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Late-onset Pompe disease (LOPD) is a multisystem disorder with significant myopathy. The standard treatment is enzyme replacement therapy (ERT), a therapy that is lifesaving, yet with limitations. Clinical trials have emerged for other potential treatment options, including adeno-associated virus (AAV) gene therapy. We present clinical parameters and AAV antibody titers for 19 individuals with LOPD undergoing screening for a Phase I clinical trial with an AAV serotype 8 vector targeting hepatic transduction (AAV2/8-LSPhGAA). Reported clinical parameters included GAA genotype, assessments of muscle function, upright and supine spirometry, anti-recombinant human GAA antibody titers, and biomarkers. Variability in measured parameters and phenotypes of screened individuals was evident. Eligibility criteria required that all participants have six-minute walk test (6MWT) and upright forced vital capacity (FVC) below the expected range for normal individuals, and were stably treated with ERT for >2 years. All participants had Pompe disease diagnosed by enzyme deficiency, and all had the common c.-32-13T>G LOPD pathogenic variant. Screening identified 14 patients (74%) with no or minimal detectable neutralizing antibodies against AAV8 (titer ≤1:5). 6MWT distance varied significantly (percent of expected distance ranging from 24% to 91% with an average of 60 and standard deviation of 21). Upright FVC percent predicted ranged from 35% predicted to 91% predicted with an average of 66 and standard deviation of 18. None of the participants had significantly elevated alanine transaminase, which has been associated with LOPD and could complicate screening for hepatitis related to AAV gene therapy. We review the parameters considered in screening for eligibility for a clinical trial of AAV8 vector-mediated gene therapy.
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Glycogen storage diseases (GSDs) are a group of rare, monogenic disorders that share a defect in the synthesis or breakdown of glycogen. This Primer describes the multi-organ clinical features of hepatic GSDs and muscle GSDs, in addition to their epidemiology, biochemistry and mechanisms of disease, diagnosis, management, quality of life and future research directions. Some GSDs have available guidelines for diagnosis and management. Diagnostic considerations include phenotypic characterization, biomarkers, imaging, genetic testing, enzyme activity analysis and histology. Management includes surveillance for development of characteristic disease sequelae, avoidance of fasting in several hepatic GSDs, medically prescribed diets, appropriate exercise regimens and emergency letters. Specific therapeutic interventions are available for some diseases, such as enzyme replacement therapy to correct enzyme deficiency in Pompe disease and SGLT2 inhibitors for neutropenia and neutrophil dysfunction in GSD Ib. Progress in diagnosis, management and definitive therapies affects the natural course and hence morbidity and mortality. The natural history of GSDs is still being described. The quality of life of patients with these conditions varies, and standard sets of patient-centred outcomes have not yet been developed. The landscape of novel therapeutics and GSD clinical trials is vast, and emerging research is discussed herein.
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Doença de Depósito de Glicogênio Tipo II , Doença de Depósito de Glicogênio Tipo I , Doença de Depósito de Glicogênio , Humanos , Qualidade de Vida , Doença de Depósito de Glicogênio/diagnóstico , Doença de Depósito de Glicogênio/terapia , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/genética , Doença de Depósito de Glicogênio Tipo II/terapia , Doença de Depósito de Glicogênio Tipo I/complicações , Doença de Depósito de Glicogênio Tipo I/diagnóstico , Doença de Depósito de Glicogênio Tipo I/terapia , Progressão da DoençaRESUMO
There is a broad differential diagnosis of infantile hepatosplenomegaly, with some etiologies being debilitating and treatable. A structured approach to history, examination, and laboratory and radiographic findings is important in diagnosis. Herein, we present a case of Wolman disease presenting as hepatosplenomegaly in an infant. This case details important learning points to help distinguish the diagnosis of Wolman disease from other conditions with overlapping clinical features, such as hemophagocytic lymphohistiocytosis (HLH). The advent of enzyme replacement therapy has dramatically changed the natural history of Wolman disease, and this child showed remarkable improvement with treatment. This child was later found to have extensive adenopathy with retroperitoneal lymph node biopsy demonstrating diffuse infiltration by lipid-laden macrophages, fatty deposits, cholesterol crystals, and calcifications. Similar to the collection of characteristic cells in other lysosomal storage disorders, we postulate that this is characteristic of underlying Wolman disease. We conclude with a summary of learning points from this presentation on infantile hepatosplenomegaly, pertinent to the geneticist, pediatrician, and pediatric subspecialists.
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Linfo-Histiocitose Hemofagocítica , Doença de Wolman , Criança , Colesterol , Hepatomegalia/diagnóstico , Humanos , Lactente , Lipídeos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Esplenomegalia/complicações , Esplenomegalia/diagnóstico , Doença de Wolman/diagnóstico , Doença de Wolman/tratamento farmacológico , Doença de Wolman/genéticaRESUMO
Although inflammatory bowel disease is a well-described feature of glycogen storage disease type Ib, it has been reported in only a small number of individuals with glycogen storage disease type Ia (GSDIa). We describe, to our knowledge, the first patient with GSDIa and very early-onset inflammatory bowel disease (VEO-IBD). Larger studies are needed to better understand this possible association, elucidate the mechanism of VEO-IBD in GSDIa, and inform management.
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BACKGROUND: Primary ciliary dyskinesia (PCD) is a motile ciliopathy characterised by otosinopulmonary infections. Inheritance is commonly autosomal recessive, with extensive locus and allelic heterogeneity. The prevalence is uncertain. Most genetic studies have been done in North America or Europe. The aim of the study was to estimate the worldwide prevalence and ethnic heterogeneity of PCD. METHODS: We calculated the allele frequency of disease-causing variants in 29 PCD genes associated with autosomal recessive inheritance in 182 681 unique individuals to estimate the global prevalence of PCD in seven ethnicities (African or African American, Latino, Ashkenazi Jewish, Finnish, non-Finnish European, east Asian, and south Asian). We began by aggregating variants that had been interpreted by Invitae, San Francisco, CA, USA, a genetics laboratory with PCD expertise. We then determined the allele frequency of each variant (pathogenic, likely pathogenic, or variant of uncertain significance [VUS]) in the Genome Aggregation Database (gnomAD), a publicly available next-generation sequencing database that aggregates exome and genome sequencing information from a wide variety of large-scale projects and stratifies allele counts by ethnicity. Using the Hardy-Weinberg equilibrium equation, we were able to calculate a lower-end prevalence of PCD for each ethnicity by including only pathogenic and likely pathogenic variants; and upper-end prevalence by also including VUS. This approach was similar to previous work on Li-Fraumeni (TP53 variants) prevalence. We were not diagnosing PCD, but rather estimating prevalence based on known variants. FINDINGS: The overall minimum global prevalence of PCD is calculated to be at least one in 7554 individuals, although this is likely to be an underestimate because some variants currently classified as VUS might be disease-causing and some pathogenic variants might not be detected by our methods. In the overall cohort, Invitae data could be included for variants without gnomAD data for a primary ethnicity. When using only gnomAD allele frequencies to calculate prevalence in individual ethnicities, the estimated prevalence of PCD was lower in each ethnicity compared with the overall cohort. This is because the overall cohort includes additional data from the Invitae database such as copy number variants and other variants not present in gnomAD. With gnomAD we found the expected PCD frequency to be higher in individuals of African ancestry than in most other populations (excluding VUS: 1 in 9906 in African or African American vs 1 in 10 388 in non-Finnish European vs 1 in 14 606 in east Asian vs 1 in 16 309 in Latino; including VUS: 1 in 106 in African or African American vs 1 in 178 in non-Finnish European vs 1 in 196 in Latino vs 1 in 188 in east Asian). In addition, we found that the top 5 genes most commonly implicated in PCD differed across ethnic ancestries and contrasted commonly published findings. INTERPRETATION: PCD appears to be more common than has been recognised, particularly in individuals of African ancestry. We identified gene distributions that differ from those in previous European and North American studies. These results could have an international impact on case identification. Our analytic approach can be expanded as more PCD loci are identified, and could be adapted to study the prevalence of other inherited diseases. FUNDING: None.
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Transtornos da Motilidade Ciliar , Etnicidade , Bases de Dados Genéticas , Etnicidade/genética , Frequência do Gene , Humanos , PrevalênciaRESUMO
BACKGROUND: Cytokine release syndrome is a life-threatening condition known to cause fever and multiple organ dysfunction and is suspected to be related to the severity of coronavirus disease 2019 (COVID-19). We sought to examine the utility of the HScore and non-cytokine markers of inflammation for predicting COVID-19 outcomes. We hypothesized that cytokine storm, assessed by a modified HScore, would be linked to more severe COVID-19 symptoms and higher mortality. METHODS: A retrospective review of records from a large, private hospital system was conducted on patients with hemophagocytic lymphohistiocytosis (HLH) (2014-2019) and compared to a large cohort of COVID-19-positive patients (2020). Patients with a sufficient number of elements in their record for a modified HScore calculation (n=4663), were further subdivided into population 1 (POP1, n=67; HLH, n=493 COVID-19), which had eight HScore elements, and population 2 (POP2) with six available HScore elements (POP2, n=102; HLH, n=4561 COVID-19). RESULTS: Modified HScore predicted COVID-19 severity in POP1 and POP2 as measured by higher odds of being on a ventilator (POP2 OR: 1.46, CI: 1.42-1.5), ICU admission (POP2 OR: 1.38, CI: 1.34-1.42), a longer length of stay (p<0.0001), and higher mortality (POP2 OR: 1.34, CI: 1.31-1.39). C-reactive protein (CRP) and white blood cell (WBC) count were the most consistent non-cytokine predictors of COVID-19 severity. CONCLUSION: Cytokine storm, evaluated using a modified HScore, appeared to play a role in the severity of COVID-19 infection, and selected non-cytokine markers of inflammation were predictive of disease severity.
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Among etiologies of hyperammonemic emergencies, infection must be considered in certain clinical contexts, particularly among immunocompromised individuals. Although Cryptococcus neoformans is known to be urease-producing, to our knowledge it has not previously been described as a cause of hyperammonemia in patients. We report an immunocompromised man with acute on chronic kidney disease with hyperammonemic crisis due to Cryptococcal meningitis and fungemia. It is important to be aware of C. neoformans as a possible cause of hyperammonemia.
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BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) requires sponsoring institutions to demonstrate effective oversight through an annual institutional review (AIR). The ACGME only requires 3 elements to be reported, and it is up to the discretion of the designated institutional official (DIO) whether other supporting information should be included. This leads to uncertainty and inconsistency for DIOs as they decide what to report. OBJECTIVE: We surveyed DIOs in an effort to provide national data on key performance indicators and other relevant components of the AIR process. METHODS: In July 2019, we conducted a national survey of 847 DIOs. The survey had 16 questions that explored basic institutional demographics, timelines, and processes for the AIR and key performance indicators. Written answers were grouped by similar responses, and we performed descriptive statistics on all variables to assess distributions of responses. We also explored associations between variables using cross-tabulation and chi-square statistics. RESULTS: A total of 267 DIOs responded to the survey (32% response rate). There were 7 institutional performance measures that achieved over 50% consensus. These reviews required the majority of DIOs (62%, 167 of 267) 5 to 20 hours to complete. Less than one-third of sponsoring institutions reported diversity data. The majority of DIOs (68%, 182 of 267) felt the AIR process added substantial value. CONCLUSIONS: This survey reports key performance measures and processes included by DIOs in the AIR. Our results show a wide range of institutional responses though consensus was achieved on 7 key performance measures.
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Internato e Residência , Acreditação , Educação de Pós-Graduação em Medicina , Humanos , Inquéritos e QuestionáriosRESUMO
Although individuals of Amish descent with propionic acidemia (PA) are generally thought to have a milder disease phenotype, we now have a better understanding of the natural history of PA in this population. Here we describe two Amish patients with emergent presentations of PA, one with metabolic decompensation and another with cardiogenic shock. PA can present with life-threatening metabolic decompensation or an adult-onset severe cardiomyopathy. We discuss critical clinical implications of this observation.
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OBJECTIVE: To evaluate whether cystic fibrosis transmembrane conductance regulator (CFTR) variants are more common among individuals tested for primary ciliary dyskinesia (PCD) compared with controls. STUDY DESIGN: Data were studied from 1021 individuals with commercial genetic testing for suspected PCD and 91â777 controls with genetic testing at the same company (Invitae) for symptoms/diseases unrelated to PCD or CFTR testing. The prevalence of CFTR variants was compared between controls and each of 3 groups of individuals tested for PCD (PCD-positive, -uncertain, and -negative molecular diagnosis). RESULTS: The prevalence of 1 pathogenic CFTR variant was similar among the individual groups. When combining the PCD-uncertain and PCR-negative molecular diagnosis groups, there was a higher prevalence of single pathogenic CFTR variants compared with controls (P = .03). Importantly, >1% of individuals who had negative genetic testing results for PCD had 2 pathogenic CFTR variants (8 of 723), and the incidence of cystic fibrosis (CF) (2 pathogenic variants) is roughly 1 in 3000 individuals of Caucasian ethnicity (â¼0.03%). This incidence was also greater than that of 2 pathogenic CFTR variants in the control population (0.09% [84 of 91â777]; P = 9.60 × 10-16). These variants correlate with mild CFTR-related disease. CONCLUSIONS: Our results suggest that a single pathogenic CFTR variant is not likely to be a PCD-mimetic, but ongoing studies are needed in individuals in whom PCD is suspected and genetic testing results are uncertain or negative. Furthermore, CF may be misdiagnosed as PCD, reflecting phenotypic overlap. Among individuals evaluated for PCD, CF should be considered in the differential even in the CF newborn screening era.
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Transtornos da Motilidade Ciliar/etiologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/complicações , Mutação , Transtornos da Motilidade Ciliar/diagnóstico , Transtornos da Motilidade Ciliar/genética , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Análise Mutacional de DNA , Feminino , Seguimentos , Testes Genéticos/métodos , Humanos , Recém-Nascido , Masculino , Prevalência , Estudos RetrospectivosRESUMO
While joint damage is the primary co-morbidity of hemophilia, osteoporosis and osteopenia are also observed. Coagulation factor VIII deficient (FVIII-/-) mice develop an osteoporotic phenotype in the absence of induced hemarthrosis that is exacerbated two weeks after an induced joint injury. Here we have compared comprehensively the bone health of clotting factor VIII, factor IX, and Von Willebrand Factor knockout (FVIII-/-, FIX-/-, and VWF-/- respectively) mice both in the absence of joint hemorrhage and following induced joint injury. We found FVIII-/- and FIX-/- mice, but not VWF-/- mice, developmentally have an osteoporotic phenotype. Unilateral induced hemarthrosis causes further bone damage in both FVIII-/- and FIX-/- mice, but has little effect on VWF-/- bone health, indicating that the FVIII.VWF complex is not required for normal bone remodeling in vivo. To further investigate the bone healing following hemarthrosis in hemophilia we examined a two week time course using microCT, serum chemistry, and histological analysis. Elevated ratio of osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL), increased osterix+ osteoblastic cells, and decreased smoothness of the cortical bone surface were evident within several days of injury, indicative of acute heterotopic mineralization along the cortical surface. This was closely followed by increased interleukin-6 (IL-6) levels, increased osteoclast numbers, and significant trabecular bone loss. Uncoupled and disorganized bone formation and resorption continued for the duration of the study resulting in significant deterioration of the joint. Further elucidation of the shared mechanisms underlying abnormal bone homeostasis in the absence of FVIII or FIX is needed to guide evidence-based approaches to the screening and treatment of the prevalent bone defects in hemophilia A and B.
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Fator IX/genética , Fator VIII/genética , Hemofilia A/metabolismo , Hemofilia B/metabolismo , Fator de von Willebrand/genética , Animais , Testes de Coagulação Sanguínea , Osso e Ossos/metabolismo , Hemofilia A/genética , Hemofilia A/patologia , Hemofilia B/genética , Hemofilia B/patologia , Humanos , Interleucina-6/genética , Masculino , Camundongos , Camundongos Knockout , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoporose/genética , Osteoporose/patologia , Fenótipo , Ligante RANK/genética , Fator de Transcrição Sp7/genéticaRESUMO
BACKGROUND: OFD1 has long been recognized as the gene implicated in the classic dysmorphology syndrome, oral-facial-digital syndrome type I (OFDSI). Over time, pathogenic variants in OFD1 were found to be associated with X-linked intellectual disability, Joubert syndrome type 10 (JBTS10), Simpson-Golabi-Behmel syndrome type 2 (SGBS2), and retinitis pigmentosa. Recently, OFD1 pathogenic variants have been implicated in primary ciliary dyskinesia (PCD), a disorder of the motile cilia with a phenotype that includes recurrent oto-sino-pulmonary infections, situs abnormalities, and decreased fertility. METHODS: We describe three male patients with PCD who were found to have hemizygous pathogenic variants in OFD1, further supporting that PCD is part of a clinical spectrum of OFD1-related disorders. In addition, we provide a review of the available clinical literature describing patients with OFD1 variants and highlight the phenotypic variability of OFD1-related disease. RESULTS: Some individuals with hemizygous OFD1 variants have PCD, either apparently isolated or in combination with other features of OFD1-related disorders. CONCLUSION: As clinicians consider the presence or absence of conditions allelic at OFD1, PCD should be considered part of the spectrum of OFD1-related disorders. Understanding the OFD1-related disease spectrum may allow for more focused genetic testing and more timely management of treatable sequelae.
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Transtornos da Motilidade Ciliar/genética , Hemizigoto , Mutação com Perda de Função , Proteínas/genética , Anormalidades Múltiplas/genética , Adolescente , Adulto , Doenças Cerebelares/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Masculino , Hipotonia Muscular/genética , Retinose Pigmentar/genéticaRESUMO
Previous reports of lung function in cystic fibrosis (CF) patients with liver disease have shown worse, similar, or even better forced expiratory volume in 1 second (FEV1), compared to CF patients without liver disease. Varying definitions of CF liver disease likely contribute to these inconsistent relationships reported between CF lung function and liver disease. We retrospectively evaluated spirometric data in 179 subjects (62% male; 58% Phe508del homozygous) with severe CF liver disease (CFLD; defined by presence of portal hypertension due to cirrhosis). FEV1 values were referenced to both a normal population (FEV1% predicted) and CF population (CF-specific FEV1 percentile). We utilized a linear mixed model with repeated measures to assess changes in lung function (before and after diagnosis of CFLD), relative to both the normal and CF populations. At diagnosis of CFLD, the mean FEV1 was 81% predicted, or at the 53rd percentile referenced to CF patients without CFLD. There was a significant difference in post-CFLD slope compared to pre-CFLD slope (post-pre) using FEV1% predicted (-1.94, p-value < 0.0001). However, there was insignificant evidence of this difference using the CF-specific FEV1 percentile measure (-0.99, p-value = 0.1268). Although FEV1% predicted values declined in patients following CFLD diagnosis, there was not significant evidence of lung function decline in CF-specific FEV1 percentiles. Thus, the observed study cohort indicates diagnosis of severe CFLD was not associated with worsened CF lung disease when compared to a large CF reference population.
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Fibrose Cística/fisiopatologia , Volume Expiratório Forçado/fisiologia , Hipertensão Portal/fisiopatologia , Cirrose Hepática/fisiopatologia , Pulmão/fisiopatologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Feminino , Humanos , Hipertensão Portal/diagnóstico , Hipertensão Portal/etiologia , Fígado/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Espirometria , Adulto JovemRESUMO
The purposes of this study are to (1) introduce our novel Applicant Ranking Tool that aligns with the Accreditation Council for Graduate Medical Education competencies and (2) share our preliminary results comparing applicant rank to current performance. After a thorough literature review and multiple roundtable discussions, an Applicant Ranking Tool was created. Feasibility, satisfaction, and critiques were discussed via open feedback session. Inter-rater reliability was assessed using weighted kappa statistic (κ) and Kendall coefficient of concordance (W). Fisher's exact tests evaluated the ability of the tool to stratify performance into the top or bottom half of their class. Internal medicine and anesthesiology residents served as the pilot cohorts. The tool was considered user-friendly for both data input and analysis. Inter-rater reliability was strongest with intradisciplinary evaluation (W = 0.8-0.975). Resident performance was successfully stratified into those functioning in the upper vs. lower half of their class within the Clinical Anesthesia-3 grouping (p = 0.008). This novel Applicant Ranking Tool lends support for the use of both cognitive and noncognitive traits in predicting resident performance. While the ability of this instrument to accurately predict future resident performance will take years to answer, this pilot study suggests the instrument is worthy of ongoing investigation.
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Sucesso Acadêmico , Avaliação Educacional/métodos , Internato e Residência/tendências , Critérios de Admissão Escolar/tendências , Desempenho Profissional/normas , Anestesiologia/educação , Competência Clínica/normas , Educação de Pós-Graduação em Medicina/métodos , Educação de Pós-Graduação em Medicina/normas , Humanos , Medicina Interna/educação , Candidatura a Emprego , Otolaringologia/educação , Determinação da Personalidade , Projetos Piloto , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Natural, synthetic and analogues of peptides have shown prospects for application in cancer chemotherapy. Notably, some food protein-derived peptides are known to possess anticancer activities in cultured cancer cells, and also in animal cancer models via different mechanisms including induction of apoptosis, cell cycle arrest, cellular membrane disruption, inhibition of intracellular signalling, topoisomerases and proteases, and antiangiogenic activity. Although the mechanism of several anticancer food peptides is yet to be clearly elucidated, there is potential for practical applications of the peptides as functional food and nutraceutical ingredients, especially in adjuvant cancer therapy. This review describes the aetiological mechanisms of cancers and the production, structures, mechanisms of action, availability, and cellular and physiological anticancer activities of the food peptides.
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Antineoplásicos/farmacologia , Proteínas Alimentares/química , Neoplasias/tratamento farmacológico , Peptídeos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Apoptose , Ciclo Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias/metabolismo , Peptídeos/química , Peptídeos/uso terapêutico , Transdução de Sinais/efeitos dos fármacosRESUMO
Mandatory HIV screening of United States Air Force (USAF) personnel every two years effectively identifies incident cases, however testing frequency limits the ability to detect early HIV infection. Identifying clinical indicators of HIV in the USAF population is necessary to develop a supplemental provider-based targeted testing strategy. We conducted a matched case-control study of male active duty USAF personnel with a new HIV diagnosis (n = 452) between 1996 and 2011 matched to five randomly selected controls (n = 2176). The relationship between clinical diagnoses, determined by ICD-9 codes, and HIV infection was assessed using conditional logistic regression. In unadjusted analyses of ICD-9 codes ever and within the last two years before HIV diagnosis, the conditional odds of HIV infection were greater in those with clinical signs and symptoms of HIV (cOR 5.05, 95% CI 4.00-6.39), mental health diagnoses (cOR 2.61, 95% CI 1.86-3.67), and STI diagnoses (cOR 2.33, 95% CI 1.50-3.60). Compared to those with ≤10 medical encounters in the two years prior to HIV diagnosis, individuals with 11-35 medical encounters (cOR 2.19, 95% CI 1.73-2.79) and >35 medical encounters (cOR 4.15, 95% CI 2.69-6.39) had a higher odds of HIV acquisition. In multivariate analyses, clinical signs and symptoms of HIV within the last two years of HIV diagnosis (cOR 4.10, 95% CI 3.22-5.22) and ever having a mental health diagnosis (cOR 1.97, 95% CI 1.44-2.70) remained significant (p < .01). Clinical encounters, particularly those featuring clinical signs and symptoms of HIV or a history of mental health complaints, provide an opportunity for targeted testing as a supplement to mandated testing at two-year intervals. Provider education to increase HIV testing in persons at risk would enhance early HIV diagnosis and potentially reduce forward transmission in the USAF population.
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Infecções por HIV/diagnóstico , Infecções por HIV/transmissão , Militares/estatística & dados numéricos , Adulto , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Classificação Internacional de Doenças , Modelos Logísticos , Masculino , Testes Obrigatórios , Transtornos Mentais/complicações , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Medição de Risco , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/transmissão , Estados Unidos , Adulto JovemRESUMO
INTRODUCTION: Mast cell leukemia (MCL) is a rare variant of systemic mastocytosis. Most cases of mast cell leukemia do not have cytogenics performed. Furthermore, there is no consistent chromosomal abnormality identified in MCL. This is the first reported case of MCL with a (9;22) translocation. CASE REPORT: An 80-year-old female presented with pancytopenia and was diagnosed with MDS. Over time, she required hospitalizations for platelet transfusions with increased frequency. She developed fatigue and weakness along with gastrointestinal symptoms. On exam, she had diffuse abdominal tenderness and a maculopapular rash. Her lab results revealed a new basophilia. A bone marrow biopsy showed 100% cellularity with many aggregates of mast cells. Chromosomal analysis showed t(9;22) with confirmed BCR/ABL1 fusion by fluorescence in situ hybridization (FISH). DISCUSSION: MCL has a poor prognosis due to the aggressive nature of the disease and ineffective therapies. Translocation (9;22) is known to be associated with MDS transformations to acute leukemia; however, this translocation has never been reported in MCL. Further research on the relationship between t(9;22) and MCL could lead to development of improved therapeutic options.