Neuroendocrine Cell Hyperplasia of Infancy. Clinical Score and Comorbidities.
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SUBMITTER: Liptzin DR
PROVIDER: S-EPMC7258416 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:RATIONALE:Neuroendocrine cell hyperplasia of infancy (NEHI) typically presents in infancy with tachypnea, retractions, and hypoxemia. Some infants have failure to thrive, yet the frequency of this and other non-respiratory phenotypic features have not been delineated. While gradual improvement occurs, the clinical course is variable and the duration of supplemental oxygen requirement has not been defined. OBJECTIVES:Our objective was to identify factors in NEHI that may drive differences in clinical course. We hypothesized that failure to thrive would be associated with greater duration of supplemental oxygen use. METHODS:Children with NEHI were identified as a nested retrospective cohort within an ongoing observational prospective study. An electronic questionnaire evaluating health status was distributed to the parents/guardians. Clinical data were obtained via chart review and parent interview. RESULTS:Of 42 children, 74% had a diagnosis of failure to thrive during their clinical course. Time to event analysis demonstrated that 50% discontinued daytime and nighttime oxygen at 32 and 87.5 months after initiation, respectively. Diagnosis of failure to thrive was associated with longer continuous oxygen supplementation, P?=?0.03. Additional parental concerns identified through the electronic questionnaire included developmental delays, multiple hospitalizations, and delays in diagnosis. CONCLUSIONS:NEHI is associated with substantial respiratory and extra-pulmonary morbidity. Failure to thrive may be associated with greater respiratory morbidity, though further studies are required to define this interaction. Determining the association of these comorbidities and respiratory course in NEHI may enable development of strategies to improve these modifiable factors and potentially pulmonary outcomes.
| S-EPMC5903936 | biostudies-literature
Project description:BackgroundNeuroendocrine cell hyperplasia of infancy (NEHI) is a childhood diffuse lung disease of unknown etiology. We investigated the mechanism for lung disease in a subject whose clinical, imaging, and lung biopsy specimen findings were consistent with NEHI; the subject's extended family and eight other unrelated patients with NEHI were also investigated.MethodsThe proband's lung biopsy specimen (at age 7 months) and serial CT scans were diagnostic of NEHI. Her mother, an aunt, an uncle, and two first cousins had failure to thrive in infancy and chronic respiratory symptoms that improved with age. Genes associated with autosomal-dominant forms of childhood interstitial lung disease were sequenced.ResultsA heterozygous NKX2.1 mutation was identified in the proband and the four other adult family members with histories of childhood lung disease. The mutation results in a nonconservative amino acid substitution in the homeodomain in a codon extensively conserved through evolution. None of these individuals have thyroid disease or movement disorders. NKX2.1 mutations were not identified by sequence analysis in eight other unrelated subjects with NEHI.ConclusionsThe nature of the mutation and its segregation with disease support that it is disease-causing. Previously reported NKX2.1 mutations have been associated with "brain-thyroid-lung" syndrome and a spectrum of more severe pulmonary phenotypes. We conclude that genetic mechanisms may cause NEHI and that NKX2.1 mutations may result in, but are not the predominant cause of, this phenotype. We speculate that altered expression of NKX2.1 target genes other than those in the surfactant system may be responsible for the pulmonary pathophysiology of NEHI.
| S-EPMC3787915 | biostudies-literature
Project description:OBJECTIVE:Adrenonodular hyperplasia and tumour formation are potential long-term complications of congenital adrenal hyperplasia (CAH) with little known regarding the clinical implications. Our aim was to describe volumetric adrenal morphology and determine the association between radiological findings and comorbidities in adults with classic CAH. DESIGN:This was a cross-sectional study of 88 patients (mean age 29.2 ± 13 years, 47 females) with classic CAH seen in a tertiary referral centre. METHODS:CT imaging, performed at study entry or when reaching adulthood, was used to create 3-dimensional volumetric models. Clinical, genetic and hormonal evaluations were collected and correlated with adrenal morphology and tumour formation. RESULTS:Over one-third of the cohort was obese. 53% had elevated 17-OH-progesterone or androstenedione; and 60% had adrenal hyperplasia. Tumours included 11 myelolipomas, 8 benign adrenocortical adenomas, 1 pheochromocytoma and 50% of men had testicular adrenal rest tissue. CAH patients with adrenal hyperplasia had significantly higher number of comorbidities than those with morphologically normal adrenals (P = 0.03). Variables that positively correlated with adrenal volume included hypogonadal/oligomenorrhoeic status, hypertension, androstenedione, aldosterone, and triglyceride levels, and in women, low HDL and insulin resistance. Elevated aldosterone was observed in a subset of patients with simple virilizing CAH. CONCLUSIONS:Adrenocortical hyperplasia is associated with a number of comorbidities, especially hypogonadism. Aldosterone production associated with adrenal enlargement may play a role in the development of metabolic risk factors. Further studies are needed to assess the long-term impact of the excess adrenal steroid milieu associated with adrenal enlargement to develop improved management strategies for CAH.
| S-EPMC6635023 | biostudies-literature
Project description:IntroductionDeformational plagiocephaly (DP) is one of the most common cranial shape disorders in infancy. It is characterised by unilateral flattening of the skull due to head preference to one side. The literature suggests that DP is associated with comorbidities such as developmental delay, but the nature and prevalence of the comorbid impairments are still unclear and controversial. Therefore, our scoping review (ScR) aims to explore systematically the extent and nature of literature by identifying, mapping and categorising the most relevant comorbidities of DP in children up to the age of 2 years.Methods and analysisThis protocol is based on the framework outlined by Arksey and O'Malley. A systematic search will be conducted to identify relevant full text studies from 1992 to 2021 using the databases of Cochrane, MEDLINE, Google Scholar, EMBASE, PubMed and University of Nicosia EBSCO. Two independent reviewers will screen abstracts and full articles in parallel, using specific inclusion and exclusion criteria. Specifically, this review will consider studies investigating DP and relevant comorbidities in children up to the age of 2 years of life without craniosynostosis, torticollis and any other diagnosed neurodevelopmental deficiency.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for ScR Checklist will be considered for results' analysis and reporting. The results will be described in a narrative form in relation to the research question and in the context of the overall study purpose.Ethics and disseminationResearch ethics approval is not required for this ScR since data will be retrieved from publicly available studies. Dissemination activities will include research findings' submission for publication in a relevant peer-reviewed journal and presentation of the results at relevant conferences.RegistrationOur protocol was registered prospectively with the Open Science Framework (https://osf.io/48am3/).
| S-EPMC8174490 | biostudies-literature
Project description:Mucus overproduction is a major contributor to morbidity and mortality in asthma. Mucus overproduction is induced by orchestrated actions of multiple factors that include inflammatory cytokines and γ-aminobutyric acid (GABA). GABA is produced only by pulmonary neuroendocrine cells (PNECs) in the mouse lung. Recent studies in a neonatal mouse model of allergic inflammation have shown that PNECs play an essential role in mucus overproduction by GABA hypersecretion. Whether PNECs mediate dysregulated GABA signaling for mucus overproduction in asthma is unknown. In this study, we characterized the cellular source of GABA in the lungs of nonhuman primates and humans and assessed GABA secretion and signaling in primate disease models. We found that like in mice, PNECs were the major source of GABA in primate lungs. In addition, an infant nonhuman primate model of asthma exhibited an increase in GABA secretion. Furthermore, subjects with asthma had elevated levels of expression of a subset of GABA type α (GABAα) and type β (GABAβ) receptors in airway epithelium compared with those of healthy control subjects. Last, employing a normal human bronchial epithelial cell model of preinduced mucus overproduction, we showed pharmaceutical blockade of GABAα and GABAβ receptor signaling reversed the effect of IL-13 on MUC5AC gene expression and goblet cell proliferation. Together, our data demonstrate an evolutionarily conserved intraepithelial GABA signaling that, in concert with IL-13, plays an essential role in mucus overproduction. Our findings may offer new strategies to ameliorate mucus overproduction in patients with asthma by targeting PNEC secretion and GABA signaling.
| S-EPMC6543741 | biostudies-literature
Project description:BackgroundSeveral risk factors predict clinical outcome in gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs); however, the impact of their combination has not been investigated so far.Patients and methodsA retrospective analysis of stage IV GEP-NENs was performed. Multivariate analysis for progression of disease (PD) was performed by Cox proportional hazards method to obtain a risk score. Area under the curve obtained by receiver operating characteristic analysis was used to assess the score performance. Progression-free survival analysis was performed by Kaplan-Meier method.ResultsTwo hundred eighty-three stage IV GEP-NENs were evaluated, including 93 grade 1 neuroendocrine tumors (32.9%), 153 grade 2 neuroendocrine tumors (54%), and 37 grade 3 neuroendocrine carcinomas (13.1%). Independent risk factors for PD were Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The risk score was calculated as follows: (0.025 × Ki67) + [(0 if no liver metastases or liver involvement <25%) OR (0.405 if liver involvement 25%-50%) OR (0.462 if liver involvement >50%)] + [(0 if no extra-abdominal metastases) OR (0.528 if extra-abdominal metastases present)]. The risk score accuracy to predict PD was superior compared with the G grading system (area under the curve: 0.705 and 0.622, respectively). Three subgroups of patients with low, intermediate, and high risk of PD according to risk score were identified, median progression-free survival being 26 months, 19 months, and 12 months, respectively.ConclusionIn stage IV GEP-NENs, a risk score able to predict PD was obtained by combining Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The score may help to discriminate patients with different progression risk level to plan tailored therapeutic approaches and follow-up programs. The Oncologist 2017;22:409-415Implications for Practice: Clinical outcome of patients with advanced gastro-entero-pancreatic neuroendocrine neoplasms is affected by several risk factors, including the proliferative index Ki67, extension of liver metastases, and the presence of distant extra-abdominal lesions. A risk score that combines these variables may help physicians dealing with these diseases to plan the optimal therapeutic approach and follow-up program.
| S-EPMC5388376 | biostudies-literature
Project description:We developed a clinical score (CS) at Vanderbilt Ingram Cancer Center (VICC) that we hoped would predict outcomes for patients with progressive well-differentiated neuroendocrine tumors (NETs) receiving therapy with Lutetium-177 (177Lu)-DOTATATE. Patients under consideration for 177Lu-DOTATATE between March 1, 2016 and March 17, 2020 at VICC were assigned a CS prospectively. The CS included 5 categories: available treatments for tumor type outside of 177Lu-DOTATATE, prior systemic treatments, patient symptoms, tumor burden in critical organs and presence of peritoneal carcinomatosis. The primary outcome of the analysis was progression-free survival (PFS). To evaluate the effect of the CS on PFS, a multivariable Cox regression analysis was performed adjusting for tumor grade, primary tumor location, and the interaction between 177Lu-DOTATATE doses received (zero, 1-2, 3-4) and CS. A total of 91 patients and 31 patients received 3-4 doses and zero doses of 177Lu-DOTATATE, respectively. On multivariable analysis, in patients treated with 3-4 doses of 177Lu-DOTATATE, for each 1-point increase in CS, the estimated hazard ratio (HR) for PFS was 2.0 (95% CI 1.61-2.48). On multivariable analysis, in patients who received zero doses of 177Lu-DOTATATE, for each 1-point increase in CS, the estimated HR for PFS was 1.22 (95% CI 0.91-1.65). Among patients treated with 3-4 doses of 177Lu-DOTATATE, those with lower CS experienced improved PFS with the treatment compared to patients with higher CS. This PFS difference, based upon CS, was not observed in patients who did not receive 177Lu-DOTATATE, suggesting the predictive utility of the score.
| S-EPMC8026653 | biostudies-literature
Project description:ObjectivesDiffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) occurs due to abnormal proliferation of pulmonary neuroendocrine cells. We hypothesized that performing a quantitative analysis of airway features on chest CT may reveal differences to matched controls, which could ultimately help provide an imaging biomarker.MethodsA retrospective quantitative analysis of chest CTs in patients with DIPNECH and age matched controls was carried out using semi-automated post-processing software. Paired segmental airway and artery diameters were measured for each bronchopulmonary segment, and the airway:artery (AA) ratio, airway wall thickness:artery ratio (AWTA ratio) and wall area percentage (WAP) calculated. Nodule number, size, shape and location was recorded. Correlation between CT measurements and pulmonary function testing was performed.Results16 DIPNECH and 16 control subjects were analysed (all female, mean age 61.7 +/- 11.8 years), a combined total of 425 bronchopulmonary segments. The mean AwtA ratio, AA ratio and WAP for the DIPNECH group was 0.57, 1.18 and 68.8%, respectively, compared with 0.38, 1.03 and 58.3% in controls (p < 0.001, <0.001, 0.03, respectively). DIPNECH patients had more nodules than controls (22.4 +/- 32.6 vs. 3.6 +/- 3.6, p = 0.03). AA ratio correlated with FVC (R2 = 0.47, p = 0.02). A multivariable model incorporating nodule number, AA ratio and AWTA-ratio demonstrated good performance for discriminating DIPNECH and controls (AUC 0.971; 95% CI: 0.925-1.0).ConclusionsQuantitative CT airway analysis in patients with DIPNECH demonstrates increased airway wall thickness and airway:artery ratio compared to controls.Advances in knowledgeQuantitative CT measurement of airway wall thickening offers a potential imaging biomarker for treatment response.
| S-EPMC9776594 | biostudies-literature
Project description:ObjectivesWe investigated the relationship between the ultrasonographic Halo Score and temporal artery biopsy (TAB) findings in GCA.MethodsThis is a prospective study including 90 patients suspected of having GCA. Ultrasonography of temporal/axillary arteries and a TAB were obtained in all patients at baseline. An experienced pathologist evaluated whether TAB findings were consistent with GCA, and whether transmural inflammation, giant cells and intimal hyperplasia were present. Ultrasonographic Halo Scores were determined. Receiver operating characteristic analysis was performed.ResultsTwenty-seven patients had a positive TAB, while 32 patients with a negative TAB received a clinical diagnosis of GCA after 6 months of follow-up. Patients with a positive TAB showed higher Halo Scores than patients with a negative TAB. The presence of intimal hyperplasia in the biopsy, rather than the presence of transmural inflammation or giant cells, was associated with elevated Halo Scores in patients with GCA. The Halo Score discriminated well between TAB-positive patients with and without intimal hyperplasia, as indicated by an area under the curve of 0.82 in the receiver operating characteristic analysis. Patients with a positive TAB and intimal hyperplasia more frequently presented with ocular ischaemia (40%) than the other patients with GCA (13-14%).ConclusionThe ultrasonographic Halo Score may help to identify a subset of GCA patients with intimal hyperplasia, a TAB feature associated with ischaemic sight loss.
| S-EPMC8410002 | biostudies-literature
Project description:Background: Nowadays, the characteristics and treatment of advanced pulmonary large cell neuroendocrine carcinoma (LCNEC) remain controversial. This study aimed to analyze the similarity of clinical characteristics, survival outcomes and treatment modalities between advanced LCNEC and advanced small cell lung cancer (SCLC) to provide more evidence for the study of advanced LCNEC. Methods: All SCLC and LCNEC patient data were obtained from the SEER database (2010-2019). Pearson's χ2 test was used to compare the differences in clinical characteristics. Propensity score matching (PSM) was utilized to balance the bias of the variables between patients. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify prognostic factors. KM analysis was used to calculate survival. Results: A total of 1094 patients with IV LCNEC and 20939 patients with IV SCLC were included in this study. The demographic characteristics and tumor characteristics of IV LCNEC and IV SCLC were different (p < 0.05). After PSM, the overall survival (OS) for IV LCNEC and IV SCLC was 6.0 months, the cancer-specific survival (CSS) was 7.0 months, and there was no significant difference in OS or CSS between the two groups. Risk/protective factors for OS and CSS were similar for IV LCNEC and IV SCLC patients. Survival outcomes were similar in patients with IV LCNEC and IV SCLC with different treatment modalities; chemoradiotherapy significantly improved OS and CSS in patients with IV LCNEC (9.0 months) and SCLC (10.0 months), however, radiotherapy alone did not improve survival in patients with IV LCNEC. Conclusions: These results confirmed that the prognosis and treatment modalities are similar and that advanced LCNEC could be treated as advanced SCLC, which provide new evidence for the treatment of advanced LCNEC patients.
| S-EPMC10266246 | biostudies-literature