Retrospective case analysis of antiviral therapies for HHV‐6 encephalitis after hematopoietic stem cell transplantation

Human herpesvirus 6 (HHV‐6) is one of the most common causes of encephalitis in allogeneic hematopoietic stem cell transplant (HCT) recipients and is associated with significant morbidity and mortality. There are no FDA‐approved treatments specifically for HHV‐6 encephalitis; HHV‐6 disease is typically treated with CMV antivirals. A review of antiviral medications used to treat HHV‐6 encephalitis was conducted by aggregating data from case reports found on PubMed. Articles were included if they examined at least one HCT patient diagnosed with HHV‐6 encephalitis and described their treatment course and outcome. Key data were abstracted from 123 cases described in 52 studies. The proportion of patients with encephalitis who died or developed sequelae was 63.6% among ganciclovir monotherapy recipients (n = 44), 55.3% among foscarnet monotherapy recipients (n = 47), and 37.5% among recipients of combination therapy with foscarnet and ganciclovir (n = 32). Logistic regression revealed that recipients of foscarnet (OR 4.286, 95% CI 1.235‐14.877, P = .022) and ganciclovir (OR 5.625, 95% CI 1.584‐19.975, P = .008) monotherapies were more likely to develop sequelae compared to recipients of combination therapy, respectively. In multivariate analyses, non‐cord blood transplant was identified as an independent risk factor for developing sequelae after receiving ganciclovir monotherapy (OR 5.999, 95% CI 1.274‐28.254, P = .023). There was no difference in mortality between patients who received combination therapy and those who received monotherapy. In conclusion, combination therapy with foscarnet and ganciclovir may reduce sequelae, but not mortality, secondary to HHV‐6 encephalitis.     

Multidrug resistant gram-negative bacilli as predominant bacteremic pathogens in liver transplant recipients

Background. Bacteremias, which are often caused by gram‐negative bacteria, are the most frequently occurring infectious complications after liver transplantation (LT). The aim of this study was to investigate bacteremic incidence, pathogenic spectrum, risk factors for bacteremia due to multidrug resistant (MDR) gram‐negative bacilli, and its impact on mortality after LT. Methods. A cohort analysis of prospectively recorded data was done in 475 LT recipients, who were divided into 3 categories: cases with gram‐negative bacteremia, cases with MDR gram‐negative bacteremia, and cases without bacteremia as controls. Results. In 475 LT recipients, there were 152 (32.0%) patients with gram‐negative bacillus bacteremia in the first 6 months after LT. Out of 152 patients, there were 225 bacteremic episodes, which accounted for 69.7% in a total 323 bacteremic episodes. A total of 190 bacteremic episodes were caused by Stenotrophomonas maltophilia, Enterobacteriaceae, Ochrobactrum anthropi, Pseudomonas, and Acinetobacter baumanii, all of which were the most frequent gram‐negative isolates in this study, and MDR bacilli constituted 56.3%. The most frequent source was intravascular catheters. There were 70 patients with MDR gram‐negative bacillus bacteremia. Independent risk factors for bacteremia due to MDR gram‐negative bacillus were as follows: post‐LT abdominal infection (P<0.0001, odds ratio [OR] 0.066, 95% confidence interval [CI] 0.019–0.226), post‐LT reoperative episodes (P<0.0001, OR 10.505, 95% CI 3.055–36.121), or one or more episodes of acute rejection (P=0.042, OR 4.457, 95% CI 0.988–20.103). In the first 6 months after LT, MDR gram‐negative bacillus bacteremia‐related mortality was significantly higher than that due to antibiotic‐susceptible bacillus (38.6% vs. 14.6%, P<0.001). Conclusion. Post‐LT bacteremias caused by MDR gram‐negative bacilli are common, and associated with allograft acute rejection, post‐LT reoperation, and abdominal infection. The increasing isolates of MDR gram‐negative bacilli pose a great challenge for clinical treatment.     

Risk factors for enterococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients

M. Mikulska, V. Del Bono, R. Prinapori, L. Boni, A.M. Raiola, F. Gualandi, M.T. Van Lint, A. Dominietto, T. Lamparelli, P. Cappellano, A. Bacigalupo, C. Viscoli. Risk factors for enterococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients.
Transpl Infect Dis 2010: 12: 505–512. All rights reserved Abstract: Bacteremia is a well known cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients and enterococci are among the most frequently isolated pathogens. The aim of this study was to identify risk factors for enterococcal bacteremia during the first 30 days after allogeneic HSCT. A retrospective case–control study was performed; for each case, 3 controls were randomly selected among 306 patients transplanted during the study period (January 1, 2004 to December 31, 2007). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for variables influencing the risk for bacteremia. Overall, 33 patients developed enterococcal bacteremia, within a median of 9 days after HSCT (range, 2–24). The cumulative incidence was 10.8%. Multivariate analysis identified the following variables as risk factors for enterococcal bacteremia: donor and transplant type (greater risk for mismatched related or cord blood) (OR=8.98, 95% CI, 1.65–48.99 and OR=7.52, 95% CI, 1.56–36.31, respectively, P=0.047); severe (grades 3–4) mucositis (OR=9.04, 95% CI, 1.97–41.52, P=0.018); pharyngeal enterococcal colonization (OR=4.48, 95% CI, 1.11–18.03, P=0.035); and previous empirical therapy with cephalosporins (OR=4.16, 95% CI, 0.93–18.66 for 1–7 days of therapy, and OR=7.31, 95% CI, 1.78–30.12 for 8–23 days, P=0.018). Higher Karnofsky score (≥50) and previous empirical therapy with glycopeptides were associated with a decreased risk (OR=0.25, 95% CI, 0.06–0.97, P=0.045 and OR=0.11, 95% CI, 0.02–0.59, P=0.010, respectively). The crude mortality at 7 and 30 days was 12% (4/33) and 24% (8/33), respectively. Enterococcal bacteremia is frequent after allogeneic HSCT. The factors associated with this infection are type of transplant, pharyngeal colonization, severe mucositis, and use of cephalosporins. Good general conditions and the use of vancomycin were associated with lower risk of enterococcal bacteremia.     

SARS-CoV-2-reactive antibody detection after SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Prospective survey from the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group

This is a multicenter prospective observational study that included a large cohort (n = 397) of allogeneic (allo-HSCT; (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3–6 weeks after complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from February 1, 2021, to July 20, 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of the recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia < 1 × 10⁹/ml (odds ratio [OR] 0.33, 95% confidence interval [95% CI] 0.16–0.69, p = .003), active graft versus host disease (GvHD; OR 0.51, 95% CI 0.27–0.98, p = .04) and vaccination within the first year of transplant (OR 0.3, 95% CI 0.15–0.9, p = .04) associated with lower antibody detection whereas. In ASCT, non-Hodgkin's lymphoma (NHL; OR 0.09, 95% CI 0.02–0.44, p = .003) and active corticosteroid therapy (OR 0.2, 95% CI 0.02–0.87, p = .03) were associated with lower detection rate. We report an encouraging rate of SARS-CoV-2-reactive antibodies detection in these severe immunocompromised patients. Lymphopenia, GvHD, the timing of vaccine, and NHL and corticosteroids therapy should be considered in allo-HSCT and ASCT, respectively, to identify candidates for SARS-CoV-2 antibodies monitoring.     

Trends in invasive disease due to Candida species following heart and lung transplantation

Abstract: Although invasive candidiasis (IC) causes significant morbidity and mortality in patients who undergo heart, lung, or heart–lung transplantation, a systematic study in a large cohort of thoracic organ transplant recipients has not been reported to date. Clinical and microbiological data were reviewed for 1305 patients who underwent thoracic organ transplantation at Stanford University Medical Center between 1980 and 2004. We identified and analyzed 76 episodes of IC in 68 patients (overall incidence 5.2% per patient). The incidence of IC was higher in lung (LTx) and heart–lung transplant (HLTx) recipients as compared with heart transplant (HTx) recipients (risk ratio [RR] 1.7, 95% confidence interval [CI] 1.1–2.7). The incidence of IC decreased over time in all thoracic organ transplant recipients, decreasing from 6.1% in the 1980–1986 time period to 2.1% in the 2001–2004 era in the HTx recipients, and from 20% in the 1980–1986 period to 1.8% in the 2001–2004 period in the LTx and HLTx recipients. The most common site of infection differed between the HTx and LTx cohorts, with bloodstream or disseminated disease in the former and tracheobronchitis in the latter. IC in the first year after transplant was significantly associated with death in both HTx (RR 2.9, 95% CI 1.8–4.6, P=0.001) and LTx and HLTx patients (RR 3.0, 95% CI 1.9–4.6, P<0.001). The attributable mortality from IC decreased during the 25‐year period of observation, from 36% to 20% in the HTx recipients and from 39% to 15% in the LTx and HLTx recipients. There were a significant number of cases caused by non‐albicans Candida species in all patients, with a trend toward higher mortality in the HTx group. In conclusion, the incidence and attributable mortality of IC in thoracic organ transplant recipients has significantly declined over the past 25 years. The use of newer antifungal agents for prophylaxis and treatment, the decrease in the incidence of cytomegalovirus disease, and the use of more selective immunosuppression, among other factors, may have been responsible for this change.     

Early predictors of antiviral treatment response in liver transplant recipients with recurrent hepatitis C genotype 1

The success of current antiviral treatment for hepatitis C virus (HCV) recurrence in liver transplant (LT) recipients remains limited. We aimed at evaluating the value of IL28B genotype and early viral kinetics to predict response to standard treatment in the transplant setting. We retrospectively evaluated 104 LT recipients treated for HCV genotype 1 recurrence between 2001 and 2010. Baseline variables, including IL28B genotype, and early viral kinetics were compared among patients who did or did not achieve a sustained virological response (SVR). Logistic regression analyses of candidate variables were conducted to generate a reliable predictive model based on the minimum set of variables. Twenty‐nine (28%) achieved an SVR. On multivariate analysis, the magnitude of HCV RNA decline at 4 weeks (OR: 3.74, 95% CI: 1.64–9.39; P = 0.003) and treatment compliance (OR: 35.27, 95% CI: 3.35–365.54; P = 0.003) were the only independent predictors of SVR. Favourable recipient IL28B genotype significantly correlates with virological response at week 4 (OR 3.23; 95% CI, 1.12–9.15; P = 0.03). By logistic regression analysis, a model including donor age, recipient rs12979860 genotype and viral load at 4 weeks showed the best predictive value for SVR with an area under the receiver operating curve of 0.861. Favourable recipient IL28B genotype strongly correlates with the viral response at week 4 which is the strongest predictor of response. The combination of recipient IL28B genotype and donor age with the week 4 response reliably estimates the probability of SVR early on‐treatment and may facilitate therapeutic strategies incorporating new antiviral agents.     

Risk factors and clinical outcomes of pediatric liver transplant recipients with post‐transplant lymphoproliferative disease in a multi‐ethnic Asian cohort

Background

We aimed to evaluate clinical characteristics, risk factors, and disease outcomes for liver transplant recipients (LTR) with post‐transplant lymphoproliferative disease (PTLD) at our center.

Methods

Retrospective review of data of all pediatric LTR (1991‐2015) was conducted.

Results

The overall incidence of PTLD was 16.4% (18/110), the majority (13/18) were early lesions, while 3/18 were polymorphic/monomorphic PTLD. The risk factors significant on univariate analysis were as follows: mean age (years) at transplant (1.66 vs 4.76, P = .006); age <2 years at transplant (odds ratio [OR] 3.53 [95% confidence interval [CI]: 1.16‐10.73], P = .026); cytomegalovirus (CMV) primary infection (OR 11.39 [95% CI: 3.44‐37.7], P < .001); recipient CMV seronegativity (OR 7.50 [95% CI: 2.02‐27.78], P = .003); presence of CMV end‐organ disease (OR 4.00 [95% CI: 1.22‐13.16], P = .022); Chinese ethnicity; and higher mean duration of intravenous ganciclovir prophylaxis. In multivariate analysis, CMV primary infection (OR 5.22 [95% CI: 1.25‐21.87], P = .024), CMV seronegativity (OR 5.91 [95% CI: 1.13‐30.90, P = .035]), and having acute cellular rejections (ACR) prior to PTLD (OR 5.53 [95% CI: 1.43‐21.48, P = .013]) were significant risk factors for PTLD, with the latter two factors having a synergistic effect in increasing PTLD risk in a stratified analysis. The final multivariate model in predicting the risk of PTLD, utilizing CMV primary infection, recipient CMV seronegativity, and ACR before PTLD as predictive variables, was statistically significant (likelihood ratio chi square statistic = 25.18, P < .0001 with df = 3).

Conclusions

We report a unique clinicopathologic and risk factor profile in our cohort—early lesion PTLD accounts for the majority and the incidence of monomorphic PTLD remains low. In addition, we show a synergism between CMV naivety and ACR on PTLD risk, a higher prevalence of gastrointestinal manifestations, and a lack of significant association with Epstein‐Barr virus seronegativity.     

Poor adherence to HIV monitoring and treatment guidelines for HIV-infected injection drug users

Objectives

There is growing concern about access to HIV/AIDS care among injection drug users (IDUs). We examined rates of CD4 cell count monitoring and correlates among HIV‐infected IDUs.

Methods

This prospective observational cohort study of 460 community‐recruited HIV‐infected IDUs was situated in a Canadian city where all medical care is provided free of charge. Over a median follow‐up period of 76 months, we evaluated factors associated with CD4 cell count monitoring through a linkage with a centralized CD4 registry.

Results

Overall, <5% of IDUs had CD4 monitoring consistent with local therapeutic guidelines. In multivariate analyses, after adjustment for being on antiretroviral therapy [odds ratio (OR) 2.21, 95% confidence interval (CI) 1.84–2.70, P<0.001] female gender (OR 0.71, 95% CI 0.57–0.89, P=0.003), non‐White ethnicity (OR 0.75, 95% CI 0.60–0.94, P=0.014), use of methadone maintenance therapy (OR 1.66, 95% CI 1.42–1.94, P<0.001) and daily heroin use (OR 0.72, 95% CI 0.61–0.85, P<0.001) were independently associated with CD4 monitoring.

Conclusions

Strategies to improve CD4 surveillance among IDUs are critically important, particularly for female and non‐White IDUs. Expanded treatment for heroin dependence appears to have the greatest potential for improved care.     

Assessment of factors associated with smoking cessation at diagnosis or during follow‐up of Crohn's disease

Background and Aim

Smoking cessation is known to improve the course of Crohn's disease (CD). However, the factors associated with smoking cessation after CD diagnosis have not been well established.

Methods

Clinical characteristics and change in smoking status were evaluated in 445 current smokers at the time of CD diagnosis. Patients were classified into three subgroups based on their final smoking status and time of smoking cessation: non‐quitters, quitters at diagnosis, and quitters during follow‐up.

Results

The overall smoking cessation rate was 55.7% (248 of 445 patients). The diagnosis of CD was the main reason for quitting (41.5%, 103 of 248 patients). Smoking cessation at the time of CD diagnosis was associated with intestinal resection within 3 months from CD diagnosis (odds ratio [OR] 2.355, 95% confidence interval [CI] 1.348–4.116, P = 0.003), light smoking (OR 2.041, 95% CI 1.157–3.602, P = 0.014), and initiation of smoking before 18 years of age (OR 0.570, 95% CI 0.327–0.994, P = 0.047). Light smoking (OR 1.762, 95% CI 1.019–3.144, P = 0.043) and initiation of smoking before 18 years (OR 0.588, 95% CI 0.381–0.908, P = 0.017) were also associated with overall smoking cessation.

Conclusion

Quitters after CD diagnosis, including quitters at diagnosis and quitters during follow‐up, had features distinct from those of non‐quitters. Given the motivation at CD diagnosis, a detailed history of smoking habits should be taken and all current smokers should be encouraged to quit smoking at the time of CD diagnosis.     

Ofloxacin: new applications for the prevention of urinary tract infections in renal graft recipients

C. Rafat, S. Vimont, P.Y. Ancel, Y.C. Xu‐Dubois, L. Mesnard, N. Ouali, M. Denis, A. Vandewalle, E. Rondeau, A. Hertig. Ofloxacin: new applications for the prevention of urinary tract infections in renal graft recipients
Transpl Infect Dis 2011: 13: 344–352. All rights reserved Abstract: Background. Urinary tract infections (UTIs), the most common form of bacterial infection in kidney transplant recipients, recently have been demonstrated to be detrimental for long‐term graft outcome. Therefore, reinforcing antibiotic prophylaxis might be vital, in addition to basic hygiene recommendations, surgical care, and prophylaxis by trimethoprim–sulfamethoxazole. Methods. In 2006, a Legionella pneumophila contamination of our department's water pipes meant that all the patients undergoing renal transplantation underwent a 1‐month regimen of ofloxacin (OFLO) (200 mg every other day). We took this opportunity to measure the incidence of UTI, including acute pyelonephritis (APN), in 100 consecutive patients transplanted before (n=50) and after (n=50) this treatment decision was reached. We also studied the antimicrobial resistance profiles in our department and in the rest of the hospital. Results. No patient developed Legionnaire's disease. A dramatic decrease in the incidence of UTI (?63%) was also seen in patients undergoing OFLO treatment. Logistic regression analysis demonstrated that the use of OFLO was independently associated with a reduction in UTI (odd ratio [OR]=0.31%, 95% confidence interval [CI] 0.11–0.84, P=0.02) and APN (OR=0.21%, 95% CI 0.07–0.98, P=0.045). This protection was sustained during the whole first year post transplantation. As for resistance rates, we observed a decrease in the susceptibility of Pseudomonas aeruginosa to ciprofloxacin in our nephrology department, compared with that observed in the rest of the hospital. The incidence of multi‐resistant bacteria was stable. Discussion. Our unintentional extension of prophylactic antibiotherapy with OFLO gave rise to a dramatic decrease in the 1‐year incidence of UTI and APN in kidney recipients. Emergence of resistant strains is, however, a major concern.     

Bloodstream Infections in Patients With Solid Tumors: Epidemiology,Antibiotic Therapy,and Outcomes in 528 Episodes in a Single Cancer Center

Current information regarding bloodstream infection (BSI) in patients with solid tumors is scarce. We assessed the epidemiology, antibiotic therapy, and outcomes of BSI in these patients. We also compared patients who died with those who survived to identify risk factors associated with mortality. From January 2006 to July 2012 all episodes of BSI in patients with solid tumors at a cancer center were prospectively recorded and analyzed. A total of 528 episodes of BSI were documented in 489 patients. The most frequent neoplasms were hepatobiliary tumors (19%), followed by lung cancer (18%) and lower gastrointestinal malignancies (16%). Many patients had received corticosteroid therapy (41%), and 15% had neutropenia (<500 neutrophils/μL) at the time of BSI. The most common source of BSI was cholangitis (21%), followed by other abdominal (19.5%) and urinary tract infections (17%). Gram-negative BSI occurred in 55% of cases, mainly due to Escherichia coli (55%), Pseudomonas aeruginosa (18%), and Klebsiella pneumoniae (16%). Among gram-positive BSI (35%), viridans group streptococci were the most frequent causative organisms (22%), followed by Staphylococcus aureus (21%) and Enterococcus species (18%). We identified 61 multidrug-resistant (MDR) organisms (13%), mainly extended-spectrum β-lactamase-producing Enterobacteriaceae (n = 20) and AmpC-producing Enterobacteriaceae (n = 13). The majority of patients with BSI caused by MDR organisms had received antibiotics (70%), and they had been previously hospitalized (61.4%) more frequently than patients with BSI caused by susceptible strains. Inadequate empirical antibiotic therapy was given to 23% of patients, with a higher proportion in those with BSI due to a MDR strain (69%). Early (<48 h) and overall (30 d) case-fatality rates were 7% and 32%, respectively. The overall case-fatality rate was higher among cases caused by MDR organisms (39.3%). The only independent risk factors for the early case-fatality rate were the endogenous source of BSI (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.06–12.02), shock at presentation (OR, 3.63; 95% CI, 1.63–8.09), and corticosteroid therapy (OR, 3.245; 95% CI, 1.43–7.32). The independent risk factors for overall case-fatality rate were the presence of a chronic advanced cancer (OR, 35.39; 95% CI, 2.48–504.91), shock at presentation (OR, 25.84; 95% CI, 3.73–179.0), and corticosteroid therapy (OR, 6.98; 95% CI, 1.61–30.21).BSI in patients with solid tumors occurred mainly among those with hepatobiliary cancer, and cholangitis was the most frequent source; gram-negative bacilli were the most frequent causative agents. MDR organisms were relatively common, particularly in patients who had previously received antibiotics and had been hospitalized; these patients were frequently treated with inadequate empirical antibiotic therapy and had a poorer outcome. The case-fatality rate of patients with solid tumors and BSI was high and was associated with chronic advanced cancer, corticosteroid therapy, and shock at presentation.     

Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis

M.G.J. de Boer, F.P. Kroon, S. le Cessie, J.W. de Fijter, J.T. van Dissel. Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis.
Transpl Infect Dis 2011: 13: 559–569. All rights reserved Abstract: Risk stratification‐based duration of trimethoprim‐sulfamethoxazole (TMP‐SMX) chemoprophylaxis to prevent Pneumocystis pneumonia (PCP) in kidney transplant recipients is not a universally adapted strategy and supporting evidence‐based sources are limited. We performed a large retrospective study to identify risk factors for PCP in kidney transplant recipients and to define parameters for use in clinical prophylaxis guidelines. Fifty consecutive patients with confirmed PCP and 2 time‐matched controls per case were enrolled. All patients were participants of the kidney transplantation program of the Leiden University Medical Center, a tertiary care hospital in the Netherlands. Potential risk factors were compared between groups by uni‐ and multivariate matched analyses. At transplantation, age >55 years (adjusted odds ratio [OR] 2.7, 95% confidence interval [CI] 1.3–5.9) and not receiving basiliximab induction therapy (adjusted OR 4.3, 95% CI 1.1–17.1) predicted development of PCP. In the final multivariate analysis, only cytomegalovirus infection (adjusted OR 3.0, 95% CI 1.2–7.9) and rejection treatment (adjusted OR 5.8, 95% CI 1.9–18) were found to be independently associated with PCP. Using the variables identified by the multivariate analyses, effects of different hypothetical chemoprophylaxis strategies were systematically evaluated. Exploring different scenarios showed that chemoprophylaxis in the first 6 months for all renal transplant patients – and during the first year posttransplantation for patients >55 years of age or those treated for rejection – would result in very low PCP incidence and optimal avoidance of TMP‐SMX toxicity. The results provide a rationale for further prospective study on targeted provision of chemoprophylaxis to prevent PCP in kidney transplant patients.     

Human papillomavirus (HPV) infection and the risk of esophageal squamous cell carcinoma

There is currently no consensus on the relationship between human papillomavirus (HPV) infection and the pathogenic process of esophageal squamous cell carcinoma (ESCC). Therefore, a retrospective study was performed to explore the association between HPV infection and ESCC, where 225 patients with diagnosed ESCC and 224 matched controls were enrolled in the study and stratified according to smoking and alcohol consumption. Enzyme‐linked immunosorbent assay was used to determine seropositivity to HPV by the detection of either IgG or IgM anti‐HPV antibodies. In the non‐smoking and non‐alcohol‐consuming subgroup, the incidence of ESCC of HPV seropositive subjects was similar with that of HPV seronegative subjects (P= 0.737, odds ratio [OR] 1.14, 95% confidence interval [CI] 0.54–2.40). However, in the smoking subgroup, there was a significant difference in the incidence of ESCC between HPV seropositive subjects and HPV seronegative subjects (P= 0.009, OR 2.22, 95% CI 1.22–4.04). In addition, there was a significantly higher association of the development of ESCC in HPV seropositive patients that smoke and drink than those that do not (P < 0.001, OR 10.31, 95% CI 4.04–26.29). Therefore, HPV infection is not an independent risk factor for developing ESCC in the non‐smoking and non‐alcohol‐consuming group. For smokers, however, HPV infection increases the risk of the incidence of ESCC.     

Trends and Outcomes of Left Atrial Appendage Occlusion in Renal and Liver Transplant Recipients: Insights From the United States National Inpatient and Readmission Database

Left atrial appendage occlusion using the Watchman device has emerged as an alternative treatment strategy for preventing strokes in patients with atrial fibrillation. However, there is no data on its safety and clinical outcomes in prior renal or liver transplant recipients. We included a total of 61,995 patients from the National Inpatient Sample (NIS, in-hospital outcomes) and 55,048 patients from the National Readmission Database (NRD, 30-day outcomes) who underwent percutaneous left atrial appendage occlusion (LAAO). From this group, 0.65% (n=405) and 0.62% (n=339) were renal and liver transplant recipients in NIS and NRD respectively. Transplant recipients were younger compared with non-transplant recipients (mean age 69 vs 77 years, P=<0.01). There was little difference in terms of in-hospital mortality (0% vs 0.2%, P=0.43), major complications (6.2% vs 5.6%, P=0.61), cardiovascular complications (2.5% vs 2.8%, P=0.73), neurological complications (1.2% vs 0.7%, P=0.21) or bleeding complications (1.2% vs 0.7%, P=0.99) between transplant vs. non-transplant patients. Based on the NRD database, 30-day readmission rate was not meaningfully different for transplant recipients undergoing LAAO (9.44%) when compared to non-transplant patients (8.12%, [log-rank, P=0.56]). There was no difference between 30-day major or cardiovascular complications, however vascular complication rates were significantly higher for transplant recipients (OR 2.56, 95% CI [(1.66-3.47]). Our study findings suggest that LAAO may be safe for patients with a prior renal or liver transplant in terms of major complications, cardiovascular complications, and all-cause readmission rates. However vascular complications may be higher in transplant recipients. Further large-scale studies are needed to confirm these findings.     

Pediatric‐inspired therapy compared to allografting for Philadelphia chromosome‐negative adult ALL in first complete remission

For adults with Philadelphia chromosome‐negative (Ph?) acute lymphoblastic leukemia (ALL) in first complete remission (CR1), allogeneic hematopoietic cell transplantation (HCT) is an established curative strategy. However, pediatric‐inspired chemotherapy may also offer durable leukemia‐free survival in the absence of HCT. We compared 422 HCT recipients aged 18–50 years with Ph‐ALL in CR1 reported to the CIBMTR with an age‐matched concurrent cohort of 108 Ph? ALL CR1 patients who received a Dana‐Farber Consortium pediatric‐inspired non‐HCT regimen. At 4 years of follow‐up, incidence of relapse after HCT was 24% (95% CI 19–28) versus 23% (95% CI 15–32) for the non‐HCT (chemo) cohort (P=0.97). Treatment‐related mortality (TRM) was higher in the HCT cohort [HCT 37% (95% CI 31–42) versus chemo 6% (95% CI 3–12), P<0.0001]. DFS in the HCT cohort was 40% (95% CI 35–45) versus 71% (95% CI 60–79) for chemo, P<0.0001. Similarly, OS favored chemo [HCT 45% (95% CI 40–50)] versus chemo 73% [(95% CI 63–81), P<0.0001]. In multivariable analysis, the sole factor predictive of shorter OS was the administration of HCT [hazard ratio 3.12 (1.99–4.90), P<0.0001]. For younger adults with Ph? ALL, pediatric‐inspired chemotherapy had lower TRM, no increase in relapse, and superior overall survival compared to HCT. Am. J. Hematol. 91:322–329, 2016. © 2015 Wiley Periodicals, Inc.     

Risk factors for Pneumocystis carinii pneumonia in kidney transplant recipients: a case–control study

Objective. To analyze risk factors for Pneumocystis carinii pneumonia (PCP) in kidney transplant recipients. Study design. In a case–control study, 17 PCP cases diagnosed between July 1994 and July 2000 were matched with two controls each (previous and subsequent kidney transplant recipients who did not develop PCP during the same follow‐up period). Demographics, organ origin, human leukocyte antigen (HLA) mismatches, use of poly‐ or monoclonal anti‐CD3 antibodies (Po/MoAb) for induction or rejection treatment, rejection episodes, cumulative steroid dose for rejection treatment, immunosuppressive regimens, and other infections were analyzed. Results. No significant differences were seen in gender (male 10 vs. 15), mean age (39.7 vs. 35.4 years), organ origin (cadaver donor 13 vs. 19), HLA mismatches, or Po/MoAb use in induction treatment. Significant differences were observed in PCP cases for rejection history (P=0.02), and median and total number of rejection episodes (P=0.0018). The relative risks for PCP for 1, 2, and ≥3 rejection treatments vs. no such treatment were 1, 1.05, and 6.30, respectively (P=0.021). The relative risk for PCP for steroid‐resistant rejection was 4.34 (95% confidence interval [CI], 1.04–18.89) (P=0.019), and that for the use of Po/MoAb for rejection treatment was 7.23 (95% CI, 1.28–49.34) (P=0.006). The relative risk for PCP for 0, 1, and ≥2 previous or concomitant cytomegalovirus (CMV) infection vs. no such infections were 1.0, 2.32, and 13.0, respectively (P=0.012). The relative risks for PCP for tuberculosis (TB) was 18 (95% CI, 1.76–852.03), that for bacterial pneumonia was 14.22 (95% CI, 2.16–150.23), and that for hepatitis C virus infection was 5.25 (95% CI, 1.03–28.91). Immunosuppressive regimens with tacrolimus, mycophenolate mofetil (MMF), steroids (P=0.06), and MMF as a single variable (P=0.05) were more frequently used in cases. Primary trimethoprim‐sulfamethoxazole prophylaxis failure was observed in 12 patients in association with heavy immunosuppression and concomitant infections. Conclusions. The risk of PCP in kidney transplant recipients is related to the number and type of rejection treatments. It is also related to the occurrence of CMV infection, and to other immunomodulating infections such as TB and hepatitis C, and might also be increased with the use of newer and more potent immunosuppressive agents. Primary prophylaxis failure may occur in association with some of these risk factors.     

Epidemiology,Risk Factors,and Outcome of Bloodstream Infection Within the First Year After Kidney Transplantation

BackgroundMulti-drug resistant organisms have been emerging among kidney transplant (KT) recipients with bloodstream infections (BSI). The investigation for epidemiology, risk factors and outcome of these infections following KT was initiated.Materials and MethodsA retrospective study of all adult KT recipients who developed a BSI within the first year after KT in 2016 at a single transplant center was conducted. The cumulative incidence of BSI was estimated with Kaplan-Meier methodology. Clinical characteristics and outcome were extracted. Risk factors were analyzed with Cox proportional hazards models.ResultsAmong 171 KT recipients, there were 26 (15.2%) episodes of BSI. Fifty-nine percent were men and the mean ± SD age was 43 ± 12 years. The cumulative incidence of BSIs was 10.1% at 1 month, 13.5% at 6 months, and 15.2% at 12 months. Gram-negative bacteria were responsible for 92% of BSIs, Escherichia coli was the most common pathogen (65%) followed by Klebsiella pneumoniae (11%). Among those, 71% were resistant to extended-spectrum cephalosporins. The genitourinary tracts were the predominant source of BSIs (85%). The second kidney transplantation (HR, 4.55; 95% CI, 1.24–16.79 [P = 0.02]) and receiving induction therapy (HR, 3.05; 95% CI, 1.15‐8.10 [P < 0.03]) were associated with BSI in a multivariate analysis. One patient (4%) developed allograft rejection, allograft failure and death from septic shock.ConclusionsOne out of six KT recipients could develop BSI from gram-negative bacteria within the first year after transplant, particularly in those that received the second transplantation or induction therapy.     

Association of vitamin D serum levels and its common genetic determinants,with severity of liver fibrosis in genotype 1 chronic hepatitis C patients

Lower 25‐hydroxyvitamin D [25(OH)D] serum levels have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC). In addition, a recent genome‐wide study identified genetic variants (rs12785878, near dehydrocholesterol reductase, DHCR7; rs10741657, near CYP2R1; and rs7041, near vitamin D‐binding protein, GC) affecting 25(OH)D serum levels in healthy populations. We aimed to assess the association between vitamin D serum levels and its genetic determinants, with the severity of liver fibrosis. Two hundred and sixty patients with biopsy‐proven G1CHC were consecutively evaluated. The 25(OH)D serum levels were measured by high‐pressure liquid chromatography. All patients were genotyped for DHCR7 rs12785878, CYP2R1 rs10741657 and GC rs7041 single nucleotide polymorphisms. DHCR7 GG genotype (P = 0.003) and the severity of fibrosis (P = 0.03) were independent factors associated with lower 25(OH)D serum levels in multiple linear regression analysis. Interestingly, 53.8% (7/13) of patients with DHCR7 GG genotype had severe liver fibrosis, compared to 27.1% (67/247) of those with DHCR7 TT/TG genotype (P = 0.03). By multivariate logistic regression analysis, severe fibrosis was independently associated with older age (OR, 1.056; 95% CI, 1.023–1.089, P = 0.001), low cholesterol (OR, 0.984; 95% CI, 0.974–0.994, P = 0.002), high triglycerides (OR, 1.008; 95% CI, 1.002–1.015, P = 0.01), low 25(OH)D (OR, 0.958; 95% CI, 0.919–0.999, P = 0.04), DHCR7 GG genotype (OR, 4.222; 95% CI, 1.106–16.120; P = 0.03), moderate–severe steatosis (OR, 2.588; 95% CI, 1.355–4.943; P = 0.004) and moderate–severe necroinflammatory activity (grading) (OR, 2.437; 95% CI, 1.307–4.763; P = 0.001). No associations were found between liver fibrosis and both CYP2R1 and GC genotypes. In patients with G1CHC, GG homozygosis for DHCR7 gene and lower 25(OH)D levels are independently associated with the severity of liver fibrosis.     

Influence of clinically significant portal hypertension on surgical outcomes and survival following hepatectomy for hepatocellular carcinoma: a systematic review and meta‐analysis

Surgical resection is not indicated in patients with portal hypertension in the current guideline of Barcelona Clinic Liver Cancer (BCLC) stage. We report a systematic review and meta‐analysis to determine the impact of clinically significant portal hypertension on survival in patients with hepatocellular carcinoma (HCC) following hepatectomy. Searched data in PubMed, EMBASE, and the Cochrane Library were reviewed and 11 publications were included in the meta‐analysis. The inclusion criteria of clinically significant portal hypertension were esophageal varices and/or thrombocytopenia with splenomegaly. Pooled data were extracted and computed into odds ratios (ORs) for clinical outcome and hazard ratios (HRs) for overall survival. The final pooled data were composed of 2,285 patients. There were 775 patients with clinically significant portal hypertension (PHT group) and 1,510 patients without clinically significant portal hypertension (non‐PHT group). Pooled proportion of mortality was 6.1% (95% confidence interval [CI] 0.032–0.116) in PHT group and 2.8% (95% CI 0.014–0.054) in the non‐PHT group. The pooled proportion of morbidity was 41.7% (95% CI 0.274–0.575) in PHT group and 34.7% (95% CI 0.243–0.467) in non‐PHT group. Pooled data confirmed a significantly higher postoperative mortality in the PHT group, with OR 3.02 (P < 0.001). The PHT group also demonstrated significantly higher occurrence of postoperative complications (OR 1.39, P = 0.008), liver‐related morbidity (OR 3.10, P < 0.00001), and liver failure (OR 2.14, P = 0.0005) compared to the non‐PHT group. According to the overall survival, pooled analysis demonstrated that the PHT group demonstrated poorer survival than the non‐PHT group (HR 1.48, P = 0.007). The analyses support significantly higher rates of postoperative mortality, complications, liver‐related morbidity, liver failure, and poorer overall survival in PHT group compared with the non‐PHT group. Surgical resection should be selected carefully with strict surgical strategy in patients with clinically significant portal hypertension when surgical resection is planned.     

Humoral and cellular immune monitoring might be useful to identify liver transplant recipients at risk for development of infection

Abstract: Orthotopic liver transplantation (OLT) is a successful therapy for patients with end‐stage liver disease, and infection remains a significant cause of morbidity and mortality for patients undergoing this procedure. To assess humoral and cellular immunity markers as potential risk factors for development of infection, 46 consecutive liver transplant recipients (hepatitis C virus cirrhosis [n=17], alcoholic liver disease [n=15], hepatocellular carcinoma [n=9], autoimmune hepatitis [n=2], and other [n=3]) performed at a single center were prospectively studied. Maintenance therapy included tacrolimus (n=37) or cyclosporine (n=9) and prednisone. During follow‐up, 27 patients had at least 1 episode of infection (58.7%). Pre‐OLT immunoglobulin G (IgG) hypergammaglobulinemia (relative risk [RR] 2.78; 95% confidence interval [CI], 1.17–6.60, P=0.02), pre‐OLT IgA hypergammaglobulinemia (RR 2.77, CI=1.24–6.19, P=0.012), and pre‐OLT C3 hypocomplementemia (RR 3.02, CI=1.21–7.55, P=0.018) were associated with an increased risk for development of infection. Monitoring of Ig and complement levels might help to identify the risk of developing infection in OLT.