bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resting Energy Expenditure and Substrate Oxidation in Malnourished Patients With Type 1 Glycogenosis
Authors: Buscemi Silvio , Noto Davide , Buscemi Carola , Barile Anna Maria , Rosafio Giuseppe , Settipani Valentina , Giammanco Antonina , Averna Maurizio 
Published: August 2019

Abstract

Context
Type 1a and 1b glycogenosis [glycogen storage disorder (GSD)1a, GSD1b] are rare diseases generally associated with malnutrition. Although abnormal substrate oxidation rates and elevated energy expenditures might contribute to malnutrition, this issue has not been investigated.

Objective
To investigate whether abnormal resting energy expenditure (REE) and substrate oxidation rate characterize patients with GSD1.

Design
Cross-sectional study

Setting
Outpatient referral center for rare diseases and laboratory of clinical nutrition at the University Hospital of Palermo

Patients
Five consecutive patients with GSD1 (4 type a, 1 type b; 3 men, 2 women; age range, 19 to 49 years)

Main Outcome Measures
The usual clinical procedures for patients with malnutrition, including REE and basal substrate oxidation rate (both indirect calorimetry), body composition (bioimpedance method), muscle strength (hand-grip test), and the usual laboratory tests, were performed.

Results
Malnutrition was clearly diagnosed in 2 patients (1 GSD1a and 1 GSD1b), with REE elevated in all five patients, and especially, in the two malnourished patients (+124% and +32.1% vs predictive values using Harris-Benedict equations). The two malnourished patients also exhibited lower basal protein oxidation rates (7.7% and 6.6%) than the nourished patients (range, 12.1% to 24.7%), with higher carbohydrate or lipid oxidation rates. Additionally, the two malnourished patients exhibited higher blood concentrations of lactic acid than the nourished patients.

Conclusions
According to data obtained from our small sample of patients with GSD1, elevated REEs seem to be a common characteristic that might contribute to malnutrition. Low basal protein oxidation rates and elevated blood lactic acid concentrations appear to be associated with malnutrition.
Genetic Variation of the Vitamin D Binding Protein Affects Vitamin D Status and Response to Supplementation in Infants
Authors: Enlund-Cerullo Maria , Koljonen Laura , Holmlund-Suila Elisa , Hauta-alus Helena , Rosendahl Jenni , Valkama Saara , Helve Otto , Hytinantti Timo , Viljakainen Heli , Andersson Sture , Mäkitie Outi , Pekkinen Minna 
Published: August 2019

AbstractContextSingle nucleotide polymorphisms (SNPs) of the vitamin D binding protein encoding the GC (group component) gene affect 25-hydroxyvitamin D (25OHD) concentrations, but their influence on vitamin D status and response to vitamin D supplementation in infants is unknown.ObjectiveTo study GC genotype–related differences in 25OHD concentrations and the response to supplementation during a vitamin D intervention study in infants.DesignIn this randomized controlled trial, healthy term infants received vitamin D3 (10 or 30 μg/d) from 2 weeks to 24 months of age. GC SNPs rs2282679, rs4588, rs7041, and rs1155563 were genotyped. rs4588/7041 diplotype and haplotypes of rs2282679, rs4588, and rs7041 (Haplo3SNP) and of all four SNPs (Haplo4SNP) were determined.Main Outcome Measures25OHD measured in cord blood at birth and at 12 and 24 months during intervention.ResultsA total of 913 infants were included. Minor allele homozygosity of all studied GC SNPs, their combined haplotypes, and rs4588/rs7041 diplotype 2/2 were associated with lower 25OHD concentrations at all time points in one or both intervention groups [analysis of covariance (ANCOVA) P < 0.043], with the exception of rs7041, which did not affect 25OHD at birth. In the high-dose supplementation group receiving 30 μg/d vitamin D3, but not in those receiving 10 µg/d, genotype of rs2282679, rs4588, and rs7041; diplotype; and Haplo3SNP significantly affected intervention response (repeated measurement ANCOVA Pinteraction < 0.019). Minor allele homozygotes had lower 25OHD concentrations and smaller increases in 25OHD throughout the intervention.ConclusionsIn infants, vitamin D binding protein genotype affects 25OHD concentration and efficiency of high-dose vitamin D3 supplementation.
Predictors of Poor Bone Microarchitecture Assessed by Trabecular Bone Score in Postsurgical Hypoparathyroidism
Authors: Sakane Eliane Naomi , Vieira Maria Carolina Camargo , Lazaretti-Castro Marise , Maeda Sergio Setsuo 
Published: August 2019

Abstract

Context
The effects of PTH deprivation on bone are still unclear. Our objective was to report the characteristics of patients with postsurgical hypoparathyroidism (PsH) at a specialized outpatient service and correlate their trabecular bone score (TBS) values to clinical, densitometric, and laboratory findings. A secondary objective was to evaluate the fracture rates and look for associations between these events and the collected data.

Results
Eighty-two patients were enrolled, of whom 70 (85.4%) were female and 17 (20.7%) had type 2 diabetes mellitus (T2DM). The median body mass index (BMI) was 27.7 kg/m2 and the median age was 59 years. Of 68 dual-energy x-ray absorptiometry (DXA) scans obtained, osteopenia and osteoporosis were present in 32.4% and 2.9%, respectively. In all, 62 lumbar scans were analyzed by using TBS. The mean TBS value (±SD) was 1.386 ± 0.140, and 32.2% of the results were <1.310. TBS values correlated negatively with BMI (mainly > 30 kg/m2), age (mainly > 60 years), and glycemia, whereas abnormal TBS correlated with osteopenia, T2DM, low-impact fracture, and menopause. Six female patients had low-impact fractures, which were associated with a lower TBS (1.178 ± 0.065 vs. 1.404 ± 0.130 in the group without fractures; P < 0.001), older age, higher BMI, impaired renal function, abnormal glycemia, and osteopenia.

Conclusion
The findings suggests that known risk factors for bone loss compromise the bone microarchitecture of individuals with PsH, regardless of DXA results. Menopausal women with PsH and older patients with PsH who have osteopenia, a higher BMI, or T2DM may be candidates for a more detailed assessment by using, for example, TBS.
National Treatment Practice for Adrenocortical Carcinoma: Have They Changed and Have We Made Any Progress?
Authors: Tierney John F , Chivukula Sitaram V , Poirier Jennifer , Pappas Sam G , Schadde Erik , Hertl Martin , Kebebew Electron , Keutgen Xavier 
Published: August 2019

Abstract

Background
Adrenocortical carcinoma (ACC) is a rare malignancy with a dismal prognosis. Two landmark trials published in 2007 and 2012 showed efficacy for adjuvant mitotane in resectable ACC and etoposide/doxorubicin/cisplatin plus mitotane for unresectable ACC, respectively. In this study, we used the National Cancer Database to examine whether treatment patterns and outcomes changed after these trials.

Methods
The National Cancer Database was used to examine treatment patterns and survival in patients diagnosed with ACC from 2006 to 2015. Treatment modalities were compared within that group and with a historical cohort (1985 to 2005). χ2 tests were performed, and Cox proportional hazards models were created.

Results
From 2006 to 2015, 2752 patients were included; 38% of patients (1042) underwent surgery alone, and 31% (859) underwent surgery with adjuvant therapy. Overall 5-year survival rates for all stages after resection were 43% (median, 41 months) in the contemporary cohort and 39% (median, 32 months) in the historical cohort. After 2007, patients who underwent surgery were more likely to receive adjuvant chemotherapy (P = 0.005), and 5-year survival with adjuvant chemotherapy improved (41% vs 25%; P = 0.02). However, survival did not improve in patients with unresectable tumors after 2011 compared with 2006 to 2011 (P = 0.79). Older age, tumor size ≥10 cm, distant metastases, and positive margins were associated with lower survival after resection (hazard ratio range: 1.39 to 3.09; P < 0.03).

Conclusions
Since 2007, adjuvant therapy has been used more frequently in patients with resected ACC, and survival for these patients has improved but remains low. More effective systemic therapies for patients with ACC, especially those in advanced stages, are desperately needed.
Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism
Authors: Mannstadt Michael , Clarke Bart L , Bilezikian John P , Bone Henry , Denham Douglas , Levine Michael A , Peacock Munro , Rothman Jeffrey , Shoback Dolores M , Warren Mark L , Watts Nelson B , Lee Hak-Myung , Sherry Nicole , Vokes Tamara J 
Published: August 2019

Abstract

Context
Conventional hypoparathyroidism treatment with oral calcium and active vitamin D is aimed at correcting hypocalcemia but does not address other physiologic defects caused by PTH deficiency.

Objective
To evaluate long-term safety and tolerability of recombinant human PTH (1-84) [rhPTH(1-84)].

Design
Open-label extension study; 5-year interim analysis.

Setting
12 US centers.

Patients
Adults (N = 49) with chronic hypoparathyroidism.

Intervention(s)
rhPTH(1-84) 25 or 50 µg/d initially, with 25-µg adjustments permitted to a 100 µg/d maximum.

Main Outcome Measure(s)
Safety parameters; composite efficacy outcome was the proportion of patients with ≥50% reduction in oral calcium (or ≤500 mg/d) and calcitriol (or ≤0.25 µg/d) doses, and albumin-corrected serum calcium normalized or maintained compared with baseline, not exceeding upper limit of normal.

Results
Forty patients completed 60 months of treatment. Mean albumin-corrected serum calcium levels remained between 8.2 and 8.7 mg/dL. Between baseline and month 60, levels ± SD of urinary calcium, serum phosphorus, and calcium-phosphorus product decreased by 101.2 ± 236.24 mg/24 hours, 1.0 ± 0.78 mg/dL, and 8.5 ± 8.29 mg2/dL2, respectively. Serum creatinine level and estimated glomerular filtration rate were unchanged. Treatment-emergent adverse events (AEs) were reported in 48 patients (98.0%; hypocalcemia, 36.7%; muscle spasms, 32.7%; paresthesia, 30.6%; sinusitis, 30.6%; nausea, 30.6%) and serious AEs in 13 (26.5%). At month 60, 28 patients (70.0%) achieved the composite efficacy outcome. Bone turnover markers increased, peaked at ∼12 months, and then declined to values that remained above baseline.

Conclusion
Treatment with rhPTH(1-84) for 5 years demonstrated a safety profile consistent with previous studies and improved key biochemical parameters.
Epigenetic Reprogramming of Immune Cells in Women With PCOS Impact Genes Controlling Reproductive Function
Authors: Hiam Danielle , Simar David , Laker Rhianna , Altıntaş Ali , Gibson-Helm Melanie , Fletcher Elly , Moreno-Asso Alba , Trewin Adam J , Barres Romain , Stepto Nigel K 
Published: August 2019

Abstract

Context
Polycystic ovary syndrome (PCOS) is a chronic disease affecting reproductive function and whole-body metabolism. Although the etiology is unclear, emerging evidence indicates that the epigenetics may be a contributing factor.

Objective
To determine the role of global and genome-wide epigenetic modifications in specific immune cells in PCOS compared with controls and whether these could be related to clinical features of PCOS.

Design
Cross-sectional study.

Participants
Women with (n = 17) or without PCOS (n = 17).

Setting
Recruited from the general community.

Main Outcome Measures
Isolated peripheral blood mononuclear cells were analyzed using multicolor flow cytometry methods to determine global DNA methylation levels in a cell-specific fashion. Transcriptomic and genome-wide DNA methylation analyses were performed on T helper cells using RNA sequencing and reduced representation bisulfite sequencing.

Results
Women with PCOS had lower global DNA methylation in monocytes (P = 0.006) and in T helper (P = 0.004), T cytotoxic (P = 0.004), and B cells (P = 0.03). Specific genome-wide DNA methylation analysis of T helper cells from women with PCOS identified 5581 differentially methylated CpG sites. Functional gene ontology enrichment analysis showed that genes located at the proximity of differentially methylated CpG sites belong to pathways related to reproductive function and immune cell function. However, these genes were not altered at the transcriptomic level.

Conclusions
It was shown that PCOS is associated with global and gene-specific DNA methylation remodeling in a cell type–specific manner. Further investigation is warranted to determine whether epigenetic reprogramming of immune cells is important in determining the different phenotypes of PCOS.
Plasma Agouti-Related Protein Levels in Acromegaly and Effects of Surgical or Pegvisomant Therapy
Authors: Freda Pamela U , Reyes-Vidal Carlos , Jin Zhezhen , Pugh Mya , Panigrahi Sunil K , Bruce Jeffrey N , Wardlaw Sharon L 
Published: August 2019

Abstract

Context
GH activates agouti-related protein (AgRP) neurons, leading to orexigenic responses in mice. The relationship between serum GH and plasma AgRP, which has been shown to reflect hypothalamic AgRP, has not been evaluated in humans.

Objective
To test the hypothesis that central stimulatory actions of GH on hypothalamic AgRP could be reflected in plasma AgRP in acromegaly.

Methods
We studied 23 patients with active acromegaly before and for ≤2 years after surgical (n = 13) or GH receptor antagonist therapy with pegvisomant (n = 10), and 100 healthy subjects with morning fasting blood samples for AgRP, leptin, GH, and IGF-1 and anthropometric measurements.

Results
The plasma AgRP levels were higher in those with active acromegaly than in the matched healthy subjects [median, 100 pg/mL; interquartile range (IQR), 78 to 139 pg/mL vs median, 63 pg/mL; IQR, 58 to 67 pg/mL; P < 0.0001]. Plasma AgRP decreased from before to after surgery (median, 102 pg/mL; IQR, 82 to 124 pg/mL vs median, 63 pg/mL; IQR, 55.6 to 83 pg/mL; P = 0.0024) and from before to during pegvisomant therapy (median, 97 pg/mL; IQR, 77 to 175 pg/mL vs median, 63; IQR, 61 to 109 pg/mL; P = 0.006). The plasma AgRP level correlated with GH (r = 0.319; P = 0.011) and IGF-1 (r = 0.292; P = 0.002). In repeated measure analysis, AgRP was significantly associated with IGF-1.

Conclusions
Our data have provided evidence of a stimulatory effect of GH on plasma AgRP in humans. The levels were greater in active acromegaly and decreased in parallel with GH and IGF-1 decreases with acromegaly treatment. Data from mice suggest that AgRP may mediate some of the known effects of GH on energy metabolism. This warrants further study in patients with acromegaly and other populations.
Hypernatremic Hydrophobic Transient Adipsia Without Organic or Severe Psychiatric Disorder
Authors: Rodriguez Aleida , Fogelfeld Leon , Robertson Gary 
Published: August 2019

Abstract

Context
Psychogenic adipsic hypernatremia is an exceedingly rare and life-threatening condition, occurring in those with severe psychiatric disorders. Its diagnosis requires exclusion of congenital or acquired hypothalamic pathologic entities. We present the case of a patient who experienced transient severe hypernatremia without evidence of brain pathologic features or known psychiatric disease. In our patient, the transient adipsic hypernatremia had resulted from an episode of mild depression that resolved spontaneously.

Case Description
A 46-year-old healthy woman who had had three recurrent admissions within 1 month had presented for evaluation of intractable nausea and vomiting with a history of a recent episode of a depressive mood change. Each admission had shown substantial hypernatremia (maximum plasma sodium, 166 mEq/L) accompanied by a strong aversion to consuming water. The findings from the diagnostic evaluation showed elevated serum osmolality and lower than expected urine osmolality (urine osmolality range, 474–501 mOsm/kg). This finding, along with an MRI scan showing the presence of a normal posterior pituitary bright spot, suggested that the osmoregulation of her thirst and arginine vasopressin (AVP) secretion were both defective during the attack. The patient was evaluated by psychiatry. Mild depression was diagnosed, and the patient started treatment with mirtazapine, which she only took for a few days. The patient’s hypernatremia had completely recovered with resolution of her depression within 2 months.

Conclusion
A mild mood disorder can cause transient dysregulation of the thirst mechanism and AVP secretion through not yet identified mechanisms.
Hyperinsulinemia: An Early Indicator of Metabolic Dysfunction
Authors: Thomas Dylan D , Corkey Barbara E , Istfan Nawfal W , Apovian Caroline M 
Published: August 2019

AbstractHyperinsulinemia is strongly associated with type 2 diabetes. Racial and ethnic minority populations are disproportionately affected by diabetes and obesity-related complications. This mini-review provides an overview of the genetic and environmental factors associated with hyperinsulinemia with a focus on racial and ethnic differences and its metabolic consequences. The data used in this narrative review were collected through research in PubMed and reference review of relevant retrieved articles. Insulin secretion and clearance are regulated processes that influence the development and progression of hyperinsulinemia. Environmental, genetic, and dietary factors are associated with hyperinsulinemia. Certain pharmacotherapies for obesity and bariatric surgery are effective at mitigating hyperinsulinemia and are associated with improved metabolic health. Hyperinsulinemia is associated with many environmental and genetic factors that interact with a wide network of hormones. Recent studies have advanced our understanding of the factors affecting insulin secretion and clearance. Further basic and translational work on hyperinsulinemia may allow for earlier and more personalized treatments for obesity and metabolic diseases.
Residual Tumor Confers a 10-Fold Increased Risk of Regrowth in Clinically Nonfunctioning Pituitary Tumors
Authors: Maletkovic Jelena , Dabbagh Asmaa , Zhang Dongyun , Zahid Abdul , Bergsneider Marvin , Wang Marilene B , Linetsky Michael , Salamon Noriko , Yong William H , Vinters Harry V , Heaney Anthony P 
Published: August 2019

Abstract

Objective
We evaluated tumor recurrence and regrowth rates following endoscopic transnasal transsphenoidal (TNTS) surgical removal in a consecutive series of clinically nonfunctioning pituitary adenomas (CNFTs).

Design
Retrospective chart review of clinical, biochemical, and sellar MRI findings in all TNTS surgeries in patients with CNFT, performed by a single surgeon, between 2008 and 2015 (n = 280).

Patients
Ninety-three patients met eligibility criteria, with complete clinical, biochemical, and imaging follow-up for a 3-year minimum.

Results
Of 85 patients who were not irradiated, 3-month postsurgical MRI demonstrated no residual tumor in 58 of 85 (68.2%), equivocal findings in 12 of 85 (14.1%), and definite residual tumor in 15 of 85 (17.6%) patients. Six of 85 (7.1%) demonstrated tumor regrowth by 3 years, and 2 further patients demonstrated true tumor recurrence at 3 and 6 years after surgery, respectively, for a total recurrence rate of 9.4% (8 of 85). Eight of the 93 patients were irradiated between 3 months and 4 years after pituitary surgery. In 3 patients with tumor regrowth, 2 exhibited residual tumor and 1 had no residual findings at the 3-month postoperative imaging. Overall, Ki-67 labeling index or Knosp grading did not predict recurrence.

Conclusion
Tumor recurrence at 3 years was low (1 of 58; 1.7%) if the 3-month postoperative MRI showed no residual tumor. The findings support a less frequent imaging schedule for this group. Patients with definite residual tumor visible at 3 months harbor the greatest risk for tumor growth, but regrowth does not occur in all patients (6 of 15; 40%).
MGMT Promoter Methylation and Parathyroid Carcinoma
Authors: Storvall Sara , Ryhänen Eeva , Heiskanen Ilkka , Vesterinen Tiina , Bensch Frank V , Schildt Jukka , Kytölä Soili , Karhu Auli , Arola Johanna , Schalin-Jäntti Camilla 
Published: August 2019

Abstract

Context
Parathyroid carcinoma (PC) is extremely rare. Prognosis is poor, with no known evidence-based systemic therapies. We previously reported complete remission in a patient with metastasized parathyroid carcinoma and high tumor MGMT promoter methylation status who was treated with temozolomide.

Objective
To study MGMT promoter methylation status in an additional set of aggressive parathyroid tumors.

Design/Setting
The study included 12 patients: 7 with sporadic and 5 with familial primary hyperparathyroidism (two of the latter carried a CDC73 gross deletion). Patient 9 is the previously described patient with PC and high MGMT methylation status. Her daughter (patient 12) had surgery for severe primary hyperparathyroidism due to atypical parathyroid adenoma during pregnancy. Eleven patients thus had PC and one had atypical parathyroid adenoma. MGMT promoter methylation status was determined from DNA extracted from primary (n = 10) or metastatic (n = 2) tumors. A mean methylation level >20% was considered high. Patient 11 had metastatic PC and received temozolomide cycles.

Results
Only the previously published patient (patient 9) had high tumor MGMT promoter methylation status. This was not a characteristic of the atypical parathyroid adenoma of the daughter (patient 12). Patient 11 (CDC73 intragenic deletion) has disseminated PC, low MGMT promoter methylation, and stable disease on follow-up after temozolomide treatment.

Conclusion
High MGMT promoter methylation status seems rare in PC. However, as demonstrated in other neuroendocrine tumors, some patients with disseminated PC might benefit from temozolomide. Demonstration of high methylation status could be a predictor of positive response to temozolomide treatment.
Whole-Exome Sequencing of Syndromic Adrenocortical Carcinoma Reveals Distinct Mutational Profile From Sporadic ACC
Authors: Nicolson Norman G , Healy James M , Korah Reju , Carling Tobias 
Published: August 2019

Abstract
Next-generation sequencing has provided genetic profiles of a large number of sporadic adrenocortical carcinomas (ACCs), but the applicability of these results to ACC cases associated with tumor predisposition syndromes is unclear. Although the germline features of these syndromes have been well described, the somatic mutational landscape of the tumors they give rise to is less clear. Our group obtained germline and tumor tissue from a pediatric patient who developed ACC during her first year of life, which was treated successfully. She was subsequently diagnosed with additional tumors later in childhood. Whole exome sequencing analysis was performed followed by in silico protein function prediction, revealing a probably deleterious germline TP53 L265P mutation. The somatic mutational burden was comparable between the index case and a previously published cohort of 40 sporadic cases, but the mutational spectrum was distinct in terms of raw base-change frequency as well as in a trinucleotide context-specific analysis. No canonical somatic genetic drivers of ACC were identified in the reported case, suggesting that syndromic adrenocortical tumors may represent a genetically distinct entity from sporadic tumors.