Risk factors associated with Hepatitis E virus infection in kidney transplant recipients in a single tertiary Center in the United States

BackgroundHepatitis E virus (HEV), the causative agent of hepatitis E, is a common but self-limiting disease. However, in immunosuppressed kidney transplant 47 recipients (KTRs), HEV infection can become chronic. We investigated risk factors associated with HEV infection among 271 KTRs at the Johns Hopkins Hospital transplanted between 1988 and 2012.MethodsHEV infection was defined as having positive anti-HEV IgM, anti-HEV IgG, or HEV RNA. The risk factors included: age at transplant, sex, hemodialysis/peritoneal dialysis, plasmapheresis, transfusions, community urbanization, and other socioeconomic factors. Logistic regression was used to determine independent risk factors associated with HEV infection.ResultsOut of 271 KTRs, 43 (16%) had HEV infection though not active disease. HEV infection in KTRs was associated with older age (≥45 years; OR = 4.04; 95% CI = 1.81–57 10.03; p = 0.001) and living in communities with low proportions of minorities (OR = 0.22; 95% 58 CI = 0.04–0.90; p = 0.046).ConclusionKTRs who had HEV infection may be at an increased risk of developing chronic HEV.     

Risk Factors for Mortality in Liver Transplant Recipients With ESKAPE Infection

BackgroundAlthough infections caused by the pathogens Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp (ESKAPE) have recently been identified as serious emerging problems in solid organ transplant, no information in liver transplant (LT) recipients is available. We sought to investigate the risk factors for associated mortality in LT recipients with ESKAPE infections.MethodsA retrospective analysis of infection after LT was reviewed. Risk factors for mortality caused by ESKAPE infection were identified.ResultsFifty-three episodes of infections caused by ESKAPE were documented in 51 LT recipients. The main sites of infection were the bloodstream (49.0%), the lungs (33.3%), and the intra-abdominal/biliary tract (17.6%). The risk factors for mortality independently associated with ESKAPE infection were female sex (odds ratio [OR] = 6.6, 95% confidence interval [CI] = 1.1–40.8, P = .042), septic shock (OR = 30.1, 95% CI = 3.7–244.8, P = .001), and lymphocyte counts <300/mm³ (OR = 20.2, 95% CI = 2.9–142.2, P = .003).ConclusionsTo improve the results of LT, more effective therapeutic treatments are of paramount importance when female LT recipients with ESKAPE infection present with septic shock and decreased lymphocyte counts.     

Risk factors for acute rejection in liver transplantation and its impact on the outcomes of recipients

ObjectiveTo determine the risk factors for acute rejection in liver transplantation and its impact on the outcomes of the recipients.MethodsClinicopathological data of 290 patients who underwent liver transplantation from January 2012 to December 2021 at our center were retrospectively evaluated. Patients were grouped into an acute rejection (AR) group and a normal (NM) group based on the confirmed histopathological diagnosis of acute rejection. Univariate and multivariate logistic regression were used to determine the risk factors for acute rejection.Results244 patients were included in the study. Acute rejection occurred in 27 (11.1%) of the patients. Warm ischemia time (P = 0.137), cold ischemia time (P = 0.064) and chronic liver failure (P = 0.001) were potential risk factors for acute rejection. Chronic liver failure (P < 0.001, OR = 8.22, 95% CI = 2.47–27.32) was the independent risk factor. There was no significant difference in overall survival between recipients with acute rejection and those without it (P = 0.985). The 1-, 3- and 5-year overall survival in the NM group was 98.1%, 85.7% and 78.6% respectively vs 88.9%, 82.5% and 82.5% respectively in the AR group.ConclusionAcute rejection does not appear to affect the long-term survival of the recipients. Only chronic liver failure was an independent risk factor for acute rejection. Our findings further illustrate that contradictions still exist on which factors influence acute rejection in liver transplant recipients.SummaryClinicopathological data of 290 liver transplant recipients at our center between January 2012 and December 2021 were retrospectively evaluated to determine the risk factors for acute rejection and its impact on the outcomes of the recipients. 244 patients were included in the analysis. 27 of the 244 experienced acute rejection. Propensity score matching was performed to reduce the confounding effect. Patients were assigned to an acute rejection group (n = 27) and a normal group (n = 54). Chronic liver failure (P < 0.001, OR = 8.22, 95% CI = 2.47–27.32) was the determined to be independent risk factor for acute rejection. Acute rejection did not appear to affect the long-term survival of the recipients and there was no significant difference in overall survival between the patients with acute rejection and those without it.     

Considering extended right lobe grafts as major extended donor criteria in liver transplantation is justified

The outcomes of split-liver transplantation are controversial. This study compared outcomes and morbidity after extended right lobe liver transplantation (ERLT) and whole liver transplantation (WLT) in adults. MEDLINE and Web of Science databases were searched systematically and unrestrictedly for studies on ERLT and its impact on graft and patient survival, and postoperative complications. Graft loss and patient mortality odds ratios (OR) and 95% confidence intervals (CI) were assessed by meta-analyses using Mantel–Haenszel tests with a random-effects model. Vascular and biliary complications, primary nonfunction, 3-month, 1-, and 3-year graft and patient survival, and retransplantation after ERLT and WLT were analyzed. The literature search yielded 10 594 articles. After exclusion, 22 studies (n = 75 799 adult transplant patients) were included in the analysis. ERLT was associated with lower 3-month (OR = 1.43, 95% CI = 1.09–1.89, P = 0.01), 1-year (OR = 1.46, 95% CI = 1.08–1.97, P = 0.01), and 3-year (OR = 1.37, 95% CI = 1.01–1.84, P = 0.04) graft survival. WL grafts were less associated with retransplantation (OR = 0.57; 95% CI = 0.41–0.80; P < 0.01), vascular complications (OR = 0.53, 95% CI = 0.38–0.74, P < 0.01) and biliary complications (OR = 0.67; 95% CI = 0.47–0.95; P = 0.03). Considering ERLT as major Extended Donor Criteria is justified because ERL grafts are associated with vasculobiliary complications and the need for retransplantation, and have a negative influence on graft survival.     

Association studies of cytochrome P450, family 2, subfamily E,polypeptide 1 (CYP2E1) gene polymorphisms with acute rejection in kidney transplantation recipients

Recent studies have shown that single‐nucleotide polymorphisms (SNPs) are associated with allograft rejection in kidney transplantation recipients. We evaluated the possible association between SNPs of the cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1) gene, and acute rejection (AR) among renal transplant patients in a Korean population. We conducted a case–control association study in 63 AR and 284 non‐AR kidney transplant recipients. The SNPs of CYP2E1 were genotyped by direct sequencing. Recipient sex (p = 0.023) and the use of tacrolimus (p = 0.017) were significantly different between the two groups. The use of mycophenolate mofetil (MMF) and antibody induction therapy was significantly lower in the AR group. Multiple logistic regression models (codominant, dominant, recessive, and log‐additive models) adjusted by sex and type of immunosuppressive regimens were applied to determine the odds ratios (ORs), 95% confidence intervals (CIs), and p‐values. The rs2515641 of CYP2E1 showed significant differences between the AR patient group and non‐AR group (p = 0.003, OR = 2.55, 95% CI = 1.37–4.75 in the codominant 1 model; p = 0.002, OR = 2.61, 95% CI = 1.43–4.77 in the dominant model; p = 0.0035, OR = 2.13, 95% CI = 1.29–3.50 in the log‐additive model). The allele of the rs2515641 SNP also showed a significant association (p = 0.004, OR = 1.99, 95% CI = 1.24–3.21). This study suggests that the CYP2E1 polymorphism may be related to the development of AR in Korean kidney transplantation recipients.     

Changes in humoral immune response after SARS-CoV-2 infection in liver transplant recipients compared to immunocompetent patients

The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case–control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p < .001) and at 6 months (63.4% vs. 90.1%, p < .001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p = .001) and 6 months (p < .001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17–83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03–1.36), and therapy with renin–angiotensin–aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47–34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline.     

High levels of soluble Major Histocompatibility Complex class I related chain A (MICA) are associated with biliary cast syndrome after liver transplantation

BackgroundThe biliary cast syndrome (BCS) is a frequent problem following liver transplantation. The pathogenesis of this complication is not well understood. Previous research has demonstrated that the soluble form of MICA (sMICA) is significantly higher in patients with chronic liver disease and hepatocellular carcinoma (HCC) than in healthy volunteers. The aim of this study is to investigate the possible involvement of sMICA in the formation of BCS after liver transplantation.MethodsSerum soluble MICA was retrospectively evaluated in pre- and post-transplant sera from 133 consecutive primary liver transplant patients and in sera from 88 healthy volunteers using sandwich ELISA. Normal distribution of serum sMICA was described by the data obtained from healthy population and sMICA concentration that was greater than the upper bound 95% normal range was considered as high levels of sMICA. Patient records were reviewed to identify patients who developed BCS.ResultsThe results demonstrated that 37.6% of patients with end-stage liver diseases had significantly higher pre-transplant serum sMICA than in healthy population. 34.4% of recipients with post-transplant high levels of sMICA developed BCS. In contrast, 17.3% of patients with post-transplant normal levels of sMICA developed BCS. The risk of BCS development is significantly associated with the presence of post-transplant high levels of sMICA (P = 0.0365). Further analysis disclosed that patients with decreased post-transplant sMICA following liver transplantation had a lower incidence rate of BCS than those with remained high levels of sMICA after transplantation (10.5% vs. 38.7%, P = 0.0302). Furthermore, log-rank test showed that BCS occurrence was significantly associated with dynamic changes of sMICA among different groups (P = 0.0188).ConclusionsBiliary cast syndrome is more likely to develop in recipients who have post-transplant high levels of sMICA. The data suggested that sMICA might have some immunologic effect on BCS development following liver transplant. Monitoring of serum sMICA could have a prognostic value in assessment of patients with liver transplantation.     

Genetic polymorphism in hOGG1 is associated with triple-negative breast cancer risk in Chinese Han women

8-hydroxy-2′-deoxyguanine (8-OHdG), a typical product of oxidative stress-induced DNA damage, can cause a G–T transversion during DNA replication if it is not removed. Human 8-oxoguanine glycosylase 1 (hOGG1), a key DNA repair gene, recognizes and excises 8-OHdG from damaged DNA accurately; however, a c.977C>G (Ser326Cys) polymorphism in hOGG1 can inhibit the gene's ability to remove 8-OHdG. The aim of present study was to investigate the association between the c.977C>G polymorphism in hOGG1 and the risk of breast cancer in Chinese Han women. We used high-resolution melting and sequencing to analyze the genotypes of 630 patients with sporadic breast cancer patients and 777 healthy controls. We also performed risk-stratified subgroup analyses to determine the association between the c.977C>G polymorphism and other characteristics of breast cancer subgroups. Breast cancer patients and healthy controls did not have significantly different of c.977C/G genotypes (odds ratio [OR] = 1.10, 95% confidence interval [CI] = 0.82–1.49, p = 0.57) and c.977G/G genotypes (OR = 1.34, 95% CI = 0.97–1.84, p = 0.09). However, the c.977G/G genotype was especially prevalent in breast cancer patients who were younger than 55 years (OR = 1.58, 95% CI = 1.05–2.39, p = 0.04), were premenopausal status (OR = 1.87, 95% CI = 1.14–3.06, p = 0.02), had triple-negative disease (OR = 2.14, 95% CI = 1.06–4.29, p = 0.04), or p53-positive disease (OR = 1.56, 95% CI = 1.14–2.12, p = 0.005). These findings suggest that the c.977C>G polymorphism in hOGG1 is associated with an increased risk of breast cancer in Chinese Han women who are younger than 55 years, premenopausal, triple-negative, or p53-positive subgroups.     

Long-term outcomes of retransplantation after live donor liver transplantation: A Western experience

BackgroundDespite most liver transplants in North America being from deceased donors, the number of living donor liver transplants has increased over the last decade. Although outcomes of liver retransplantation after deceased donor liver transplantation have been widely published, outcomes of retransplant after living donor liver transplant need to be further elucidated.MethodWe aimed to compare waitlist outcomes and survival post-retransplant in recipients of initial living or deceased donor grafts. Adult liver recipients relisted at University Health Network between April 2000 and October 2020 were retrospectively identified and grouped according to their initial graft: living donor liver transplants or deceased donor liver transplant. A competing risk multivariable model evaluated the association between graft type at first transplant and outcomes after relisting. Survival after retransplant waitlisting (intention-to-treat) and after retransplant (per protocol) were also assessed. Multivariable Cox regression evaluated the effect of initial graft type on survival after retransplant.ResultsA total of 201 recipients were relisted (living donor liver transplants, n = 67; donor liver transplants, n = 134) and 114 underwent retransplant (living donor liver transplants, n = 48; deceased donor liver transplants, n = 66). The waitlist mortality with an initial living donor liver transplant was not significantly different (hazard ratio = 0.51; 95% confidence interval, 0.23–1.10; P = .08). Both unadjusted and adjusted graft loss risks were similar post-retransplant. The risk-adjusted overall intention-to-treat survival after relisting (hazard ratio = 0.76; 95% confidence interval, 0.44–1.32; P = .30) and per protocol survival after retransplant (hazard ratio:1.51; 95% confidence interval, 0.54–4.19; P = .40) were equivalent in those who initially received a living donor liver transplant.ConclusionPatients requiring relisting and retransplant after either living donor liver transplants or deceased donor liver transplantation experience similar waitlist and survival outcomes.     

Short-term decreased post transplant lymphoproliferative disorder risk after kidney transplantation using two novel regimens

BackgroundBelatacept is employed alongside calcineurin inhibitor (CNI) therapy to prevent graft rejection in kidney transplant patients who are Epstein-Barr virus (EBV) seropositive. Preliminary data suggested that rates of post-transplant lymphoproliferative disorder (PTLD) were higher in individuals treated with belatacept compared to CNI therapy alone.MethodsThe records of 354 adults who underwent kidney only transplantation from January 2015 through September 2021 at one medical center were evaluated. Patients underwent treatment with either low-doses of mycophenolate, tacrolimus and sirolimus (B⁰, n = 235) or low-doses of mycophenolate, tacrolimus and belatacept (B¹, n = 119). All recipients underwent induction with antithymocyte globulin and a rapid glucocorticosteroid taper. Relevant donor and recipient information were analyzed and endpoints of PTLD were assessed.ResultsThere were no cases of PTLD in either cohort within the study period. Recipients in the belatacept cohort experienced lower estimated glomerular filtration rates at 12 months (B⁰: 67.48 vs. B¹: 59.10, p = 0.0014). Graft failure at 12 (B⁰: 1.28% vs. B¹: 0.84%, p = 1.0) and 24 months (B⁰:2.55% vs. B¹: 0.84%, p = 0.431) were similar. There was no difference in rejection rates at 12 (B⁰: 1.27% vs. B¹: 2.52%, p = 0.408) or 24 months (B⁰: 2.12% vs. B¹: 2.52%, p = 1.000). Both groups had similar rates of malignancy, mortality and CMV/BK viremia.ConclusionNon-belatacept (MMF, tacrolimus and sirolimus) and belatacept-based (MMF, tacrolimus and belatacept) regimens do not appear to pose any increased risk of early onset PTLD. Both cohorts benefited from low rates of rejection, malignancy, mortality and graft failure. Recipients will continue to be monitored as PTLD can manifest as a long-term complication.     

Sex- and age-based comparison of serum immunoglobulins following liver transplantation

BackgroundOver a quarter of organ transplant recipients have low immunoglobulin levels in their early post-transplant course, which is associated with increased risk of infection and mortality. Although immunoglobulin level varies by sex among healthy individuals, it is unknown how such differences are affected by transplant-related immunosuppression. This study compared post-liver transplant immunoglobulin G (IgG) between sexes at varying ages.MethodsSerum specimens from a prospective cohort of 130 liver transplant recipients were analyzed. IgG was measured at time of transplant and from one-month post-transplant samples. Post-transplant IgG was compared between sexes using multivariable linear regression. Four age and sex categories were created (women<50, women≥50, men<50, men≥50) and the model repeated with this as the explanatory variable. The relationship between sex hormone concentrations and post-transplant IgG was also explored. Infection type and incidence were examined within groups.ResultsThe cohort included 99 men, 31 women (mean age 53). In adjusted linear regression, post-transplant IgG was not significantly different by sex (p = 0.92). However, when broken into four categories by age and sex, the contrast in IgG levels between younger versus older patients was strikingly greater among women than among men. An interaction term including age and sex was statistically significant (p = 0.03). The combined age-sex categorical variable was also significantly associated with post-transplant IgG (p = 0.01). Finally, an association was identified between baseline estradiol level and post-transplant change in IgG (p = 0.04).ConclusionsSex and age have an important relationship with post-transplant IgG with older women demonstrating lowest concentrations. Immunoglobulin levels have previously demonstrated association with post-transplant outcomes.     

The value of three-dimensional visualization techniques in hepatectomy for complicated hepatolithiasis: A propensity score matching study

ObjectiveThe present study aimed to investigate the safety, feasibility, and efficacy of three-dimensional visualization technique (3DVT)-guided hepatectomy in the treatment of complicated hepatolithiasis.MethodsThe clinical and follow-up data of 279 patients with complicated hepatolithiasis were retrospectively analyzed. The patients were divided into a 3DVT group (group A, 66 cases) and a non-3DVT group (group B, 213 cases). After baseline data were balanced using propensity score matching (PSM), the clinical characteristics and follow-up data of the two groups were observed.ResultsAfter 1:1 PSM, 58 patients in each group were successfully matched with each other. When the groups were compared, the surgical duration (p = 0.033) and intraoperative blood loss (p = 0.002) of group A were lower than those of group B. The immediate stone clearance rate (91.4% vs. 75.9%, p = 0.024) and quality of life outcome (p = 0.034) of group A were significantly higher than those of group B. Logistic regression analysis showed that history of two or more biliary tract operations (odds ratio [OR] = 6.544, 95% confidence interval [CI] = 1.193–35.890, p = 0.031), bilateral stone distribution (OR = 4.198, 95% CI = 1.186–14.854, p = 0.026), and Geng grade III or IV (OR = 12.262, 95% CI = 2.224–67.617, p = 0.004) were independent risk factors for poor outcomes in patients with complicated hepatolithiasis.ConclusionCompared to conventional imaging examinations, 3DVT can be used to guide and achieve accurate preoperative diagnosis of complicated hepatolithiasis and has good safety, feasibility, and efficacy.     

Parvovirus B19 infection in kidney transplant recipients: A prospective study in a teaching hospital in Shanghai,China

BackgroundThere is a lack of epidemiological studies on the course and clinical characteristics of Parvovirus B19 (B19V) infections in kidney transplant (KT) recipients. This study was undertaken to provide recommendations for clinical B19V infection diagnosis and treatment.MethodsSerum samples of KT recipients were regularly collected and tested for B19V-DNA copies, B19V-IgG/IgM levels, as well as hematological parameters and functions of kidney and liver. The course of B19V infection was described according to the results of serology and DNA testing, and the clinical and epidemiological data were combined for analysis.Results75% B19V infections occurred within 2 weeks after KT(n = 9). The infection rate of B19V in KT recipients was high, namely 10.17% (n = 12). The number of 10 patients IgM antibodies against B19V (IgM+) and the DNA B19V (DNA+), whereas 2 patients were IgM negative (IgM-) but DNA+. The B19V infected KT patients showed several symptoms, including anemia (100%), reduction of platelets (8.33%), and damage to liver (75%) and kidney function (16.67%) Patients with progressive anemia in the first two weeks after KT, which combined with the decrease of reticulocytes, are more likely to have B19V infection. Associations of four main therapeutic risk factors for B19V infections in KT patients have been analyzed. B19V infection was associated with use of basiliximab (OR = 1.19; 95%- CI: 1.08–1.32; P = 0.003) and use of thymoglobulins (OR = 0.84; 95%-CI: 0.76–0.93; P = 0.003).ConclusionsDoctors should be alert to B19V infection, especially in the immunodeficient patients within the first two weeks after transplantation.     

Predicting Inpatient Status After Primary Total Knee Arthroplasty in Medicare-Aged Patients

BackgroundThe Centers for Medicare and Medicaid Services (CMS) removed total knee arthroplasty (TKA) from its inpatient only (IPO) list as of January 1, 2018. The purpose of this study was to establish a risk-stratifying nomogram to aid in determining the need for inpatient admission among Medicare-aged patients undergoing primary TKA.MethodsThe American College of Surgeons National Surgical Quality Improvement Program database was queried to identify all patients aged ≥65 years who underwent primary TKA between 2006 and 2015. The primary outcome measure was inpatient admission, as defined by hospital length of stay longer than 2 days. Multiple demographic, comorbid, and perioperative variables were incorporated in a multivariate logistic regression model to yield a risk stratification nomogram.ResultsSixty-one thousand two hundred eighty-four inpatient and 26,066 outpatient admissions were analyzed. Age >80 years (odds ratio [OR] = 2.27, P < .0001, 95% confidence interval [CI] = 2.13-2.42), simultaneous bilateral TKA (OR = 2.02, P < .0001, 95% CI = 1.77-2.30), dependent functional status (OR = 1.95, P < .0001, 95% CI = 1.62-2.35), metastatic cancer (OR = 1.91, P = .055, 95% CI = 0.99-3.73), and female gender (OR = 1.76, P < .0001, 95% CI = 1.70-1.82) were the greatest determinants of inpatient stay. The resulting predictive model demonstrated acceptable discrimination and excellent calibration.ConclusionOur model enabled a reliable and straightforward identification of the most suitable candidates for inpatient admission in Medicare aged–patients undergoing primary TKA. Larger multicenter studies are necessary to externally validate the proposed predictive nomogram.     

Are Patients Being Appropriately Selected for Same-Day Discharge Total Knee Arthroplasty?

BackgroundDecreased cost associated with same-day discharge (SDD) total knee arthroplasty (TKA) has led to an increased interest in this topic. The purpose of this study is to investigate whether there is a population of TKA patients in which SDD has similar rates of 30-day complications compared to patients discharged on postoperative day 1 or 2.MethodsUsing the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2018, 6,327 TKA patients who had a SDD (length of stay [LOS] = 0) were matched to TKA patients who had an LOS of 1 or 2 days. All SDD patients were successfully matched 1:1 using the morbidity probability variable (a composite variable of demographics, comorbidities, and laboratory values). Patients were divided into quartiles based on their morbidity probability. Bivariate logistic regressions were then used to compare any complication and major complication rates in the SDD quartiles to the corresponding quartiles with an LOS of 1 or 2 days.ResultsWhen comparing the 1st quartiles (healthiest), there was no difference between the cohorts in any complication (odds ratio [OR] = 0.960, 95% CI 0.552-1.670, P = .866) and major complications (OR = 0.999, 95% CI = 0.448-2.231, P = .999). The same was observed in quartile 2 (any complications: OR = 1.161, 95% CI = 0.720-1.874, P = .540). Comparing the third quartiles, there was an increase in all complications with SDD (OR = 1.784, 95% CI = 1.125-2.829, P = .014), but no difference in major complications (OR = 1.635, 95% CI = 0.874-3.061, P = .124). Comparing the fourth quartiles (least healthy), there was an increase in all complications (OR = 1.384, 95% CI = 1.013-1.892, P = .042) and major complications (OR = 1.711, 95% CI = 1.048-2.793, P = .032) with SDD.ConclusionThe unhealthiest 50% of patients in this study who underwent SDD TKA were at an increased risk of having any complication, calling into question the current state of patient selection for SDD TKA.Level of EvidenceIII.     

Risk Factors for Hepatotoxicity in Solid Organ Transplants Recipients Being Treated for Tuberculosis

BackgroundTuberculosis (TB) is associated with high morbidity and mortality in solid organ transplant (SOT) recipients. Also, SOT patients have a 20- to 74-fold increase in the chance of developing TB compared to the general population. Here we evaluated the incidence of hepatotoxicity in SOT recipients on treatment for TB and determined risk factors for liver toxicity in these patients.Patients and MethodsRetrospective cohort conducted in a reference hospital for SOT in Southern Brazil. All SOT recipients who underwent TB treatment during the years 2000–2012 were considered for the study.ResultsA total of 69 patients were included in the study and 23 had liver toxicity (incidence 33.3%). Independent risk factors for hepatotoxicity were rifampin use at doses of ≥600 mg daily (P = .016; OR 2.47; 95% CI, 1.18–5.15) and lung transplantation (P = .017; OR 2.05; 95% CI, 1.14–3.70). Kidney transplantation appeared as a protective factor (P = .036; OR 0.50; 95% CI, 0.26–0.96). Mortality was higher in the patients who had hepatotoxicity (43.5%), compared with those who did not (19.6%).ConclusionIn this study, the use of rifampin at doses of 600 mg daily or higher was found to be an independent risk factor for liver toxicity in SOT recipients. The importance of additional risk factors for hepatotoxicity, such as lung transplantation as well as the protective role of kidney transplantation, should be better investigated in SOT recipients being treated for TB.     

Risk factors for the development of invasive aspergillosis after kidney transplantation: Systematic review and meta-analysis

To investigate risk factors for invasive aspergillosis (IA) after kidney transplantation (KT), we conducted a systematic search in PubMed and EMBASE to identify studies published until June 2020. We included case-control or cohort design studies comprising KT recipients with a diagnosis of IA, defined according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria, and assessed risk factors for the development of IA. Random-effect models meta-analysis served to pool data. We identified eleven case-control studies (319 IA cases and 835 controls). There was an increased risk of IA among recipients with underlying chronic lung diseases (odds ratio [OR] = 7.26; 95% confidence interval [CI] = 1.05-50.06) and among those with diabetic nephropathy (OR = 1.65; 95% CI = 1.10-2.48). Requiring posttransplant hemodialysis (OR = 3.69; 95% CI = 2.13-6.37) or surgical reintervention (OR = 6.28; 95% CI = 1.67-23.66) were also associated with an increased risk. Moreover, a positive link was identified between IA and posttransplant bacterial infection (OR = 7.51; 95% CI = 4.37-12.91), respiratory tract viral infection (OR = 7.75; 95% CI = 1.60-37.57), cytomegalovirus infection or disease (OR = 2.67; 95% CI = 1.12-6.32), and acute graft rejection (OR = 3.01; 95% CI = 1.78-5.09). In contrast, receiving a kidney from a living donor was associated with a reduced risk (OR = 0.65; 95% CI = 0.46-0.93). KT recipients that accumulate several of these conditions should be closely monitored and a low threshold of suspicion for IA should be maintained. Future studies should explore the benefit of mold-active prophylaxis to this subgroup of KT recipients at highest risk.     

Smoking Cessation has no Influence on Quality of Life in Patients with Peripheral Arterial Disease 5 Years Post-vascular Surgery

ObjectivesSmoking is an important modifiable risk factor in patients with peripheral arterial disease (PAD). We investigated differences in quality of life (QoL) between patients who quitted smoking during follow-up and persistent smokers.DesignCohort study.MethodsData of 711 consecutively enrolled patients undergoing vascular surgery were collected in 11 hospitals in the Netherlands. Smoking status was obtained at baseline and at 3-year follow-up. A 5-year follow-up to measure QoL was performed with the EuroQol-5D (EQ-5D) and Peripheral Arterial Questionnaire (PAQ).ResultsAfter adjusting for clinical risk factors, patients, who quit smoking within 3 years after vascular surgery, did not report an impaired QoL (EQ-5D: odds ratio (OR) = 0.63, 95% confidence interval (CI) = 0.28–1.43; PAQ: OR = 0.76, 95% CI = 0.35–1.65; visual analogue scale (VAS): OR = 0.88, 95% CI = 0.42–1.84) compared with patients, who continued smoking. Current smokers were significantly more likely to have an impaired QoL (EQ-5D: OR = 1.86, 95% CI = 1.09–3.17; PAQ: OR = 1.63, 95% CI = 1.00–2.65), although no differences in VAS scores were found (OR = 1.17, 95% CI = 0.72–1.90).ConclusionsThere was no effect of smoking cessation on QoL in PAD patients undergoing vascular surgery. Nevertheless, given the link between smoking, complications and mortality in this patient group, smoking cessation should be a primary target in secondary prevention.     

Role of standard HLA mismatch in modifying associations between non-pharmacologic risk factors and solid organ malignancy after kidney transplantation

BackgroundHuman leukocyte antigen mismatch(es) (HLA-mm) between donors and recipients has not been extensively studied either as a risk factor for solid organ malignancy (SOM) or as a modifier of associations between nonpharmacologic risk factors and SOM in kidney transplant recipients (KTRs).MethodsIn a secondary analysis from a previous study, 166,256 adult KTRs in 2000–2018 who survived the first 12 months post-transplant free of graft loss or malignancy were classified into 0, 1–3, and 4–6 standard HLA-mm cohorts. Multivariable cause-specific Cox regressions analyzed the risks of SOM and all-cause mortality (ac-mortality) in 5 years following the first KT year. Comparisons of associations between SOM and risk factors in HLA mismatch cohorts were made by estimating the ratios of adjusted hazard ratios.ResultsCompared with 0 HLA-mm, 1–3 HLA-mm was not associated, and 4–6 HLA-mm was equivocally associated with increased risk of SOM [hazard ratio, (HR) = 1.05, 95%, confidence interval (CI) = 0.94–1.17 and HR = 1.11, 95% CI = 1.00–1.34, respectively]. Both 1–3 HLA-mm and 4–6 HLA-mm were associated with increased risk of ac-mortality compared with 0 HLA mm [hazard ratio (HR) = 1.12, 95%, Confidence Interval (CI) = 1.08–1.18) and (HR = 1.16, 95% CI = 1.09–1.22), respectively]. KTR's history of pre-transplant cancer, age 50–64, and >/=65 years were associated with increased risks of SOM and ac-mortality in all HLA mismatch cohorts. Pre-transplant dialysis >2 years, diabetes as the primary renal disease, and expanded or standard criteria deceased donor transplantation were risk factors for SOM in the 0 and 1–3 HLA-mm cohorts and of ac-mortality in all HLA-mm cohorts. KTRs male sex or history of previous kidney transplant was a risk factor for SOM in the 1–3 and 4–6 HLA-mm cohorts and of ac-mortality in all HLA-mm cohorts.ConclusionDirect association between SOM and the degree of HLA mismatching is equivocal and limited to the 4–6 HLA-mm stratum; however, the degree of HLA mismatching has significant modifying effects on the associations between specific nonpharmacologic risk factors and SOM in KTRs.