ABSTRACT
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.
Subject(s)
Hematologic Neoplasms , Procalcitonin , Humans , Procalcitonin/blood , Hematologic Neoplasms/complications , Retrospective Studies , Male , Female , Biomarkers/blood , ROC Curve , Middle Aged , Adult , Hematologic Diseases/complications , Hematologic Diseases/bloodABSTRACT
INTRODUCTION: New diagnostic methods and antifungal strategies may improve prognosis of mucormycosis. We describe the diagnostic value of metagenomic nextâgeneration 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.
Subject(s)
Amphotericin B , Antifungal Agents , Hematologic Diseases , High-Throughput Nucleotide Sequencing , Mucormycosis , Humans , Mucormycosis/diagnosis , Mucormycosis/drug therapy , Mucormycosis/mortality , Mucormycosis/microbiology , Male , Female , Retrospective Studies , Middle Aged , Prognosis , Antifungal Agents/therapeutic use , Adult , Aged , Hematologic Diseases/complications , Amphotericin B/therapeutic use , Metagenomics/methods , Triazoles/therapeutic use , Young Adult , Drug Therapy, Combination , Survival Analysis , Treatment OutcomeABSTRACT
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.
Subject(s)
Lung Diseases, Fungal , Mucormycosis , Rhizopus , Humans , Mucormycosis/diagnosis , Mucormycosis/complications , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/microbiology , Lung Diseases, Fungal/complications , Rhizopus/isolation & purification , Male , Bronchoalveolar Lavage Fluid/microbiology , Antifungal Agents/therapeutic use , Middle Aged , Hematologic Diseases/complications , Hematologic Diseases/diagnosis , Hematologic Diseases/microbiology , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/microbiology , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/complicationsABSTRACT
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.
Subject(s)
Emergencies , Humans , Hematologic Diseases/therapy , Hematologic Diseases/diagnosis , Hematologic Diseases/complications , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/therapy , Blood Coagulation Disorders/etiology , Diagnosis, DifferentialABSTRACT
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.
Subject(s)
DNA Viruses , Hematologic Diseases , RNA Viruses , Virus Diseases , Humans , Male , Female , DNA Viruses/isolation & purification , DNA Viruses/genetics , Middle Aged , Virus Diseases/blood , Virus Diseases/virology , Adult , Hematologic Diseases/complications , Hematologic Diseases/blood , RNA Viruses/isolation & purification , Virome , Aged , Torque teno virus/isolation & purification , Torque teno virus/genetics , Cohort Studies , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/isolation & purification , Young AdultABSTRACT
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 caseâcontrol 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, ß-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-ß-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.
Subject(s)
Anti-Bacterial Agents , Carbapenems , Gram-Negative Bacteria , Gram-Negative Bacterial Infections , Hematologic Diseases , Humans , Case-Control Studies , Male , Female , Risk Factors , Middle Aged , Carbapenems/pharmacology , Adult , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/epidemiology , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/genetics , Gram-Negative Bacteria/isolation & purification , China/epidemiology , Aged , Anti-Bacterial Agents/pharmacology , Hematologic Diseases/complications , Hematologic Diseases/microbiology , Hematologic Diseases/epidemiology , Molecular Epidemiology , Retrospective Studies , Microbial Sensitivity Tests , Young Adult , Intestines/microbiology , Adolescent , Aged, 80 and overABSTRACT
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.
Subject(s)
Hematologic Diseases , Mitochondrial Diseases , Humans , Mitochondrial Diseases/complications , Hematologic Diseases/blood , Hematologic Diseases/complications , Hematologic Diseases/pathology , Mitochondria/pathology , Hematopoiesis , Anemia, Sideroblastic/diagnosis , Anemia, Sideroblastic/therapyABSTRACT
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.
Subject(s)
Antifungal Agents , Hematologic Diseases , Invasive Fungal Infections , Triazoles , Voriconazole , Humans , Antifungal Agents/therapeutic use , Invasive Fungal Infections/prevention & control , Invasive Fungal Infections/drug therapy , Voriconazole/therapeutic use , Hematologic Diseases/complications , Triazoles/therapeutic use , Drug Resistance, Fungal , Aspergillus/drug effectsSubject(s)
Face , Hematologic Diseases , Mutation , Purpura, Thrombocytopenic, Idiopathic , Thyroiditis, Autoimmune , Vestibular Diseases , Humans , Vestibular Diseases/genetics , Vestibular Diseases/complications , Purpura, Thrombocytopenic, Idiopathic/genetics , Purpura, Thrombocytopenic, Idiopathic/complications , Hematologic Diseases/genetics , Hematologic Diseases/complications , Face/abnormalities , Face/pathology , Thyroiditis, Autoimmune/complications , Thyroiditis, Autoimmune/genetics , Female , Abnormalities, Multiple/genetics , MaleABSTRACT
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.
Subject(s)
COVID-19 , Hematologic Diseases , Pre-Exposure Prophylaxis , SARS-CoV-2 , Humans , Male , COVID-19/prevention & control , COVID-19/epidemiology , COVID-19/mortality , Female , Middle Aged , Pre-Exposure Prophylaxis/methods , Hematologic Diseases/complications , Aged , Adult , Incidence , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Hospitalization , Antiviral Agents/therapeutic use , Antiviral Agents/administration & dosage , Breakthrough InfectionsABSTRACT
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.
Subject(s)
Abnormalities, Multiple , Face/abnormalities , Vestibular Diseases , Humans , Female , Male , Vestibular Diseases/complications , Child , Child, Preschool , Adolescent , Tooth Abnormalities , Adult , Intellectual Disability/complications , Infant , Cleft Palate/complications , Hematologic Diseases/complicationsABSTRACT
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.
Subject(s)
Bacteremia , Corynebacterium Infections , Corynebacterium , Hematologic Diseases , Humans , Bacteremia/microbiology , Bacteremia/diagnosis , Bacteremia/etiology , Corynebacterium Infections/complications , Corynebacterium Infections/diagnosis , Corynebacterium Infections/microbiology , Corynebacterium/isolation & purification , Aged , Adult , Middle Aged , Aged, 80 and over , Male , Adolescent , Hematologic Diseases/complications , Hematologic Diseases/microbiology , Young Adult , Female , Child , Child, Preschool , Risk FactorsABSTRACT
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.
Subject(s)
Accidental Falls , Hematologic Diseases , Humans , Hematologic Diseases/diagnosis , Hematologic Diseases/complications , Female , Male , Middle Aged , Aged , Prospective Studies , ROC Curve , Cohort Studies , Adult , Risk Factors , Risk Assessment , China/epidemiology , Aged, 80 and overABSTRACT
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.
Subject(s)
Hematologic Diseases , Nervous System Diseases , Stroke , Humans , Hematologic Diseases/complications , Hematologic Diseases/therapy , Nervous System Diseases/complications , Nervous System Diseases/therapyABSTRACT
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.
Subject(s)
Abnormalities, Multiple , Face/abnormalities , Hematologic Diseases , Intellectual Disability , Vestibular Diseases , Child , Humans , Retrospective Studies , Hematologic Diseases/complications , Hematologic Diseases/geneticsABSTRACT
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.
Subject(s)
Abnormalities, Multiple , Craniosynostoses , Face/abnormalities , Hematologic Diseases , Vestibular Diseases , Humans , Retrospective Studies , Prevalence , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/epidemiology , Abnormalities, Multiple/genetics , Hematologic Diseases/complications , Hematologic Diseases/diagnosis , Hematologic Diseases/epidemiology , Vestibular Diseases/diagnosis , Vestibular Diseases/epidemiology , Vestibular Diseases/genetics , Craniosynostoses/complications , Craniosynostoses/diagnosis , Craniosynostoses/epidemiology , Histone Demethylases/genetics , MutationABSTRACT
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.
Subject(s)
COVID-19 , Drug-Related Side Effects and Adverse Reactions , Hematologic Diseases , Humans , Aged , Breakthrough Infections , SARS-CoV-2 , Antibodies, Monoclonal , Hematologic Diseases/complicationsABSTRACT
OBJECTIVE: To assess risk factors (RF) and severity grade of Posterior reversible encephalopathy syndrome (PRES) in children with hematological diseases. MATERIAL AND METHODS: We analyzed cases of PRES in children during chemotherapy (CT) and after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We estimated the following RF: arterial hypertension, steroid therapy, CT, immunosuppressive therapy (IST), infection and renal injury. RESULTS: Thirty-five cases of PRES occurred in 32 patients (8 after allo-HSCT and 27 during CT) were included in this study. In the most of cases (94.3%), there were 2 and more RF. An increase in blood pressure level (88.6%), CT and IST (82.8%) administration, steroid therapy (71.4%) were the most significant for PRES development. Infectious process and the decline in renal function played a lesser role in this syndrome (31.4% and 14%). At the initial presentation of PRES, there were seizures (94.3%), a decrease of consciousness (28.6%), headache, vision disturbances and stomachache (20%). In the most of cases (91.4%), the 2nd and 3d grade according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0) were observed. Brain magnetic resonance imaging (MRI) revealed the vasogenic edema of temporal (88.6%), occipital (74.3%), frontal (40%) lobes and the cerebellum (22.9%) more often than the cytotoxic edema (p=0.03). The cytotoxic edema was observed in the thalamus and the basal ganglia (2.9%) more often than in other parts of the brain (p<0.01). CONCLUSION: The majority of PRES cases are caused by more than two RF. Arterial hypertension does not have a leading role among its causes. There is a significant correlation between the grade of PRES according to CTCAE 5.0 score and RF number (p<0.05).
Subject(s)
Hematologic Diseases , Hypertension , Posterior Leukoencephalopathy Syndrome , Humans , Child , Posterior Leukoencephalopathy Syndrome/diagnostic imaging , Posterior Leukoencephalopathy Syndrome/etiology , Hypertension/complications , Magnetic Resonance Imaging/methods , Hematologic Diseases/complications , Edema/complications , SteroidsABSTRACT
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.