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  • Gao S
  • Huang X
  • Zhou X
  • Dai X
  • Han J
  • et al.
Ann Med. 2024 Dec;56(1):2314236 doi: 10.1080/07853890.2024.2314236.
BACKGROUND:

The burden of carbapenem-resistant gram-negative bacteria (CRGNB) among solid organ transplant (SOT) recipients has not been systematically explored. Here, we discern the risk factors associated with CRGNB infection and colonization in SOT recipients.

METHODS:

This study included observational studies conducted among CRGNB-infected SOT patients, which reported risk factors associated with mortality, infection or colonization. Relevant records will be searched in PubMed, Embase and Web of Science for the period from the time of database construction to 1 March 2023.

RESULTS:

A total of 23 studies with 13,511 participants were included, enabling the assessment of 27 potential risk factors. The pooled prevalence of 1-year mortality among SOT recipients with CRGNB was 44.5%. Prolonged mechanical ventilation, combined transplantation, reoperation and pre-transplantation CRGNB colonization are salient contributors to the occurrence of CRGNB infections in SOT recipients. Renal replacement therapy, post-LT CRGNB colonization, pre-LT liver disease and model for end-stage liver disease score increased the risk of infection. Re-transplantation, carbapenem use before transplantation and ureteral stent utilization increaesd risk of CRGNB colonization.

CONCLUSION:

Our study demonstrated that SOT recipients with CRGNB infections had a higher mortality risk. Invasive procedure may be the main factor contribute to CRGNB infection.

  • Stier EA
  • Clarke MA
  • Deshmukh AA
  • Wentzensen N
  • Liu Y
  • et al.
Int J Cancer. 2024 May 15;154(10):1694-1702 doi: 10.1002/ijc.34850.

The International Anal Neoplasia Society (IANS) developed consensus guidelines to inform anal cancer screening use among various high-risk groups. Anal cancer incidence estimates by age among risk groups provided the basis to identify risk thresholds to recommend screening. Guided by risk thresholds, screening initiation at age 35 years was recommended for men who have sex with men (MSM) and transgender women (TW) with HIV. For other people with HIV and MSM and TW not with HIV, screening initiation at age 45 years was recommended. For solid organ transplant recipients, screening initiation beginning from 10 years post-transplant was recommended. For persons with a history of vulvar precancer or cancer, screening initiation was recommended starting within 1 year of diagnosis of vulvar precancer or cancer. Persons aged ≥45 years with a history of cervical/vaginal HSIL or cancer, perianal warts, persistent (>1 year) cervical HPV16, or autoimmune conditions could be considered for screening with shared decision-making, provided there is adequate capacity to perform diagnostic procedures (high-resolution anoscopy [HRA]). Anal cytology, high-risk (hr) human papillomavirus (HPV) testing (including genotyping for HPV16), and hrHPV-cytology co-testing are different strategies currently used for anal cancer screening that show acceptable performance. Thresholds for referral for HRA or follow-up screening tests are delineated. These recommendations from IANS provide the basis to inform management of abnormal screening results, considering currently available screening tools. These guidelines provide a pivotal foundation to help generate consensus among providers and inform the introduction and implementation of risk-targeted screening for anal cancer prevention.

  • Taneja V
  • Anand RS
  • El-Dallal M
  • Dong J
  • Desai N
  • et al.
Inflamm Bowel Dis. 2024 Apr 3;30(4):585-593 doi: 10.1093/ibd/izad108.
BACKGROUND:

Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant immunosuppression for inflammatory bowel disease (IBD) and organ transplant management are limited. This study sought to evaluate the safety of biologic and small molecule therapy for the treatment of IBD among solid organ transplant recipients.

METHODS:

Medline, Embase, and Web of Science databases were systematically searched for studies reporting on safety outcomes associated with the use of biologic and small molecule therapy (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) in patients with IBD postsolid organ transplant (eg, liver, kidney, heart, lung, pancreas). The primary outcome was infectious complications. Secondary outcomes included serious infections, colectomy, and discontinuation of biologic therapy.

RESULTS:

Seven hundred ninety-seven articles were identified for screening, yielding 16 articles for the meta-analyses with information on 163 patients. Antitumor necrosis factor α (Anti-TNFs; infliximab and adalimumab) were used in 8 studies, vedolizumab in 6 studies, and a combination of ustekinumab or vedolizumab and anti-TNFs in 2 studies. Two studies reported outcomes after kidney and cardiac transplant respectively, whereas the rest of the studies included patients with liver transplants. The rates of all infections and serious infections were 20.09 per 100 person-years (100-PY; 95% CI, 12.23-32.99 per 100-PY, I2 = 54%) and 17.39 per 100-PY (95% CI, 11.73-25.78 per 100-PY, I2 = 21%), respectively. The rates of colectomy and biologic medication discontinuation were 12.62 per 100-PY (95% CI, 6.34-25.11 per 100-PY, I2 = 34%) and 19.68 per 100-PY (95% CI, 9.97-38.84 per 100-PY, I2 = 74%), respectively. No cases of venous thromboembolism or death attributable to biologic use were reported.

CONCLUSION:

Biologic therapy is overall well tolerated in patients with solid organ transplant. Long-term studies are needed to better define the role of specific agents in this patient population.

  • Schultz BG
  • Bullano M
  • Paratane D
  • Rajagopalan K
Transpl Infect Dis. 2024 Apr;26(2):e14216 doi: 10.1111/tid.14216.
CET Conclusion
Reviewer: Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: CMV infection which is refractory to standard treatment is a challenging clinical problem, resulting in patient morbidity and increased healthcare costs, mainly due to prolonged and repeat admissions. In the SOLSTICE trail, Maribavir was shown to be more effective than standard treatment protocols for refractory CMV infection in post-transplant patients. This post-hoc analysis of the SOLISTICE trial used trial data to calculate the reduction in healthcare costs that could be achieved by using Maribavir in this patient population. The analysis demonstrated a third to two thirds reduction in costs over an 8-week period when using Maribavir. Healthcare cost analyses are complex and subject to many assumptions, which the authors acknowledge introduces significant bias. However, the most striking omission from the analysis is the cost of the Maribavir treatment itself, which is significantly higher than standard therapy. With the additional limitation of a short duration of study, the reliability and applicability of the reported cost savings cannot be readily determined.
Aims: The aim of this study was to use the data from the randomised controlled trial, SOLSTICE, to estimate the cytomegalovirus (CMV) related health care resource utilization (HCRU) costs of maribavir (MBV) versus investigator-assigned therapy (IAT), among hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients.
Interventions: Participants in the SOLSTICE trial were randomised to either receive IAT or MBV therapy.
Participants: 352 patients that had either HSCT (40%) or SOT (60%).
Outcomes: The key outcomes were the cost of hospitalisation with IAT versus MBV therapy, and cost difference (i.e. cost savings) with MBV.
Follow Up: N/A
BACKGROUND:

Cytomegalovirus (CMV) infections among hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients impose a significant health care resource utilization (HCRU)-related economic burden. Maribavir (MBV), a novel anti-viral therapy (AVT), approved by the United States Food and Drug Administration for post-transplant CMV infections refractory (with/without resistance) to conventional AVTs has demonstrated lower hospital length of stay (LOS) versus investigator-assigned therapy (IAT; valgancilovir, ganciclovir, foscarnet, or cidofovir) in a phase 3 trial (SOLSTICE). This study estimated the HCRU costs of MBV versus IAT.

METHODS:

An economic model was developed to estimate HCRU costs for patients treated with MBV or IAT. Mean per-patient-per-year (PPPY) HCRU costs were calculated using (i) annualized mean hospital LOS in SOLSTICE, and (ii) CMV-related direct costs from published literature. Probabilistic sensitivity analysis with Monte-Carlo simulations assessed model robustness.

RESULTS:

Of 352 randomized patients receiving MBV (n = 235) or IAT (n = 117) for 8 weeks in SOLSTICE, 40% had HSCT and 60% had SOT. Mean overall PPPY HCRU costs of overall hospital-LOS were $67,205 (95% confidence interval [CI]: $33,767, $231,275) versus $145,501 (95% CI: $62,064, $589,505) for MBV and IAT groups, respectively. Mean PPPY ICU and non-ICU stay costs were: $32,231 (95% CI: $5,248, $184,524) versus $45,307 (95% CI: $3,957, $481,740) for MBV and IAT groups, and $82,237 (95% CI: $40,397, $156,945) MBV versus $228,329 (95% CI: $94,442, $517,476) for MBV and IAT groups, respectively. MBV demonstrated cost savings in over 99.99% of simulations.

CONCLUSIONS:

This analysis suggests that Mean PPPY HCRU costs were 29%-64% lower with MBV versus other-AVTs.

  • Pennington KM
  • Martin MJ
  • Murad MH
  • Sanborn D
  • Saddoughi SA
  • et al.
Transplantation. 2024 Apr 1;108(4):970-984 doi: 10.1097/TP.0000000000004871.
BACKGROUND:

Invasive fungal infections are associated with high morbidity in solid organ transplant recipients. Risk factor modification may help with preventative efforts. The objective of this study was to identify risk factors for the development of fungal infections within the first year following solid organ transplant.

METHODS:

We searched for eligible articles through February 3, 2023. Studies published after January 1, 2001, that pertained to risk factors for development of invasive fungal infections in solid organ transplant were reviewed for inclusion. Of 3087 articles screened, 58 were included. Meta-analysis was conducted using a random-effects model to evaluate individual risk factors for the primary outcome of any invasive fungal infections and invasive candidiasis or invasive aspergillosis (when possible) within 1 y posttransplant.

RESULTS:

We found 3 variables with a high certainty of evidence and strong associations (relative effect estimate ≥ 2) to any early invasive fungal infections across all solid organ transplant groups: reoperation (odds ratio [OR], 2.92; confidence interval [CI], 1.79-4.75), posttransplant renal replacement therapy (OR, 2.91; CI, 1.87-4.51), and cytomegalovirus disease (OR, 2.97; CI, 1.78-4.94). Both posttransplant renal replacement therapy (OR, 3.36; CI, 1.78-6.34) and posttransplant cytomegalovirus disease (OR, 2.81; CI, 1.47-5.36) increased the odds of early posttransplant invasive aspergillosis. No individual variables could be pooled across groups for invasive candidiasis.

CONCLUSIONS:

Several common risk factors exist for the development of any invasive fungal infections in solid organ transplant recipients. Additional risk factors for invasive candidiasis and aspergillosis may be unique to the pathogen, transplanted organ, or both.

  • Pimentel MCDS
  • Fernandes MM
  • Vogel JO
  • Freire CH
  • Pereira CM
  • et al.
Spec Care Dentist. 2024 Mar 31; doi: 10.1111/scd.12999.
OBJECTIVE:

The purpose of this scoping review is to evaluate the oral manifestations (OM) of heart transplant (HT) patients undergoing immunosuppressive therapy (IT).

MATERIAL AND METHODS:

A literature search was performed using keywords and MeSH terms related to OM and HT in the Medline/PubMed, Web of Science, Cochrane Library, Scopus, LILACS/BBO databases and in gray literature without language or date restrictions until June 2023. Studies that evaluated HT individuals who used any IT and who reported the occurrence of OM were considered eligible. The results from the search were imported to EndNote Web, and duplicates were removed followed by title/abstract and full-text analysis.

RESULTS:

A total of 402 nonduplicated studies were found and 13 fulfilled the criteria and were included in the present review: 10 cross-sectional, 2 cohorts, and 1 clinical trial. The most reported OM were periodontal diseases, including drug-induced gingival enlargement (DIGE), gingival bleeding, gingivitis, and periodontitis. Reported in a minority of studies are oral cancer, opportunistic infections (oral hairy leukoplakia and erythematous candidiasis), enamel defects, and burning mouth.

CONCLUSION:

Considering the methodological heterogeneity of the studies analyzed, DIGE is the most commonly observed oral manifestation in HT individuals.

  • Long X
  • Yang X
  • Yao S
  • Wu J
Ann Transplant. 2024 Mar 26;29:e943433 doi: 10.12659/AOT.943433.

BACKGROUND Antineutrophil cytoplasmic antibody-associated vasculitis is characterized by small-vessel inflammation and ANCA-positive serology that often lead to end-stage kidney disease. This study investigated the outcomes of renal transplantation in patients with antineutrophil cytoplasmic antibody-associated vasculitis. MATERIAL AND METHODS A comprehensive search of PubMed, Scopus, and Embase databases was done to retrieve studies that reported on the outcomes of renal transplantation in these patients. Data on mortality, survival, infection, and relapse rates were analyzed. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale for cohort studies. RESULTS Twenty-three retrospective cohort studies were included in this review. Antineutrophil cytoplasmic antibody-associated vasculitis was associated with high post-transplantation mortality rates, with a pooled rate ratio of 11.99 per 100 patient-years, but relatively favorable survival rate (hazard rate of 0.80). After renal transplantation, these patients had elevated infection rates (pooled rate ratio of 52.70 per 100 patient-years), and high risk of relapse (pooled rate ratio of 6.96), emphasizing the importance of vigilant post-transplantation monitoring. CONCLUSIONS End-stage kidney disease patients with vasculitis, undergoing renal transplantation, are at elevated risk of mortality and postoperative infection compared to patients without antineutrophil cytoplasmic antibody-associated vasculitis. The risk of relapse is also high in these patients. However, renal transplantation offers a survival advantage for vasculitis patients who survive the early post-transplantation period.

  • Du Q
  • Li T
  • Yi X
  • Song S
  • Kang J
  • et al.
Acta Diabetol. 2024 Mar 20; doi: 10.1007/s00592-024-02253-w.
AIMS:

Post-transplant diabetes is a prevalent and consequential complication following kidney transplantation, which significantly augments the risk of cardiovascular disease, graft loss, infection, and mortality, thereby profoundly impacting both graft and patient survival. However, the early stages of post-transplant diabetes often go unnoticed or receive inadequate management. Consequently, this study systematically assesses the incidence of new-onset diabetes after kidney transplantation with the aim to enhance medical staff awareness regarding post-transplantation diabetes and provide clinical management guidance.

METHODS:

We conducted a comprehensive search across multiple databases including PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang, VIP, and SinoMed until September 21, 2023. Data extraction was performed using standardized tables and meta-analysis was conducted using Stata 16.0 software. A random effects model was employed to estimate the combined prevalence along with its corresponding 95% confidence interval. The source of heterogeneity was explored using subgroup analysis and sensitivity analysis, while publication bias was assessed through funnel plot and Egger's test. This study has been registered with PROSPERO under the registration number CRD42023465768.

RESULTS:

This meta-analysis comprised 39 studies with a total sample size of 16,584 patients. The prevalence of new-onset diabetes after transplantation was found to be 20% [95% CI (18.0, 22.0)]. Subgroup analyses were conducted based on age, gender, body mass index, family history of diabetes, type of kidney donor, immunosuppressive regimen, acute rejection episodes, hepatitis C infection status and cytomegalovirus infection.

CONCLUSIONS:

The incidence of post-kidney transplantation diabetes is substantial, necessitating early implementation of preventive and control measures to mitigate its occurrence, enhance prognosis, and optimize patients' quality of life.

CLINICAL TRIAL REGISTRATION:

PROSPERO: CRD42023465768.

  • Kumar L
  • Dasgupta S
  • Murray-Krezan C
  • Singh N
  • Rakita RM
  • et al.
Clin Infect Dis. 2024 Mar 20;78(3):719-722 doi: 10.1093/cid/ciad643.

In a post-hoc analysis of the association of CMV DNAemia with long-term mortality in a randomized trial of CMV preemptive therapy vs. antiviral prophylaxis in D+R- liver transplant recipients, post-intervention CMV DNAemia was associated with increased mortality after adjusting for study arm.

  • Kim J
  • Joh JW
  • Lee KW
  • Choi DL
  • Wang HJ
Ann Hepatobiliary Pancreat Surg. 2024 Mar 15; doi: 10.14701/ahbps.23-129.
BACKGROUNDS/AIMS:

Prolonged use of steroids after liver transplantation (LT) significantly increases the risk of diabetes or cardiovascular disease, which can adversely affect patient outcomes. Our study evaluated the effectiveness and safety of early steroid withdrawal within the first year following LT.

METHODS:

This study was conducted as an open-label, multicenter, randomized controlled trial. Liver transplant recipients were randomly assigned to one of the following two groups: Group 1, in which steroids were withdrawn two weeks posttransplantation, and Group 2, in which steroids were withdrawn three months posttransplantation. This study included participants aged 20 to 70 years who were scheduled to undergo a single-organ liver transplant from a living or deceased donor at one of the four participating centers.

RESULTS:

Between November 2012 and August 2020, 115 patients were selected and randomized into two groups, with 60 in Group 1 and 55 in Group 2. The incidence of new-onset diabetes after transplantation (NODAT) was notably higher in Group 1 (32.4%) than in Group 2 (10.0%) in the per-protocol set. Although biopsy-proven acute rejection, graft failure, and mortality did not occur, the median tacrolimus trough level/dose/weight in Group 1 exceeded that in Group 2. No significant differences in safety parameters, such as infection and recurrence of hepatocellular carcinoma, were observed between the two groups.

CONCLUSIONS:

The present study did not find a significant reduction in the incidence of NODAT in the early steroid withdrawal group. Our study suggests that steroid withdrawal three months posttransplantation is a standard and safe immunosuppressive strategy for LT patients.