Objectives Cladribine, a synthetic analog of deoxyadenosine, exhibits potent activity against hematological malignancies. While cladribine-containing regimens combined with allogeneic hematopoietic stem cell transplantation (allo-HSCT) have been proposed as a potential strategy to improve outcomes in relapsed or refractory (R/R) acute myeloid leukemia (AML), additional clinical evidence is needed, particularly in pediatric populations. This single-center retrospective study aimed to describe the efficacy and safety of a cladribine-based conditioning regimen for allo-HSCT in children with R/R AML. Materials and methods Clinical data of 16 children with R/R AML who underwent allo-HSCT following a cladribine-based conditioning regimen at our hospital from October 2020 to June 2024 were analyzed retrospectively. Key outcomes included hematopoietic reconstruction, regimen-related toxicity (RRT), cumulative incidence of graft-versus-host disease (GVHD), infection profiles, overall survival (OS), disease-free survival (DFS), relapse rate, and non-relapse mortality (NRM). Flow-cytometry minimal residual disease (MRD) results before HSCT were collected and analyzed as an additional key baseline index. Results All 16 patients attained hematopoietic reconstruction, with pre-transplant flow-cytometry MRD negative in 13 cases (81.25%) and positive (MRD ≥0.01%) in three cases (18.75%). The median time of neutrophil and platelet engraftment was 12 (10–16) days and 15 (10–25) days, respectively. The incidence of I/II grade RRT was 31.3% (oral cavity: three cases, liver: two cases), with no III/IV grade RRT observed. The cumulative incidence of acute GVHD (aGVHD) was 50.0% (grade I/II skin: five cases, grade IIIl: three cases). Among 15 evaluable patients, the cumulative incidence of chronic GVHD (cGVHD) was 26.7% (local skin: three cases, ocular keratoconjunctivitis sicca: one case). Post-transplant infections occurred in 31.3% of patients, predominantly viral pathogens: one case of BK virus-associated hemorrhagic cystitis, one case of BK virus combined with bacterial infection, and three cases of cytomegalovirus (CMV) DNAemia. The median follow-up time was 28.03 (11.67–55.34) months (follow-up cutoff: 30 June 2024). Using the Kaplan–Meier method, the 1-year OS rate was 87.5% (95% CI: 65.2%−96.4%), and the 1-year DFS rate was 87.4% (95% CI: 64.9%−96.3%). The relapse rate and NRM were both 6.3% (95% CI: 0.8%−29.1%); the NRM case was confirmed as bronchiolitis obliterans syndrome (BOS) induced by pulmonary cGVHD. Conclusion In this small single-center retrospective series, the cladribine-based conditioning regimen was associated with favorable hematopoietic reconstruction, mild RRT, and promising survival outcomes in children with R/R AML, even in partial patients with pre-transplant MRD positivity. However, due to the limited sample size, single-arm design, and lack of a control group, conclusions regarding superiority (e.g., improved OS or reduced relapse) cannot be drawn. Larger prospective multi-center studies are required to validate these preliminary findings.

Background Immune dysregulation and excessive inflammatory responses can lead to hemophagocytic syndrome (HPS) involving autologous blood cell phagocytosis, with fatal outcomes occurring in some cases. This case report describes an 80-year-old man who was simultaneously diagnosed with diffuse large B-cell lymphoma (DLBCL) and rectal cancer and developed HPS during neoadjuvant chemotherapy for the latter. Case description Treatment for DLBCL was initiated first, and six courses of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy were administered, which led to a clinical complete response of the lymphoma lesions. Following the completion of DLBCL treatment, preoperative chemoradiotherapy with tegafur–uracil/leucovorin (UFT/UZEL) was initiated for rectal cancer. On Day 18, a fever of 38.3 °C developed. Blood tests conducted on Day 24 revealed Grade 4 neutropenia and Grade 4 thrombocytopenia. Granulocyte colony-stimulating factor (G-CSF) preparation, antibiotic therapy, and recombinant human soluble thrombomodulin (rTM) were initiated as disseminated intravascular coagulopathy (DIC) therapy. A poor therapeutic response was achieved, and acute respiratory distress syndrome (ARDS) developed on Day 34. Imaging of the biopsied bone marrow confirmed that hemophagocytosis by macrophages was occurring. The patient was ultimately diagnosed with HPS. Epstein–Barr virus (EBV) and cytomegalovirus (CMV) infections were identified, and treatment to combat the infections was initiated; however, the patient passed away on Day 37. Conclusion It is important to consider the possibility of HPS, and diagnosis and treatment initiation should occur in a timely manner when fever of an unknown origin and decreased blood cell counts are observed during malignant disease treatment.

Background Human cytomegalovirus (HCMV) infection has adverse effects on very low-birth-weight infants (VLBW) and is complicated with liver dysfunction, thrombocytopenia, and hearing impairment. Therefore, we explored new potential intervention targets in VLBW infants with HCMV infection. Methods Enrichment analysis of adult HCMV infection and control groups was performed in the GSE81246 dataset. Peripheral blood mononuclear cells (PBMCs) from VLBW infants with HCMV and those without HCMV ( n = 3 per group) (collection: 9–10 a.m.) were sent for RNA-seq to enrich the transcriptome of the obtained GSE290897 dataset. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways with the same enrichment results and significant changes in the two datasets were selected and analyzed. Then the screened genes were verified using reverse transcription polymerase chain reaction (RT-PCR) and quantitative PCR (qPCR). Results The key circadian rhythm genes PER1 and CRY1 were screened. RT-qPCR was used to detect PER1 and CRY1 mRNA levels in the PBMCs of VLBW infants with HCMV ( n = 12) and the controls ( n = 6) (collection: 9–10 a.m.). And results showed that PER1 and CRY1 mRNA was significantly decreased in HCMV infection than in the controls ( P < 0.0001; P < 0.0001). Conclusion PER1 and CRY1 mRNA was significantly decreased in PBMCs from HCMV infected VLBW infants, providing new ideas for studying potential effective therapeutic targets for HCMV infection in VLBW infants.

Background: Kawasaki disease (KD) is a systemic vasculitis of unknown origin, though recent evidence implicates viral pathogens in its pathogenesis. Given the central role of T cell receptors (TCRs) in antigen recognition and immune response, this study investigated the association between KD and viral infection through comparative analysis of TCR repertoires. Methods: TCR repertoires from KD patients, healthy children, and individuals with viral infections were comparatively analyzed. TCR diversity and V(D)J usage were assessed using Shannon’s entropy, the Mann–Whitney U test, and Fisher’s exact test. Positional motif enrichment analysis within CDR3 regions was performed based on paratope hotspot classification. Results: Relatively reduced TCR clonal abundance and diversity were observed in KD patients compared to healthy controls. While substantial overlap in VJ gene segment usage was detected between KD and cytomegalovirus (CMV) infection, limited overlap in clonal TCRαβ chains was found between KD and viral infection groups. A predominant TCR combination, TRAV14DV4-J13-TRBV20-1-J2-5, enriched with characteristic amino acid motifs (EET, YNE, LAG, GQG, and AYE), was frequently identified in KD. Conclusions: These observations suggest potential differences in TCR repertoire features between KD patients and both healthy and virus-infected groups. However, the relationship between KD pathogenesis and the viruses examined requires further investigation with larger cohorts.

Introduction Steroid-refractory (SR) hepatic acute graft-versus-host disease (aGVHD) remains a life-threatening complication following allogeneic hematopoietic stem cell transplantation, characterized by limited responsiveness to both first- and second-line therapies and an overall poor prognosis. This study aimed to evaluate the efficacy and safety of cyclophosphamide (CTX) as a salvage treatment for SR- hepatic aGVHD. Methods A total of 50 patients with SR-hepatic aGVHD who underwent CTX treatment were retrospectively included in the analysis. Seventeen patients (34.0%) received CTX as second-line therapy, whereas the majority (n=33, 66.0%) were administered CTX as salvage therapy following failure of prior second-line interventions. Results The overall response rate (ORR) at day 28 was 70.0%, with a durable ORR of 66.0% at day 56. Patients with the hepatitic variant of aGVHD showed a superior response compared to those with the classic variant (complete response: 6 of 8 [75.0%] vs. 14 of 42 [33.3%], P = 0.042). The probabilities of overall survival (OS) and nonrelapse mortality (NRM) at 3 years after CTX treatment were 36.9% (95% CI, 24.8%–54.9%) and 56.5% (95% CI, 41.4%–71.6%). Using propensity score matching (PSM), we compared 35 patients receiving CTX with 35 BAT (best available treatment) controls during the same study period. CTX initiation occurred later than BAT (median line: 3 vs 2, P < 0.001). Response rates and survival outcomes were comparable between two groups and CTX demonstrated consistent efficacy even when used as later-line therapy. Additionally, CTX did not significantly increase the risk of adverse events compared to the BAT group up to day 28. The most common adverse events in both groups were neutropenia (71.4% in the CTX group vs. 62.9% in the BAT group, P = 0.445), anemia (68.6% vs. 60.0%, P = 0.454), and cytomegalovirus infection (51.4% vs. 45.7%, P = 0.632). Discussion These findings suggest that CTX is a promising and well-tolerated treatment option for patients with SR-hepatic aGVHD.

Logical versus absolute lymphocyte count-guided preemptive therapy for cytomegalovirus prevention in kidney transplant recipients: a randomized controlled trial.

Nicotinamide-based Sirtuin 2 inhibitors as anti-HCMV agents.

Virus antibody responses in patients with myelin oligodendrocyte glycoprotein antibody-associated disease and multiple sclerosis.

Characterizing the interactions between murine cytomegalovirus M72 and the carbon catabolite repression 4-negative on TATA-less (CCR4-NOT) complex.

Sexually transmitted infections (STIs) are prevalent worldwide and pose a significant challenge to national healthcare systems. Human papillomavirus (HPV) annually causes over 600,000 cases and 350,000 deaths from cervical cancer (CC). Coinfections with HPV and other STIs often potentiate the development of dysplastic processes and CC. The role of STI and HPV coinfection in carcinogenesis and the impact of multiple HPV infections on the development of CC have been poorly studied. Aim of the study : to assess the prevalence and risks of carcinogenesis in various variants of coinfection with human papillomavirus and other sexually transmitted infection agents. Materials and methods . A total of 9,310 HPV-positive women with STIs and/or other diseases were examined. Detection of 14 HPV genotypes was performed using PCR. The diagnosis of cervical intraepithelial neoplasia (CIN) was established based on extended colposcopy and cytological examination. Methods: PCR, clinical, epidemiological, and statistical methods. Results and discussion . In case of coinfection with STIs, the prevalence of HPV genotypes 16, 18, and 45 had statistically significant differences (32.0%, 9.7%, and 11.4%, respectively, p<0.001). The prevalence of HPV type 16 was characterized by an asymmetric distribution between STIs, demonstrating maximum values for urogenital candidiasis, anogenital warts, and chlamydial infection (40.7–36.8%) and lower values for anogenital herpes and cytomegalovirus infection (28.3–26.8%, p=0.02). The prevalence of CIN in the group of patients with STIs (11.8%) significantly exceeded the indicator in all examined patients (5.0%, p<0.001). The combination of STIs with a single HPV type was the most common coinfection (92%). The presence of multiple HPV infections during coinfection with STIs in patients in the study group did not increase the risk or severity of CIN (p>0.05). Conclusion . The prevalence of HPV among patients with STIs (30.7%) was significantly higher than in the comparison group (p<0.001). In HPV and STI coinfections, a high prevalence of HPV type 16 (25–40.7%) and CIN of varying severity (3.7–16.7%) was observed. A potentially high risk of carcinogenesis cannot be excluded in cases of HPV coinfections with mycoureaplasmosis and anogenital herpes infection due to the significant prevalence of CIN (12.1–14.1%), comparable to the prevalence of CIN in chlamydial infection (16.7%, p>0.05). The obtained results are consistent with existing data on the negative impact of the association of HPV and chlamydial infection on the risk of neoplasia development and complement the existing knowledge base in terms of assessing the impact of HPV coinfections with mycoureaplasmosis, anogenital herpes, anogenital warts, as well as multiple HPV infections on the risk of carcinogenesis.

Filiform Polyposis (FP) is a rare form of pseudopolyps, occurring most commonly in the large intestine. It usually occurs as a rare complication of inflammatory bowel disease (Crohn’s disease or, more commonly, ulcerative colitis). But it can also occur in other chronic inflammatory or infectious diseases affecting the large bowel. Most common locations are the rectum and sigmoid colon for FP, but they can involve any length of the large intestine. They can occur as finger-like projections, sometimes with interconnections and can affect the entire colonic mucosa in a diffuse manner. Colonoscopy is the usual and most common modality for diagnosis. They are known to occur as a reparative process to chronic inflammatory conditions affecting the bowel. Inflammatory Bowel Disease (IBD) patients harbouring Cytomegalovirus (CMV) infection can also predispose the colonic mucosa to develop FP. Management usually depends on the symptoms. Surgical management is restricted in cases of complications like intestinal obstruction or bleeding and pain. Here, we report a case of a 55-year-old male with pre-existing ulcerative colitis with co-existing CMV infection, now presenting with severe intestinal obstruction. Colonoscopy revealed many polypoidal projections involving the rectum and sigmoid colon, following which he underwent subtotal colectomy. The colon specimen histopathologically revealed to have multiple interconnecting polypoidal projections lined by normal colonic mucosa with areas of chronic inflammatory changes, which was confirmed to be FP in a known case of ulcerative colitis. Though FP has no malignant potential, it can lead to intestinal obstruction and other complications, making routine follow-up necessary for patients with IBD.

Idiopathic pulmonary fibrosis (IPF) is a serious progressive complication of the respiratory system, which is profoundly associated with persistent extracellular matrix (ECM) deposition, fibrosis, and disrupted tissue regeneration. Emerging evidence shows that epithelial-mesenchymal transition (EMT) acts as a key factor in the pathogenesis of this idiopathic interstitial lung disease by connecting long-lasting epithelial damage to fibroblast accumulation and fibrotic processes. Viral pathogens, particularly emerging and re-emerging viruses, such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Influenza Virus, and Dengue Virus (DENV) and also those with oncogenic potential such as Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), and Hepatitis C Virus (HCV), have been demonstrated to be significantly associated with impaired epithelial signalling, persistent inflammation, and EMT induction. This underscores the presence of potential mechanistic overlap between viral infections and fibrotic complications of the respiratory system. On the other hand, investigations have also suggested the capacity of Traditional Chinese Medicine (TCM) agents to modulate various EMT-linked pathways, which are simultaneously involved in both viral infections and IPF development. These common signalling pathways include TGF-β, Wnt/β-catenin, PI3K/AKT, and NF-κB signalling, acting as potential therapeutic targets against fibrotic complications such as IPF. The present review aims to comprehensively describe current evidence on the dynamic cross-talk between viral pathogens, particularly SARS-CoV-2, Influenza Virus, and DENV, EMT, and lung fibrosis. Additionally, it critically discusses how TCM-derived bioactive agents can interfere with these interconnected processes. This review elucidates the mechanistic basis and therapeutic potential of TCM compounds in lung fibrosis, considering the wider context of virus-related EMT dysregulation.

Understanding the burden of congenital cytomegalovirus (cCMV) infection: concept elicitation interviews with caregivers of pediatric cCMV patients and development of a conceptual disease model.

Recent insights into the immunobiology of congenital cytomegalovirus infection

Purpose: This study aimed to evaluate the clinical and laboratory features of cytomegalovirus (CMV) reactivation in immunosuppressed patients with rheumatic diseases and to compare the characteristics of patients with and without mortality. Materials and Methods: This retrospective cohort study included 30 adult patients with rheumatic diseases who were receiving immunosuppressive therapy and underwent CMV polymerase chain reaction (PCR) testing due to clinical and/or laboratory suspicion between November 2016 and April 2024. Patients with CMV PCR positivity were included in the analysis. Demographic, clinical, and laboratory data were collected. Comparisons of clinical and laboratory parameters were conducted according to antiviral treatment use and survival status. Results: Granulomatosis with polyangiitis (23%) and adult-onset Still’s disease (20%) were the most frequent underlying diagnoses. CMV reactivation predominantly occurred during periods of intensive immunosuppressive therapy. Antiviral treatment with ganciclovir was administered in 70% of patients, who had higher CMV viral loads, lower lymphocyte and albumin levels, and higher C-reactive protein levels compared with untreated patients. The overall mortality rate was 23.3%. In multivariable analysis, CMV-associated pneumonia was the only variable independently associated with mortality. Conclusion: CMV reactivation is a serious complication in immunosuppressed patients with rheumatic diseases and is associated with substantial mortality, particularly in the presence of pulmonary involvement.

Shifts in immune cell proportions underlie disease progression and immunotherapy response, positioning them as promising diagnostic biomarkers and therapeutic targets. However, these shifts also occur naturally across the lifespan and vary with demographic factors such as age and sex, which may complicate their interpretation and clinical utility. While demographic associations have been explored previously, there have been mixed results likely due to small sample sizes and cross-cohort population specific differences. To address these limitations, we conducted a meta-analysis across three large, diverse cohort studies to evaluate associations between twenty immune cell subtypes, three informative cell ratios, and a range of sociodemographic variables such as age, sex, self-identified race and ethnicity (SIRE), and socioeconomic status. We find consistent and significant associations across all sociodemographic dimensions. Cytomegalovirus (CMV)-a key driver of immune senescence-emerged as a major contributor to variation in immune composition and CMV antibody levels were higher among women, individuals of lower socioeconomic status, and marginalized racial and ethnic groups. In addition, male sex showed similar patterns of association with immune profiles as aging, whereas race did not. These findings underscore the need to account for diverse sociodemographic factors in immunology study design and participant recruitment to avoid population-specific biases and ensure broadly generalizable results.

A Rare Presentation of Cytomegalovirus Mononucleosis in a Nine-Year-Old Girl: A Case Report

Introduction: Cytomegalovirus (CMV) infection is a common complication following solid organ transplantation and is associated with significant morbidity. While CMV classically presents with systemic symptoms, bone marrow suppression or gastrointestinal disease, atypical manifestations may occur. Anasarca and refractory ascites in liver transplant recipients are more commonly attributed to graft dysfunction, vascular complications, cardiac disease or renal pathology, and CMV is not often considered as a primary aetiology. Case description: A 63-year-old woman with a history of alcohol-related cirrhosis underwent deceased donor liver transplantation and later presented with progressive abdominal distension and bilateral lower extremity oedema. Evaluation demonstrated tense ascites and anasarca without evidence of graft dysfunction, acute rejection, portal vascular complications, cardiac disease or nephrotic syndrome. Liver function tests were normal, transthoracic echocardiography revealed preserved systolic function, and urinalysis was negative for proteinuria. Further workup identified CMV viremia, and the patient was treated with valganciclovir per infectious disease recommendations, along with supportive measures including diuresis and large-volume paracentesis. Serial monitoring demonstrated improvement in CMV viral load with corresponding gradual resolution of fluid retention. Conclusion: This case highlights CMV viremia as an important and potentially reversible cause of anasarca in post-liver transplant patients, likely mediated by CMV-induced endothelial dysfunction. Recognition of CMV-related fluid retention is essential to avoid unnecessary invasive procedures and to guide timely antiviral therapy in immunosuppressed individuals.

Cytomegalovirus (CMV) antiviral drugs can cause side effects and promote the emergence of drug-resistance after transplantation. T cell-mediated immunity to CMV (CMI) can be used to limit and optimize the duration of antiviral therapy. However, interferon-gamma release assays show varying rates of CMI in CMV-seronegative recipients (R-), who are at the highest risk of CMV infection with CMV-seropositive donors (D+). Here, we characterize CMI with CMV-specific T cells that express CD154 in R- liver transplant and intestine transplant recipients. Pretransplant blood leukocyte samples from 42 R- recipients were stimulated with a 15-mer overlapping peptide mixture representing the pp65 CMV antigen. CMI was measured by flow cytometry with CMV-specific CD154+ T-cell frequencies. Recipients, median age (range) 3.3 (0.4-36.5 y), included 39 liver transplant and 3 intestine transplant. CMV serostatus was D+/R- in 21, and D-/R- in 21. Protective CMI levels of >1.7% previously established in 142 liver or intestine recipients were observed in 25 of 42 total R- recipients (60%), including 11 of 21 D+/R- (52%) and 14 of 21 D-/R- (67%) participants. CMV DNAemia was observed in the first 60 d after transplantation in 10 of 42 (24%) R- recipients, including 8 of 17 with CMI <1.7% and 2 of 25 with CMI >1.7%. Adjusted for D+/R-, CMI<1.7% was independently associated with a higher risk of DNAemia (hazard ratio 6.04 [1.2-29.4], P = 0.026). CMV-specific T cells that express CD154 demonstrate protective levels of CMI in half of all seronegative recipients and can be used to optimize antiviral prophylaxis across all risk categories.

Background: Cytomegalovirus (CMV) reactivation is frequently observed in patients with moderate-to-severe ulcerative colitis (UC), particularly in steroid-refractory cases; however, the clinical significance of tissue CMV DNA detection by polymerase chain reaction (PCR) in the absence of classical histopathological findings remains controversial. Methods: This retrospective cohort study included 110 patients with moderate-to-severe UC who underwent colonoscopy between January 2021 and April 2024 at a tertiary referral center. Tissue and serum samples were analyzed for CMV DNA using PCR. Tissue CMV DNA positivity was defined as ≥250 copies. Endoscopic disease activity was assessed using the Mayo clinical score, Mayo endoscopic score, and the Rachmilewitz Endoscopic Activity Index. Associations between tissue CMV DNA positivity, endoscopic activity scores, inflammatory markers, recent immunosuppressive therapy, and serum CMV PCR results were evaluated. Sensitivity analyses using different tissue CMV DNA thresholds and receiver operating characteristic (ROC) curve analysis for serum CMV PCR were also performed. Results: Tissue CMV DNA positivity was detected in 37.3% of patients. Patients with tissue CMV DNA positivity had significantly higher Mayo clinical scores and Rachmilewitz Endoscopic Activity Index scores compared with CMV-negative patients, whereas Mayo endoscopic scores did not differ significantly between groups. Serum CMV PCR levels were markedly higher in patients with tissue CMV DNA positivity (p < 0.001). Tissue CMV DNA copy number showed a strong correlation with serum CMV PCR levels but did not demonstrate a consistent linear association with endoscopic activity scores. In multivariable logistic regression analysis, recent corticosteroid use was independently associated with tissue CMV DNA positivity, while anti-TNF therapy and endoscopic activity indices were not independent predictors. ROC analysis demonstrated good diagnostic performance of serum CMV PCR for predicting tissue CMV DNA positivity (AUC = 0.82). Conclusions: In patients with moderate-to-severe UC, tissue CMV DNA positivity (≥250 copies) is associated with increased clinical and endoscopic disease activity, even in the absence of classical histopathological evidence of CMV infection. These findings suggest that molecular detection of CMV in colonic tissue may provide clinically relevant information in selected patient populations, particularly those with recent corticosteroid exposure. However, tissue CMV DNA positivity should be interpreted as a molecular association rather than definitive evidence of causality or an indication for antiviral therapy. Prospective multicenter studies are warranted to further clarify the clinical implications of tissue CMV DNA detection in UC.