-
RMD Open May 2024Patients with X linked agammaglobulinemia are susceptible to enterovirus (EV) infections. Similarly, severe EV infections have been described in patients with impaired...
OBJECTIVE
Patients with X linked agammaglobulinemia are susceptible to enterovirus (EV) infections. Similarly, severe EV infections have been described in patients with impaired B-cell response following treatment with anti-CD20 monoclonal antibodies (mAbs), mostly in those treated for haematological malignancies. We aimed to describe severe EV infections in patients receiving anti-CD20 mAbs for immune-mediated inflammatory diseases (IMIDs).
METHODS
Patients were included following a screening of data collected through the routine surveillance of EV infections coordinated by the National Reference Center and a review of the literature. Additionally, neutralising antibodies were assessed in a patient with chronic EV-A71 meningoencephalitis.
RESULTS
Nine original and 17 previously published cases were retrieved. Meningoencephalitis (n=21/26, 81%) associated with EV-positive cerebrospinal fluid (n=20/22, 91%) was the most common manifestation. The mortality rate was high (27%). EV was the only causal agents in all reported cases. Patients received multiple anti-CD20 mAbs infusions (median 8 (5-10)), resulting in complete B-cell depletion and moderate hypogammaglobulinemia (median 4.9 g/L (4.3-6.7)), and had limited concomitant immunosuppressive treatments. Finally, in a patient with EV-A71 meningoencephalitis, a lack of B-cell response to EV was shown.
CONCLUSION
EV infection should be evoked in patients with IMIDs presenting with atypical organ involvement, especially meningoencephalitis. Anti-CD20 mAbs may lead to impaired B-cell response against EV, although an underlying primary immunodeficiency should systematically be discussed.
Topics: Humans; Enterovirus Infections; Male; Female; Antibodies, Monoclonal; Antigens, CD20; Middle Aged; Adult; Meningoencephalitis; Aged; Rituximab; B-Lymphocytes; Agammaglobulinemia; Inflammation
PubMed: 38772678
DOI: 10.1136/rmdopen-2023-004036 -
CMAJ : Canadian Medical Association... May 2024
Topics: Humans; Pregnancy; Female; Hypertension, Portal; Polycythemia Vera; Adult; Pregnancy Complications, Cardiovascular
PubMed: 38772602
DOI: 10.1503/cmaj.231170 -
American Society of Clinical Oncology... Jun 2024Despite significant improvement in the outcomes of patients with newly diagnosed multiple myeloma (NDMM) with novel therapies, there is still an underserved high-risk... (Review)
Review
Despite significant improvement in the outcomes of patients with newly diagnosed multiple myeloma (NDMM) with novel therapies, there is still an underserved high-risk (HR) population that experiences early disease progression and death. With the median survival crossing 10 years, we defined ultrahigh-risk (uHR)MM as MM leading to death within 24-36 months of diagnosis and HRMM as MM leading to death within 36-60 months. Several features have emerged as markers of uHRMM: the co-occurrence of two or more high-risk cytogenetic abnormalities, extramedullary disease, plasma cell leukemia and a high-risk gene expression profiling signature. The heterogeneous risk definition across trials, the few trials available designed for HR patients, and the small HR subgroups in all-comers trials make it difficult to generate recommendations with high levels of evidence. Nevertheless, regardless of treatment administered, several studies consistently showed that achieving and maintaining measurable residual disease negativity is now considered the main factor able to mitigate the adverse prognosis related to baseline features. For fit patients with HR transplant-eligible (TE) NDMM, quadruplet induction/consolidation treatment with anti-CD38 monoclonal antibodies, immunomodulatory agents, proteasome inhibitors and dexamethasone, and autologous stem-cell transplant and maintenance with, if available, at least a doublet combination could be considered the option of choice. For non-TE NDMM, considering the recent data generated and carefully reviewing those upcoming, quadruplet treatment consisting of anti-CD38 monoclonal antibodies, immunomodulatory agents, proteasome inhibitors, and dexamethasone should also be considered. Future trials integrating BCMA-directed novel generation immunotherapies hold great potential for further advancing the treatment landscape in all NDMM patients with HR disease.
Topics: Humans; Multiple Myeloma; Prognosis; Risk Factors; Antineoplastic Combined Chemotherapy Protocols; Risk Assessment
PubMed: 38772002
DOI: 10.1200/EDBK_433520 -
PloS One 2024Acute myeloid leukemia (AML) is a severe and fatal form of leukemia that is prevalent in the older population. In this longitudinal retrospective study, we investigated...
Acute myeloid leukemia (AML) is a severe and fatal form of leukemia that is prevalent in the older population. In this longitudinal retrospective study, we investigated the epidemiology and survival rates of patients diagnosed with de novo acute myeloid leukemia in South Korea from Jan 1, 2011, to Aug 31, 2020. We used real-world data from the Health Insurance Review and Assessment Service database. We observed an increase in the number of acute myeloid leukemia cases, with age-specific incidence rates escalating in older patients. In contrast a long-term decrease from 1.94 to 1.77 per 100,000 individuals was found in the age-standardized incidence rates. Meanwhile, age-standardized prevalence rates ascended from 8.93 to 9.67 per 100,000 individuals, with a remarkable increase in the age-specific prevalence rate for those aged 80 years and above. Survival rates were notably better in younger or treated patients, and in those who underwent Hematopoietic stem cell transplantation. The time of diagnosis did not affect the survival of patients younger than 65 years. However, the most recent survival rates were significantly lower for patients 65 or older, as shown in the unadjusted Cox survival analysis. After adjustments in the analysis, it was found that the overall survival rates of the most recently diagnosed group improved significantly compared with those diagnosed earlier, with a hazard ratio of 0.90 (95% confidence interval, 0.84-0.97). This improvement may potentially be influenced by the enhanced treatment alternatives available for newly diagnosed older patients aged 65 years or older. In conclusion, aging appears to fuel an increase in the number of acute myeloid leukemia cases and mortality. Further studies are warranted to understand the impact of aging on acute myeloid leukemia treatment outcomes and devise efficacious care strategies for older patients.
Topics: Humans; Leukemia, Myeloid, Acute; Aged; Male; Female; Aged, 80 and over; Longitudinal Studies; Middle Aged; Republic of Korea; Adult; Aging; Retrospective Studies; Young Adult; Adolescent; Survival Rate; Incidence; Prevalence; Child; Infant; Child, Preschool; Age Factors
PubMed: 38771863
DOI: 10.1371/journal.pone.0300637 -
PloS One 2024Anemia is the most common hematologic disorder of children worldwide. Since dietary diversity is a main requirement of children is to get all the essential nutrients, it...
BACKGROUND
Anemia is the most common hematologic disorder of children worldwide. Since dietary diversity is a main requirement of children is to get all the essential nutrients, it can thus use as one of the basic indicator when assessing the child's anemia. Although dietary diversity plays a major role in anemia among children in sub-Saharan Africa, there is little evidence of an association between the dietary diversity and anemia level to identified potential strategies for prevention of anemia level in sub-Saharan Africa.
OBJECTIVE
To examine the association between dietary diversity and anemia levels among children aged 6-23 months in sub-Saharan Africa.
METHODS
The most recent Demographic and Health Surveys from 32 countries in SSA were considered for this study, which used pooled data from those surveys. In this study, a total weighted sample of 52,180 children aged 6-23 months was included. The diversity of the diet given to children was assessed using the minimum dietary diversity (MDD), which considers only four of the seven food groups. A multilevel ordinal logistic regression model was applied due to the DHS data's hierarchical structure and the ordinal nature of anemia. With a p-value of 0.08, the Brant test found that the proportional odds assumption was satisfied. In addition, model comparisons were done using deviance. In the bi-variable analysis, variables having a p-value ≤0.2 were taken into account for multivariable analysis. The Adjusted Odds Ratio (AOR) with 95% Confidence Interval (CI) was presented for potential determinants of levels of anemia in the multivariable multilevel proportional odds model.
RESULTS
The overall prevalence of minimum dietary diversity and anemia among children aged 6-23 months were 43% [95% CI: 42.6%, 43.4%] and 72.0% [95% CI: 70.9%, 72.9%] respectively. Of which, 26.2% had mild anemia, 43.4% had moderate anemia, and 2.4% had severe anemia. MDD, being female child, being 18-23 months age, born from mothers aged ≥25, taking drugs for the intestinal parasite, higher level of maternal education, number of ANC visits, middle and richer household wealth status, distance of health facility and being born in Central and Southern Africa were significantly associated with the lower odds of levels of anemia. Contrarily, being 9-11- and 12-17-months age, size of child, having fever and diarrhea in the last two weeks, higher birth order, stunting, wasting, and underweight and being in West Africa were significantly associated with higher odds of levels of anemia.
CONCLUSION
Anemia was a significant public health issue among children aged 6-23 months in sub-Saharan Africa. Minimum dietary diversity intake is associated with reduced anemia in children aged 6 to 23 months in sub-Saharan Africa. Children should be fed a variety of foods to improve their anemia status. Reducing anemia in children aged 6-23 months can be achieved by raising mother education levels, treating febrile illnesses, and improve the family's financial situation. Finally, iron fortification or vitamin supplementation could help to better reduce the risk of anemia and raise children's hemoglobin levels in order to treat anemia.
Topics: Humans; Infant; Anemia; Africa South of the Sahara; Female; Male; Diet; Logistic Models
PubMed: 38771790
DOI: 10.1371/journal.pone.0298647 -
Cancer Medicine May 2024Medical mistrust, rooted in unethical research, is a barrier to cancer-related health care for Black/African American (AA) persons. Understanding trust, mistrust, and...
BACKGROUND
Medical mistrust, rooted in unethical research, is a barrier to cancer-related health care for Black/African American (AA) persons. Understanding trust, mistrust, and health care experiences is crucial, especially in multiple myeloma (MM), which disproportionately burdens Black/AA persons in incidence and survival.
STUDY PURPOSE
This study qualitatively examines the experiences of Black/AA and White dyads (patient with MM and adult caregiver) to gain insights into these phenomena.
METHODS
From November 2021 to April 2022, we recruited 21 dyads from the UNC Lineberger Comprehensive Cancer Center. Participants completed a sociodemographic survey and a 60-90 min semi-structured interview. We used ATLAS.ti v9 for project management and to facilitate data analysis using the Sort and Sift, Think and Shift approach (ResearchTalk Inc).
RESULTS
We interviewed 21 racially concordant dyads (11 Black/AA, 10 White) with mean patient ages of 70 (Black/AA) and 72 (White) at enrollment. Both Black/AA and White caregivers had a mean enrollment age of 68. The mean duration from MM diagnosis to enrollment for all patients was 5.5 years. Four key themes emerged: (1) knowledge and trust, (2) heightened emotions and discomfort, (3) differing mental constructs of health care experiences, and (4) mitigating mistrust, which varied by self-identified race. Black/AA participants had greater knowledge of historical events like the U.S. Public Health Service Untreated Syphilis Study at Tuskegee and carried the emotional burden longer. They also emphasized self-learning and self-guided research about MM for informed medical decision-making. Both Black/AA and White dyads emphasized the pivotal role of patient-provider relationships and effective communication in fostering trust and addressing concerns.
CONCLUSION
Our study offers contextual insights into the enduring challenges of medical mistrust, particularly within the Black/AA community, and its implications for patients and caregivers accessing and receiving MM-related care. Future studies should leverage these insights to guide the development of multilevel interventions addressing medical mistrust within the Black/AA community.
Topics: Humans; Multiple Myeloma; Trust; Male; Female; Aged; Caregivers; Black or African American; Middle Aged; White People; Aged, 80 and over; Qualitative Research
PubMed: 38770636
DOI: 10.1002/cam4.7297 -
Therapeutics and Clinical Risk... 2024Lymphoproliferation is defined by lymphadenopathy, splenomegaly, hepatomegaly, or lymphocytic organ and tissue infiltration. The most common etiologies of... (Review)
Review
The Etiologic Landscape of Lymphoproliferation in Childhood: Proposal for a Diagnostic Approach Exploring from Infections to Inborn Errors of Immunity and Metabolic Diseases.
Lymphoproliferation is defined by lymphadenopathy, splenomegaly, hepatomegaly, or lymphocytic organ and tissue infiltration. The most common etiologies of lymphoproliferation are represented by infectious diseases and lymphoid malignancies. However, it is increasingly recognized that lymphoproliferative features can be the presenting sign of rare conditions, including inborn errors of immunity (IEI) and inborn errors of metabolism (IEM). Among IEI, lymphoproliferation is frequently observed in autoimmune lymphoproliferative syndrome (ALPS) and related disorders, common variable immunodeficiency (CVID), activated phosphoinositide 3-kinase δ syndrome, and Epstein-Barr virus (EBV)-related disorders. Gaucher disease and Niemann-Pick disease are the most common IEMs that can present with isolated lymphoproliferative features. Notably, other rare conditions, such as sarcoidosis, Castleman disease, systemic autoimmune diseases, and autoinflammatory disorders, should be considered in the differential diagnosis of patients with persistent lymphoproliferation when infectious and malignant diseases have been reasonably ruled out. The clinical features of lymphoproliferative diseases, as well as the associated clinical findings and data deriving from imaging and first-level laboratory investigations, could significantly help in providing the correct diagnostic suspicion for the underlying etiology. This paper reviews the most relevant diseases associated with lymphoproliferation, including infectious diseases, hematological malignancies, IEI, and IEM. Moreover, some practical indications to orient the initial diagnostic process are provided, and two diagnostic algorithms are proposed for the first-level assessment and the approach to persistent lymphoproliferation, respectively.
PubMed: 38770035
DOI: 10.2147/TCRM.S462996 -
Annals of Palliative Medicine May 2024The suffering experienced by terminally-ill patients encompasses physiological, psychosocial and spiritual dimensions. While previous studies have investigated symptom...
BACKGROUND
The suffering experienced by terminally-ill patients encompasses physiological, psychosocial and spiritual dimensions. While previous studies have investigated symptom burden intensity for specific disease groups, such as cancer or heart failure patients, a research gap exists in understanding major distressing symptoms among diverse terminally-ill patients. This study assessed symptom burden intensity and explored its influential factors among diverse patient disease groups.
METHODS
This cross-sectional study utilized the baseline Integrated Palliative care Outcome Scale (IPOS) assessment data. The study participants were terminally-ill patients enrolled in an end-of-life care (EoLC) intervention in Hong Kong. Statistical methods including relative importance index (RII), one-way analysis of variance (ANOVA), and generalized linear regression (GLR) were employed.
RESULTS
Final sample consisted of 1,549 terminally-ill patients (mean age =77.4 years, SD =11.6). The five top-rated distressing symptoms among these patients, revealed by the RII analysis, were poor mobility (RII =64.4%), family anxiety (RII =63.5%), sharing feelings with family/friends (RII =61.4%), weakness/ lack of energy (RII =58.1%), and hardly feeling at peace (RII =50.7%). One-way ANOVA showed significant differences among the eight disease groups in perceived physical and emotional symptom burden intensity (P<0.05). Analysis of RII symptom scores for each disease group revealed that poor mobility was rated as the most distressing symptom (RII =85.1-62.9%) by patients with motor neurone disease, Parkinson's disease, heart failure, dementia, end-stage renal disease and other serious diseases (including stroke, hematological disease, multiple sclerosis and liver diseases). Perceived family anxiety (RII =66.1%) and shortness of breath (RII =63.8%) were the most distressing symptoms for cancer patients and those with chronic obstructive pulmonary disease, respectively. GLR analysis showed that illness type is the most significant factor influencing the perceived burden intensity in terms of the IPOS total and subscale scores of physical symptoms, emotional symptoms and communication/practical issues. Demographic characteristics such as age, gender, marital status and co-residing status were also identified as influential factors of various symptom categories. However, patients' educational level and relationship with primary caregiver did not significantly influence any perceived symptom burden.
CONCLUSIONS
This study provides valuable insights into the symptom burdens experienced by diverse patient disease groups at end-stage of life. The findings highlight the major distressing symptoms of poor mobility, family anxiety, and shortness of breath. Addressing these symptoms is crucial in improving the quality of care for terminally-ill patients. Furthermore, the study identifies influential factors that can affect the perceived intensity of symptom burden, primarily the main type of terminal illness and patient's age. Tailored care support and improved clinical care should be implemented, particularly for high-risk groups such as patients with non-cancer terminal illnesses and older aged patients. These findings contribute to existing literature and emphasize the need for comprehensive and individualized care in EoLC.
PubMed: 38769801
DOI: 10.21037/apm-23-565 -
Genome Medicine May 2024Rare oncogenic driver events, particularly affecting the expression or splicing of driver genes, are suspected to substantially contribute to the large heterogeneity of...
BACKGROUND
Rare oncogenic driver events, particularly affecting the expression or splicing of driver genes, are suspected to substantially contribute to the large heterogeneity of hematologic malignancies. However, their identification remains challenging.
METHODS
To address this issue, we generated the largest dataset to date of matched whole genome sequencing and total RNA sequencing of hematologic malignancies from 3760 patients spanning 24 disease entities. Taking advantage of our dataset size, we focused on discovering rare regulatory aberrations. Therefore, we called expression and splicing outliers using an extension of the workflow DROP (Detection of RNA Outliers Pipeline) and AbSplice, a variant effect predictor that identifies genetic variants causing aberrant splicing. We next trained a machine learning model integrating these results to prioritize new candidate disease-specific driver genes.
RESULTS
We found a median of seven expression outlier genes, two splicing outlier genes, and two rare splice-affecting variants per sample. Each category showed significant enrichment for already well-characterized driver genes, with odds ratios exceeding three among genes called in more than five samples. On held-out data, our integrative modeling significantly outperformed modeling based solely on genomic data and revealed promising novel candidate driver genes. Remarkably, we found a truncated form of the low density lipoprotein receptor LRP1B transcript to be aberrantly overexpressed in about half of hairy cell leukemia variant (HCL-V) samples and, to a lesser extent, in closely related B-cell neoplasms. This observation, which was confirmed in an independent cohort, suggests LRP1B as a novel marker for a HCL-V subclass and a yet unreported functional role of LRP1B within these rare entities.
CONCLUSIONS
Altogether, our census of expression and splicing outliers for 24 hematologic malignancy entities and the companion computational workflow constitute unique resources to deepen our understanding of rare oncogenic events in hematologic cancers.
Topics: Humans; Hematologic Neoplasms; Transcriptome; RNA Splicing; Gene Expression Regulation, Neoplastic; Oncogenes; Gene Expression Profiling; Receptors, LDL
PubMed: 38769532
DOI: 10.1186/s13073-024-01331-6 -
Journal of Orthopaedic Surgery and... May 2024It is beneficial for society to discover the risk factors associated with surgery and to carry out some early interventions for patients with these risk factors. Few...
BACKGROUND
It is beneficial for society to discover the risk factors associated with surgery and to carry out some early interventions for patients with these risk factors. Few studies specifically explored the relationship between bone marrow lesions (BMLs) and long-term incident joint surgery.
OBJECTIVE
To investigate the association between BML severity observed in knee osteoarthritis (OA) patients' first MRI examination and incident knee surgery within 5 years. Additionally, to assess the predictive value of BMLs for the incident knee surgery.
DESIGN
Retrospective cohort study.
METHODS
We identified patients diagnosed with knee OA and treated at our institution between January 2015 and January 2018, and retrieved their baseline clinical data and first MRI examination films from the information system. Next, we proceeded to determine the Max BML grades, BML burden grades and Presence BML grades for the medial, lateral, patellofemoral, and total compartments, respectively. Multi-variable logistic regression models examined the association of the BML grades with 5-year incident knee surgery. Positive and negative predictive values (PPVs and NPVs) were determined for BML grades referring to 5-year incident knee surgery.
RESULTS
Totally, 1011 participants (knees) were found eligible to form the study population. Within the 5 years, surgery was performed on 74 knees. Max BML grade 2 and grade 3 of medial, patellofemoral and total compartments were strongly and significantly associated with incident surgery. None of the BML grades from lateral compartment was associated with incident surgery. The PPV was low and NPV was high for BMLs.
CONCLUSIONS
BMLs found in the first MRI examination were associated with 5-year incident joint surgery, except for those allocated in lateral compartments. The high NPVs imply that patients without BMLs have a low risk of requiring surgery within 5 years.
Topics: Humans; Osteoarthritis, Knee; Retrospective Studies; Male; Female; Middle Aged; Aged; Magnetic Resonance Imaging; Bone Marrow; Cohort Studies; Time Factors; Risk Factors; Knee Joint; Bone Marrow Diseases; Arthroplasty, Replacement, Knee; Severity of Illness Index
PubMed: 38769508
DOI: 10.1186/s13018-024-04705-z