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Children and adolescents in rural areas with chronic kidney disease (CKD) face unique challenges related to accessing pediatric nephrology care. Challenges to obtaining care begin with living increased distances from pediatric health care centers. Recent trends of increasing centralization of pediatric care mean fewer locations have pediatric nephrology, inpatient, and intensive care services. In addition, access to care for rural populations expands beyond distance and encompasses domains of approachability, acceptability, availability and accommodation, affordability, and appropriateness. Furthermore, the current literature identifies additional barriers to care for rural patients that include limited resources, including finances, education, and community/neighborhood social resources. Rural pediatric kidney failure patients have barriers to kidney replacement therapy options that may be even more limited for rural pediatric kidney failure patients when compared to rural adults with kidney failure. This educational review identifies possible strategies to improve health systems for rural CKD patients and their families: (1) increasing rural patient and hospital/clinic representation and focus in research, (2) understanding and mediating gaps in the geographic distribution of the pediatric nephrology workforce, (3) introducing regionalization models for delivering pediatric nephrology care to geographic areas, and (4) employing telehealth to expand the geographic reach of services and reduce family time and travel burden.
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Nefrologia , Insuficiência Renal Crônica , Insuficiência Renal , Telemedicina , Adulto , Adolescente , Humanos , Criança , População Rural , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Acessibilidade aos Serviços de SaúdeRESUMO
NTHL1-associated tumor syndrome (NATS) is an autosomal recessive condition characterized by an increased risk for colorectal polyposis and colorectal cancer (CRC). Only 46 case reports have been previously published. In a retrospective review, we analyzed the clinical histories of six patients found to have NATS after genetic counseling and testing. NATS appears to be associated with an increased risk for colorectal polyposis, CRC, female breast cancer, meningiomas, and endometrial cancer. Although research is limited, prior publications have reported a multi-tumor predisposition for individuals with biallelic pathogenic or likely pathogenic variants in NTHL1. Additional data are necessary to further define the cancer risks so affected individuals can be appropriately managed.
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Polipose Adenomatosa do Colo , Neoplasias Colorretais , Desoxirribonuclease (Dímero de Pirimidina) , Feminino , Humanos , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Desoxirribonuclease (Dímero de Pirimidina)/genética , Predisposição Genética para Doença , Neoplasias da Mama/genética , Meningioma/genética , Neoplasias do Endométrio/genéticaRESUMO
The increased use of next-generation sequencing has led to the detection of pathogenic TP53 variants in the germline setting in patients without a personal or family history consistent with Li-Fraumeni syndrome (LFS). These variants can represent low-penetrance LFS, mosaic LFS, or clonal hematopoiesis of indeterminate potential. Additionally, TP53 variants of uncertain significance can be detected in patients with a history suspicious for LFS. The interpretation of the significance of these variants can be challenging but is crucial for an accurate diagnosis and appropriate medical management. This retrospective case review provides illustrative examples of the interpretation of challenging TP53 results through multidisciplinary expertise and use of a flowchart. The authors describe eight patients with TP53 variants associated with ambiguous diagnoses and, for each case, describe how the results were interpreted and the medical care that was implemented. This report presents illustrative cases to help guide clinicians to reach definitive diagnoses for patients when confronted with TP53 variants that are inconsistent with the clinical picture and to add to the body of literature regarding interpretation and medical management of TP53 variants discovered on germline testing.
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Pediatric chronic kidney disease (CKD) is characterized by many co-morbidities, including impaired growth and development, CKD-mineral and bone disorder, anemia, dysregulated iron metabolism, and cardiovascular disease. In pediatric CKD cohorts, higher circulating concentrations of fibroblast growth factor 23 (FGF23) are associated with some of these adverse clinical outcomes, including CKD progression and left ventricular hypertrophy. It is hypothesized that lowering FGF23 levels will reduce the risk of these events and improve clinical outcomes. Reducing FGF23 levels in CKD may be accomplished by targeting two key stimuli of FGF23 production-dietary phosphate absorption and iron deficiency. Ferric citrate is approved for use as an enteral phosphate binder and iron replacement product in adults with CKD. Clinical trials in adult CKD cohorts have also demonstrated that ferric citrate decreases circulating FGF23 concentrations. This review outlines the possible deleterious effects of excess FGF23 in CKD, summarizes data from the adult CKD clinical trials of ferric citrate, and presents the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) study, a randomized, placebo-controlled trial to evaluate the effects of ferric citrate on FGF23 in pediatric patients with CKD stages 3-4 (ClinicalTrials.gov Identifier NCT04741646).
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Insuficiência Renal Crônica , Criança , Compostos Férricos , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Ferro/uso terapêutico , Minerais , Fosfatos , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/complicaçõesRESUMO
Motor skills are an important aspect of development during infancy and have been found to predict development in other domains. Therefore, fast and reliable assessments of infant motor skills are needed. The current study revisited a time and cost-effective parent-report measure of infants' motor skills-the Early Motor Questionnaire (EMQ)-and aimed to improve the utility of the EMQ as a tool to examine variability, stability, and individual differences in early motor development. A sample of 446 parents of infants provided a total of 775 EMQ responses for analyses. Using this large sample, regression was used to create age-independent scores for global, gross motor, fine motor, and perception-action scores on the EMQ. Age-adjusted scores were then converted to t-scores to facilitate score interpretation for past and future studies using the EMQ. Finally, starting flags for different age groups were created to decrease the time it takes parents to complete the EMQ. Together, these changes to the EMQ will improve the utility and interpretability of the measure. The EMQ is free to use and available in the supplemental materials or via www.onlinebabylab.com/emq.
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Destreza Motora , Pais , Desenvolvimento Infantil/fisiologia , Humanos , Individualidade , Lactente , Destreza Motora/fisiologia , Inquéritos e QuestionáriosRESUMO
Frameworks have been developed to help conceptualize clinical genetic counseling (GC), and observational studies have helped understand the process and content of GC sessions. However, additional research is needed to identify GC skills (behaviors or strategies) that practicing genetic counselors report consciously using to meet certain GC goals and determine what common terminology, if any, is being used to describe the various skills. Nineteen practicing genetic counselors in prenatal, pediatric, or cancer specialties were interviewed to elicit how they achieve session goals. Interview recordings were transcribed, coded thematically, and categorized using process categories from the communication strategy domain of the Framework for Outcomes in Clinical Communication Services (FOCUS). Reported skills largely fit within FOCUS, though findings prompted minor modifications of several FOCUS process categories and consolidation of the categories from 13 into 10. Although genetic counselor respondents reported a broad range of strategies and behaviors, they rarely had terms for skills they described. Results reveal concrete examples of GC skills, provide evidence for refinement of FOCUS, and highlight the need for establishing common terminology to describe these skills.
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Conselheiros , Criança , Comunicação , Aconselhamento , Conselheiros/psicologia , Feminino , Aconselhamento Genético/psicologia , Humanos , Gravidez , AutorrelatoRESUMO
The emergency life-history stage (ELHS) can be divided into two subcategories that describe distinct, coordinated responses to disease- or non-disease-related physiological challenges. Whether an individual can simultaneously express aspects of both subcategories when faced with multiple challenges is poorly understood. Emergency life-history theory suggests that disease- and non-disease-related responses are coordinated at the level of the whole organism and therefore cannot be expressed simultaneously. However, the reactive scope and physiological regulatory network models suggest that traits can be independently regulated, allowing for components of both disease- and non-disease-related responses to be simultaneously expressed within a single organism. To test these ideas experimentally, we subjected female zebra finches to food deprivation, an immune challenge, both, or neither, and measured a suite of behavioural and physiological traits involved in the ELHS. We examined whether the trait values expressed by birds experiencing simultaneous challenges resembled trait values of birds experiencing a single challenge or if birds could express a mixture of trait values concurrently. We find that birds can respond to simultaneous challenges by regulating components of the behavioural and immune responses independently of one another. Modularity within these physio-behavioural networks adds additional dimensions to how we evaluate the intensity or quality of an ELHS. Whether modularity provides fitness advantages or costs in nature remains to be determined.
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Tentilhões/fisiologia , Animais , Corticosterona , Feminino , Privação de Alimentos , Comportamento de Doença , Estágios do Ciclo de Vida , MasculinoRESUMO
RATIONALE & OBJECTIVE: Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker associated with incident chronic kidney disease (CKD) and has been identified as an independent risk factor for CKD progression in children, although these findings remain preliminary, limited to a single point in time, and unreplicated in pediatric cohorts. STUDY DESIGN: Prospective longitudinal cohort study. SETTING & PARTICIPANTS: 565 participants aged 1 to 16 years enrolled in the Chronic Kidney Disease in Children (CKiD) Study. EXPOSURE: Plasma suPAR levels, categorized by quartiles, measured at study entry and a 6-month follow-up interval. OUTCOME: CKD progression, defined as the initiation of kidney replacement therapy (dialysis or transplantation) or >50% decline in estimated glomerular filtrate rate (eGFR). ANALYTIC APPROACH: Associations between plasma suPAR quartiles and risk for CKD progression were estimated using lognormal survival models, adjusting for potential confounders. RESULTS: Participants in the highest suPAR quartile experienced 54% faster progression compared with the lowest quartile after adjustment for demographic and traditional CKD risk factors (P < 0.001). Addition of eGFR to the model attenuated the risk, although those in the highest quartile experienced 33% faster progression compared with the lowest quartile (P = 0.008). Plasma suPAR levels showed little change over 6 months. LIMITATIONS: Potential for residual confounding, reliance on observational data, relatively fewer patients with higher eGFRs for subgroup analysis. CONCLUSIONS: Higher suPAR levels are associated with shorter time to kidney replacement therapy or halving of eGFR in children with CKD. This association is attenuated slightly with inclusion of eGFR in regression modeling but remains a significant association for participants with the highest suPAR levels.
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Taxa de Filtração Glomerular , Falência Renal Crônica/sangue , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Insuficiência Renal Crônica/sangue , Terapia de Substituição Renal , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Lactente , Falência Renal Crônica/terapia , Transplante de Rim , Estudos Longitudinais , Masculino , Estudos Prospectivos , Diálise Renal , Insuficiência Renal Crônica/metabolismo , Fatores de TempoRESUMO
The purpose of this study was to compare injury patterns between recreational skiers and snowboarders. Injured skiers (n = 3,961) and snowboarders (n = 2,428) presented to a mountainside medical clinic, 2012/13-2016/17. Variables investigated for analysis included demographics/characteristics, injury event information, and injury information. Skiers were older than snowboarders (34.3 ± 19.3 vs. 23.2 ± 10.5 years, p < 0.001); a greater proportion of skiers were female (46.3% vs. 27.8%, p < 0.001). Most skiers (84.4%) and snowboarders (84.5%) were helmeted at the time of injury (p = 0.93). Snowboarders were most frequently beginners (38.9%), skiers were intermediates (37.8%). Falls to snow (skiers = 72.3%, snowboarders = 84.8%) and collisions with natural objects (skiers = 9.7%, snowboarders = 7.4%) were common injury mechanisms. Common skiing injuries were knee sprains (20.5%) and head trauma (8.9%); common snowboarding injuries were wrist fractures (25.7%), shoulder separations (9.1%), and head trauma (9.0%). Given that injury patterns significantly differ between sports, it is important for clinicians, ski patrollers, and resorts to develop and deliver sport-specific injury prevention interventions to most effectively decrease injury burden.
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Traumatismos em Atletas/epidemiologia , Esqui/lesões , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Colorado/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Telehealth can overcome access and availability barriers that often impede receiving needed mental health services. This case report describes an interdisciplinary approach to treatment for an individual with chronic physical health conditions and comorbid mental health concerns, which resulted in high utilization (and associated costs) of preventable emergency services. The report describes clinical case progression on anxiety symptoms and emergency service utilization while concurrently highlighting telehealth-specific practice implications, especially as they pertain to training settings.
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Transtornos de Ansiedade/terapia , Serviços de Saúde Mental , Equipe de Assistência ao Paciente , Atenção Primária à Saúde , Transtornos Somatoformes/terapia , Telemedicina , Adulto , Feminino , Humanos , Atenção Primária à Saúde/métodos , Serviços de Saúde Rural , Telemedicina/métodosRESUMO
When working with ultra-low-frequency (ULF) magnetic datasets, as with most geophysical time-series data, it is important to be able to distinguish between cultural signals, internal instrument noise, and natural external signals with their induced telluric fields. This distinction is commonly attempted using simultaneously recorded data from a spatially remote reference site. Here, instead, we compared data recorded by two systems with different instrumental characteristics at the same location over the same time period. We collocated two independent ULF magnetic systems, one from the QuakeFinder network and the other from the United States Geological Survey (USGS)-Stanford network, in order to cross-compare their data, characterize data reproducibility, and characterize signal origin. In addition, we used simultaneous measurements at a remote geomagnetic observatory to distinguish global atmospheric signals from local cultural signals. We demonstrated that the QuakeFinder and USGS-Stanford systems have excellent coherence, despite their different sensors and digitizers. Rare instances of isolated signals recorded by only one system or only one sensor indicate that caution is needed when attributing specific recorded signal features to specific origins.
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Recent studies of the onset of breeding in long-day photoperiodic breeders have focused on the roles of type 2 and 3 iodothyronine deiodinases (DIO2 and DIO3) in the conversion of thyroxine (T4) to triiodothyronine (T3) and subsequent activation of the reproductive axis. It has been hypothesized that an increase in DIO2 and a reciprocal decrease in DIO3 causes the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, setting off a reproductive cascade, and that this DIO mechanism for GnRH release is conserved across vertebrate taxa. We sought to test whether social cues that are known to stimulate reproductive behaviors can activate the DIO system to initiate reproduction in a non-photoperiodic bird, the zebra finch (Taeniopygia guttata). Isolation of males and subsequent presentation of females did not increase DIO2 or GnRH expression in the hypothalamus, nor did it decrease gonadotropin-inhibitory hormone (GnIH) or DIO3. Males receiving a female stimulus showed significantly higher mRNA expression and immunoreactive cell count of the immediate-early gene early growth response protein 1 (EGR-1) than isolated males, indicating hypothalamic activation in response to a female. Cells immunoreactive for EGR-1 were not co-localized with those immunoreactive for GnRH. Reproductive behaviors (singing, copulation attempts and overall activity) were significantly higher in males receiving a female stimulus. This study presents a social effect on behavior and EGR-1 expression in the hypothalamus of males in response to females, but more research is needed to determine whether the DIO2 system and the GnRH system are responsive to social stimulation in this species.
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Sinais (Psicologia) , Tentilhões/fisiologia , Reprodução/fisiologia , Comportamento Sexual Animal/fisiologia , Animais , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Feminino , Regulação da Expressão Gênica , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Iodeto Peroxidase/metabolismo , Masculino , Vocalização Animal/fisiologiaRESUMO
High-level exposures to a number of agents are known to have direct nephrotoxic effects in children. A growing body of literature supports the hypothesis that chronic, relatively low-level exposure to various nephrotoxicants may also increase the risk for chronic kidney disease (CKD) or accelerate its progression. In this review we highlight several environmental nephrotoxicants and their association with CKD in children and adolescents. We also discuss unique epidemiological challenges in the use of kidney biomarkers in environmental nephrotoxicology.
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Exposição Ambiental/efeitos adversos , Rim/fisiopatologia , Metais Pesados/toxicidade , Insuficiência Renal Crônica/induzido quimicamente , Adolescente , Ácidos Aristolóquicos/toxicidade , Criança , Progressão da Doença , Disuria/epidemiologia , Disuria/etiologia , Humanos , Rim/crescimento & desenvolvimento , Micotoxinas/toxicidade , Prevalência , Insuficiência Renal Crônica/epidemiologia , Triazinas/toxicidadeRESUMO
Gonadotropin-inhibitory hormone (GnIH) acts to inhibit reproduction at all levels of the hypothalamo-pituitary-gonad axis. GnIH expression and/or immunoreactivity in the hypothalamus increase with acute stress in some birds and mammals, and thus may be involved in stress-induced reproductive inhibition. Much is known about GnIH and stress in seasonal and continuous breeders, but far less is known about these interactions in opportunistic breeders. For opportunistically breeding animals, reproductive readiness is closely associated with unpredictable environmental cues, and thus the GnIH system may be more sensitive to stress. To test this, we collected tissues from zebra finches immediately following capture or after 60 min of restraint. Restraint significantly increased plasma corticosterone in males and females but, contrary to studies on other species, restrained birds had significantly fewer GnIH immunoreactive (GnIH-ir) cell bodies than control birds. GnIH-ir cell number did not differ between the sexes. Stressed females had lower mRNA expression of the beta subunit of follicle stimulating hormone (FSHß) in the pituitary, suggesting that the reduction in observed GnIH immunoreactivity in females may have been due to increased GnIH release in response to acute stress. GnIH expression increased in the testes, but not the ovaries, of restrained animals. Our data suggest that although GnIH responsiveness to stress appears to be conserved across species, specific tissue response and direction of GnIH regulation is not. Variation in the GnIH response to stress between species might be the result of ecological adaptations or other species differences in the response of the GnIH system to stress.
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Encéfalo/metabolismo , Hormônios Hipotalâmicos/metabolismo , Hipotálamo/metabolismo , Ovário/metabolismo , Estresse Fisiológico/fisiologia , Estresse Psicológico/metabolismo , Testículo/metabolismo , Animais , Corticosterona/sangue , Sinais (Psicologia) , Feminino , Tentilhões , Masculino , Hipófise/metabolismo , Reprodução/fisiologiaRESUMO
BACKGROUND: Antibiotics are highly utilized in nursing homes. The aim of the study was to test the effectiveness of a decision-making aid for urinary tract infection management on reducing antibiotic prescriptions for suspected bacteriuria in the urine without symptoms, known as asymptomatic bacteriuria (ASB) in twelve nursing homes in Texas. METHOD: A pre- and post-test with comparison group design was used. The data was collected through retrospective chart review. The study sample included 669 antibiotic prescriptions for suspected urinary tract infections ordered for 547 nursing home residents. The main measurement for the outcome variable was whether an antibiotic was prescribed for suspected urinary tract infections with no symptoms present. RESULTS: Most of the prescriptions for antibiotics UTIs were written without documented symptoms - thus for asymptomatic bacteuria (ASB) (71 % during the pre-intervention period). Exposure to the decision-making aid decreased the number of prescriptions written for ASB (from 78 % to 65 % in the low-intensity homes and from 65 % to 57 % in the high-intensity homes), and decreased odds of a prescription being written for ASB (OR = 0.63, 95 % CI = 0.25 - 1.60 for low-intensity homes; OR = 0.79, 95 % CI = 0.33 - 1.88 for high-intensity homes). The odds of a prescription being written for ASB decreased significantly in homes that succeeded in implementing the decision-making aid (OR = 0.35, 95 % CI = 0.16-0.76), compared to homes with no fidelity. CONCLUSIONS: The decision-making aid improved antibiotic stewardship in nursing homes.
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Antibacterianos/uso terapêutico , Técnicas de Apoio para a Decisão , Instituição de Longa Permanência para Idosos , Casas de Saúde , Uso Excessivo de Medicamentos Prescritos/enfermagem , Uso Excessivo de Medicamentos Prescritos/prevenção & controle , Infecções Urinárias/diagnóstico , Infecções Urinárias/enfermagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriúria/diagnóstico , Bacteriúria/tratamento farmacológico , Bacteriúria/enfermagem , Feminino , Humanos , Masculino , Diagnóstico de Enfermagem , Estudos Retrospectivos , Estados Unidos , Infecções Urinárias/tratamento farmacológicoRESUMO
BACKGROUND: The majority of patients diagnosed with advanced epithelial ovarian carcinoma (EOC) relapse with resistant disease, and there are no biomarkers that possess clinical utility to identify or monitor these patients. This study aimed to identify secreted proteins ('secretome') collected from human EOC cell lines that differ in their inherent platinum sensitivity. METHODS: Secreted proteins collected from conditioned medium from ovarian cancer cell lines that vary in their sensitivity to cisplatin were digested with trypsin and analysed by liquid chromatography-tandem mass spectrometry for peptide identification. RESULTS: Of the 1688 proteins identified, 16 possessed significant differential abundances (P<0.05) between the platinum-resistant and -sensitive cell lines. A number of these were verified by immunoblot, including COL11A1, which was also found to be associated with worse progression-free survival (PFS; N=723) and overall survival (OS; N=1183) as assessed from publicly available transcript expression data from ovarian cancer tumour specimens. CONCLUSION: Secretome proteomics of EOC cells resulted in the identification of a novel candidate biomarker, COL11A1. The expression level of COL11A1 correlates to worse PFS and OS, and is predicted to reside in peripheral circulation making this an attractive candidate for validation in sera as a biomarker of cisplatin resistance and poor outcome.
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Biomarcadores Tumorais/sangue , Colágeno Tipo XI/sangue , Proteínas de Neoplasias/sangue , Neoplasias Epiteliais e Glandulares/sangue , Neoplasias Ovarianas/sangue , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Cisplatino/farmacologia , Colágeno Tipo XI/biossíntese , Colágeno Tipo XI/genética , Meios de Cultura , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Expressão Gênica , Humanos , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Proteômica , Taxa de SobrevidaRESUMO
Pediatric nephrology is dedicated to caring for children with kidney disease, a unique blend of acute care and chronic longitudinal patient relationships. Though historically a small field, trainee interest has declined over the past 2 decades. This has led to growing alarm about the health of the pediatric nephrology workforce, although concerns have been hampered by a lack of available data to enable feasible projections. This article is part of a supplement that anticipates the future pediatric subspecialty workforce supply. It draws on existing literature, data from the American Board of Pediatrics, and findings from a model that estimates the future supply of pediatric subspecialists developed by the Carolina Health Workforce Research Center at the University of North Carolina Chapel Hill's Cecil G. Sheps Center for Health Services Research and Strategic Modeling Analytics & Planning Ltd. The workforce projections from 2020 to 2040 incorporate population growth, clinical effort, and geographic trends and model alternate scenarios adjusting for changes in trainee interest, clinical efforts, and workforce attrition. The baseline model predicts growth of clinical work equivalents by 26% by 2040, but further widening geographic disparities worsen the existing mismatch between supply, clinical need, and market demand. The worst-case scenario projects 13% growth by 2040 which, at best, maintains the status quo of an already strained workforce. The models do not account for many factors expected to heighten demand over the coming decades. Urgent reforms are necessary now. Proposed solutions require multipronged changes in education and training pathways, remuneration, clinical practice models, and government policy.
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Nefrologia , Humanos , Criança , Saúde da Criança , Recursos Humanos , Mão de Obra em Saúde , EscolaridadeRESUMO
BACKGROUND: Lobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. It has been proposed that LEGH may represent a precursor lesion to a group of mucinous adenocarcinoma with gastric phenotype (GA) that is independent of high-risk human papillomavirus (H-HPV) infection. Carbonic anhydrase-IX (CA-IX) is highly expressed in conventional glandular lesions (CGLs). However, expression of CA-IX in LEGH or GA has not been studied. METHODS: In all, 12 CGLs, 7 LEGHs, 6 LEGHs with coexisting adenocarcinoma in situ (AIS, 3) and GA (3) were identified from Japanese women with a cytological diagnosis of atypical glandular cells of undetermined significance. Immunostaining was used to detect CA-IX and p16(INK)4(a) (hereafter termed p16) protein expression in the tissues and CA-IX protein expression in the Papanicolaou smears (PSs). Polymerase chain reaction was used to detect H-HPV DNA in liquid-based cytology. RESULTS: Out of 12 (83%) CGLs, 10 were positive with H-HPV and high levels of CA-IX expression were seen in all (100%) cases. P16 protein expression was observed in 11 out of 12 (92%) cases. None of the LEGHs, LEGHs with AIS or GA were positive for H-HPV and only 8 out of 13 (62%) showed focal weak (1+) p16 expression. In contrast, all cases (100%) exhibited strong CA-IX protein expression. CONCLUSION: Our study suggests that there are different molecular mechanisms of carcinogenesis resulting in CGLs vs LEGHs associated with AIS or GA. There is also a possible link between LEGHs and GAs. Furthermore, CA-IX expression may serve as a useful biomarker for the detection of GAs in the absence of H-HPV infection.