meet National Kidney Foundation criteria for stages 3 to 5 CKD would differ substantially across age groups. We tested this hypothesis among a national cohort J Am Soc Nephrol

HIV persists in a small pool of latently infected cells despite antiretroviral therapy (ART). Identifying cellular markers expressed at the surface of these cells may lead to novel therapeutic strategies to reduce the size of the HIV reservoir. We hypothesized that CD4+ T cells expressing immune checkpoint molecules would be enriched in HIV-infected cells in individuals receiving suppressive ART. Expression levels of 7 immune checkpoint molecules (PD-1, CTLA-4, LAG-3, TIGIT, TIM-3, CD160 and 2B4) as well as 4 markers of HIV persistence (integrated and total HIV DNA, 2-LTR circles and cell-associated unspliced HIV RNA) were measured in PBMCs from 48 virally suppressed individuals. Using negative binomial regression models, we identified PD-1, TIGIT and LAG-3 as immune checkpoint molecules positively associated with the frequency of CD4+ T cells harboring integrated HIV DNA. The frequency of CD4+ T cells co-expressing PD-1, TIGIT and LAG-3 independently predicted the frequency of cells harboring integrated HIV DNA. Quantification of HIV genomes in highly purified cell subsets from blood further revealed that expressions of PD-1, TIGIT and LAG-3 were associated with HIV-infected cells in distinct memory CD4+ T cell subsets. CD4+ T cells co-expressing the three markers were highly enriched for integrated viral genomes (median of 8.2 fold compared to total CD4+ T cells). Importantly, most cells carrying inducible HIV genomes expressed at least one of these markers (median contribution of cells expressing LAG-3, PD-1 or TIGIT to the inducible reservoir = 76%). Our data provide evidence that CD4+ T cells expressing PD-1, TIGIT and LAG-3 alone or in combination are enriched for persistent HIV during ART and suggest that immune checkpoint blockers directed against these receptors may represent valuable tools to target latently infected cells in virally suppressed individuals.

Significance Identifying the source and dynamics of persistent HIV-1 during combinational antiretroviral therapy (cART) is crucial for understanding the barriers to curing HIV infection. Through genetic characterization of HIV-1 DNA in infected cells from peripheral blood and gut-associated lymphoid tissue from patients after long-term suppressive cART, our study reveals that the primary barrier to a cure is a remarkably stable pool of infected memory CD4 + T cells. Through in-depth phylogenetic analyses, we determined that the HIV-1 reservoir in these cells from eight patients is kept stable during long-term cART and, with little evidence of viral replication, this population could be maintained by homeostatic cell proliferation or other processes.