Outcomes after liver transplantation in Korea: Incidence and risk factors from Korean transplantation registry

Background/AimsTo analyze the incidence and risk factors of outcomes after liver transplantation (LT) in the Korean population.MethodsThis study analyzed data from the liver cohort of Korean Organ Transplantation Registry (KOTRY) who had LT between May 2014 and December 2017. Study measures included the incidence of post-LT outcomes in recipients of living donor LT (LDLT) and deceased donor LT (DDLT). Cox multivariate proportional hazards model was used to determine the potential risk factors predicting the outcomes.ResultsA total of 2,563 adult recipients with LT (LDLT, n=1,956; DDLT, n=607) were included, with mean±standard deviation age of 53.9±8.9 years, and 72.2% were male. The post-LT outcomes observed in each LDLT and DDLT recipients were death (4.0% and 14.7%), graft loss (5.0% and 16.1%), rejection (7.0% and 12.0%), renal failure (2.7% and 13.8%), new onset of diabetes (12.5% and 15.4%), and hepatocellular carcinoma (HCC) recurrence (both 6.7%). In both LDLT and DDLT recipients, the most common post-LT complications were renal dysfunction (33.6% and 51.4%), infection (26.7% and 48.4%), and surgical complication (22.5% and 23.9%). Incidence of these outcomes were generally higher among recipients of DDLT than LDLT. Multivariate analysis indicated recipient age and DDLT as significant risk factors associated with death and graft loss. DDLT and ABO incompatible transplant were prognostic factors for rejection, and HCC beyond Milan criteria at pre-transplant was a strong predictor of HCC recurrence.ConclusionsThis study is a good indicator of the post-LT prognosis in the Korean population and suggests a significant burden of post-LT complications.     

Effect of the immunosuppressive regimen on the incidence of cytomegalovirus infection in 378 heart transplant recipients: A single centre,prospective cohort study

BackgroundCytomegalovirus (CMV) infection is a major complication of immunosuppression after heart transplant. Recent studies suggest the actual immunosuppressive regimen may affect the risk of CMV infection.ObjectivesTo evaluate incidence, risk factors and clinical consequences of CMV infection and assess the possible differential effect of distinct immunosuppressive protocols.Study designSingle centre, prospective cohort study of 378 consecutive heart transplant recipients undergoing CMV monitoring. Preemptive treatment was the standard of care. Patients were grouped as follows: group A, without any CMV infection; group B, with CMV infection not requiring pre-emptive treatment; group C, treated for CMV infection or disease.ResultsMost recipients never required antiviral therapy because of no CMV infection/disease (group A, 31%) or CMV levels below the cut-off for pre-emptive treatment (group B, 28%). Group C recipients (41%) were significantly older than group A patients (49.1 ± 13.2 vs. 44.8 ± 15.1 years; p = 0.028). Most cases occurred within the second month post-transplant. CMV viremia was detected in 77% and 62% of patients primed with thymoglobulin or ATG Fresenius, respectively, (OR 2.06, 95% C.I. 1.27–3.34; p = 0.0034). Use of everolimus was associated with a significantly lower rate of CMV infection compared to azathioprine or mycophenolate (OR 0.19, 95% C.I. 0.09–0.39; p < 0.0001). Major opportunistic infections were significantly more common in groups B and C.ConclusionIn a large and homogeneous cohort of heart transplant recipients, we observed a strong relationship between the immune suppressive regimen and CMV infection, as well as an increased incidence of other opportunistic infections in recipients with CMV infection/disease.     

Antibody response to SARS-CoV-2 mRNA vaccine among kidney transplant recipients: a prospective cohort study

ObjectivesWe aimed to evaluate the rates of antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine among kidney transplant recipients, and to identify factors associated with reduced immunogenicity.MethodsThis was a prospective cohort study including consecutive kidney transplant recipients in a single referral transplant centre. Participants were tested for anti-spike (anti-S) antibodies 2–4 weeks after a second vaccine dose. Primary outcome was rate of seropositivity. Univariate and multivariate analyses were conducted to identify factors associated with seropositivity.ResultsOf 308 kidney transplant recipients included, only 112 (36.4%) tested positive for anti-S antibodies 2–4 weeks after receiving the second dose of BNT162b2 vaccine. Median antibody titre was 15.5 AU/mL (interquartile range (IQR) 3.5–163.6). Factors associated with antibody response were higher estimated glomerular filtration rate (eGFR) (odds ratio (OR) 1.025 per mL/min/1.73 m², 95% confidence interval (CI) 1.014–1.037, p < 0.001), lower mycophenolic acid dose (OR 2.347 per 360 mg decrease, 95%CI 1.782–3.089, p < 0.001), younger age (OR 1.032 per year decrease, 95%CI 1.015–1.05, p < 0.001) and lower calcineurin inhibitor (CNI) blood level (OR 1.987, 95%CI 1.146–3.443, p 0.014). No serious adverse events resulting from the vaccine were reported.ConclusionsKidney transplant recipients demonstrated an inadequate antibody response to SARS-CoV-2 mRNA vaccination. Immunosuppression level was a significant factor in this response. Strategies to improve immunogenicity should be examined in future studies.     

Mycobacterial infections in adult recipients of allogeneic hematopoietic stem cell transplantation: A cohort study in a high endemic area

BackgroundMycobacterial infections are important and potentially life-threatening complications after organ transplantations. Notably, for the recipients of allogeneic hematopoietic stem cell transplantation (HSCT), there are a few supporting results to explore post-transplant mycobacterial infections. Taiwan is a high endemic area of the infection. We aim to investigate the incidence, risk factors, and survival of post-transplant mycobacterial infections, including mycobacterium tuberculosis (MTB) and non-tuberculous mycobacterium (NTM).MethodsWe included 422 adult patients undergoing allogeneic HSCT at an Asian tertiary medical center between January 2003 and December 2014. A total 26 subjects developed post-transplant mycobacterial infections. Risk factors, clinical features, and survival for post-transplant mycobacterial infections were collected and analyzed.ResultsPost-transplant mycobacterial infections occurred in 26 (6.2%) of 422 HSCT patients. Two-year cumulative incidences in MTB and NTM were 1.4% and 5.4%. In the multivariate analysis, being age >45 years (adjusted HR 2.21, 95% CI 1.01–4.83) and extensive chronic graft-versus-host disease (cGVHD) (adjusted HR 4.95, 95% CI 2.14–11.46) were identified as independent risk factors of infections. There was a trend as a risk factors in relapsed patients (P = 0.088). For patients with cGVHD, there was a significant difference of post-transplant survival between mycobacterial infections and none (P = 0.036). Pneumonia contributed most to mortality (n = 11, 42.3%).ConclusionMycobacterial infections are worth to note in a high endemic area. Once a high-risk group is identified, much effort is required to target new approaches for prevention, early detection and treatment of infections.     

Early post-operative acute phase response in patients with early graft dysfunction is predictive of 6-month and 12-month mortality in liver transplant recipients

Early allograft dysfunction (EAD) after liver transplantation is mostly a reversible event caused by factors related to ischemia/reperfusion (I/R) injury. EAD represents a hepatic injury associated with pre- and early post-transplant inflammatory cytokine responses. Aim of the present study was to evaluate the prognostic and diagnostic value of CRP in liver transplant recipients with EAD.Materials and methodsForty-seven patients with EAD were compared with 115 non-EAD patients. Pre- and post-transplant parameters were analyzed. EAD was defined based on postoperative liver function tests such as INR, bilirubin and liver enzymes. Statistical analysis was performed using SPSS version 18.0.ResultsPre-transplant liver enzyme were not significantly different in the two groups. At day 3, 5 and 10 post-transplant CRP was significantly higher in patients with EAD than in non-EAD patients (p ⩽ 0.001 for all investigations) and remained consistently high in patients with EAD and low in non-EAD patients. EAD patients with high CRP at post-transplant days 3 and 5 showed lower survival at 6-month and 12-month post-transplant than patients with low CRP.ConclusionOur results indicate a prognostic and diagnostic value of CRP in patients with early graft dysfunction and predict 6-month and 12-month mortality in liver transplant recipients.     

The association of cytomegalovirus infection and cytomegalovirus serostatus with invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients: a systematic review and meta-analysis

BackgroundIn allogeneic haematopoietic stem cell transplant (allo-HSCT) recipients, the inter-relationship between post-transplant cytomegalovirus (CMV) and subsequent invasive fungal infections (IFIs) is conflicting and the association of CMV serostatus with IFIs has not been evaluated.ObjectivesTo determine the relationship between CMV infection/serostatus and IFIs in allo-HSCT populations.Data sourcesA systematic literature search was conducted from existence until 11 July 2021 using Medline, Embase and ISI Web of Science databases.Study eligibility criteriaCross-sectional, prospective cohort, retrospective cohort and case–control studies that reported allo-HSCT recipients with CMV and without CMV who developed or did not develop IFIs after CMV infection.ParticipantsAllo-HSCT recipients.InterventionsNot applicable.MethodsA systematic search, screening, data extracting and assessing study quality were independently conducted by two reviewers. The Newcastle–Ottawa scale was used to assess risk of bias. data were analysed using the pooled effect estimates of a random-effects model.ResultsA total of 18 and 12 studies were included for systematic review and meta-analysis, respectively. Post-transplant CMV infection significantly increased the risk of IFIs with a pooled hazard ratio (pHR) of 2.58 (1.78, 3.74), I² = 75%. Further subgroup analyses by timing of IFIs, CMV definitions, study continents, study design and adjustment of effect estimates showed that post-transplant CMV infection consistently increased the risk of subsequent IFIs. High-risk CMV serostatus (D–/R+) increased the risk of IFIs with a pooled odds ratio (OR) of 1.33 (1.04, 1.71), I² = 0%, but low-risk CMV serostatus (D–/R–) decreased the risk of IFIs with a pOR of 0.69 (0.55, 0.87), I² = 0%.ConclusionsPost-transplant CMV infection and high-risk CMV serostatus increased the risk of IFIs, but low-risk CMV serostatus decreased risk of IFIs among allo-HSCT recipients. Further studies are needed to identify at-risk allo-HSCT recipients as well as to focus on fungal diagnostics and prophylaxis to prevent this fungal-after-viral phenomenon.     

The impact of carbapenemase-producing Enterobacteriaceae colonization on infection risk after liver transplantation: a prospective observational cohort study

ObjectiveTo investigate the impact of colonization with carbapenemase-producing Enterobacteriaceae (CPE) on the CPE infection risk after liver transplantation (LT).MethodsProspective cohort study of all adult patients undergoing LT at our centre over an 8-year period (2010–2017). Individuals were screened for CPE colonization by rectal swabs at inclusion onto the waiting list, immediately before LT and weekly after LT until hospital discharge. Asymptomatic carriers did not receive decolonization, anti-CPE prophylaxis or pre-emptive antibiotic therapy. Participants were followed up for 1 year after LT.ResultsWe analysed 553 individuals who underwent a first LT, 38 were colonized with CPE at LT and 104 acquired colonization after LT. CPE colonization rates at LT and acquired after LT increased significantly over the study period: incidence rate ratios (IRR) 1.21 (95% CI 1.05–1.39) and 1.17 (95% CI 1.07–1.27), respectively. Overall, 57 patients developed CPE infection within a median of 31 (interquartile range 11–115) days after LT, with an incidence of 3.05 cases per 10 000 LT-recipient-days and a non-significant increase over the study period (IRR 1.11, 95% CI 0.98–1.26). In multivariable analysis, CPE colonization at LT (hazard ratio (HR) 18.50, 95% CI 6.76–50.54) and CPE colonization acquired after LT (HR 16.89, 95% CI 6.95–41.00) were the strongest risk factors for CPE infection, along with combined transplant (HR 2.60, 95% CI 1.20–5.59), higher Model for End-Stage Liver Disease at the time of LT (HR 1.03, 95% CI 1.00–1.07), prolonged mechanical ventilation (HR 2.63, 95% CI 1.48–4.67), re-intervention (HR 2.16, 95% CI 1.21–3.84) and rejection (HR 2.81, 95% CI 1.52–5.21).ConclusionsCPE colonization at LT or acquired after LT were the strongest predictors of CPE infection. Prevention strategies focused on LT candidates and recipients colonized with CPE should be investigated.     

Microbiological epidemiology of preservation fluids in transplanted kidney: a nationwide retrospective observational study

ObjectivesKidney transplant recipients are at high-risk for donor-derived infections in the early post-transplant period. Transplant preservation fluid (PF) samples are collected for microbiological analysis. In case of positive PF cultures, the risk for the recipient is unknown and there is no consensus for prescribing prophylactic antibiotics. This nationwide observational study aimed to determine the epidemiology of bacterial and fungal agents in kidney transplant PF cultures and identify risk factors associated with positive PF cultures.MethodsWe performed a retrospective observational study on the following data collected from a national database between October 2015 and December 2016: characteristics of donor, recipient, transplantation, infection in donor and PF microbiological data.ResultsOf 4487 kidney transplant procedures, including 725 (16.2%, 725/4487) from living donors, 20.5% had positive PF cultures (living donors: 1.8%, 13/725; deceased donors: 24.1%, 907/3762). Polymicrobial contamination was found in 59.9% (485/810) of positive PF cultures. Coagulase-negative staphylococci (65.8%, 533/810) and Enterobacteriaceae (28.0%, 227/810) were the most common microorganisms. Factors associated with an increased risk of positive PF cultures in multivariable analysis were (for deceased-donor kidney transplants): intestinal perforation during procurement (OR 4.4, 95% CI 2.1–9.1), multiorgan procurement (OR 1.4, 95% CI 1.1–1.7) and en bloc transplantation (OR 2.5, 95% CI 1.3–4.9). Use of perfusion pump and donor antibiotic therapy were associated with a lower risk of positive PF cultures (OR 0.4, 95% CI 0.3–0.5 and OR 0.6, 95% CI 0.5–0.7, respectively).ConclusionIn conclusion, 24% of deceased-donor PF cultures were positive, and PF contamination during procurement seemed to be the major cause.     

Toxoplasmosis after allogeneic haematopoietic cell transplantation: experience using a PCR-guided pre-emptive approach

ObjectivesProphylaxis with trimethoprim–sulphamethoxazole (TMP-SMZ) is recommended in Toxoplasma-seropositive allogeneic haematopoietic cell transplant (HCT) recipients to prevent reactivation, but it is associated with numerous side effects. We report our experience of a pre-emptive approach guided by a polymerase chain reaction (PCR) in patients not receiving prophylaxis.MethodsIn this retrospective, single-centre experience, seropositive recipients and seronegative recipients receiving a graft from a seropositive donor were screened by PCR for the presence of Toxoplasma gondii DNA in peripheral blood until at least 6 months after transplantation. Confirmed PCR positivity triggered a pre-emptive anti-Toxoplasma therapy. Cases of Toxoplasma reactivation (using the European Society for Blood and Marrow Transplantation definitions) were compared with four controls (without reactivation), matched in time and recipient serostatus, to identify risk factors for reactivation by multivariate analysis.ResultsFrom November 2001 to August 2020, 1455 consecutive adult patients (59 cases and 1396 controls) were screened. The overall 1-year cumulative incidence of toxoplasmosis was 4.1% and the 1-year cumulative incidence in the seropositive recipients was 8.8%. Reactivation was associated with second transplant (OR 2.51, 95%CI 1.28–4.94, p 0.011), myeloablative conditioning (OR 2.24, 95%CI 1.17–4.41, p 0.011), total body irradiation (OR 2.29, 95%CI 1.17–4.44, p 0.010), acute graft-versus-host disease (GvHD) (OR 2.27, 95%CI 1.26–4.08, p 0.008) and use of high-dose corticosteroids (OR 2.08, 95%CI 1.14–3.78, p 0.018). In multivariate analysis only acute GvHD remained significant (adjusted OR 2.54, 95%CI 1.16–5.71, p 0.021).ConclusionsA PCR-based pre-emptive approach might serve as an acceptable alternative for patients unable to start with or to continue TMP-SMZ prophylaxis. Acute GvHD was identified as the single independent predictor for reactivation.     

Predictors for treatment outcomes among patients with drug-susceptible tuberculosis in the Netherlands: a retrospective cohort study

ObjectivesWe evaluated treatment outcomes and predictors for poor treatment outcomes for tuberculosis (TB) among native- and foreign-born patients with drug-susceptible TB (DSTB) in the Netherlands.MethodsThis retrospective cohort study included adult patients with DSTB treated from 2005 to 2015 from a nationwide exhaustive registry. Predictors for unsuccessful treatment outcomes (default and failure) and TB-associated mortality were analysed using multivariate logistic regression.ResultsAmong 5674 identified cases, the cumulative incidence of unsuccessful treatment and mortality were 2.6% (n/N = 146/5674) and 2.0% (112/5674), respectively. Although most patients were foreign-born (71%; 4042/5674), no significant differences in these outcomes were observed between native- and foreign-born patients (p > 0.05). Significant predictors for unsuccessful treatment were aged 18–24 years (odds ratio (OR), 2.04; 95% CI 1.34–3.10), homelessness (OR, 2.56; 95% CI 1.16–5.63), prisoner status (OR, 5.39; 95% CI 2.90–10.05) and diabetes (OR, 2.02; 95% CI 1.03–3.97). Furthermore, predictors for mortality were aged 74–84 years (OR, 5.58; 95% CI 3.10–10.03) or ≥85 years (OR, 9.35, 95% CI 4.31–20.30), combined pulmonary and extra-pulmonary TB (OR, 4.97; 95% CI 1.42–17.41), central nervous system (OR, 120, 95% CI 34.43–418.54) or miliary TB (OR, 10.73, 95% CI 2.50–46.02), drug addiction (OR, 3.56; 95% CI 1.34–9.47) and renal insufficiency/dialysis (OR, 3.23; 95% CI 1.17–8.96).ConclusionsNative- and foreign-born patients exhibited similar TB treatment outcomes. To further reduce disease transmission and inhibit drug resistance, special attention should be given to high-risk patients.     

Multinational case-control study of risk factors for the development of late invasive pulmonary aspergillosis following kidney transplantation

ObjectivesTo assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT).MethodsWe performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy.ResultsWe identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07–179.46; p 0.009) was identified as an independent risk factor for late IPA.ConclusionMore than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.     

Pneumocystis jirovecii pneumonia in renal transplant recipients occurring after discontinuation of prophylaxis: a case–control study

A case–control study was conducted to identify risk factors for Pneumocystis jirovecii pneumonia (PCP) in renal transplant recipients. Eleven cases of PCP were matched with 22 controls. Cases occurred a median of 18 months after transplantation, and none of the recipients was receiving prophylaxis. Univariate analysis showed that graft rejection, duration of steroid use, use of mammalian target of rapamycin (mTOR) inhibitors and lymphocytopenia at the time of prophylaxis discontinuation were risk factors for PCP. In the multivariate model, only graft rejection (OR 8.66, p 0.017) remained significantly associated with PCP. In patients with a history of graft rejection, PCP prophylaxis should be maintained, especially among those with lymphocytopenia.     

Bacterial and fungal bloodstream infections in solid organ transplant recipients: results from a Danish cohort with nationwide follow-up

ObjectivesBloodstream infections (BSI) are prevalent after solid organ transplantation (SOT). In this study, we aimed to investigate the incidence and risk factors for BSI in the first 5 years post-transplantation.MethodsThe study included 1322 SOT (kidney, liver, lung and heart) recipients transplanted from 2010 to 2017 with a total of 5616 years of follow-up. Clinical characteristics and microbiology were obtained from the Centre of Excellence for Personalized Medicine of Infectious Complications in Immune Deficiency (PERSIMUNE) data repository with nationwide follow-up. Incidence was investigated in the different SOT groups. Risk factors associated with BSI were assed in the combined group in time-updated multivariable Cox regressions.ResultsThe cumulative incidence of first BSI in the first 5 years post-transplantation differed in the SOT groups with a lower incidence in heart transplant recipients than in the other SOT groups (heart: 4.4%, CI 0.0–9.7%, vs. kidney: 24.6%, CI 20.9–28.2%, liver: 24.7%, CI 19.4–29.9%, and lung: 19.6%, CI 14.5–24.8%, p <0.001). Age above 55 years (HR 1.71, CI 1.2–2.4, p=0.002) and higher Charlson comorbidity index score (HR per unit increase: 1.25, CI 1.1–1.4, p<0.001) at transplantation, current cytomegalovirus (CMV) infection (HR 4.5, CI 2.6–7.9, p<0.001) and current leucopenia (HR 13.3, CI 3.7–47.9, p<0.001) were all associated with an increased risk of BSI.ConclusionIn SOT recipients, the incidence of BSI differed with the type of transplanted organ. Risk of BSI was higher in older recipients and in recipients with comorbidity, current CMV infection or leucopenia. Thus, increased attention towards BSI in recipients with these characteristics is warranted.     

Seroprevalence of Aspergillus IgG and disease prevalence of chronic pulmonary aspergillosis in a country with intermediate burden of tuberculosis: a prospective observational study

ObjectivesChronic pulmonary aspergillosis (CPA) is an emerging global disease with tuberculosis (TB) being the most important risk factor. Epidemiologic data on the seroprevalence of Aspergillus IgG and prevalence of CPA in different areas, especially in country with intermediate burden of TB, are lacking.MethodsWe prospectively recruited healthy volunteers, TB close contacts, active TB patients and participants with old pulmonary TB in Taiwan during 2012–2019. We measured serum Aspergillus fumigatus and niger-specific IgG levels and assessed if the participants were having CPA.ResultsA total of 1242 participants (including 200 healthy volunteers, 326 TB close contacts, 524 active TB patients and 192 old TB cases) were recruited. Using 27 mgA/L (milligrams of antigen-specific antibodies per liter) as cut-off level, the seropositive rate of A. fumigatus-specific IgG was 33.0% (66/200), 37.7% (123/326), 26.5% (139/524) and 43.2% (83/192) among the four groups, respectively. In multivariate logistic regression, pulmonary cavitation (OR 1.73; 95% CI 1.07–2.80), female sex (OR 1.49; 95% CI 1.14–1.95), old TB (OR 1.59; 1.05–2.42) were independent risk factors for Aspergillus IgG positivity. One (0.2%) active TB patient and four (2.1%) old TB patients developed CPA. Correlation between A. fumigatus and A. niger-specific IgG was high (Spearman correlation coefficient: 0.942).DiscussionGeographic variation in Aspergillus IgG seroprevalence and CPA prevalence exists. A universal cut-off value for Aspergillus IgG may not exist. In areas and populations in which background Aspergillus IgG level is unknown, Aspergillus IgG may be better used as a test of exclusion for CPA using prespecified cut-off level.     

Patient pathway analysis of tuberculosis diagnostic delay: a multicentre retrospective cohort study in China

ObjectivesDelay in diagnosis of tuberculosis (TB) is an important but under-appreciated problem. Our study aimed to analyse the patient pathway and possible risk factors of long diagnostic delay (LDD).MethodsWe enrolled 400 new bacteriologically diagnosed patients with pulmonary TB from 20 hospitals across China. LDD was defined as an interval between the initial care visit and the confirmation of diagnosis exceeding 14 days. Its potential risk factors were investigated by multivariate logistic regression and multilevel logistic regression. Hospitals in China were classified by increasing size, from level 0 to level 3. TB laboratory equipment in hospitals was also evaluated.ResultsThe median diagnostic delay was 20 days (IQR: 7–72 days), and 229 of 400 patients (57.3%, 95%CI 52.4–62.1) had LDD; 15% of participants were diagnosed at the initial care visit. Compared to level 0 facilities, choosing level 2 (OR 0.27, 95%CI 0.12–0.62, p 0.002) and level 3 facilities (OR 0.34, 95%CI 0.14–0.84, p 0.019) for the initial care visit was independently associated with shorter LDD. Equipping with smear, culture, and Xpert at initial care visit simultaneously also helped to avoid LDD (OR 0.28, 95%CI 0.09–0.82, p 0.020). The multilevel logistic regression yielded similar results. Availability of smear, culture, and Xpert was lower in level 0–1 facilities than in level 2–3 facilities (p < 0.001, respectively).ConclusionsMost patients failed to be diagnosed at the initial care visit. Patients who went to low-level facilities initially had a higher risk of LDD. Improvement of TB laboratory equipment, especially at low-level facilities, is urgently needed.     

Predictors and outcome of early- versus late-onset major bacterial infections in liver transplant recipients receiving tacrolimus (FK506) as primary immunosuppression

Major bacterial infections and the predictors of early (within 100 days of transplantation) versus late onset (after 100 days post-transplant) bacterial infections were prospectively assessed in 130 consecutive liver transplant recipients receiving tacrolimus (FK506) as primary immunosuppression. The median follow-up period was 38 months. Overall, 35% (45/130) of the patients developed 67 episodes of major bacterial infections (0.52 episodes/patient). Sixty-three percent of the major bacterial infections occurred early, and 37% occurred in the late post-transplant period. Eighty-four percent of the abdominal infections occurred early, whereas 38% of the cases of pneumonia, 60% of the cases of primary bacteremia, and 50% of the biliary infections occurred late. By logistic regression analysis, portal vein thrombosis was the most significant independent risk factor for early-onset major bacterial infection (odds ratio 4.1;95% Cl 1.4–12.2), and recurrent hepatitis C was the most significant independent predictor of late-onset major bacterial infections (odds ratio 6.21;95% Cl 1.9–20.2). Thus, sources and risk factors differ for early versus late-onset bacterial infections after liver transplantation. Knowledge of the differences in the potential sources, the pathogens, and the predictors of early versus late-onset bacterial infections can be valuable in the evaluation and empiric treatment of liver transplant recipients with bacterial infections.     

Recurrent pulmonary tuberculosis after treatment success: a population-based retrospective study in China

ObjectivesPost-treatment recurrence remains a challenge for the global control of tuberculosis (TB). This study investigated longitudinal data on pulmonary TB recurrence rates and risk factors for recurrence among successfully treated smear-positive tuberculosis cases in China.MethodsBetween 1st January 2009 and 31st December 2016 we evaluated 33 441 treatment-naïve patients diagnosed with sputum-smear-positive, non-multidrug-resistant TB in Hangzhou, China. We included the data of 9828 patients with TB who were treated successfully.ResultsA total of 4.9% of the cases were recurrent (479/9828), identified within a median observation period lasting 1565 days. Altogether, 51.1% (245/479) of the recurrences occurred within 1 year. The cumulative 2- and 5-year recurrence rates were 3.90% (95% confidence interval (CI) 3.3–4.5%) and 5.4% (95%CI 4.8–6.0%), respectively. Prolonged treatment (over 7 months) occurred in 64.7% (6363/9828), with a median treatment duration of 242 days (interquartile range 195–348 days). Male sex (adjusted hazard ratio (aHR) (95%CI) 1.61 (1.30–2.00), p < 0.001), age 60 years old or older (aHR (95%CI) 2.03 (1.70–2.44), p < 0.001), pulmonary cavity (aHR (95%CI) 1.51 (1.25–1.82), p < 0.001) and sputum positivity at 2 months (aHR (95%CI) 1.39 (1.05–1.81), p 0.02) all increased the risk of TB recurrence. Prolonged treatment was associated with reduced TB recurrence (aHR (95%CI) 0.73 (0.61–0.88), p 0.001).ConclusionsRecurrence remains a problem for successfully treated patients with sputum-smear-positive pulmonary TB, especially those with independent risk factors. Further analysis of prolonged treatment is required.     

Clinical outcome in solid organ transplant recipients affected by COVID-19 compared to general population: a systematic review and meta-analysis

BackgroundA significant increased risk of complications and mortality in immunocompromised patients affected by COVID-19 has been described. However, the impact of COVID-19 in solid organ transplant (SOT) recipients is an issue still under debate, due to conflicting evidence that has emerged from different observational studies.ObjectivesWe performed a systematic review with a meta-analysis to assess the clinical outcome in SOT recipients with COVID-19 compared with the general population.Data sourcesPubMed-MEDLINE and Scopus were independently searched until 13 October 2021.Study eligibility criteriaProspective or retrospective observational studies comparing clinical outcome in SOT recipients versus general populations affected by COVID-19 were included. The primary endpoint was 30-day mortality.ParticipantsParticipants were patients with confirmed COVID-19.InterventionsInterventions reviewed were SOTs.MethodsThe quality of the included studies was independently assessed with the Risk of Bias in Non-randomized Studies of Interventions tool for observational studies. The meta-analysis was performed by pooling ORs retrieved from studies providing adjustment for confounders using a random-effects model with the inverse variance method. Multiple subgroups and sensitivity analyses were conducted to investigate the source of heterogeneity.ResultsA total of 3501 articles were screened, and 31 observational studies (N = 590 375; 5759 SOT recipients vs. 584 616 general population) were included in the meta-analyses. No difference in 30-day mortality rate was found in the primary analysis, including studies providing adjustment for confounders (N = 17; 3752 SOT recipients vs. 159 745 general population; OR: 1.13; 95% CI, 0.94–1.35; I² = 33.9%). No evidence of publication bias was reported. A higher risk of intensive care unit admission (OR: 1.56; 95% CI, 1.03–2.63) and occurrence of acute kidney injury (OR: 2.50; 95% CI, 1.81–3.45) was found in SOT recipients.ConclusionsNo increased risk in mortality was found in SOT recipients affected by COVID-19 compared with the general population when adjusted for demographic and clinical features and COVID-19 severity.     

Long term SARS-CoV-2-specific cellular immunity after COVID-19 in liver transplant recipients

PurposeLong-term immunity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in immunosuppressed patients is not well characterized. We aimed to explore the long-term natural immunity against SARS-CoV-2 in liver transplant (LT) recipients compared to the non-transplanted population (control group).MethodsFifteen LT recipients and 15 controls matched according to variables associated with disease severity were included at 12 months following the coronavirus disease 2019 (COVID-19) onset. Peripheral blood mononuclear cells were stimulated with peptide pools covering spike (S), nucleocapside (N), and membrane (M) proteins. Reactive CD4+ and CD8+ T cells were identified using flow cytometry, and cytokine production was evaluated in the culture supernatants using cytometric bead array. Serum anti-N and anti-S IgG antibodies were detected with chemiluminescence.ResultsThe percentage of patients with a positive response in both CD4+ and CD8+ T cells against each viral protein and IL2, IL10, TNF-α, and IFN-γ levels was similar between LT recipients and controls. IFN-γ levels were positively correlated with the percentage of reactive CD4+ (p = 0.022) and CD8+ (p = 0.043) T cells to a mixture of M + N + S peptide pools. The prevalence and levels of anti-N and anti-S IgG antibodies were slightly lower in the LT recipients, but the difference was not statistically significant.ConclusionLT recipients exhibited a similar T cell response compared to non-transplanted individuals one year after COVID-19 diagnosis.     

Impact of Perioperative Massive Transfusion on Long Term Outcomes of Liver Transplantation: a Retrospective Cohort Study

Background: Liver transplantation (LT) is associated with a significant risk of intraoperative hemorrhage and massive blood transfusion. However, there are few relevant reports addressing the long-term impacts of massive transfusion (MT) on liver transplantation recipients.Aim: To assess the effects of MT on the short and long-term outcomes of adult liver transplantation recipients.Methods: We included adult patients who underwent liver transplantation at West China Hospital from January 2011 to February 2015. MT was defined as red blood cell (RBC) transfusion of ≥10 units within 48 hours since the application of LT. Preoperative, intraoperative and postoperative information were collected for data analyzing. We used one-to-one propensity-matching to create pairs. Kaplan-Meier survival analysis was used to compare long-term outcomes of LT recipients between the MT and non-MT groups. Univariate and multivariate logistic regression analyses were performed to evaluate the risk factors associated with MT in LT.Results: Finally, a total of 227 patients were included in our study. After propensity score matching, 59 patients were categorized into the MT and 59 patients in non-MT groups. Compared with the non-MT group, the MT group had a higher 30-day mortality (15.3% vs 0, p=0.006), and a higher incidence of postoperative complications, including postoperative pulmonary infection, abdominal hemorrhage, pleural effusion and severe acute kidney injury. Furthermore, MT group had prolonged postoperative ventilation support (42 vs 25 h, p=0.007) and prolonged durations of ICU (12.9 vs 9.5 d, p<0.001) stay. Multivariate COX regression indicated that massive transfusion (OR: 2.393, 95% CI: 1.164-4.923, p=0.018) and acute rejection (OR: 7.295, 95% CI: 2.108-25.246, p=0.02) were significant risk factors affecting long-term survivals of LT patients. The 1-year and 3-year survival rates patients in MT group were 82.5% and 67.3%, respectively, while those of non-MT group were 93.9% and 90.5%, respectively. The MT group exhibited a lower long-term survival rate than the non-MT group (HR: 2.393, 95% CI: 1.164-4.923, p<0.001). Finally, the multivariate logistic regression revealed that preoperative hemoglobin <118 g/L (OR: 5.062, 95% CI: 2.292-11.181, p<0.001) and intraoperative blood loss ≥1100 ml (OR: 3.212, 95% CI: 1.586-6.506, p = 0.001) were the independent risk factor of MT in patients undergoing LT.Conclusion: Patients receiving MT in perioperative periods of LT had worse short-term and long-term outcomes than the non-MT patients. Massive transfusion and acute rejection were significant risk factors affecting long-term survivals of LT patients, and intraoperative blood loss of over 1100 ml was the independent risk factor of MT in patients undergoing LT. The results may offer valuable information on perioperative management in LT recipients who experience high risk of MT.