Preemptive Therapy Research Articles

QuantiFERON-CMV and monitor predict cytomegalovirus, mortality, and graft-versus-host disease in transplant recipients.

Cytomegalovirus (CMV) is the most prevalent infection in recipients of hematopoietic stem cell transplant (HSCT). QuantiFERON-CMV (QF-CMV) and QuantiFERON-Monitor (QFM) assays were used to test whether immune-competent adult allogeneic HSCT recipients with CMV-specific T cells can control CMV infection or reactivation. Our data demonstrated a significant correlation between CMV infection measured by CMV-antigenemia test and QF-CMV results, graft versus host disease (GvHD), and mortality rates. The QF-CMV test revealed that CMV-specific T cells with higher interferon-γ (IFN-γ) release were correlated with lower CMV infection rates. There was a significant negative association between QF-CMV results, GvHD, and mortality rates. Data showed that a one-unit rise in IFN-γ was linked with a 12.7% reduction in GvHD and a 20.7% reduction in the mortality odds ratio. In addition, a negative correlation was found between QF-M results and CMV infection, with the QFM test predicting protection against CMV infection by 1.9%. This is one of the few studies establishing the QF-CMV test's predictive value for GvHD and mortality, its use to monitor HSCT patients for pre-emptive therapy, and the use of the QFM test to predict CMV infection and mortality in HSCT patients. Thus, these assays could be utilized to optimize preventive and pre-emptive therapy procedures to reduce transplant recipient adverse effects and posttransplant therapy costs.

Updates in Cytomegalovirus Prevention and Treatment in Solid Organ Transplantation.

The authors summarize recent updates in the prevention and management of cytomegalovirus (CMV) in solid organ transplant (SOT) recipients with a focus on CMV seronegative recipients of organs from seropositive donors (CMV D+/R-) who are at highest risk of CMV infection and disease. They discuss advantages of preemptive therapy for CMV disease prevention in CMV D+/R- liver transplant recipients, letermovir for CMV prophylaxis, and updates in the development of monoclonal antibodies and vaccines as immune-based preventative strategies. They review the roles of maribavir and virus-specific Tcells for management of resistant or refractory CMV infection in SOT recipients.

Association of Cytomegalovirus (CMV) DNAemia With Long-Term Mortality in a Randomized Trial of Preemptive Therapy and Antiviral Prophylaxis for Prevention of CMV Disease in High-Risk Donor Seropositive, Recipient Seronegative Liver Transplant Recipients.

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.

Tolerability of pulsed high-dose L-AmB as pre-emptive therapy in patients at high risk for intra-abdominal candidiasis: A phase 2 study (LAMBDA study)

Background. Intra-abdominal candidiasis (IAC) is burdened by high mortality rates. However, the correct management of a critically ill patient with suspected IAC is an issue still on debate. The aim of our study was to evaluate the safety of pulse high-dose of liposomal amphotericin B (L-AmB) in patients with suspected IAC managed with a Beta-D-Glucan (BDG)-guided strategy. Methods. Phase 2 prospective study enrolling adult patients with intra-abdominal sepsis following surgery. Patients received a single dose of L-AmB 5mg/kg on day 1. At day 3, L-AmB was discontinued in case of negativity of basal serum (1,3)-Beta-D-Glucan (BDG) and was continued (3 mg/kg/daily) in case of positive basal BDG, or microbiologically confirmed IAC. The main endpoint was occurrence of adverse events according with common toxic criteria definition. Results. Overall, 40 patients were enrolled from January 2019 until August 2022. Of them 15 (37.5%) were male, median age was 65 (49-76) years. Urgent surgery accounted for 31 (77.5%) cases, principal indication was secondary/tertiary peritonitis (22, 55%), half of patients had a previous surgical operation within 30 days. Five (12.5%) patients had criteria for septic shock at enrolment. The median APACHE II score at ICU admission was 12 (10-15). In 33 (85%) cases IAC was excluded, whereas 5 (12.5%) and 2 (5%) patients had a probable and proven IAC, respectively. The single dose of L-AmB 5 mg/Kg was well tolerated in all patients, no early and late severe adverse events related to the drug were reported. L-AmB was discontinued in 65% of patients following a negative basal BDG result. All-cause 30-day mortality rate was 15%, in none case death was related to L-AmB administration or uncontrolled IAC. More specifically, mortality rates between patients with and without proven IAC was 0% vs. 15.8%, p=0.99. Conclusions. The rate of proven IAC among critically ill high-risk patients was low, attesting at 5%. A single dose of L-AmB 5 mg/Kg following prompt withdrawal in case of basal negative BDG result seems to be a safe and effective approach in such population.

Profilaksis vs. Terapi Preemtif Penyakit Cytomegalovirus (CMV) pada Pasien Transplantasi Ginjal Risiko Tinggi: Suatu Laporan Kasus Berbasis Bukti

Kidney transplant recipients require the use of immunosuppressive agents to prevent multiple organ rejection. Administration of immunosuppressive agents triggers an increased risk of impaired immunity and microbial infections, one of which is cytomegalovirus (CMV). Prevention of cytomegalovirus infection can be given as a prophylaxis or preemptive therapy. However, the efficacy of choosing prophylaxis or preemptive therapy is still under debate, thus we conducted this study to identify current approach in preventing CMV disease in clinical practice. A literature search was carried out using the PubMed, Cochrane Library, Embase and Scopus databases with the keywords “high risk kidney transplant”, “prophylaxis”, “preemptive” and “CMV infection disease”. Inclusion criteria were only studies in adult kidney transplant patients as a population. , prophylaxis as intervention, preemptive therapy as comparison, and cytomegalovirus infection as outcome. The exclusion criteria of this study were the study articles that were not in Bahasa Indonesia or English, case reports and studies with subjects <18 years old. Critical review using Oxford Center for Evidence Based Medicine (CEBM) Critical Appraisal Tools for Prognostic Study And Systematic Review. The total number of articles identified based on the keywords used is 115 articles. Eliminating duplication with EndNote resulted in 92 articles. Furthermore, exclusion was carried out based on title and abstract so that 29 articles were filtered for which the full text was available. Of these, 23 articles did not have appropriate research questions, 3 studies did not have appropriate patient populations, and 3 articles with types that did not meet the inclusion criteria of this study. As a result, there were 4 articles that can be used in this report. Based on those four articles, it can be concluded that prophylaxis is more effective in preventing CMV disease but had more side effects, when compared to preemptive therapy. However, there was no difference in long term outcome between kidney transplant patients with CMV prophylactic or preemptive therapy.

Urinary Protein-Biomarkers Reliably Indicate Very Early Kidney Damage in Children With Alport Syndrome Independently of Albuminuria and Inflammation

Alport syndrome (AS) is a hereditary type IV collagen disease. It starts shortly after birth, without clinical symptoms, and progresses to end-stage kidney disease early in life. The earlier therapy starts, the more effectively end-stage kidney disease can be delayed. Clearly then, to ensure preemptive therapy, early diagnosis is an essential prerequisite. To provide early diagnosis, we searched for protein biomarkers (BMs) by mass spectrometry in dogs with AS stage 0. At this very early stage, we identified 74 candidate BMs. Of these, using commercial enzyme-linked immunosorbent assays (ELISAs), we evaluated 27 in dogs and 28 in children, 50 with AS and 104 healthy controls. Most BMs from blood appeared as fractions of multiple variants of the same protein, as shown by their chromatographic distribution before mass spectrometry. Blood samples showed only minor differences because ELISAs rarely detect disease-specific variants. However, in urine , several proteins, individually or in combination, were promising indicators of very early and preclinical kidney injury. The BMs with the highest sensitivity and specificity were collagen type XIII, hyaluronan binding protein 2 (HABP2), and complement C4 binding protein (C4BP). We generated very strong candidate BMs by our approach of first examining preclinical AS in dogs and then validating these BMs in children at early stages of disease. These BMs might serve for screening purposes for AS before the onset of kidney damage and therefore allow preemptive therapy.

Significant Increase in Cytomegalovirus (CMV) Infection in Solid Organ Transplants Associated With Increased Use of Thymoglobulin as Induction Therapy?

Cytomegalovirus (CMV) infection remains one of the most common viral pathogens affecting solid organ transplants (SOT). In 10 years of following the outcome of transplants, we noticed an increased incidence of CMV infection, along with increased use of rabbit anti-thymocyte globulin (rATG). The study aims to assess the incidence of active CMV infection and disease, response to treatment, and recurrence in a cohort of SOT. Furthermore, we look for correlating the CMV incidence with the type of induction therapy: r-ATG or interleukin 2 receptor-blocking antibody (basiliximab). This was a single-center, retrospective 10-year study in patients submitted to kidney, kidney-liver, and kidney-pancreas transplants who used a preemptive therapy protocol for CMV. Among the 476 enrolled transplant recipients, 306 (64.2 %) had at least one episode of CMV infection (replication), and 71/306 patients (23.2 %) presented CMV-related disease. The most frequent clinical conditions associated with CMV disease were gastrointestinal. Among the 476 transplant patients, 333 received immunosuppressive induction with rATG (69.9 %); 140 (29.4 %) received induction with interleukin 2 receptor-blocking antibody (basiliximab). The initial maintenance immunosuppressive therapy in the patients who presented CMV infection was primarily performed with prednisone, tacrolimus, and sodium mycophenolate (91.7 %). The induction with rATG increased from 35.2%-94.6% in 10 years. The incidence of CMV infection was 20.7 % in the first year of observation and gradually increased to 87.3 % in the last year. The data suggest that the increase in the use of rATG in recent years could be responsible for the very expressive increase in the incidence of CMV infection/disease.

The assembly of gut microbiota implicates shrimp acute hepatopancreas necrosis disease progression.

Ample evidence shows dysbiosis in the gut microbiota when comparing healthy shrimp with those affected by severe acute hepatopancreatic necrosis disease (AHPND). However, the static comparison used in available studies leads to the uncertainties regarding how and to what extent the gut microbiota responds to the progressive severity of AHPND. In addition, shrimp AHPND is featured by rapid and massive mortality, thus the initiation of AHPND must be diagnosed for preemptive therapy. For these reasons, we explored the ecological assembly of gut microbiota over shrimp AHPND progression. Increasing AHPND severity was associated with linear increase in the copies of pirAB genes, relative abundance of gut Vibrio and potentially pathogenic, and reduction in the gut bacterial diversity, stability, and relative abundance of Bdellovibrio. Negative and significant association between gut Vibrio and Bdellovibrio were noted, indicating that compromised predation exerts a role in AHPND progression. Notably, the extents of departure to the healthy shrimp gut microbiota were positively coupled with the increasing severity of AHPND. After controlling the temporal variation in the gut microbiota as healthy shrimp age, we constructed a diagnosis model that accurately diagnosed the initial, progressed or moribund stages of AHPND, with an overall accuracy of 86.5%. Shrimp AHPND induced more stochastic gut microbiotas as a consequence of the attenuated ability of diseased shrimp to select their commensals, resulting in convergent bacterial communities between gut and rearing water over AHPND progression. Collectively, our findings provide important step toward the ecological assembly of gut microbiota implicating in AHPND etiology and in diagnosing AHPND stages. KEY POINTS: • The departure of shrimp gut microbiota positively linked with AHPND severity. • The diagnosis model accurately diagnosed the stages of AHPND. • Shrimp AHPND induced more stochastic gut microbiota.

Gut microbiota-derived short-chain fatty acids ameliorate methamphetamine-induced depression- and anxiety-like behaviors in a Sigmar-1 receptor-dependent manner

Methamphetamine (Meth) abuse can cause serious mental disorders, including anxiety and depression. The gut microbiota is a crucial contributor to maintaining host mental health. Here, we aim to investigate if microbiota participate in Meth-induced mental disorders, and the potential mechanisms involved. Here, 15 mg/kg Meth resulted in anxiety- and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor (SIGMAR1)/BDNF/TRKB pathway in the hippocampus. Meanwhile, Meth impaired gut homeostasis by arousing the Toll-like receptor 4 (TLR4)-related colonic inflammation, disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids (SCFAs). Moreover, fecal microbiota from Meth-administrated mice mediated the colonic inflammation and reproduced anxiety- and depression-like behaviors in recipients. Further, SCFAs supplementation optimized Meth-induced microbial dysbiosis, ameliorated colonic inflammation, and repressed anxiety- and depression-like behaviors. Finally, Sigmar1 knockout (Sigmar1−/−) repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure, and eliminated the anti-anxiety and -depression effects of SCFAs. The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety- and depression-like behaviors. Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis, and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner. This study confirms the crucial role of microbiota in Meth-related mental disorders and provides a potential preemptive therapy.

Efficacy of olokizumab in patients with mild or moderate COVID-19 and risk factors of progression

The COronaVIrus Disease 2019 (COVID-19) is a common infectious disease characterized by hyperactivation of the immune response and the development of a “cytokine storm” upon progression. The aim of this study was to obtain additional information about the efficacy of the drug olokizumab in comparison with the Janus kinase inhibitor upadacitinib in real clinical practice in patients with mild to moderate COVID-19 and combined risk factors for disease progression. Methods. A single-center, non-interventional, prospective study was conducted in specialized day hospital patients (n = 125) who received therapy with olokizumab (n = 62) (64 mg once intravenously) and the Janus kinase inhibitor upadacitinib (n = 63) (orally, according to selected dosing regimen). The primary endpoint was the frequency of hospitalizations in the 24-hour hospital over the entire observation period. We also analyzed the frequencies of intensive care unit (ICU) transfer, prescription of respyratory therapy, use of “rescue” therapy (monoclonal antibodies/therapeutic proteins acting on interleukins (IL) and their receptors: IL-6 receptor inhibitors and Janus kinase inhibitors (baricitinib, tofacitinib, upadacitinib, etc.)), mortality, dynamics of laboratory and instrumental parameters, as well as frequency of negative and positive changes according to the clinical progression scale of the World Health Organization. Results. All study subjects showed rapid clinical improvement and recovery. Patients in both groups did not experience any negative clinical events, such as admission to a 24-hour hospital, prescription of respyratory therapy, use of “rescue” therapy, etc. Thus, the hyperinflammatory reaction and adverse clinical outcomes are effectively prevented by the timely use of both drugs. Those who received olokizumab had slightly higher levels of C-reactive protein (CRP) at baseline than those who received upadacitinib (p < 0.001). The median CRP value returned to normal on the 4th day in both groups. Patients treated with olokizumab showed a more pronounced change in CRP levels relative to baseline values. A similar trend was also established in body temperature. Conclusion. The study confirmed that early administration of olokizumab in patients with mild to moderate COVID-19 with several risk factors for the severe course is as effective a method of preemptive anti-inflammatory therapy as the use of Janus kinase inhibitors but more stronger suppression of markers and symptoms of intoxication.

Q-HAM: a multicenter upfront randomized phase II trial of quizartinib and high-dose Ara-C plus mitoxantrone in relapsed/refractory AML with FLT3-ITD

BackgroundAbout 50% of older patients with acute myeloid leukemia (AML) fail to attain complete remission (CR) following cytarabine plus anthracycline-based induction therapy. Salvage chemotherapy regimens are based on high-dose cytarabine (HiDAC), which is frequently combined with mitoxantrone (HAM regimen). However, CR rates remain low, with less than one-third of the patients achieving a CR. FLT3-ITD has consistently been identified as an unfavorable molecular marker in both relapsed and refractory (r/r)-AML. One-quarter of patients who received midostaurin are refractory to induction therapy and relapse rate at 2 years exceeds 40%. The oral second-generation bis-aryl urea tyrosine kinase inhibitor quizartinib is a very selective FLT3 inhibitor, has a high capacity for sustained FLT3 inhibition, and has an acceptable toxicity profile.MethodsIn this multicenter, upfront randomized phase II trial, all patients receive quizartinib combined with HAM (cytarabine 3g/m2 bidaily day one to day three, mitoxantrone 10mg/m2 days two and three) during salvage therapy. Efficacy is assessed by comparison to historical controls based on the matched threshold crossing approach with achievement of CR, complete remission with incomplete hematologic recovery (CRi), or complete remission with partial recovery of peripheral blood counts (CRh) as primary endpoint. During consolidation therapy (chemotherapy and allogeneic hematopoietic cell transplantation), patients receive either prophylactic quizartinib therapy or measurable residual disease (MRD)-triggered preemptive continuation therapy with quizartinib according to up-front randomization.The matched threshold crossing approach is a novel study-design to enhance the classic single-arm trial design by including matched historical controls from previous clinical studies. It overcomes common disadvantages of single-armed and small randomized studies, since the expected outcome of the observed study population can be adjusted based on the matched controls with a comparable distribution of known prognostic and predictive factors. Furthermore, balanced treatment groups lead to stable statistical models. However, one of the limitations of our study is the inability to adjust for unobserved or unknown confounders.Addressing the primary endpoint, CR/CRi/CRh after salvage therapy, the maximal sample size of 80 patients is assessed generating a desirable power of the used adaptive design, assuming a logistic regression is performed at a one-sided significance level α=0.05, the aspired power is 0.8, and the number of matching partners per intervention patient is at least 1. After enrolling 20 patients, the trial sample size will be recalculated in an interim analysis based on a conditional power argument.ConclusionCurrently, there is no commonly accepted standard for salvage chemotherapy treatment. The objective of the salvage therapy is to reduce leukemic burden, achieve the best possible remission, and perform a hemopoietic stem-cell transplantation. Thus, in patients with FLT3-ITD mutation, the comparison of quizartinib with intensive salvage therapy versus chemotherapy alone appears as a logical consequence in terms of efficacy and safety.Ethics and disseminationEthical approval and approvals from the local and federal competent authorities were granted. Trial results will be reported via peer-reviewed journals and presented at conferences and scientific meetings.Trial registrationClinicalTrials.gov NCT03989713; EudraCT Number: 2018-002675-17.

Cytomegalovirus reactivation under pre-emptive therapy following allogeneic hematopoietic stem cell transplant: Pattern, survival, and risk factors in the Republic of Korea.

Pre-emptive therapy for cytomegalovirus (CMV) reactivation has been used in allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is unclear if this strategy has poorer clinical outcomes in CMV-endemic areas and if more aggressive prophylaxis is required. We retrospectively analyzed the patterns and survival after CMV reactivation in patients undergoing pre-emptive therapy following allo-HSCT and assessed high-risk patients who could benefit from aggressive CMV prophylaxis in endemic areas. Of the 292 patients who underwent allo-HSCT, 70.5% (donor+ or recipient+) were CMV seropositive. CMV reactivation occurred in 139 patients (47.6%), with a median of 31.5 days from day 0 of allo-HSCT. The overall survival of patients with CMV reactivation who received pre-emptive therapy did not differ from those without reactivation. Of the 139 patients with CMV reactivation, 78 (56.1%) underwent ≥2 rounds of pre-emptive therapy. In multivariate analysis, the risk of CMV reactivation was higher in patients with multiple myeloma, with CMV seropositivity of the recipient and donor, administered with a higher dose of anti-thymocyte globulin (ATG), and with acute graft-versus-host disease (aGVHD) ≥ grade 2. Although half of the patients with allo-HSCT were administered with pre-emptive therapy for CMV, CMV reactivation did not affect their survival, indicating the advantages of pre-emptive therapy, even in CMV-endemic areas. The cost-effectiveness of more aggressive CMV prophylaxis should be re-evaluated in patients at a high risk for CMV reactivation.

Oral Versus Intravenous Anti-CMV Preemptive Strategies in Allogeneic Stem Cell Transplant Patients with CMV Reactivation: Experience from the National Center of Bone Marrow Transplantation, Tunis, Tunisia

Cytomegalovirus (CMV) infection is a common and severe complication following allogeneic stem cell transplantation (ASCT) and requires effective preemptive antiviral therapy. Both oral and intravenous (IV) antiviral agents effectively reduce CMV viral load and achieve viral clearance. Studies comparing oral and IV anti-CMV preemptive treatment in ASCT patients with CMV reactivation showed a potential difference in treatment response and safety profiles between the two administration routes. We retrospectively compared the efficacy and safety of oral with intravenous (IV) anti-CMV preemptive therapy in ASCT recipients with CMV reactivation. A descriptive retrospective study included patients who received their first ASCT between January 2018 and June 2022. The monitoring oral load was assessed weekly using a quantitative polymerase chain reaction in plasma. Fifty-five patients developing 72 CMV reactivations were included. The median age was 29 years (range, 6-50). The main underlying diseases were acute leukemia and aplastic anemia. Before ASCT, 96% of patients were at high risk of CMV reactivation. CMV reactivations were observed at a median of 43 days (range, 16-270) post-ASCT. The median viral load at CMV reactivation was 248 copies/mL (range, 150-4800). The first-line preemptive treatment was oral in 51 (71%) of the episodes (Valganciclovir, n = 40; Leflunomide, n = 11) and IV in 21 (29%) of the episodes (Foscarnet, n = 16; Ganciclovir, n = 5). Response to first-line therapy was not statistically significant between the two groups (74% vs 76%, p = 0.88). Thirteen (25%) and 5 (24%) episodes needed second or subsequent-line therapy in the oral and IV groups, respectively. The hematological toxicity was significantly higher in the oral group (61% vs 29%, p = 0.01). The mean duration of hospital stay per patient in the oral and IV groups was 7 days and 49 days (p < 10<sup>-3</sup>), respectively. More non-CMV documented infections were observed in the IV group (38% vs 4%, p = 0.001). After a median follow-up of 18 months (range, 2-55), the 2-year-overall survival, event-free survival and cumulative incidence of non-relapse mortality were 85%, 75% and 6%, respectively. Our results showed that the oral preemptive therapy for CMV reactivations after ASCT was as effective as IV formulations and needed less hospital stay time. However, it is associated with more hematological toxicity.

Cytomegalovirus Viral Load Threshold to Guide Preemptive Therapy in Hematopoietic Cell Transplant Recipients: Correlation With Cytomegalovirus Disease.

A systematic review of randomized and observational studies from 2013 to 2023 demonstrated that antiviral preemptive therapy started at cytomegalovirus viral load thresholds between 2 and 3 log10 IU/mL was associated with similar cytomegalovirus disease rates. Thus, viral thresholds in this range appear to effectively protect patients not receiving prophylaxis.

Letermovir for pre-emptive cytomegalovirus therapy after allogeneic hematopoietic cell transplantation.

Cytomegalovirus (CMV) is a common cause of morbidity after allogeneic haematopoietic cell transplantation (alloHCT). Pre-emptive therapy (PET) with valganciclovir (VGC) is associated with haematological toxicity. We included alloHCT patients from 2018 to 2021 where letermovir (LTV) was used for CMV PET because of cytopenias. Ten patients were included. Six received VGC prior to LTV. VGC was commenced at median d42, given for median 40 days. LTV was commenced at median d90, given for median 54 days. At commencement of antiviral, CMV viral load was higher for VGC at 3.7 log10 IU/mL, compared to LTV at 2.9 log10 IU/mL. Viral load reduction occurred at 0.18 log10 IU/mL per week for VGC, compared to 0.17 log10 IU/mL per week for LTV. There was no clinically significant CMV viremia after stopping LTV. Cytopenias improved on LTV. LTV was effective in controlling CMV viremia when it was given at a lower starting CMV viral load and later post alloHCT than VGC. Further study is required of LTV as upfront PET following alloHCT.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era.

Hepatitis due to hepatitis B virus (HBV) reactivation can be serious and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver. The expression of these silent genomes is controlled by the immune system. Suppression or ablation of immune cells, most importantly B cells, may lead to reactivation of seemingly resolved HBV infection. Thus, all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen. Patients found to be positive for HBsAg should be given prophylactic antiviral therapy. For patients with resolved HBV infection, there are two approaches. The first is pre-emptive therapy guided by serial HBV DNA monitoring, and treatment with antiviral therapy as soon as HBV DNA becomes detectable. The second approach is prophylactic antiviral therapy, particularly for patients receiving high-risk therapy, especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation. Entecavir and tenofovir are the preferred antiviral choices. Many new effective therapies for hematological malignancies have been introduced in the past decade, for example, chimeric antigen receptor (CAR)-T cell therapy, novel monoclonal antibodies, bispecific antibody drug conjugates, and small molecule inhibitors, which may be associated with HBV reactivation. Although there is limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, including Bruton's tyrosine kinase inhibitors, B-cell lymphoma 2 inhibitors, and CAR-T cell therapy. Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.

A quick algorithmic review on management of viral infectious diseases in pediatric solid organ transplant recipients.

Pediatric solid organ transplant is a life-saving procedure for children with end-stage organ failure. Viral infections are a common complication following pediatric solid organ transplantation (SOT), which can lead to increased morbidity and mortality. Pediatric solid organ transplant recipients are at an increased risk of viral infections due to their immunosuppressed state. The most commonly encountered viruses include cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), varicella-zoster virus (VZV), adenoviruses, and BK polyomavirus. Prevention strategies include vaccination prior to transplantation, post-transplant prophylaxis with antiviral agents, and preemptive therapy. Treatment options vary depending on the virus and may include antiviral therapy and sometimes immunosuppression modification. This review provides a Quick Algorithmic overview of prevention and treatment strategies for viral infectious diseases in pediatric solid organ transplant recipient.

Efficacy and safety of preemptive therapy for cytomegalovirus end-organ disease in people living with HIV: a systematic review and meta-analysis.

Cytomegalovirus end-organ-disease (CMV EOD) is still a major cause of debilitating illness in people living with HIV, especially in developing countries. To evaluate the efficacy and safety of preemptive therapy against CMV EOD in HIV-positive adults with CMV viremia. Systematic review of clinical trials by searching electronic databases and clinical trial registries, screening and selection of references, data extraction and assessment of risk of bias. The results were presented in a narrative synthesis. Aggregated analyzes for dichotomous outcomes were reported as odds ratios with 95% Confidence Intervals. Four RTC were included. A reduction in the risk of CMV EOD with preemptive therapy was found OR=0.49 (95% CI 0.31‒0.76). We did not identify significant differences for all-cause mortality, adverse events, and withdrawal of the therapy secondary to adverse events. Preemptive therapy could be a potential option for preventing CMV EOD in people living with HIV.

Factors Influencing Postoperative Complications Following Minimally Invasive Ivor Lewis Esophagectomy: A Retrospective Cohort Study.

Complications arising following minimally invasive Ivor Lewis esophagectomy often result from inadequate enteral nutrition, highlighting the need for proactive measures to prevent such issues. One approach involves identifying high-risk cases prone to complications and implementing percutaneous endoscopic jejunostomy (PEJ) tube placement during esophageal resection to ensure timely enteral nutrition. In this single-center, retrospective cohort study, we examined patients who underwent minimally invasive esophagectomy for esophageal cancer at a high-volume center. The dataset encompassed demographic information, comorbidities, laboratory parameters, and intraoperative details. Our center utilized the EndoVac system pre-emptively to safeguard the anastomosis from harmful secretions and to enhance local oxygen partial pressure. All patients received pre-emptive EndoVac therapy and underwent esophagogastroduodenoscopy in the early postoperative days. The need for multiple postoperative EndoVac cycles indicated complications, including anastomotic insufficiency and subsequent requirement for a PEJ. The primary objectives were identifying predictive factors for anastomotic insufficiency and the need for multi-cycle EndoVac therapy, quantifying their effects, and assessing the likelihood of postoperative complications. 149 patients who underwent minimally invasive or hybrid Ivor Lewis esophagectomy were analyzed and 21 perioperative and demographic features were evaluated. Postoperative complications were associated with the body mass index (BMI) category, the use of blood pressure medication, and surgery duration. Anastomotic insufficiency as a specific complication was correlated with BMI and the Charlson comorbidity index. The odds ratio of being in the high-risk group significantly increased with higher BMI (OR = 1.074, p = 0.048) and longer surgery duration (OR = 1.005, p = 0.004). Based on our findings, high BMI and longer surgery duration are potential risk factors for postoperative complications following minimally invasive esophagectomy. Identifying such factors can aid in pre-emptively addressing nutritional challenges and reducing the incidence of complications in high-risk patients.

392. PLANNING IS THE KEY—ESOPHAGECTOMY WITH COLONIC INTERPOSITION FOLLOWING: WHIPPLE’S, LEFT LOWER LOBECTOMY, RIGHT PLEURECTOMY AND COLONIC SURGERY

Abstract Link to Video: https://www.dropbox.com/s/wpr3s097g50oadl/Colonic%20interposition%20%28ISDE%20SUBMISSION%29.mp4?dl=0. Description of Video: We report our learnings from a complex surgical case of Ivor Lewis esophagectomy with colonic conduit in a patient who had undergone multiple previous abdominal and thoracic operations. This seventy-two-year-old man was found to have an esophageal adenocarcinoma (T4N0M0) in the distal esophagus with a significant surgical background: Whipple’s procedure for pancreatic cancer; Left lower lobectomy for lung cancer; Right pneumonectomy for recurrent pneumothoraces and a defunctioning stoma for chemotherapy associated anal fistula. To our knowledge, no such case of colonic interposition for esophagectomy has been reported in the literature for a patient with such extensive surgical history. This presented significant surgical and anaesthetic challenges which are explored in the video. Principally the need for extensive planning to anticipate risk and modify procedural steps to account for these accordingly. For example, the operation began with a right thoracotomy, given the possibility that dense adhesions from previous surgery could obstruct safe dissection and subsequently the procedure could be aborted before any critical steps were made. Additionally, we consider the importance of involving other surgical specialities to aid with safe dissection and delineation of anatomy. Each of the key operative steps are described and paired with real-time video footage. Post-operatively we describe how the risk of anastomotic leak given a high-risk anastomosis may be reduced through pre-emptive Endoluminal Vacuum therapy. We also discuss the importance of recognising and managing feculent aspiration pneumonia which is common following this surgery. Discussion of this case and our operative approach would serve to highlight how surgery remains a feasible option for patients despite complex anatomy and surgical history; provided risks are anticipated and appropriately managed.