Effects of Share 35 Policy on Liver Transplantation Outcomes for Patients With Nonalcoholic Steatohepatitis.

BACKGROUND: To examine the temporal variation and outcomes of liver transplantation between pre- and post-Share 35 eras for patients with nonalcoholic steatohepatitis. METHODS: A retrospective analysis was performed among 4380 patients with end-stage liver disease from the United Network for Organ Sharing database from 2009 to 2017 due to primary diagnosis of nonalcoholic steatohepatitis or cryptogenic cirrhosis with body mass index greater than 30. Cox regressions were used to model the effect of Share 35 policy on patient and graft survival comparing the first 3 years of Share 35 policy to an equivalent time period before. RESULTS: The number of nonalcoholic steatohepatitis-related transplants increased from 232 (14.1%) in 2009 to 266 (20.5%) in 2017. In post-Share 35 era, average waitlist time and cold ischemic time decreased, while Model for End-Stage Liver Disease (MELD) scores increased with higher proportion of recipients having MELD ≥35. No significant difference in average length of hospitalization or survival was found after Share 35. CONCLUSIONS: The Share 35 policy benefits patients with nonalcoholic steatohepatitis from reduced liver transplantation waiting time. It is also associated with comparable outcomes in 2 eras without increasing cold ischemic time or posttransplant length of hospitalization.

The Impact of Share 35 Policy on Patient Survival in Patients Undergoing Liver Transplantation With Gender- and Race-Mismatched Donors: An Analysis of the United Network for Organ Sharing Registry.

INTRODUCTION: The United Network for Organ Sharing (UNOS) instituted the Share 35 policy in June 2013 in order to reduce death on liver transplant waitlist. The effect of this policy on patient survival among patients with gender- and race-mismatched donors has not been examined. RESEARCH QUESTION: To assess the impact of Share 35 policy on posttransplantation patient survival among patients with end-stage liver disease (ESLD) transplanted with gender- and race-mismatched donors. DESIGN: A total of 16 467 adult patients with ESLD who underwent liver transplantation between 2012 and 2015 were identified from UNOS. An overall Cox proportional hazards model adjusting for demographic, clinical, and geographic factors and separate models with a dummy variable of pre- and post-Share 35 periods as well as its interaction with other factors were performed to model the effect of gender and race mismatch on posttransplantation patient survival and to compare the patient survival differences between the first 18 months of Share 35 policy to an equivalent time period before. RESULTS: Comparison of the pre- and post-Share 35 periods did not show significant changes in the numbers of gender- and race-mismatched transplants, or the risk of death for gender-mismatched recipients. However, black recipients with Hispanic donors (hazard ratio: 0.51, 95% confidence interval, 0.29-0.90) had significantly increased patient survival after Share 35 policy took effect. CONCLUSION: The Share 35 policy had a moderate impact on posttransplantation patient survival among recipients with racially mismatched donors according to the first 18-month experience. Future research is recommended to explore long-term transplantation.

Conventional TACE and drug-eluting bead TACE as locoregional therapy before orthotopic liver transplantation: comparison of explant pathologic response.

BACKGROUND: Hepatocellular carcinoma (HCC) is responsible for significant morbidity and mortality worldwide. Despite its increasing incidence, significant progress has been made in the clinical management of HCC. Transarterial chemoembolization (cTACE) has been shown to improve survival in patients with unresectable HCC; it has also been successfully used as bridging therapy before orthotopic liver transplantation (OLT) in efforts to delay tumor growth or to downstage HCC. TACE with drug-eluting beads (DEB-TACE), a novel drug delivery system that produces a slow and sustained release of chemotherapeutic agent, has recently been shown to have similar efficacy to conventional TACE (cTACE); it also exhibits fewer adverse effects resulting from reduced systemic drug concentrations. To date, the pathologic response rate to cTACE compared with DEB-TACE in patients undergoing OLT has not been well described. METHODS: A total of 111 consecutive patients with HCC who underwent cTACE (n=76) or DEB-TACE (n=35) before OLT at a single center between January 2005 and December 2010 were evaluated. RESULTS: Complete necrosis was achieved in 50.9% and 57.1% of cTACE and DEB-TACE patients, respectively; at least 50% necrosis was evident in approximately three fourths of patients in both groups. Rates of necrosis and tumor recurrence did not differ between groups. Dropout from the transplant list was equal in both groups. CONCLUSIONS: Either modality is an acceptable treatment to achieve tumor control for patients awaiting OLT and can be expected to result in excellent necrosis rates in the majority of patients.

Amphotericin B lipid complex versus liposomal amphotericin B monotherapy for invasive aspergillosis in patients with hematologic malignancy.

BACKGROUND: Invasive aspergillosis (IA) is a major cause of morbidity and mortality in patients with hematologic malignancy (HM). There are 2 lipid formulations of amphotericin B (AMB) currently in widespread use: AMB lipid complex (ABLC) and liposomal AMB (L-AMB). There are limited data comparing the efficacy and safety of these 2 agents in the treatment of IA in patients with cancer. METHODS: The authors retrospectively studied 381 consecutive patients with HM who had proven or probable IA (according to European Organization for Research and Treatment of Cancer/Mycosis Study Group of the National Institute of Allergy and Infectious Diseases criteria) between June 1993 and December 2005. Of these patients, 158 received primary antifungal therapy with either L-AMB (n=106) or ABLC (n=52). The number of salvage antifungal regimens given were 51 L-AMB regimens and 30 ABLC regimens. It should be noted that the population described in this report was not typical of the hematologic cancer population with IA because of the advanced stage and the severity of the underlying diseases. RESULTS: Risk factors for IA, such as underlying malignancy, neutropenia, steroid use, admission to an intensive care unit, and the presence of graft-versus-host disease, were comparable among the study drug group in the primary or salvage setting. Likewise, comparable distribution of types of Aspergillus species and the presence of disseminated IA were observed. Response to primary or salvage therapy was equally poor in both drug study groups regardless of treatment modality (range, 7.7-15.8% response). In the primary therapy group, ABLC was associated with significantly higher nephrotoxicity than L-AMB (P<.001). CONCLUSIONS: Among patients with HM, primary therapy and salvage therapy for IA with either ABLC or L-AMB as single agent were associated equally with poor outcome. L-AMB appeared to be less nephrotoxic in the primary therapy setting.

Colistin is effective in treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa in cancer patients.

The increasing incidence of infections caused by multidrug-resistant Pseudomonas aeruginosa is a worldwide health problem. Because no new antipseudomonal agents are expected to be available in the near future, we evaluated the safety and efficacy of colistin, an old drug with bactericidal activity against this organism. We collected clinical and demographic data on 95 cancer patients diagnosed with infections caused by multidrug-resistant P. aeruginosa between January 2001 and January 2004 and treated with either colistin (colistin group) or at least one active antipseudomonal agent (a beta-lactam antibiotic or a quinolone) (control group). We compared the results obtained for both groups. Thirty-one patients had been treated with colistin and 64 had been treated with an antipseudomonal non-colistin-containing regimen. Compared with the control group, patients in the colistin group had a lower median age (52 and 62 years, respectively; P = 0.012) but were more likely to have had nosocomial infections (87% and 64%, respectively; P = 0.02). Twenty-five patients (81%) in the colistin group and 40 patients (63%) in the control group had an APACHE II score of >15 (P = 0.074). The overall clinical response rates were 52% in the colistin group and 31% in the control group (P = 0.055). Multiple logistic regression analysis showed that those patients treated with colistin were 2.9 times (95% confidence interval, 1.1 to 7.6 times) more likely than those in the control group to experience a clinical response to therapy (P = 0.026). Colistin therapy was at least as effective and as safe a beta-lactam antibiotic or a quinolone in the treatment of infections caused by multidrug-resistant P. aeruginosa and, hence, may be a useful or preferred alternative therapy for this infection in cancer patients.

Aspergillus terreus: an emerging amphotericin B-resistant opportunistic mold in patients with hematologic malignancies.

BACKGROUND: Invasive aspergillosis (IA) has emerged as a common cause of morbidity and mortality among immunocompromised patients. At The University of Texas M. D. Anderson Cancer Center (Houston, TX), Aspergillus terreus is second to A. fumigatus as the most common cause of IA. In the current study, the authors compared the risk factors and outcomes associated with IA caused by A. terreus and IA caused by A. fumigatus. METHODS: The authors retrospectively reviewed the medical records of 300 patients who received care at our institution between 1995 and 2001 and who had cultures that were positive for Aspergillus infection, including 90 patients whose cultures were positive for A. fumigatus and 70 patients whose cultures were positive for A. terreus. RESULTS: Thirty-two patients with IA caused by A. terreus and 33 patients with IA caused by A. fumigatus were evaluated. The two groups were comparable in terms of age, gender, and underlying disease. Leukemia was the most common underlying malignancy (84%). More than 40% of patients in each group had undergone bone marrow transplantation. There was a trend toward a higher frequency of neutropenia among patients with IA caused by A. terreus (P = 0.12). IA caused by A. terreus was considered to be nosocomial in origin significantly more frequently compared with IA caused by A. fumigatus (P = 0.03). In vitro, A. terreus was found to be more resistant to amphotericin B (minimal inhibitory concentration [MIC90], 4.0 microg/mL) than to antifungal therapy (MIC90, 1.0 Hg/mL) in the isolates that were tested (< 50% of all isolates). The overall rate of response to antifungal therapy was 39% for patients with A. fumigatus infection, compared with 28% for patients with A. terreus infection (P = 0.43). CONCLUSIONS: Despite the decreased in vitro susceptibility of A. terreus (relative to A. fumigatus) to amphotericin B, the two groups within the current patient population had comparably poor responses to amphotericin B preparation and somewhat improved responses to posaconazole.

Multiple-species candidemia in patients with cancer.

BACKGROUND: Candidemia is a common cause of bloodstream infections in patients with cancer, with the majority of these infections being caused by a single Candida species. Studies of multiple-species candidemia (MSC) have rarely been reported. METHODS: The authors identified 33 patients with cancer who had candidemia (diagnosed between 1993 and 2000) caused by more than 1 Candida species. This group of 33 patients was compared with a control group of 66 patients with cancer who had C. albicans candidemia that arose soon before or soon after each case of MSC that was investigated in the current study. RESULTS: Patients with MSC, compared with control patients, were more likely to have leukemia (33% vs. 8%; P = 0.001), to have had prolonged neutropenia before the onset of their infection (mean +/- standard deviation, 10 +/- 17 days vs. 3 +/- 6 days; P = 0.02), and to have received chemotherapy within 1 month before their infection (42% vs. 18%; P = 0.01). Patients with MSC also had higher Acute Physiology and Chronic Health Evaluation II scores at the onset of infection (score > or = 16, 45% vs. 26%; P = 0.05) and were more likely to have received previous antifungal prophylaxis compared with patients who had candidemia caused by C. albicans (33% vs. 11%; P = 0.006). The response of C. albicans candidemia to single-agent antifungal therapy was significantly better than that of MSC (69% vs. 35% P = 0.004). CONCLUSIONS: In patients with cancer, MSC was more likely to occur as breakthrough candidemia, predominantly in those with leukemia and prolonged neutropenia, and was associated with suboptimal responses to single-agent antifungal therapy.

Treatment of febrile neutropenic patients with cancer who require hospitalization: a prospective randomized study comparing imipenem and cefepime.

BACKGROUND: The objective of the current study was to compare the efficacy and safety of imipenem and cefepime in the treatment of adult patients with cancer who had fever and neutropenia requiring hospitalization according to Infectious Disease Society of America criteria. METHODS: In the current prospective randomized clinical trial at a university-affiliated tertiary cancer center, adult patients with cancer who had fever (> or = 38.3 degrees C or > or = 38.0 degrees C for > 2 hours) and neutropenia (< or = 500/mm(3) or < 1000/mm(3) but declining) requiring hospitalization were randomized to receive either cefepime or imipenem. Vancomycin or amikacin was added on suspicion of gram-positive or gram-negative bacterial infection, respectively. RESULTS: Patients who received an imipenem regimen or a cefepime regimen were comparable in terms of age, gender, underlying malignancy, prior transplantation, degree and trend of neutropenia, and presence of central venous catheters (P > or = 0.3). An intent-to-treat analysis showed a 68% response rate to the imipenem regimen, compared with a 75% response rate to the cefepime regimen (P = 0.2). The rates of antibiotic-related adverse events and superinfections also were comparable (P = 0.6). There was no difference in response among patients who received imipenem or cefepime alone compared with patients who also received vancomycin or amikacin (P = 1.0). Leukemia was the only independent risk factor associated with a poor outcome (odds ratio, 4.6; 95% confidence interval, 1.9-10.7; P < 0.0001). CONCLUSIONS: Imipenem and cefepime had similar efficacy and safety profiles in the treatment of adult cancer patients with fever and neutropenia who required hospitalization. The addition of either vancomycin or amikacin may not be necessary.

Spectrum of bacille Calmette-Guérin (BCG) infection after intravesical BCG immunotherapy.

Intravesical instillation of bacille Calmette-Guérin (BCG) effectively treats transitional cell carcinoma of the bladder. Occasionally, BCG infection complicates such treatment. In some patients, infection appears early (within 3 months after instillation) and is characterized by generalized symptoms, with pneumonitis and hepatitis. Late-presentation disease occurs >1 year after the first BCG treatment and usually involves focal infection of the genitourinary tract (the site at which bacteria were introduced) and/or other sites that are typical for reactivation of mycobacterial disease, such as the vertebral spine or the retroperitoneal tissues. Noncaseating granulomas are found in the majority of cases, whether early or late. Most patients respond to treatment with antituberculous drugs; in early-presentation disease, when features of hypersensitivity predominate, glucocorticosteroids are sometimes added. Late localized infection often requires surgical resection.