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1.
Artigo em Inglês | MEDLINE | ID: mdl-39118208

RESUMO

BACKGROUND: Anemia is an independent predictor of mortality, which may be utilized as a signal of deteriorating health. We estimated the association between anemia severity categories and mortality following the initiation of antiretroviral therapy (ART) among people with HIV (PWH) in North America. METHODS: Within the NA-ACCORD, annual median hemoglobin measurements between 01/01/2007-12/31/2016 were categorized using World Health Organization criteria into mild (11.0-12.9g/dL men, 11.0-11.9g/dL women), moderate (8.0-10.9g/dL men/women) and severe (<8.0g/dL men/women) anemia. Discrete time-to-event analyses using complementary log-log link models estimated mortality hazards ratios adjusted for demographics, comorbidities, and HIV clinical markers with 95% confidence intervals for the association between anemia and mortality. RESULTS: Among 67,228 PWH contributing a total of 320,261 annual median hemoglobin measurements, 257,293 (80%) demonstrated no anemia, 44,041 (14%) mild, 18,259 (6%) moderate, and 668 (0.2%) severe anemia during follow-up. Mortality risk was 5.6-fold higher among PWH with (vs. without) anemia. The association was greater among males (aHR=5.8 [5.4, 6.2]) versus females (aHR=4.1 [3.2, 5.4]). Mortality risk was 3.8-fold higher among PWH with mild anemia, 13.7-fold higher with moderate anemia, and 34.5-fold higher with severe anemia (vs. no anemia). Median hemoglobin levels significantly declined within 4 years prior to death, with the maximum decrease the year prior to death. Macrocytic anemia was associated with an increased and microcytic anemia a decreased mortality risk (vs. normocytic anemia). CONCLUSIONS: Anemia among PWH who have initiated ART is an important predictive marker for mortality with macrocytic anemia having an increased and microcytic anemia a decreased association with mortality compared with normocytic anemia.

2.
AIDS Res Ther ; 21(1): 52, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39113038

RESUMO

BACKGROUND: Anemia is common and associated with increased morbidity among people with HIV (PWH). Classification of anemia using the mean corpuscular volume (MCV) can help investigate the underlying causative factors of anemia. We characterize anemia using MCV among PWH receiving antiretroviral therapy (ART), and identify the risk factors for normocytic, macrocytic, and microcytic anemias. METHODS: Including PWH with anemia (hemoglobin measure < 12.9 g/dL among men and < 11.9 g/dL among women) in the NA-ACCORD from 01/01/2007 to 12/31/2017, we estimated the annual distribution of normocytic (80-100 femtolitre (fL)), macrocytic (> 100 fL) or microcytic (< 80 fL) anemia based on the lowest hemoglobin within each year. Poisson regression models with robust variance and general estimating equations were used to estimate crude and adjusted prevalence ratios and 95% confidence intervals for risk factors for macrocytic (vs. normocytic) and microcytic (vs. normocytic) anemia stratified by sex. RESULTS: Among 37,984 hemoglobin measurements that identified anemia in 14,590 PWH, 27,909 (74%) were normocytic, 4257 (11%) were microcytic, and 5818 (15%) were macrocytic. Of the anemic PWH included over the study period, 1910 (13%) experienced at least one measure of microcytic anemia and 3208 (22%) at least one measure of macrocytic anemia. Normocytic anemia was most common among both males and females, followed by microcytic among females and macrocytic among males. Over time, the proportion of anemic PWH who have macrocytosis decreased while microcytosis increased. Macrocytic (vs. normocytic) anemia is associated with increasing age and comorbidities. With increasing age, microcytic anemia decreased among females but not males. A greater proportion of PWH with normocytic anemia had CD4 counts ≤ 200 cells/mm3 and had recently initiated ART. CONCLUSION: In anemic PWH, normocytic anemia was most common. Over time macrocytic anemia decreased, and microcytic anemia increased irrespective of sex. Normocytic anemia is often due to chronic disease and may explain the greater risk for normocytic anemia among those with lower CD4 counts or recent ART initiation. Identified risk factors for type-specific anemias including sex, age, comorbidities, and HIV factors, can help inform targeted investigation into the underlying causes.


Assuntos
Anemia , Índices de Eritrócitos , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/sangue , Masculino , Feminino , Anemia/epidemiologia , Anemia/sangue , Adulto , Pessoa de Meia-Idade , Fatores de Risco , América do Norte/epidemiologia , Prevalência , Hemoglobinas/análise , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4
4.
Dig Dis Sci ; 69(6): 2154-2163, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38580888

RESUMO

BACKGROUND: Patient-reported outcomes (PROs), such as the short CD activity index (sCDAI) and partial Mayo Score (PMS), are used to define clinical remission in IBD, but may not represent the true degree of inflammation and endoscopy is invasive. Non-invasive testing options include c-reactive protein (CRP) and fecal calprotectin (FCP). AIM: The aim of this study was to assess the degree of correlation of non-invasive biomarkers with PROs and the impact other clinical variables can have on their levels. METHODS: We reviewed data collected from the prospective cohort, Study of a Prospective Adult Research Cohort with IBD (SPARC-IBD), comprised of over 3000 patients from 17 tertiary referral centers. Demographic and clinical variables were analyzed by disease type, disease severity was based on PROs, and baseline CRP and FCP were measured. For comparative analysis, we performed Fisher's exact test and Welch's t test, where p < 0.05 was significant. RESULTS: 1547 patients were included; 63% had CD, 56% were female, with an average disease duration of 13.6 years. CRP and FCP were associated with symptom severity in inflammatory CD. CRP was useful to differentiate symptoms across different disease locations in CD, whereas FCP was associated with symptom severity in Crohn's colitis only. For UC, FCP was able to distinguish symptom severity better in distal UC, whereas in extensive or pancolitis, it was useful only to distinguish severe symptoms from other categories of symptom severity. CONCLUSION: PROs correlate with CRP and FCP; however, disease location and phenotype impact their ability to distinguish symptom severity.


Assuntos
Biomarcadores , Proteína C-Reativa , Colite Ulcerativa , Doença de Crohn , Fezes , Complexo Antígeno L1 Leucocitário , Medidas de Resultados Relatados pelo Paciente , Índice de Gravidade de Doença , Humanos , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Feminino , Masculino , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/sangue , Fezes/química , Adulto , Biomarcadores/sangue , Biomarcadores/análise , Complexo Antígeno L1 Leucocitário/análise , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos
5.
Blood Adv ; 8(12): 3092-3108, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38593221

RESUMO

ABSTRACT: Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an inborn error of immunity that manifests as immune deficiency and dysregulation; symptoms include frequent infections and lymphoproliferation. In our dose-finding and phase 3 placebo-controlled trials, treatment with the selective PI3Kδ inhibitor leniolisib reduced lymphoproliferation and normalized lymphocyte subsets. Here, we present 6 years of follow-up from the 6 adult patients in the original dose-finding trial receiving leniolisib. We used data from the ongoing open-label extension study, which was supplemented at later time points by investigators, including health-related quality of life (HRQoL) assessed through a clinician-reported questionnaire. We observed improvements in HRQoL: 5 of 6 patients experienced an increase in physical capabilities and socialization, and a decrease in prescribed medications. Immune subsets improved in all patients: mean transitional B-cell levels decreased from 38.17% to 2.47% and the CD4:CD8 T-cell ratio normalized to 1.11. Manifestations seen before and within the first year of leniolisib exposure, such as infections and gastrointestinal conditions, attenuated after year 2, with few new conditions emerging out to year 6. Thrombocytopenia or lymphopenia remained present in half of patients at year 6. Of 83 adverse events through year 5, 90.36% were grade 1; none were grade 4/5 nor deemed leniolisib related. Collectively, we saw an enhancement in HRQoL as well as durable changes in lymphocyte subsets and clinical manifestations, further supporting the use of leniolisib as a long-term therapeutic option for the treatment of APDS. This trial was registered at www.ClinicalTrials.gov as #NCT02859727.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases , Doenças da Imunodeficiência Primária , Humanos , Adulto , Masculino , Feminino , Doenças da Imunodeficiência Primária/tratamento farmacológico , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Qualidade de Vida , Resultado do Tratamento , Pessoa de Meia-Idade , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
6.
bioRxiv ; 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38293222

RESUMO

Lupus nephritis (LN) is a frequent manifestation of systemic lupus erythematosus, and fewer than half of patients achieve complete renal response with standard immunosuppressants. Identifying non-invasive, blood-based pathologic immune alterations associated with renal injury could aid therapeutic decisions. Here, we used mass cytometry immunophenotyping of peripheral blood mononuclear cells in 145 patients with biopsy-proven LN and 40 healthy controls to evaluate the heterogeneity of immune activation in patients with LN and to identify correlates of renal parameters and treatment response. Unbiased analysis identified 3 immunologically distinct groups of patients with LN that were associated with different patterns of histopathology, renal cell infiltrates, urine proteomic profiles, and treatment response at one year. Patients with enriched circulating granzyme B+ T cells at baseline showed more severe disease and increased numbers of activated CD8 T cells in the kidney, yet they had the highest likelihood of treatment response. A second group characterized primarily by a high type I interferon signature had a lower likelihood of response to therapy, while a third group appeared immunologically inactive by immunophenotyping at enrollment but with chronic renal injuries. Main immune profiles could be distilled down to 5 simple cytometric parameters that recapitulate several of the associations, highlighting the potential for blood immune profiling to translate to clinically useful non-invasive metrics to assess immune-mediated disease in LN.

7.
J Fam Psychol ; 38(2): 260-269, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38032651

RESUMO

For adolescents who have a father in their lives, father-teen conversations about sex and relationships can protect teens from risky sexual behaviors. However, little is known about the content and process of these conversations. This study explored topics of and approaches to fathers' talk with their teens about sex and relationships in interviews with a diverse sample of 43 fathers of high school-aged adolescents from across the United States. Interview data were analyzed using content analysis. The results showed how fathers talked with their adolescent children about topics of sexual behavior, risks of sex, dating and relationships, as well as less studied areas of diverse sexual and gender identities and consent, and how these conversations differed with male and female teens. Findings also showed that fathers took multiple approaches to talk about sex, including personal talk, talk about friends and family, and use of media and other distal contexts to start conversations. These findings show how fathers contribute to the sexual socialization of their adolescent children and suggest points of access for fathers who are unsure how to approach talk with their teens about sex and relationships. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Comunicação , Comportamento Sexual , Criança , Humanos , Masculino , Feminino , Adolescente , Estados Unidos , Socialização , Amigos , Assunção de Riscos
8.
Gastrointest Endosc ; 2023 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-38052328

RESUMO

BACKGROUND AND AIMS: The widespread use of peroral endoscopic myotomy (POEM) has revolutionized the management of esophageal motility disorders (EMDs). The introduction of an endoluminal functional lumen imaging probe (EndoFLIP) can serve as a complimentary diagnostic tool to assess the mechanical properties (i.e., pressure, diameter, distensibility and topography) of the esophagus. During EndoFLIP measurements, different anesthesia techniques may induce variable degrees of neuromuscular blockade, potentially affecting esophageal motility and altering the results of EndoFLIP metrics. Our study aimed to compare the impact of using total intravenous anesthesia (TIVA) versus general anesthesia with inhalational anesthetics (GAIA) on diagnostic EndoFLIP measurements. METHODS: We conducted a retrospective study of all adult patients (≥18 years) undergoing EndoFlip during the POEM procedure at our institution between February 2017 and February 2022. We obtained the differences in pressure, diameter, and distensibility index using propofol-based TIVA vs sevoflurane-based GAIA with a 30ml and 60ml balloon. The differences were divided into terciles and compared between diagnoses using univariate comparisons and logistic regression models. RESULTS: 49 patients were included (39% Type 1 achalasia, 43% Type 2 or 3 achalasia, and 18% jackhammer esophagus (JE)). Compared to spastic disorders (Type 2, 3 and JE), Type 1 had lower values of pressure differences at 60 mL in univariate (3.75 vs 15.20 p=0.001) and multivariate (aOR 0.89 95%CI 0.82-0.978) analyses. Compared to Type 1, Type 2 and 3 had higher rates of pressure differences at 60 mL in univariate (9.85 vs 3.75 p=0.04); and nearly reached significance in multivariate analysis (1.09 95%CI 1-1.20). Compared to Type 1, JE demonstrated higher values in pressure differences at 60 mL (27.7 vs 3.75 p<0.001) CONCLUSION: Esophageal pressure, as measured by EndoFLIP, was significantly reduced when patients were sedated with sevoflurane-based GAIA. The use sevoflurane-based GAIA for diagnostic EndoFLIP may potentially lead to the misclassification of spastic disorders as Type I achalasia. Therefore, propofol-based TIVA should be considered over sevoflurane-based GAIA for sedation during the diagnostic test.

9.
Arthritis Rheumatol ; 75(12): 2088-2102, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37845798

RESUMO

OBJECTIVE: The objective is to update recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) for patients with rheumatic or nonrheumatic conditions receiving >3 months treatment with glucocorticoids (GCs) ≥2.5 mg daily. METHODS: An updated systematic literature review was performed for clinical questions on nonpharmacologic, pharmacologic treatments, discontinuation of medications, and sequential therapy. Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the certainty of evidence. A Voting Panel achieved ≥70% consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: For adults beginning or continuing >3 months of GC treatment, we strongly recommend as soon as possible after initiation of GCs, initial assessment of fracture risks with clinical fracture assessment, bone mineral density with vertebral fracture assessment or spinal x-ray, and Fracture Risk Assessment Tool if ≥40 years old. For adults at medium, high, or very high fracture risk, we strongly recommend pharmacologic treatment. Choice of oral or intravenous bisphosphonates, denosumab, or parathyroid hormone analogs should be made by shared decision-making. Anabolic agents are conditionally recommended as initial therapy for those with high and very high fracture risk. Recommendations are made for special populations, including children, people with organ transplants, people who may become pregnant, and people receiving very high-dose GC treatment. New recommendations for both discontinuation of osteoporosis therapy and sequential therapies are included. CONCLUSION: This guideline provides direction for clinicians and patients making treatment decisions for management of GIOP. These recommendations should not be used to limit or deny access to therapies.


Assuntos
Fraturas Ósseas , Osteoporose , Reumatologia , Adulto , Criança , Humanos , Estados Unidos , Glucocorticoides/efeitos adversos , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Densidade Óssea
10.
Arthritis Care Res (Hoboken) ; 75(12): 2405-2419, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37884467

RESUMO

OBJECTIVE: The objective is to update recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) for patients with rheumatic or nonrheumatic conditions receiving >3 months treatment with glucocorticoids (GCs) ≥2.5 mg daily. METHODS: An updated systematic literature review was performed for clinical questions on nonpharmacologic, pharmacologic treatments, discontinuation of medications, and sequential therapy. Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the certainty of evidence. A Voting Panel achieved ≥70% consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: For adults beginning or continuing >3 months of GC treatment, we strongly recommend as soon as possible after initiation of GCs, initial assessment of fracture risks with clinical fracture assessment, bone mineral density with vertebral fracture assessment or spinal x-ray, and Fracture Risk Assessment Tool if ≥40 years old. For adults at medium, high, or very high fracture risk, we strongly recommend pharmacologic treatment. Choice of oral or intravenous bisphosphonates, denosumab, or parathyroid hormone analogs should be made by shared decision-making. Anabolic agents are conditionally recommended as initial therapy for those with high and very high fracture risk. Recommendations are made for special populations, including children, people with organ transplants, people who may become pregnant, and people receiving very high-dose GC treatment. New recommendations for both discontinuation of osteoporosis therapy and sequential therapies are included. CONCLUSION: This guideline provides direction for clinicians and patients making treatment decisions for management of GIOP. These recommendations should not be used to limit or deny access to therapies.


Assuntos
Osteoporose , Reumatologia , Adulto , Criança , Humanos , Estados Unidos , Glucocorticoides/efeitos adversos , Osteoporose/induzido quimicamente , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Densidade Óssea
11.
Sex Educ ; 23(4): 449-463, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37346469

RESUMO

Protective effects of talk with parents about sex, for delaying sex and reducing young people's risky sexual behaviour may extend from adolescence to emerging adulthood. However, little is known about the content and process of this communication, or how parents and their emerging adult children perceive their conversations about sex and relationships. This study offers a novel exploration of family talk about sex during emerging adulthood and addresses topics that are not typically assessed as part of communication research, such as consent and positive talk about sexuality. This study uses thematic analysis to investigate perceptions of family talk about sex in a qualitative sample of 16 pairs of parents and their emerging adult children in the USA, and includes talk about protection, sexual behaviour, pregnancy and parenting; the positive aspects of sex; consent; and sexual orientation. Findings identified variation across topics in terms of 1) similarities and differences in parents' and emerging adults' comfort in talking with each other about sexual topics; and 2) how they perceive this communication across a range of sexual issues. Findings can inform the development of resources to support parents on how to talk with their emerging adult children about sexual issues in a developmentally appropriate way.

13.
Transl Vis Sci Technol ; 12(3): 19, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36939711

RESUMO

Purpose: Performance comparison of optical coherence tomography (OCT) and visual field (VF) summary metrics for detecting glaucomatous progression. Methods: Thirty healthy control eyes (mean deviation [MD], -1.25 ± 2.03; pattern standard deviation [PSD] , 1.78 ± 0.77) and 91 patient eyes comprised of 54 glaucoma patients and 37 glaucoma suspects (MD, -1.58 ± 1.96; PSD, 2.82 ± 1.92) with a follow-up of at least 1 year formed a group to evaluate progression with event analyses (P-Event). A subset of eyes with an additional criterion of a minimum of four tests was used for trend analyses (P-Trend) (30 healthy controls and 73 patients). For P-Event analysis, test-retest variability thresholds (lower 5th percentile) were estimated with repeat tests within a 4-month period. A P-Event eye was considered a "progressor" if the difference between follow-up and baseline tests exceeded the variability thresholds. For the P-Trend analysis, rates of change were calculated based on least-squares regression. Negative rates with significant (P < 0.05) values were considered progressing. For a reference standard, 17 patient eyes were classified as definitely progressing based on clear evidence of structural and corresponding functional progression. Results: Isolated OCT and VF summary metrics were either inadequately sensitive or not too specific. Combinations of OCT-OCT and OCT-VF metrics markedly improved specificity to nearly 100%. A novel combination of OCT metrics (circumpapillary retinal nerve fiber layer and ganglion cell layer) showed high precision, with 13 of the 15 statistical progressors confirmed as true positives. Conclusions: Although relying solely on metrics is not recommended for clinical purposes, in situations requiring very high specificity and precision, combinations of OCT-OCT metrics can be used. Translational Relevance: All available OCT and VF metrics can miss eyes with progressive glaucomatous damage and/or can falsely identify progression in stable eyes.


Assuntos
Glaucoma , Testes de Campo Visual , Humanos , Testes de Campo Visual/métodos , Tomografia de Coerência Óptica/métodos , Pressão Intraocular , Células Ganglionares da Retina , Fibras Nervosas , Glaucoma/diagnóstico
14.
AIDS ; 37(2): 287-298, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36541641

RESUMO

OBJECTIVE: To characterize the prevalence of anemia and risk factors between 2007 and 2017 for moderate/severe anemia among people with HIV (PWH) in North America who have initiated antiretroviral therapy (ART). DESIGN: Observational study of participants in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). METHODS: We estimated the annual prevalence between 1 January 2007 and 31 December 2017 of mild (11.0-12.9 g/dl men, 11.0-11.9 g/dl women), moderate (8.0-10.9 g/dl regardless of sex) and severe (<8.0 g/dl regardless of sex) anemia. Poisson regression models with robust variance and general estimating equations estimated crude and adjusted prevalence ratios (aPR) with 95% confidence intervals ([-]) comparing risk factors for moderate/severe vs. no/mild anemia between 2007 and 2017. RESULTS: Among 73 898 PWH we observed 366 755 hemoglobin measurements following ART initiation, 37 301 (50%) had one or more measures of anemia during follow-up (mild = 17 743 [24%]; moderate = 13 383[18%]; severe = 6175 [8%]). Moderate/severe anemia was more prevalent among women, non-Hispanic Black and Hispanic PWH (vs. non-Hispanic white), those with underweight body mass index (<18.5 kg/m2) and with comorbidities and coinfections. Older age had increased prevalence of moderate/severe anemia among males and decreased prevalence among females. Prevalence of moderate/severe anemia was greater among those with lower CD4+ cell count (≤200 cells/µl) [aPR = 2.11 (2.06-2.17)] unsuppressed HIV viral load (>200 copies/ml) [aPR = 1.26 (1.23-1.29)] and within the first 6 months of ART initiation (vs. >1 year of ART) [aPR = 1.66 (1.61-1.72)]. CONCLUSION: The prevalence of anemia among PWH is reduced after ART initiation but remains high. Risk factors differ by sex and include comorbidities and HIV disease severity. The persistent, substantial prevalence of anemia among PWH merits further investigation, targeted screening, and clinical interventions.


Assuntos
Anemia , Infecções por HIV , Masculino , Humanos , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Prevalência , Fatores de Risco , América do Norte/epidemiologia , Anemia/epidemiologia , Anemia/etiologia , Contagem de Linfócito CD4
15.
Ann Hematol ; 101(10): 2297-2306, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35978181

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous, life-threatening clinical syndrome. There are scarce data on the quality of care in HLH or data comparing treatment patterns and outcomes between different triggers. We aimed to examine quality-of-care indicators and outcomes in adults with various HLH triggers. In this multi-centre retrospective cohort study of adult HLH in the province of Alberta, Canada (1999-2019), we examined quality indicators including diagnostic testing, time to diagnosis and treatment and trigger identification. We also compared treatment regimens and outcomes across HLH triggers. Logistic regression was used to identify predictors of etoposide use. Overall survival (OS) was estimated using the Kaplan-Meier method. We identified 97 patients; 66 (68%) were male. Triggers included malignancy (36%), infection (35%), autoimmune disease (21%) and idiopathic/others (8%). Specialized tests such as sCD25 (53%) and natural killer degranulation assay (19%) were under-performed, as were testing for infectious triggers. Etoposide was administered in only 33 (34%). Neutropenia, hyperbilirubinemia and hyperferritinemia, but not age, sex and comorbidities, were significant predictors of etoposide use. At median follow-up of 32 months, median OS was 18.8 months. Worse OS was seen in malignancy-associated and idiopathic HLH (log-rank P < 0.001). Our study showed low rates of specialized testing such as sCD25 and a low rate of etoposide use. Development of a standardized provincial protocol has the potential to improve quality of care in adult HLH.


Assuntos
Linfo-Histiocitose Hemofagocítica , Neoplasias , Adulto , Etoposídeo/uso terapêutico , Feminino , Humanos , Hiperbilirrubinemia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/epidemiologia , Masculino , Neoplasias/tratamento farmacológico , Estudos Retrospectivos
16.
Blood Adv ; 6(18): 5403-5414, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-35687490

RESUMO

Patients with inborn errors of immunity (IEI) have a higher risk of developing cancer, especially lymphoma. However, the molecular basis for IEI-related lymphoma is complex and remains elusive. Here, we perform an in-depth analysis of lymphoma genomes derived from 23 IEI patients. We identified and validated disease-causing or -associated germline mutations in 14 of 23 patients involving ATM, BACH2, BLM, CD70, G6PD, NBN, PIK3CD, PTEN, and TNFRSF13B. Furthermore, we profiled somatic mutations in the lymphoma genome and identified 8 genes that were mutated at a significantly higher level in IEI-associated diffuse large B-cell lymphomas (DLBCLs) than in non-IEI DLBCLs, such as BRCA2, NCOR1, KLF2, FAS, CCND3, and BRWD3. The latter, BRWD3, is furthermore preferentially mutated in tumors of a subgroup of activated phosphoinositide 3-kinase δ syndrome patients. We also identified 5 genomic mutational signatures, including 2 DNA repair deficiency-related signatures, in IEI-associated lymphomas and a strikingly high number of inter- and intrachromosomal structural variants in the tumor genome of a Bloom syndrome patient. In summary, our comprehensive genomic characterization of lymphomas derived from patients with rare genetic disorders expands our understanding of lymphomagenesis and provides new insights for targeted therapy.


Assuntos
Linfoma Difuso de Grandes Células B , Fosfatidilinositol 3-Quinases , Fatores de Transcrição de Zíper de Leucina Básica , Genômica , Humanos , Linfoma Difuso de Grandes Células B/genética , Fosfatidilinositol 3-Quinase
17.
Eur J Haematol ; 109(2): 129-137, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35434872

RESUMO

Timely diagnosis of hemophagocytic lymphohistiocytosis (HLH) is critical and relies on clinical judgment. The HLH-2004 criteria are commonly used diagnostic criteria, whereas HScore was recently developed for reactive HLH. OBJECTIVE: In this external validation study, we sought to compare the diagnostic accuracy of the HLH-2004 criteria and HScore and identify optimal cutoffs stratified by underlying etiology. METHODS: In this retrospective cohort of all hospitalized adults in Alberta, Canada, (1999-2019) who had ferritin >500 ng/ml and underwent either biopsies or soluble CD25 testing, we calculated the diagnostic accuracy of HLH-2004 and HScore for the overall population and different etiologies. RESULTS: Of 916 patients, 98 (11%) had HLH. HLH-2004 criteria ≥5 predicted HLH with a sensitivity of 91%, specificity of 93%, positive predictive value of 90%, and negative predictive value of 94% (c-statistic 92%). HScore ≥169 predicted HLH with better sensitivity (96%) but reduced specificity (71%), whereas the optimal cutoff ≥200 performed comparably to HLH-2004. HLH-2004 criteria outperformed HScore in most etiologies, whereas HScore improved sensitivity in inflammatory/autoimmune-HLH. The optimal cutoff of HScore was higher in hematopoietic cell transplant due to higher prevalence of fevers and cytopenias. CONCLUSION: HLH-2004 criteria and HScore demonstrated excellent discriminatory power in identifying HLH. HScore may improve diagnostic accuracy in autoimmune-HLH.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfo-Histiocitose Hemofagocítica , Adulto , Alberta , Ferritinas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/etiologia , Estudos Retrospectivos
18.
Ophthalmol Glaucoma ; 5(6): 614-627, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35358755

RESUMO

PURPOSE: To better understand the efficacy of the 24-2 guided progression analysis (GPA) in the detection of progression in eyes with early glaucoma (i.e., 24-2 mean deviation [MD] better than -6 dB) by comparing 24-2 GPA with a reference standard (RS) based on a combination of OCT and 24-2 and 10-2 visual field (VF) information. DESIGN: Cross-sectional study. PARTICIPANTS: Ninety-nine eyes from 99 individuals, including 70 suspected or early glaucomatous eyes (24-2 MD better than -6 dB) and 29 healthy controls (HCs). METHODS: All the eyes had at least 4 OCT and VF test dates over a period that ranged from 12 to 59 months. The 24-2 VF tests included 2 baseline tests and at least 2 follow-up tests. The 2 baseline tests were performed within an average of 5.6 days (median, 7 days), and the last follow-up test was performed at least 1 year after the first baseline visit. MAIN OUTCOME MEASURES: A commercial 24-2 GPA software, with default settings, characterized the eyes as having "likely progression" (LP) or "possible progression" (PP); both were considered "progressing" for this analysis. For RS, 3 authors graded progression using strict criteria and a combination of a custom OCT progression report and commercial 24-2 and 10-2 GPA reports for the same test dates as GPA. RESULTS: The reference standard identified 10 (14%) of the 70 patient eyes and none of the HC eyes as having progression. The 24-2 guided progression analysis identified 13 of the 70 patient eyes as having progression (PP or LP). However, it correctly classified only 4 (40%) of the 10 RS progressors. All 6 of the RS progressors missed by the 24-2 GPA showed progression in the macula. In addition, the 24-2 GPA identified 2 of the 29 HC eyes as progressors and 9 patient eyes without progression based on the RS. CONCLUSIONS: In eyes with early glaucoma (i.e., 24-2 MD, > -6 dB) in this study, the 24-2 GPA missed progression seen using OCT and exhibited a relatively high rate of false positives. Furthermore, the region progressing typically included the macula. The results suggest that including OCT and/or 10-2 VFs should improve the detection of progression.


Assuntos
Glaucoma , Disco Óptico , Humanos , Campos Visuais , Tomografia de Coerência Óptica/métodos , Estudos Transversais , Células Ganglionares da Retina , Pressão Intraocular , Progressão da Doença , Glaucoma/diagnóstico
19.
Artigo em Inglês | MEDLINE | ID: mdl-35329002

RESUMO

Talk with fathers about sex and relationships can support teens' health, but its impact is limited as few fathers talk with their teens about sexual issues. Needs assessment and fathers' input on intervention content and structure can guide the development of programs that support fathers' health-promoting talk with their teen children about sex and relationships. In the present study, we explored fathers' goals in their talk with teens about sex and relationships and barriers they perceive to these conversations, as well as what they would look for in an intervention program. Content analysis was conducted using interviews in the U.S. with 43 fathers of high school-aged teens (age 14-18). Themes explored fathers' roles in talk with teens, key messages to teens, and approaches and barriers to conversations, in addition to attitudes toward an intervention, and feedback on intervention structure, content, and process. The findings suggest that fathers see talk with teens about sex as part of their roles, but face challenges in accomplishing this goal. Fathers' feedback highlights their openness to an intervention and can guide the development of a peer-based and interactive program that addresses how to talk with teens about sex in addition to the content of these conversations.


Assuntos
Relações Familiares , Comportamento Sexual , Adolescente , Criança , Comunicação , Relações Pai-Filho , Humanos , Avaliação das Necessidades
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