Search

Introduction: Splenectomy has been used as a diagnostic and therapeutic tool in the management of hematological diseases for many years. However, the emergence of new medical therapies has modified guidelines for many hematological diseases for which splenectomy was previously considered. We aimed to evaluate the evidence of a decrease in the hematological indications for splenectomy and the reasons and justifications for this change., Material and Methods: We conducted a single-center, retrospective analysis of patients who underwent laparoscopic splenectomy for hematological disease between January 2010 and December 2023. Patients were classified into four groups: 1 autoimmune and hemolytic diseases (HAD), (2) lymphomas, (3) myeloproliferative diseases (MPN), and (4) other splenic diseases. We recorded the annual incidence of splenectomy and the ratio of new medical cases, demographic and clinical data and surgical outcomes., Results: During the study period, 98 patients were referred for splenectomy. There was a significant progressive decrease in this surgical indication, particularly regarding HAD (p < 0.001). The indication for splenectomy for immune thrombocytopenic purpura (ITP) declined to zero despite an increase in the number of patients diagnosed with this disorder (p < 0.001). The pattern of decrease in AHAI and Evans syndrome was similar to that in ITP. The group of splenectomies due to lymphoma persisted consistently during the study period, as did the indication for splenectomy in the context of lymphoma treatment. Splenectomy due to massive splenomegaly secondary to MPN was indicated only in one patient. Splenectomies due to other causes were similarly distributed over the years., Conclusions: Our findings confirm a significant decrease in the indication for elective surgery for hematological diseases, mainly regarding autoimmune disease. The surgical community and surgical departments should be aware of this situation yet maintain the skills to adopt this technique both safely and efficiently., (© 2024. The Author(s).)

The identification of patients at high risk of Herpes zoster (HZ) requiring a preventive strategy with antiviral prophylaxis and anti-HZ vaccine is a clinically relevant issue in patients with immunological impairment. The absence of trials comparing vaccination to pharmacological prophylaxis or defining their sequential use makes the optimal preventive strategy uncertain. This article presents the results of group discussion among a panel of experts convened ad hoc to review the literature regarding antiviral prophylaxis and vaccine efficacy and safety in populations with malignant and non-malignant hematologic diseases, and in subjects submitted to hematopoietic stem cell transplantation. The expert panel used consensus methodology and proposed solutions for preventive strategies, producing advice for the management of the most relevant unmet clinical needs. This comprehensive overview aims to support the practice of pharmacological and vaccination-based HZ prevention and inform the design and conduct of new studies in the field.

Despite advancements in diagnostic modalities, delineating the etiology of fever of unknown origin (FUO) remains a significant challenge for clinicians. Notably, cases with hematological malignancies often have a poor prognosis due to delayed diagnosis. This study investigated the potential of readily obtainable laboratory markers to differentiate hematological causes from other etiologies during the early stages of FUO. A retrospective analysis was conducted on the medical records of 100 patients who fulfilled the modified FUO criteria between January 2010 and April 2023. Hematological etiologies were identified in 26 of the 100 patients. Peripheral blood neutrophil, lymphocyte, platelet counts, and the systemic immune inflammation (SII) index, were significantly lower in the hematological group compared to the non-hematological group. Conversely, serum ferritin levels were demonstrably higher in the hematological group. ROC analysis identified a neutrophil-to-ferritin ratio (NFR) cutoff value of < 8.53 as optimal for predicting hematological etiology. Subsequent multivariate analysis demonstrated that the NFR was the sole independent predictor of hematological etiology (p = 0.013).This study proposes a novel approach for early diagnosis of a potentially life-threatening subset of FUO patients. The NFR presents as an inexpensive and readily available marker for predicting hematological etiology in FUO cases., (© 2024. The Author(s).)

Background: Invasive fungal disease (IFD) is a sinister complication encountered in patients with haematological disorders. When occurring in the central nervous system (CNS), IFDs can have catastrophic outcomes., Objectives: To study the clinical presentation, predisposing etiological factors, and prognosis of a CNS-IFD in a patient with a haematological disorder., Patients and Methods: This is a retrospective study focusing on the clinical profile, diagnosis, treatment strategy and outcomes of 43 patients with an underlying haematological disorder, who were diagnosed with CNS-IFD between 2018 and 2022., Results: Of the 43 patients, 18 were chemotherapy recipients, while 23 were stem cell transplant (SCT) recipients and 2 presented with CNS-IFD at diagnosis. AML/MDS (37.2%) and ALL (18.6%) were the predominant underlying diagnoses. A sudden deterioration in sensorium (53.5%) was the earliest clinical sign, while T2 hyperintensities (26.8%), vascular involvement (26.8%) and ring-enhancing lesions (16.3%) were the commonest radiological findings, with all patients exhibiting diffusion restriction in diffusion-weighted images. Microbiological evidence of infection was obtained in all patients; however, culture positivity was established in only 25 patients. Rhizopus spp (23.2%) and Aspergillus spp (20.9%) were implicated in most cases. Overall survival of the cohort was 27.9% at a median follow-up of 6 months. In patients who succumbed, the median time to death was 4 days (0-46)., Conclusion: CNS-IFD is associated with very poor survival in patients undergoing chemotherapy or an SCT, urging the need for prompt diagnosis and initiation of suitable antifungal therapy., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Distinguishing key morphologic features and understanding the pathophysiology of common cutaneous manifestations of hematologic disorders is essential to ensure prompt and appropriate treatment. In fact, classic cutaneous signs may provide the first clue to the diagnosis of an underlying hematologic disease. Disorders of coagulation, vascular abnormalities, or cutaneous infiltration and deposition are responsible for the underlying pathophysiology of cutaneous manifestations in the majority of cases. Hematologists often feel ill-equipped in identifying morphologic changes in the skin. Thus, the purpose of this review is to provide a comprehensive overview of classic cutaneous manifestations and diagnostic considerations of the associated hematologic conditions. Though there is a specific focus on non-malignant disorders, those straddling the spectrum of malignancy are also discussed. In many disease states, the skin may serve as an important marker of an emerging hematologic disorder, so close collaboration and multidisciplinary input remain essential to provide optimal and timely care for these patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To our knowledge, this is the first report of a patient with both genetically confirmed Kabuki and Marfan syndrome demonstrating a perifoveal macular degeneration in one eye. Progressive loss of the outer retinal layers was captured and demonstrated with spectral-domain optical coherence tomography imaging. Fundus autofluorescence imaging revealed perifoveal hypoautofluorescence. The patient had initially presented with a spontaneously resolved serous-exudative retinal detachment associated with tortuous retinal vasculature and preretinal proliferative vitreoretinopathy in the other eye. Prior to presentation, the patient had an ocular history of bilateral ectopia lentis treated with crystalline lens removal and placement of iris-claw intraocular lenses. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:541-544.] .

Acute myeloid leukemia with antecedent hematologic disorder (AHD-AML) and therapy related AML (t-AML) constitute a heterogenous disease with inferior outcomes. It is often characterized by high-risk cytogenetic and molecular alterations associated with AHD or prior cancer therapy. Historically, the standard of care treatment has been intensive induction with "7 + 3", with an improved overall response rate and survival with CPX-351. Results from large registry-based studies suggested that allogeneic hematopoietic stem cell transplant is preferable to consolidation chemotherapy alone for achieving long-term survival in patients with AHD-AML. Prevalence of high-risk genetic features and advanced age and comorbidities in patients make AHD-AML and t-AML clinically challenging subgroups to treat with intensive approaches. Recent reports on less intensive treatment options, particularly the hypomethylating agent-venetoclax combination, have shown encouraging response rates in these patients. However, emerging resistance mechanisms compromise duration of response and overall survival. Several novel agents targeting apoptotic machinery, signaling pathways, and immune checkpoints are under clinical investigation, with an aim to truly improve overall outcomes in this subgroup. We reviewed updates in biology, classification, and clinical data comparing safety and efficacy of intensive and less intensive treatment options, and summarized ongoing studies with promising novel therapies in AHD-AML and t-AML., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: This study aims to assess the impact of the nationwide Omicron outbreak in December 2022 on Chinese patients with plasma cell disorders (PCD), focusing on the clinical characteristics of PCD patients with COVID-19 and the risk factors contributing to adverse clinical courses (severity and hospitalization) and outcomes., Methods: A multicenter retrospective study was performed from December 1, 2022, to January 19, 2023. The study population includes 404 PCD patients, divided into a COVID-19 group ( n  = 342) and an uninfected group ( n  = 62)., Results: The frequency of COVID-19 infection was 84.7% (342/404), and 16.4% (56/342) were severe COVID-19. Among the 277 patients with complete follow-up, 2 deaths (0.7%) were reported, while 231 (83.4%) recovered from COVID-19. Age > 65 ( P  = 0.02) and prior anti-CD38 monoclonal antibody (mAb) treatment within six months ( P  = 0.03) were independent risk factors for severe infection. Additionally, previous chimeric antigen receptor T-cell (CAR-T) therapy within six months was correlated with a higher risk of hospitalization ( P  = 0.04) and prolonged recovery time ( P  = 0.03). No significant protective effect of vaccination on infection or severe infection was observed ( P  > 0.05)., Conclusions: The latest Omicron outbreak results in higher rates of severe infection and mortality in PCD patients compared with the general population in China, highlighting the need to protect this vulnerable population during the pandemic. Recent use of anti-CD38 mAb and CAR-T therapy are associated with poorer clinical courses and outcomes of PCD patients with COVID-19.

Congenital mitral stenosis is a rare anomaly. We report successful surgical management of congenital mitral stenosis in a patient with Kabuki syndrome. A 15-month-old male with Kabuki syndrome was referred and echocardiography showed isolated congenital mitral stenosis. The valve was not repairable as it was showing severe stenotic features in multilevel fashion. Valve was replaced with mechanical valve. Postoperative course was uneventful without any rhythm problem and he has been doing well clinically during the 25 months follow-up with regular international normalized ratio checks.

Background: Pulmonary mucormycosis is most common in patients with hematologic malignancies and transplant recipients. This article describes a case of mucormycosis in the lungs secondary to a hematologic disorder with suspected lung cancer., Methods: Rhizopus (Rhizopus microspores) was detected by blood NGS and bronchoalveolar lavage fluid NGS, and pulmonary mucormycosis was confirmed., Results: Secondary to hematologic disease, pulmonary pneumonia, mycosis, and symptoms improved after comprehensive treatment., Conclusions: Clinical data and radiologic knowledge are combined to diagnose invasive pulmonary mycoses; early empirical medicine is very important.

Introduction: New diagnostic methods and antifungal strategies may improve prognosis of mucormycosis. We describe the diagnostic value of metagenomic next⁃generation sequencing (mNGS) and identify the prognostic factors of mucormycosis., Methods: We conducted a retrospective study of hematologic patients suffered from mucormycosis and treated with monotherapy [amphotericin B (AmB) or posaconazole] or combination therapy (AmB and posaconazole). The primary outcome was 84-day all-cause mortality after diagnosis., Results: Ninety-five patients were included, with "proven" (n = 27), "probable" (n = 16) mucormycosis confirmed by traditional diagnostic methods, and "possible" (n = 52) mucormycosis with positive mNGS results. The mortality rate at 84 days was 44.2%. Possible + mNGS patients and probable patients had similar diagnosis processes, overall survival rates (44.2% vs 50.0%, p = 0.685) and overall response rates to effective drugs (44.0% vs 37.5%, p = 0.647). Furthermore, the median diagnostic time was shorter in possible + mNGS patients than proven and probable patients (14 vs 26 days, p < 0.001). Combination therapy was associated with better survival compared to monotherapy at six weeks after treatment (78.8% vs 53.1%, p = 0.0075). Multivariate analysis showed that combination therapy was the protective factor (HR = 0.338, 95% CI: 0.162-0.703, p = 0.004), though diabetes (HR = 3.864, 95% CI: 1.897-7.874, p < 0.001) and hypoxemia (HR = 3.536, 95% CI: 1.874-6.673, p < 0.001) were risk factors for mortality., Conclusions: Mucormycosis is a life-threatening infection. Early management of diabetes and hypoxemia may improve the prognosis. Exploring effective diagnostic and treatment methods is important, and combination antifungal therapy seems to hold potential benefits., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Haematological patients exhibit immune system abnormalities that make them susceptible to viral infections. Understanding the relationship between the virome in the blood plasma of haematological patients and their clinical characteristic is crucial for disease management. We aimed to explore the presence of viral pathogens and identify close associations between viral infections and various clinical features., Results: A total of 21 DNA viruses and 6 RNA viruses from 12 virus families were identified from 1383 patients. Patients with haematological diseases exhibited significantly higher diversity, prevalence, and co-detection rates of viral pathogens. During fever episodes, pathogen detection was notably higher, with Epstein-Barr virus (EBV) and Mucorales infections being the most probable culprits for fever symptoms in non-haematological patients. The detection rate of torque teno virus (TTV) significantly increases in haematological patients after transplantation and during primary lung infections. Additionally, TTV-positive patients demonstrate significantly higher absolute neutrophil counts, while C-reactive protein and procalcitonin levels are notably lower. Furthermore, TTV, cytomegalovirus, and parvovirus B19 (B19V) were found to be more prevalent in non-neutropenic patients, while non-viral pathogenic infections, such as Gram-negative bacteria and Mucorales, were more common in neutropenic patients. Pegivirus C (HPgV-C) infection often occurred post-transplantation, regardless of neutropenia. Additionally, some viruses such as TTV, B19V, EBV, and HPgV-C showed preferences for age and seasonal infections., Conclusions: Analysis of the plasma virome revealed the susceptibility of haematological patients to plasma viral infections at specific disease stages, along with the occurrence of mixed infections with non-viral pathogens. Close associations were observed between the plasma virome and various clinical characteristics, as well as clinical detection parameters. Understanding plasma virome aids in auxiliary clinical diagnosis and treatment, enabling early prevention to reduce infection rates in patients and improve their quality of life. Video Abstract., (© 2024. The Author(s).)

Background: Primary antifungal prophylaxis with mold-active azoles is used to prevent invasive fungal infections in patients with high-risk hematological disorders; however, breakthrough infections occur, and the reasons for treatment failure are still not fully understood. To help inform clinical decisions, we sought to define microbiological, clinical, and pharmacological characteristics of proven and probable breakthrough invasive fungal infections (bIFIs) in patients with high-risk hematological disorders receiving voriconazole or posaconazole prophylaxis., Methods: We performed a systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search strategy was last conducted on 19 April 2023., Results: We assessed 5293 studies for eligibility, and 300 were selected for data extraction. These studies described 1076 cases of bIFIs occurring under voriconazole (42.5%) or posaconazole (57.5%). The most commonly found pathogens were Aspergillus (40%), Mucorales (20%), Candida (18%), and Fusarium (9%) species. Mucorales were more frequent among voriconazole-emerging cases, whereas Aspergillus and Fusarium were more prevalent among posaconazole-emerging cases. Definitive, putative, or probable antifungal resistance was found in 31% of cases. Therapeutic drug monitoring showed subtherapeutic azole concentration in 32 of 90 (36%) cases. Infection-related mortality was reported in 117 cases and reached 35%., Conclusions: In our systemic review, the most common bIFIs were aspergillosis, mucormycosis, candidiasis, and fusariosis. Antifungal resistance explains only a minority of cases. Subtherapeutic prophylaxis was frequent but rarely reported. Prospective studies are needed to better understand these infections and to establish optimal management., Competing Interests: Potential conflicts of interest . S. F. D. has received honoraria for consultancy and research funding from AVIR Pharma Inc and Merck & Co. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Hepatosplenic candidiasis (HSC) is a rare type of candidiasis that can occur in patients with hematologic malignancies, hematopoietic stem cell transplantation. At present, there is still a lack of studies on HSC in patients with hematologic disorders. Based on The Chinese Guidelines for the Diagnosis and Treatment of Invasive Fungal Disease in Patients with Hematological Disorders and Cancers (the 6th revision), We retrospectively analyzed the clinical characteristics and prognosis of patients with HSC treated in Peking University Institute of Hematology from 2008 to 2022. Finally, eighteen patients were included, with 1 (5.6%) proven, 2 (11.1%) probable, and 15 (83.3%) possible HSC. Among them, 3 (16.7%) patients occurred after haploid hematopoietic stem cell transplantation and 15 (83.3%) patients occurred after chemotherapy. 6 (33.3%) patients had positive blood cultures, including 4 cases of Candida tropicalis and 2 cases of Candida albicans. At 4 weeks of antifungal therapy, 10 (58.8%) patients achieved partial response (PR), At 8 weeks, 1 (6.3%) patients achieved complete response and 10 (62.5%) patients achieved PR. At 6 months after diagnosis, 3 (16.7%) patients died of hematopoietic recurrence, and none of them died of HSC. As a rare fungal infection disease, HSC has a low positive rate of microbiological and histological examinations, a persistent treat cycle, and has difficulty in remission, reminding us of the need for vigilance in patients with hematopoietic disorders and persistent fever.

Objective: To investigate the efficacy and safety of liposomal amphotericin B (L-AmB) for the salvage treatment of invasive fungal disease (IFD) in patients with hematological diseases. Methods: Data were retrospectively collected from 80 patients with hematological issues treated with L-AmB between June 2023 and December 2023 after failure of previous antifungal therapy. Baseline patient information, clinical efficacy, and factors affecting the efficacy of L-AmB were analyzed by logistic regression. Moreover, adverse effects associated with L-AmB were evaluated. Results: Among the 80 patients, 9 (11.2%) had proven IFD, 43 (53.8%) had probable IFD, and 28 (35.0%) had possible IFD. The efficacy rate of L-AmB salvage therapy for IFD was 77.5%, with a median daily dose of 3 (range: 1-5) mg·kg(-1)·d(-1) and a median dosing course of 14 (range: 8-25) days. Multivariate logistic regression analysis showed that the disease remission status ( OR =4.337, 95% CI 1.167-16.122, P =0.029) and duration of medication ( OR =1.127, 95% CI 1.029-1.234, P =0.010) were independent factors affecting the efficacy of L-AmB. The incidence of infusion reactions associated with L-AmB, including fever and chills, was 5.0%. The incidence of hypokalemia was 28.8% (predominantly grades 1-2), and the incidence of nephrotoxicity was 11.3% (predominantly grades 1-2) . Conclusion: L-AmB is safe and effective in the treatment of patients with IFD who are intolerant to or who have experienced no effect of previous antifungal therapy, with a low rate of adverse reactions.

Patients with hematological diseases are considered to be at high risk for intestinal colonization by carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the epidemiological data regarding risk factors and molecular characteristics of intestinal colonized CR-GNB isolates in this population are insufficient in China. A multicenter case‒control study involving 4,641 adult patients with hematological diseases from 92 hospitals across China was conducted. Following culture of collected rectal swabs, mass spectrometry and antimicrobial susceptibility tests were performed to identify GNB species and CR phenotype. Risk factors were assessed through retrospective clinical information. Whole-genome sequencing was used to analyze the molecular characteristics of CR-GNB isolates. This trial is registered with ClinicalTrials.gov as NCT05002582. Our results demonstrated that among 4,641 adult patients, 10.8% had intestinal colonization by CR-GNB. Of these, 8.1% were colonized by carbapenem-resistant Enterobacterales (CRE), 2.6% were colonized by carbapenem-resistant Pseudomonas aeruginosa (CRPA), and 0.3% were colonized by carbapenem-resistant Acinetobacter baumannii (CRAB). The risk factors for CR-GNB colonization include male gender, acute leukemia, hematopoietic stem cell transplantation, β-lactam antibiotic usage, and the presence of non-perianal infections within 1 week. Compared with CRPA-colonized patients, patients using carbapenems were more likely to be colonized with CRE. NDM was the predominant carbapenemase in colonized CRE. This study revealed a high CR-GNB intestinal colonization rate among adult patients with hematological diseases in China, with CRE being the predominant one. Notably, a significant proportion of CRE exhibited metallo-β-lactamase production, indicating a concerning trend. These findings emphasize the importance of active screening for CR-GNB colonization in patients with hematological diseases.IMPORTANCECarbapenem-resistant Gram-negative bacteria (CR-GNB) has emerged as a significant threat to public health. Patients with hematological diseases are at high risk of CR-GNB infections due to their immunosuppressed state. CR-GNB colonization is an independent risk factor for subsequent infection. Understanding the risk factors and molecular characteristics of CR-GNB associated with intestinal colonization in patients with hematological diseases is crucial for empirical treatment, particularly in patients with febrile neutropenia. However, the epidemiology data are still insufficient, and our study aims to determine the intestinal colonization rate of CR-GNB, identify colonization risk factors, and analyze the molecular characteristics of colonized CR-GNB isolates., Competing Interests: The authors declare no conflict of interest.

Corynebacterium is generally considered a contaminant in clinical practice. However, it may cause bacteremia in patients with hematologic disorders, and factors that contribute to its mortality are unclear. A case series and systematic literature review identified 96 cases of Corynebacterium bacteremia inhematologic disorderpatients. The median age was 50.5 years (range: 2-93 years), with 79 (82%) patients 18 years or older, and 64 (67%) patients male. Most cases involved hematologic malignancies, and neutropenia was observed in approximately 75% cases. The most common sites of infection/symptoms were skin and soft tissue, respiratory, and catheter-related bloodstream infection. The infection-related mortality was 23%, and univariate analysis showed that age, respiratory infection/symptoms, and source control were significantly associated with infection-related mortality. Multivariate analysis indicates that infection-related mortality was significantly reduced by source control (OR: 0.24, 95% CI: 0.06-0.97, p  = 0.046). Therefore, when Corynebacterium infections are suspected, early source control should be considered.

Hematologic emergencies are bleeding or clotting disorders that are hereditary or acquired and must be treated emergently to avoid significant morbidity or mortality. Patients experiencing a hematologic emergency may present with spontaneous bleeding, jaundice, petechiae, or purpura. Initial diagnostic testing should include a complete blood count. Patients who have bleeding associated with a hereditary disorder should receive clotting factor replacement before diagnostic testing. Acute chest syndrome is an uncommon but serious complication of sickle cell disease. Hemolysis caused by autoimmune disorders or iatrogenic errors from blood product transfusions has a distinct clinical presentation and requires immediate action. Severe thrombocytopenia presenting as immune or thrombotic thrombocytopenic purpura should be differentiated and treated appropriately. Disseminated intravascular coagulation and trauma coagulopathy are sometimes confused with each other, but both can cause serious injury and require unique treatments. Primary care physicians should promptly recognize patients who require emergent referral to a hematologic specialist.

Primary mitochondrial disorders (PMDs) are known for their pleiotropic manifestations in humans, affecting almost any organ or system at any time. Hematologic manifestations, such as cytopenias and sideroblastic anemia, occur in 10% to 30% of patients with confirmed PMDs. These can be the initial presenting features or complications that develop over time. Surveillance for these manifestations allows for prompt identification and treatment. This article provides an overview of the pathophysiology underpinning the hematologic effects of mitochondrial dysfunction, discussing the 3 key roles of the mitochondria in hematopoiesis: providing energy for cell differentiation and function, synthesizing heme, and generating iron-sulfur clusters. Subsequently, the diagnosis and management of mitochondrial disorders are discussed, focusing on hematologic manifestations and the specific conditions commonly associated with them. Through this, we aimed to provide a concise point of reference for those considering a mitochondrial cause for a patient's hematologic abnormality, or for those considering a hematologic manifestation in a patient with known or suspected mitochondrial disease., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Whether pre-exposure prophylaxis (PrEP) with tixagevimab/cilgavimab 150 mg/150 mg (T/C) in individuals with hematologic disease (HD) may lead to a reduced risk of SARS-CoV-2 breakthrough infection (BTI)/hospitalization, or death in the Omicron era remains to be established., Methods: An observational study included participants with HD who received PrEP. BTIs were defined as SARS-CoV-2 positivity by reverse transcription-polymerase chain reaction. The incidence of BTIs (95% CI) and of BTIs/hospitalization/death was calculated using the Kaplan-Meier method and as the number of BTIs per 100 person-years of follow-up according to the circulating variant of concern (VoC). A Poisson regression model was used to evaluate the association between the rate of incidence and circulating VoCs after controlling for demographics and clinical factors., Results: We included 550 HD patients: 71% initiated T/C PrEP when BA.5 was the most prevalent, followed by XBB/EG, BA.2, and BA.1 (19%, 7%, and 3%, respectively). Overall, the 1-year incidence estimate of BTIs/hospitalization/death was 24% (18.7-29.4%). A greater risk of incident infections was observed when BA.5 and XBB/EG sub-lineages circulated (aRR 5.05 [2.17, 11.77]; P < .001 and 3.82 [1.50, 9.7]; P = 0.005, compared to BA.1, respectively)., Conclusions: The 1-year incidence of SARS-CoV-2 BTIs/hospitalization/death was 24% which is in line with what was observed in other similar studies. The risk appeared to be higher when more recent Omicron sub-lineages were circulating suggesting a reduction of in vitro neutralization., Competing Interests: Declaration of competing interest All authors report no conflicts of interest relevant to this article., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: The incidence of infections in patients with malignant hematologic diseases is extremely high and significantly affects their prognosis. Identifying early and precise biomarkers for infection is crucial for guiding the treatment of infections in these patients. Previous studies have shown that procalcitonin (PCT) can serve as an early diagnostic marker for bloodstream infections in patients with malignant hematologic diseases. This study aims to compare serum PCT levels in these patients with different pathogens, disease types, infection sites, and severity levels., Methods: Clinical data and laboratory results of infected patients with malignant hematologic diseases treated at the Department of Hematology, the Third Xiangya Hospital of Central South University from January 2018 to August 2023 were collected. General patient information was retrospectively analyzed. Serum PCT levels were compared among patients with different pathogens, types of malignant hematologic diseases, infection sites, and infection severity; Receiver operator characteristic (ROC) curves were used to determine the cut-off values and diagnostic value of serum PCT levels in diagnosing bloodstream infections versus local infections and severe infections versus non-severe infections. Mortality rates after 4-7 days of anti-infective treatment were compared among groups with rising, falling, and unchanged PCT levels., Results: A total of 526 patients with malignant hematologic diseases were included. The main pathogens were Gram-negative bacteria (272 cases, 51.7%), followed by Gram-positive bacteria (120 cases, 22.8%), fungi (65 cases, 12.4%), viruses (23 cases, 4.4%), and mixed pathogens (46 cases, 8.7%). The main types of malignant hematologic diseases were acute myeloid leukemia (216 cases, 41.1%), acute lymphoblastic leukemia (107 cases, 20.3%), and lymphoma (93 cases, 17.7%). Granulocyte deficiency was present in 68.3% (359 cases) of the patients during infection, with severe infection in 24.1% (127 cases). Significant differences in serum PCT levels were found among patients with different types of pathogens ( P <0.001), with the highest levels in Gram-negative bacterial infections. Significant differences in serum PCT levels were also found among patients with different types of malignant hematologic diseases ( P <0.05), with the highest levels in lymphoma patients. Serum PCT levels were significantly higher in systemic infections and severe infections compared to local infections and non-severe infections (both P <0.001). ROC curve analysis showed that the cut-off values for diagnosing bloodstream infections and severe infections were 0.22 and 0.28 ng/mL, with areas under the curve of 0.670 and 0.673, respectively. After 4-7 days of anti-infective treatment, the mortality rates of the PCT declining, PCT unchanged, and PCT rising groups were 11.9%, 21.2%, and 35.7%, respectively, and pairwise comparisons were statistically significant (all P <0.05)., Conclusions: PCT can be used as an auxiliary indicator for early identification of different pathogens, infection sites, and severity levels in patients with malignant hematologic diseases combined with infections. Dynamic monitoring of PCT levels after empirical antibiotic treatment provides important guidance for assessing patient's prognosis.

Objective: This study analyzed the systemic and oral abnormalities in individuals with Kabuki syndrome (KS) that might be investigated to enhance the early diagnosis and treatment by a multidisciplinary team, minimizing the consequences to the individual's health., Study Design: Clinical examination was conducted on 15 individuals to investigate orodental alterations such as tooth abnormalities and cleft lip and/or palate, and the patient records were also reviewed to investigate systemic diseases such as cardiopathies, infectious and immunologic diseases, nephropathies, and delayed neuropsychomotor development., Results: All individuals with KS presented cleft lip and/or palate, 11 (73.34%) tooth abnormalities, 5 (33.34%) congenital cardiopathies, 12 (80%) infectious or immunologic diseases, 1 (6.67%) nephropathy, and 14 (93.34%) had an intellectual disability., Conclusion: Individuals with KS often have dental anomalies such as hypodontia, cleft or palate, and systemic disorders such as congenital heart disease and infectious diseases. Intellectual disability is present in most cases. These alterations should be investigated as early as possible to prevent the increase in morbidity in these individuals., Competing Interests: Declaration of interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: To develop and internally validate a prediction model for identifying patients with hematologic diseases of fall risk., Research Design and Methods: This is a prospective cohort study from a prospective collection of data for 6 months. We recruited 412 patients with hematologic diseases in medical institutions and home environment of China. The outcome of the prediction model was fall or not. These variables were filtered via univariable logistic analysis, LASSO, and multivariable logistic analysis. We adopt an internal validation method of K-fold cross validation. The area under the ROC curve and the H-L test were used to evaluate the discrimination and calibration of the model., Results: Five influencing factors were identified multivariable logistic regression analysis. The established model equation is as follows: the H-L goodness-of-fit test of the model p  > 0.05. The area under the ROC curve of train is 0.957 (95% CI: 0.936 ~ 0.978), and the area under the ROC curve of test is 0.962 (95% CI: 0.884 ~ 1), so the model calibration and discriminant validity are good., Conclusion: Our equation has good sensitivity and specificity in predicting the fall risk of patients with hematologic diseases, and has certain positive significance for clinical assessment of their fall risk., Trial Registration Number: ChiCTR2200063940.

Many hematologic diseases can be complicated by neurological symptoms during the disease course. Hematologic diseases can contribute to strokes and neuropathies; thus, neurologists should be aware of them. Recent reports have increased of neurological side effects associated with new anticancer therapies such as immune checkpoint inhibitors and chimeric antigen receptor-T cell therapy. The relationship between hematologic diseases and neurological complications is expected to become more prevalent.

Kabuki syndrome (KS) is characterized by growth impairment, psychomotor delay, congenital heart disease, and distinctive facial features. KMT2D and KDM6A have been identified as the causative genes of KS. Craniosynostosis (CS) has been reported in individuals with KS; however, its prevalence and clinical implications remain unclear. In this retrospective study, we investigated the occurrence of CS in individuals with genetically diagnosed KS and examined its clinical significance. Among 42 individuals with genetically diagnosed KS, 21 (50%) exhibited CS, with 10 individuals requiring cranioplasty. No significant differences were observed based on sex, causative gene, and molecular consequence among individuals with KS who exhibited CS. Both individuals who underwent evaluation with three-dimensional computed tomography (3DCT) and those who required surgery tended to exhibit cranial dysmorphology. Notably, in several individuals, CS was diagnosed before KS, suggesting that CS could be one of the clinical features by which clinicians can diagnose KS. This study highlights that CS is one of the noteworthy complications in KS, emphasizing the importance of monitoring cranial deformities in the health management of individuals with KS. The findings suggest that in individuals where CS is a concern, conducting 3DCT evaluations for CS and digital impressions are crucial., (© 2023 Wiley Periodicals LLC.)

Background: Understanding the specific neurobehavioural profile of rare genetic diseases enables clinicians to provide the best possible care for patients and families, including prognostic and treatment advisement. Previous studies suggested that a subset of individuals with Kabuki syndrome (KS), a genetic disorder causing intellectual disability and other neurodevelopmental phenotypes, have attentional deficits. However, these studies looked at relatively small numbers of molecularly confirmed cases and often used retrospective clinical data instead of standardised assessments., Methods: Fifty-five individuals or caregivers of individuals with molecularly confirmed KS completed assessments to investigate behaviour and adaptive function. Additionally, information was collected on 23 unaffected biological siblings as controls., Results: Attention Problems in children was the only behavioural category that, when averaged, was clinically significant, with the individual scores of nearly 50% of the children with KS falling in the problematic range. Children with KS scored significantly higher than their unaffected sibling on nearly all behavioural categories. A significant correlation was found between Attention Problems scores and adaptive function scores (P = 0.032), which was not explained by lower general cognitive ability., Conclusions: We found that the rates of children with attentional deficits are much more elevated than would be expected in the general population, and that attention challenges are negatively correlated with adaptive function. When averaged across KS participants, none of the behavioural categories were in the clinically significant range except Attention Problems for children, which underscores the importance of clinicians screening for attention deficit hyperactivity disorder (ADHD) in children with KS., (© 2023 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Background: Managing SARS-CoV-2 infection in frail and immunosuppressed patients still represents an open challenge, but, starting from the phase 3 PROVENT study, prophylaxis with tixagevimab-cilgavimab has improved the approach in this category of patients, guaranteeing a better outcome and inferior mortality. Real-life data in a heterogeneous cohort are few., Methods: The aim of this study is to evaluate the benefit of prophylaxis with tixagevimab-cilgavimab in a cohort of 202 patients affected by different hematological diseases (lymphoproliferative, myeloproliferative, autoimmune, patients recently receiving a bone marrow transplant), active (with ongoing treatment), or in watch-and-wait strategy, followed in our center, during a median follow-up of 249 (45-325) days., Results: An incidence of 44 breakthrough infections (21.8%) is reported, with no treatment-related adverse effects. Age ≥70 years, ongoing treatment (above all with monoclonal antibodies), baseline lymphoproliferative disorders, and prior virus exposure are identified as risk factors related to subsequent infection (p < 0.05). Moreover, the incidence is higher in low/nonresponse to prior vaccination (p = .002). Patients treated with tixagevimab-cilgavimab had a mild course of the infection and a reduction of the duration compared with preprophylaxis infection (11 vs. 15 days, p < .001). The concurrent treatment with anti-CD20 monoclonal antibodies and B-non-Hodgkin lymphoma still confers a higher duration of infection despite prophylaxis. No deaths attributable to the infection occurred., Conclusion: Prophylaxis treatment seems to be a valid and safe strategy, although not preventing breakthrough infection, but the severe complications associated with the infection and the possible delays in administering lifesaving therapies from long positivity., (© 2023 American Cancer Society.)

Objective: To investigate the seroprevalence of Toxoplasma gondii infections among patients with hematological diseases, so as to provide insights into improving the prognosis and quality of life among patients with hematological diseases., Methods: A total of 240 patients with hematological diseases (including 170 patients with hematological tumors and 70 patients with non-tumor hematological diseases) admitted to The Affiliated Hospital of Putian University during the period from January 1, 2021 through October 10, 2023 and 500 healthy volunteers in the hospital during the same period were enrolled. Subjects' demographics and serum samples were collected, and serum specific IgG and IgM antibodies against T. gondii were detected using the chemiluminescence assay, with any of a positive IgG or IgM antibody defined as a positive T. gondii infection. The seroprevalence of specific IgG and IgM antibodies against T. gondii was compared between patients with hematological diseases and healthy volunteers., Results: The mean age ( F = 2.034, P > 0.05) and gender distribution (χ 2 = 0.462, P > 0.05) were comparable among patients with hematological tumors, patients with non-tumor hematological diseases and healthy volunteers, and there was no significant difference in the proportion of history of cat or dog contacts between patients with hematological diseases and healthy volunteers (χ 2 = 0, P > 0.05). The seroprevalence of anti- T. gondii antibody was significantly higher among patients with hematological diseases than among healthy volunteers (15.8% vs. 0.6%; χ 2 = 71.902, P < 0.01), and there was a significant difference in the seroprevalence of anti- T. gondii antibody among patients with hematological tumors (18.2%), patients with non-tumor hematological diseases (10.0%) and healthy volunteers (χ 2 = 78.327, P < 0.01). The seroprevalence of anti- T. gondii antibody was significantly higher among patients with hematological tumors and non-tumor hematological diseases than among healthy volunteers (both P values < 0.05), while no significant difference was seen in the seroprevalence of anti- T. gondii antibody between patients with hematological tumors and non-tumor hematological diseases ( P > 0.05). In addition, the proportion of history of cat or dog contacts was significantly higher among patients with hematological diseases that were positive for serum anti- T. gondii anti-body than among those negative for serum anti- T. gondii antibody (21.1% vs. 5.4%; χ 2 = 8.653, P < 0.05)., Conclusions: There is a high seroprevalene rate of T. gondii infections among hematological diseases, which is significantly greater than that among healthy volunteers.

The mortality risk factors in B. cereus bacteremia in hematologic disorders are still unknown. In this study, patients with B. cereus bacteremia in hematologic disorders were selected in St. lukes international hospital and from electronic databases. A total of 176 patients [median age, 41 years (3-88 years); 99 (56%) males] were included. Of these patients, 141 (80%) had acute leukemia, and 93 (53%) died. Univariate analysis showed that neutropenia, CNS, gastrointestinal, and respiratory infections/symptoms were significantly associated with infection-related death. Meanwhile, glycopeptide use and management with source control were protective factors. Multivariate logistic regression analysis showed that infection-related death was significantly associated with CNS [odds ratio (OR): 3.49, 95% confidence interval (CI) 1.25-9.80], gastrointestinal (OR: 5.22, 95% CI 1.82-8.99), and respiratory infections/symptoms (OR: 8.98, 95% CI 1.62-49.9), as well as glycopeptide use (OR: 0.10, 95% CI 0.03-0.31) and source control (OR: 0.11, 95% CI 0.03-0.37). In conclusion, early glycopeptide administration and source control should be performed upon detection of infections suspicious for B. cereus., (© 2023. Japanese Society of Hematology.)

Background: Splenic surgery in hematological disorders requires a well-weighted decision on the indications because the medical treatment has rapidly changed in recent years due to new pharmaceutical approaches., Objective: Summary of the indications, surgical procedures and perioperative management regarding operative interventions on the spleen in hematological disorders., Material and Methods: Selective literature search and summary of reviews and guideline recommendations., Results: In hematological disorders surgical procedures of the spleen (splenectomy and partial splenectomy) are an important part of the repertoire in the treatment. In recent years the indications for surgery have become narrower because of new forms of medicinal treatment. Especially in hereditary spherocytosis, immune thrombocytopenia and symptomatic splenomegaly and hypersplenism it is still of importance. The minimally invasive splenectomy is regarded as the gold standard. The spleen has an important immune and sequestration function, therefore preoperative and postoperative infectious and thromboembolic events have to be anticipated and prevented. A close interdisciplinary cooperation with hematologists is essential for an optimal outcome of patients., Conclusion: The minimally invasive splenectomy and partial splenectomy are part of the surgical repertoire in the diagnostics and treatment of hematological disorders. Because of novel medicinal approaches the therapeutic protocols are continuously changing. A close cooperation with hematologists is important for the optimal evaluation of the indications and the perioperative management., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Recent developments of assisted reproduction techniques turned possible to avoid the infertility consequences of oncologic treatments, but fertility preservation (FP) has been somewhat neglected in women with hematologic diseases undergoing gonadotoxic treatments. For these specific cases, the current options for FP include the cryopreservation of embryos, mature oocytes and ovarian tissue, and oocyte in-vitro maturation. We intend to make patients and clinicians aware of this important and relevant issue, and provide hematologists, assisted reproduction physicians and patients, with updated tools to guide decisions for FP. The physicians of the units responsible for female FP should always be available to decide on the best-individualized FP option in strict collaboration with hematologists. With a wide range of options for FP tailored to each case, a greater level of training and information is needed among clinicians, so that patients proposed to gonadotoxic treatments can be previously advised for FP techniques in hematological conditions. ABBREVIATED ABSTRACT: Recent developments of assisted reproduction techniques turned possible to preserve the fertility of women with hematologic diseases undergoing gonadotoxic treatments. Current options for fertility preservation in women with hematologic diseases are presented. It is imperative to offer fertility preservation to all women before starting any gonadotoxic treatment and in some cases after treatment. Fertility preservation methods enable to later achieve the desired pregnancy., Competing Interests: Declaration of Competing Interest Authors declare no Conflict of Interests for this article., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: At our institution, patients with hematological disease who require Pneumocystis jirovecii pneumonia (PJP) prophylaxis were administered atovaquone at a low dose (750 mg/day). However, there have been few reports on the efficacy of low-dose atovaquone administration, and the purpose of this study is, therefore, to investigate its effectiveness., Materials and Methods: We investigated the expression of PJP in patients with hematological disease who received atovaquone administration. Atovaquone was administered at a low dose of 750 mg once daily, and the follow-up time was the period of PJP prophylaxis that included atovaquone administration., Results: 85 patients were included in the study. The median age of the study population was 72 years (range: 33 - 97). The duration of atovaquone treatment and follow-up time were 150 days (22 - 1,018) and 258 days (22 - 1,457), respectively. In hematologic diseases, multiple myeloma was high in 31 patients and malignant lymphoma in 28 patients. No patients exhibited PJP during the observation period., Conclusion: In hematological disease patients with relatively low risk of PJP, low-dose atovaquone may prevent the onset of PJP.

Rhino-orbital-cerebral mucormycosis (ROCM), which is an acute fatal infectious disease with a high mortality rate, is increasingly being diagnosed in patients with hematological diseases worldwide. We aimed to investigate the clinical characteristics, treatment, and prognosis of hematological diseases complicated by ROCM. Our sample comprised a total of 60 ROCM patients with hematological diseases. The most common primary disease was acute lymphoblastic leukemia (ALL) (n=27, 45.0%), while 36 patients (60.0%) were diagnosed with a clear type of pathogen, all belonging to the Mucorales, most commonly Rhizopus (41.7%). Of the 32 patients (53.3%) who died, 19 (59.3%) died of mucormycosis, and 84.2% (n=16) of those died within 1 month. Forty-eight cases (80.0%) received antifungal treatment combined with surgical therapy, 12 of whom (25.0%) died of mucormycosis, amounting to a mortality rate that was significantly lower than in patients who received antifungal therapy alone (n=7, 58.3%) (P=0.012). The median neutrophil value of patients who underwent surgery was 0.58 (0.11-2.80) 10 3 /μL, the median platelet value was 58.00 (17.00-93.00) 10 3 /μL, and no surgery-related deaths were reported. Multivariate analysis showed that patient's advanced age (P=0.012, OR=1.035 (1.008-1.064)) and lack of surgical treatment (P=0.030, OR=4.971 (1.173-21.074)) were independent prognostic factors.In this study, hematological diseases associated with ROCM have a high mortality rate. Lack of surgical treatment is an independent prognostic factor for death from mucormycosis. Surgery may therefore be considered in patients with hematological disease even if their neutrophil and platelet values are lower than normal., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To analyze the pathogenic bacterial spectrum, drug resistance, and risk factors associated with multidrug-resistant bacterial infection and mortality in patients with hematologic diseases complicated by bloodstream infections, so as to provide reference for rational drug use and improving prognosis., Methods: Positive blood culture specimens of patients with hematologic diseases in two Class A tertiary hospitals of Shanxi province from January 2019 to December 2021 were retrospectively analyzed. Pathogen distribution, drug resistance and outcomes of patients with bloodstream infection were investigated, then the multivariate logistic analysis was performed to analyze the risk factors of multidrug-resistant bacterial infection and factors affecting prognosis., Results: 203 strains of pathogens were identified, mainly Gram-negative bacteria (GNB) (69.46%, 141/203), of which Escherichia coli (E.coli) had the highest incidence (41.13%, 58/141), followed by Klebsiella pneumoniae (20.57%, 29/141) and Pseudomonas aeruginosa (12.77%, 18/141). Extended-spectrum beta-lactamase (ESBL)-producing E.coli and Klebsiella pneumoniae were 46.55% (27/58) and 37.93% (11/29), respectively. Carbapenem-resistant Gram-negative bacteria accounted for 10.64% (15/141). And Gram-positive bacteria accounted for 27.59% (56/203), Staphylococcus epidermidis, Streptococcus pneumoniae, and Staphylococcus aureus were the most frequently isolated pathogen among Gram-positive bacteria (14.29%, 12.50% and 10.71%, respectively), of which methicillin-resistant Staphylococcus aureus accounted for 33.33% (2/6), coagulase-negative staphylococci accounted for 87.50% (7/8), without vancomycin- or linezolid-resistant strain. Additionally, fungi accounted for 2.95% (6/203), all of which were Candida. Multidrug-resistant Gram-negative bacteria (MDR-GNB) accounted for 53.90% (76/141). Duration of neutropenia >14 days was a risk factor for developing MDR-GNB infection. The 30-day all-cause mortality was 10.84%. Multivariate logistic regression analysis showed that the significant independent risk factors for mortality were age≥60 years ( P <0.01, OR =5.85, 95% CI : 1.80-19.07) and use of vasopressor drugs ( P <0.01, OR =5.89, 95% CI : 1.83-18.94)., Conclusion: The pathogenic bacteria of bloodstream infection in patients with hematological diseases are widely distributed, and the detection rate of multidrug-resistant bacteria is high. The clinicians should choose suitable antibiotics according to the results of bacterial culture and antibiotic susceptibility test.

The purpose of this study is to evaluate the efficacy of prophylactic use amphotericin B in patients with hematologic disorders complicated by neutropenia. We searched the PubMed, EMBASE, The Cochrane Library, CBM, CNKI, VIP and WanFang Data database and the China Clinical Trials Registry ( www.chictr.org.cn ) to collect randomized controlled trials (RCTs) of amphotericin B for patients with hematologic disorders complicated by neutropenia from inception to May 2023. The Cochrane risk-of-bias tool for RCTs was used to assess the bias risk of the included studies. The meta-analysis was performed using RevMan 5.3 software. A total of 6 studies with a total of 1019 patients were included. The results of the meta-analysis showed that the treatment group was superior to the control group in terms of the fungal infection rate, and the differences were statistically significant [RR = 0.47, 95% CI (0.32, 0.69), P < 0.0001]. There was no significant difference between the two groups in terms of the mortality [RR = 0.87, 95% CI (0.61, 1.23), P = 0.43] and the incidence of colonization [OR = 0.51, 95% CI (0.25, 1.03), P = 0.06]. The evidence shows that amphotericin B prophylactic use for patients with hematologic disorders complicated by neutropenia can decrease the fungal infection rate. However, there was no significant difference in reducing mortality or the incidence of colonization. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion., (© 2023. Springer Nature Limited.)

The effectiveness and safety of trimethoprim/sulfamethoxazole (TMP/SMX) desensitization therapy is insufficiently evaluated in hematological diseases. From 2002 to 2019, we retrospectively analyzed 112 patients with hematological diseases who underwent desensitization therapy after TMP/SMX prophylaxis withdrawal due to adverse events. They orally started TMP/SMX at 0.4 mg/2 mg, which was then increased daily to 80 mg/400 mg for 5 or 9 days. Eighty-eight patients (79%) had complete desensitization, and the major reason for failure was rash seen in 21 cases (19%). The cause of desensitization and reasons for failure matched in 22 cases (92%). Pneumocystis pneumonia was not observed throughout the study. In the failure group, the number of eosinophils and alanine aminotransferase (ALT) levels were significantly increased after desensitization. In particular in the failure group, the slight increase in eosinophils was seen through the beginning to halfway during desensitization (36/μL (0-900/μL) and 48/μL (0-2560/μL), respectively, p = 0.025). These data show that TMP/SMX desensitization therapy is effective and safe in hematological diseases. The recurrence of adverse events could help predict desensitization success., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: JKb antibody rarely causes severe hemolytic disease in the newborn except in 1 case, required blood exchange transfusion but later died of intractable seizure and renal failure. Here we describe 2 cases of JKb-induced severe neonatal jaundice requiring blood exchange transfusion with good neurological outcome., Case Presentation: Two female Chinese, ethnic Han, term infants with severe jaundice were transferred to us at the age of 5- and 4-day with a total bilirubin of 30.9 and 25.9 mg/dL while reticulocyte counts were 3.2% and 2.2%, respectively. Both infants were not the firstborn to their corresponding mothers. Direct and indirect Coombs' tests were positive, and JKb antibody titers were 1:64 (+) for both mothers. Phototherapy was immediately administered, and a blood exchange transfusion was performed within 5 hours of admission. Magnet resonance image showed no evidence of bilirubin-induced brain damage, and no abnormal neurological finding was detected at 6 months of life., Conclusion: JKb antibody-induced hemolytic disease of the newborn usually leads to a benign course, but severe jaundice requiring blood exchange transfusion may occur. Our cases suggest good outcomes can be achieved in this minor blood group-induced hemolytic disease of the newborn if identified and managed early enough., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Neutropenic children with hematological diseases were associated with higher morbidity of carbapenem-resistant enterobacteriaceae (CRE) blood-stream infection (BSI) or colonization. But it was still murky regarding clinical characteristics, antimicrobial susceptibility, and outcomes of CRE-BSI in these patients. We aimed to identify the potential risk factors for subsequent bacteremia and clinical outcome caused by CRE-BSI., Methods: Between 2008 and 2020, 2,465 consecutive neutropenic children were enrolled. The incidence and characteristics of CRE-BSI were explored in CRE-colonizers versus non-colonizers. Survival analysis was performed and risk factors for CRE-BSI and 30-day mortality were evaluated., Results: CRE-carriers were identified in 59/2465 (2.39%) neutropenic children and19/59 (32.2%) developed CRE-BSI, while 12/2406 (0.5%) of non-carriers developed CRE-BSI (P < 0.001). The 30-day survival probability was significantly lower in patients with CRE-BSI than in non-BSI (73.9% vs. 94.9%, P = 0.050). Moreover, the 30-day survival probability of patients with CRE-BSI was also poorer in CRE-carriers versus non-carriers (49.7% vs. 91.7%, P = 0.048). Tigecycline and amikacin exhibited satisfactory antimicrobial activity against all isolated strains. Fluoroquinolone sensitivity was lower in E. coli (26.3%) strains versus satisfactory susceptibility of E. cloacae and other CRE-strains (91.2%). CRE-BSI accompanying intestinal mucosal damage were independent risk factors for 30-day survival probability (both P < 0.05), while combined antibiotic therapy and longer duration of neutropenia were more prone to developed CRE-BSI (P < 0.05)., Conclusion: CRE-colonizers were prone to subsequent BSI and CRE-BSI was regarded as an independent predictor predisposing to high mortality in neutropenic children. Moreover, individualized antimicrobial therapy should be adopted due to different features of patients with separate CRE strains., (© 2023. The Author(s).)

Background: Infections caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) are related to higher mortality. The objective of this study was to explore clinical outcomes of CRPA bacteremia, identify risk factors and also, compare the efficacy of traditional and novel antibiotic regimens., Methods: This retrospective study was conducted at a blood diseases hospital in China. The study included hematological patients who were diagnosed with CRPA bacteremia between January 2014 and August 2022. The primary endpoint was all-cause mortality at day 30. Secondary endpoints included 7-day and 30-day clinical cure. Multivariable Cox regression analysis was employed to identify mortality-related risk factors., Results: 100 patients infected with CRPA bacteremia were included and 29 patients accepted allogenic-hematopoietic stem cell transplantation. 24 received ceftazidime-avibactam (CAZ-AVI)-based therapy and 76 received other traditional antibiotics. 30-day mortality was 21.0%. Multivariable cox regression analysis showed neutropenia >7 days after bloodstream infections (BSI) (P=0.030, HR: 4.068, 95%CI: 1.146~14.434), higher Pitt bacteremia score (P<0.001, HR:1.824, 95%CI: 1.322~2.517), higher Charlson comorbidity index (P=0.01, HR: 1.613, 95%CI: 1.124~2.315) and bacteremia due to multidrug-resistant Pseudomonas aeruginosa (MDR-PA) (P=0.024, HR:3.086, 95%CI: 1.163~8.197) were identified as independent risk factors of 30-day mortality. After controlling for confounders, an additional multivariable cox regression analysis revealed definitive regimens containing CAZ-AVI were associated with lower mortality in CRPA bacteremia (P=0.016, HR: 0.150, 95%CI: 0.032~0.702), as well as in MDR-PA bacteremia (P=0.019, HR: 0.119, 95%CI: 0.020~0.709)., Conclusions: For patients with hematological diseases and CRPA bacteremia, 30-day mortality rate was 21.0% (21/100). Neutropenia >7 days after BSI, higher Pitt bacteremia score, higher Charlson comorbidity index and bacteremia due to MDR-PA increased 30-day mortality. CAZ-AVI-based regimens were effective alternatives for bacteremia due to CRPA or MDR-PA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhen, Zhao, Chen, Zhang, Wang, Jiang, Zhang, Mi, Zhu, Han, Xiao, Wang and Feng.)

Introduction: Hematological patients are at risk of infections. It is unknown whether the pathogenic microbial spectrum differs between HSCT and non-HSCT patients, and whether metagenomic next-generation sequencing (mNGS) of peripheral blood can be used as a substitute test specimen such as alveolar lavage., Methods: A retrospective study was conducted to evaluate the clinical application value of mNGS in hematological patients with and without HSCT., Results: Viruses were prevalent pathogens in both non-HSCT (44%) and HSCT (45%) patients, chiefly human cytomegalovirus and Epstein-Barr virus. In non-HSCT patients, Gram-negative bacilli accounted for 33% (predominantly Klebsiella pneumonia), and Gram-positive cocci accounted for 7% (predominantly Enterococcus faecium) of pathogens. However, in HSCT patients, Gram-negative bacilli accounted for 13% (predominantly Stenotrophomonas maltophilia), and Gram-positive cocci accounted for 24% (predominantly Streptococcus pneumonia) of pathogens. Mucor was the most common fungu s in two groups. The positive rate of pathogens by mNGS was 85.82%, higher than conventional detection (20.47%, P < 0.05). Mixed infection accounted for 67.00%, among which the mixed infection of bacteria and virus (25.99%) was the most common. 78 cases had pulmonary infection, the positive rate of traditional laboratory tests was 42.31% (33/78), and of mNGS in peripheral blood was 73.08% (57/78), showing a statistical difference (P = 0.000). The non-HSCT patients had a higher frequency of Klebsiella pneumonia (OR=0.777, 95% CI, 0.697-0.866, P = 0.01) and Torque teno virus (OR=0.883, 95% CI, 0.820-0.950, P = 0.031) infections than HSCT patients, while the rates of Streptococcus pneumonia (OR=12.828, 95% CI, 1.378-119.367, P = 0.016), Candida pseudosmooth (OR=1.100, 95% CI, 0.987-1.225, P = 0.016), human betaherpesvirus 6B (OR=6.345, 95% CI, 1.105-36.437, P = 0.039) and human polyomavirus 1 (OR=1.100, 95% CI, 0.987-1.225, P = 0.016) infections were lower. Leishmania could be detected by mNGS., Conclusion: mNGS of peripheral blood can be used as a substitute test method for hematological patients with pulmonary infection, the detection rate of mixed infections by mNGS was high, and mNGS has high clinical recognition rate and sensitivity in pathogen detection, and provides a basis for guiding the anti-infective treatment in hematological diseases with symptoms such as fever., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Wang, Yu and Jiang.)

Breakthrough candidemia (BrC) is a significant problem in immunocompromised patients, particularly those with hematological disorders. To assess the characteristics of BrC in patients with hematologic disease treated with novel antifungal agents, we collected clinical and microbiological information on said patients from 2009 to 2020 in our institution. Forty cases were identified, of which 29 (72.5%) received hematopoietic stem cell transplant (HSCT)-related therapy. At BrC onset, the most administered class of antifungal agents were echinocandins, administered to 70% of patients. Candida guilliermondii complex was the most frequently isolated species (32.5%), followed by C. parapsilosis (30%). These two isolates were echinocandin-susceptible in vitro but had naturally occurring FKS gene polymorphisms that reduced echinocandin susceptibility. Frequent isolation of these echinocandin-reduced-susceptible strains in BrC may be associated with the widespread use of echinocandins. In this study, the 30-day crude mortality rate in the group receiving HSCT-related therapy was significantly higher than in the group not receiving it (55.2% versus 18.2%, P = .0297). Most patients affected by C. guilliermondii complex BrC (92.3%) received HSCT-related therapy and had a 30-day mortality rate of 53.8%; despite treatment administration, 3 of 13 patients had persistent candidemia. Based on our results, C. guilliermondii complex BrC is a potentially fatal condition in patients receiving HSCT-related therapy with echinocandin administration., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Influenza virus infection is a common cause of self-limiting respiratory tract infection (RTI), however immunocompromised patients are at an increased risk for a severe course of disease or fatal outcome. We therefore aimed to gain a better understanding of the molecular epidemiology of influenza viruses from patients with haematological disorders and their impact on the clinical course of disease. Molecular analysis using polymerase chain reaction (PCR) of nasopharyngeal swabs was performed for influenza virus in haematological patients at the Heidelberg University Hospital. Clinical data was evaluated to identify associated risk factors. For phylogenetic analysis, the hemagglutinin (HA) gene was sequenced. Out of 159 influenza positive patients, 117 patients developed upper RTI (influenza A: n = 73; influenza B: n = 44). Lower RTI was observed in n = 42 patients (26%), n = 22/42 patients developed severe disease and n = 16/159 (10.1%) patients died. Risk factors for lower RTI were nosocomial infection (p = 0.02), viral shedding for ≥14 days (p = 0.018), IgG levels <6 g/dL (p = 0.046), bacterial/fungal co-infections (p < 0.001). Risk factors for fatal outcome were age ≥65 years (p = 0.032), bacterial/fungal (p≤0.001) co-infections and high viral load (p = 0.026). Sequencing of the HA gene (n = 115) revealed subtype A(H3N2) (n = 46), A(H1N1)pdm09 (n = 24), B/Victoria (n = 34), B/Yamagata (n = 11). There was no correlation between influenza (sub)type and lower RTI. Influenza infection in haematological patients is associated with significant morbidity and mortality, the risk for aggravating co-infections, prolonged viral shedding and nosocomial transmission emphasizing the need for infection control., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Kabuki syndrome is a recognizable Mendelian disorder characterized by the clinical constellation of childhood hypotonia, developmental delay or intellectual impairment, and characteristic dysmorphism resulting from monoallelic pathogenic variants in KMT2D or KDM6A. In the medical literature, most reported patients are children, and data is lacking on the natural history of the condition across the lifespan, with little known about adult-specific presentations and symptoms. Here, we report the results of a retrospective chart review of eight adult patients with Kabuki syndrome, seven of whom are molecularly confirmed. We use their trajectories to highlight the diagnostic challenges unique to an adult population, expand on neurodevelopmental/psychiatric phenotypes across the lifespan, and describe adult-onset medical complications, including a potential cancer risk and unusual and striking premature/accelerated aging phenotype., (© 2023 Wiley Periodicals LLC.)

Iron deposition is closely related to developing haemophilic arthropathy (HA). Studying the relationship between ferroptosis signal expression and iron overload in HA synovium facilitates understanding the pathogenesis of joint synovial hyperplasia in bloodborne arthritis and the development of new protective methods. The knee synovium was collected from HA and osteoarthritis (OA) patients, and pathological changes were analysed by HE and Prussian blue staining. Ferroptosis phenotypes were examined by immunohistochemistry and western blotting. Moreover, ferric ammonium citrate (FAC)-induced was used to construct an in vitro iron overload model to investigate the relationship between iron overload and ferroptosis in synovial fibroblasts (FLS). Furthermore, the factors influencing ferroptosis in FLS were explored. Iron deposition, cell proliferation, and vascular proliferation in the synovium of HA were more obvious. Ferroptosis in HA synovium appears to inhibit. FLS ferroptosis increased with iron accumulation, malondialdehyde (MDA) in cells, and glutathione (GSH) depletion. TNF-α plays a protective role in this process. Blocking the action of TNF-α and inducing ferroptosis significantly reduced synovial proliferation. TNF-α inhibitors combined with a ferroptosis inducer may be a new therapeutic method for HA synovitis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Febrile neutropenia (FN) represents one of the main complications of pediatric patients with oncological and hematological diseases. In these patients, it is crucial to identify bacterial infections. The aim of this study is to evaluate presepsin as an early biomarker of bacterial infections during FN. We compared patients with oncological and hematological diseases and a 2:1 age-matched healthy control group. In the FN group, we evaluated 4 biomarkers, namely, C reactive protein (CRP), procalcitonin (PCT), interleukin 6 (IL6) and presepsin at the onset of fever (T0) and 48 h after T0 (T1). In the control group, we only evaluated presepsin. We enrolled a total of 41 children with oncological and hematological diseases disease experiencing 50 FN episodes and 100 healthy patients in the control group. In patients with FN, we found that presepsin was significantly higher than in the control group (p < 0.001). However, in the FN group, we did not find a statistically significant difference between patients with and without bacteremia (p = 0.989 at T0, p = 0.619 at T1). Presepsin values at T1 were higher in patients experiencing an unfavorable outcome (p = 0.025). This study shows that presepsin increases in neutropenic patients, but it only revealed useful in predicting an unfavorable outcome 48 h from the onset of fever., (© 2023. The Author(s).)