bluuebunny/crossref_metadata_2025 huggingface dataset:
Carotid intima–media thickness and cardiovascular risk factors in healthy volunteers
Authors: Zyriax Birgit-Christiane , Dransfeld Kira , Windler Eberhard
Published: March 2021

Background

Assessment of cardiovascular risk by scores lacks sensitivity and leaves the majority of future cardiovascular patients unidentified particularly individuals at low cardiovascular risk. The present analysis investigates into the correlation of carotid intima–media thickness (CIMT) and cardiovascular risk factors and derived scores as to the potential of improved cardiovascular risk prediction by combining the two.

Methods

The Stress, Atherosclerosis and ECG Study (STRATEGY) is a cross-sectional study of selectively healthy 107 women and 106 men without diagnosed and treated cardiovascular risk factors evenly distributed between 30 and 70 years. CIMT was determined by evaluating B-mode ultrasonograms offline according to a standardized protocol. The unpaired t-test was used to compare normal-distributed continuous variables, the Chi-squared test for normal-distributed categorical variables and the Mann–Whitney U test for non-normal distributed continuous variables. The association between risk prediction scores and CIMT was calculated by the Spearman rank correlation coefficient. Pearson correlation coefficient was used for the correlation between cardiovascular risk factors and CIMT. A multiple linear regression analysis was executed for the association of cardiovascular risk factors and CIMT.

Results

Age, systolic blood pressure, fasting glucose, total, LDL- and non-HDL-cholesterol and waist circumference were significantly associated with CIMT (each P ≤ 0.03). The Framingham Risk Score, the Prospective Cardiovascular Münster Study Score and the European Society of Cardiology Score correlated significantly but only moderately with CIMT. The Framingham Risk Score considering BMI correlated most strongly and predicted 27% of the CIMT variance in men and 20% in women.

Conclusion

In individuals without overt cardiovascular risk factors and thus at low cardiovascular risk, CIMT and cardiovascular risk factors correlated only partially suggesting that combining CIMT and conventional risk factors or common derived scores may improve risk prediction in individuals at low cardiovascular risk. The clinical benefit as to cardiovascular events of such combined risk prediction needs to be explored in large prospective cohorts of still healthy low-risk volunteers. DRKS ID DRKS00015209 07/02/2019 retrospectively registered https://www.drks.de/drks_web/navigate.do?navigationId=resultsExt
Health insurance coverage and access to child and maternal health services in West Africa: a study protocol for a systematic review
Authors: Dadjo Joshua , Omonaiye Olumuyiwa , Yaya Sanni
Published: March 2021

Background

Though many studies have discussed the impact of health insurance on access to medical services, few have considered Western Africa. Despite decades of targeted efforts, West Africa has the most elevated maternal mortality rates (MMR) and under-five mortality rates in the world. The solution to this issue is widely believed to be the implementation of universal health coverage (UHC) as most causes of death could be effectively dealt with through primary health care providers. It is possible that UHC without additional efforts to tackle important determinants of health such as education and poverty is insufficient. The objective of this study is to examine the link between being covered by health insurance and access to health services for mothers and children in West Africa.

Methods

A systematic literature review will be conducted. We will search the online databases MEDLINE complete, Embase, CINAHL complete, and Global Health from inception onwards. The focus will be on primary research studies and grey literature that examined health insurance in relation to access to maternal and child health services. Two reviewers will independently screen all citations, full-text articles, and abstract data. The primary outcome will be maternal and child access to health insurance and access to primary and secondary services such as attending the minimum number of prenatal visits and accessing services in emergency circumstances where catastrophic expenditures may have been an obstacle. A standardized data extraction form by the Cochrane library will be used. A narrative synthesis will be conducted with a summary of findings tables to be produced.

Discussion

The systematic review will present findings on the impact of access to health insurance on access to maternal and child health care. The findings will inform discussion around the pursuit of UHC as a key health systems policy. The final manuscript will be disseminated through peer-reviewed journal and scientific conferences.

Systematic review registration

PROSPERO CRD42020203859
Impact of comorbid borderline personality disorder on the outcome of inpatient treatment for anorexia nervosa: a retrospective chart review
Authors: Voderholzer Ulrich , Favreau Matthias , Schlegl Sandra , Hessler-Kaufmann Johannes Baltasar
Published: March 2021

Background

Data on patients with anorexia nervosa (AN) and comorbid Borderline personality disorder (AN+BPD) are scarce. Therefore, we investigated (1) whether patients with AN and AN+BPD differ in characteristics related to admission to, discharge from, and course of specialized inpatient eating disorder treatment and (2) how comorbid BPD affects treatment outcome.

Method

One-thousand one-hundred and sixty inpatients with AN (97.2% female, 5.9% with comorbid BPD; mean age = 26.15,SD = 9.41) were administered the Brief Symptom Inventory (BSI), the Eating Disorder Inventory 2 (EDI-2), and the Global Assessment of Functioning (GAF) at admission and discharge. Data were extracted by a retrospective chart review of naturalistic treatment data. Age, sex, weekly weight gain, length of stay, and discharge characteristics were compared with independentt-tests and χ2-tests. Changes in outcome variables, including body mass index (BMI), were analyzed with longitudinal multilevel mixed-effects models.

Results

No differences in age or sex were found between patients with AN and AN+BPD, but groups differed in previous inpatient treatments, BMI at admission, and frequency of at least one additional comorbidity with higher values for AN+BPD. Higher levels of disorder-specific and general psychopathology at admission were found for AN+BPD. Patients with AN showed statistically significant improvement in all examined variables, patients with AN+BPD improved in all variables except EDI-2 body dissatisfaction. Strongest improvements in patients with AN+BPD occurred in BMI (Cohen’sd = 1.08), EDI-2 total score (Cohen’sd = 0.99), EDI-2 interpersonal distrust (d = 0.84). Significant Group x Time Interactions were observed for BSI GSI, GAF, and EDI-2 body dissatisfaction, indicating a reduced benefit from inpatient treatment in AN+BPD. At discharge, no differences were found in weekly weight gain, BMI, length of stay, or discharge characteristics (e.g., ability to work, reason for discharge), however, patients with AN+BPD were more frequently treated with medication.

Conclusions

Patients with AN+BPD differ from patients with AN in that they show higher general and specific eating disorder psychopathology and only partially improve under specialized inpatient treatment. In particular, aspects of emotion regulation and core AN symptoms like body dissatisfaction and perfectionism need to be even more targeted in comorbid patients.
Correction to: Behavior-analytic intervention for women with fibromyalgia and insomnia: a single subject design
Authors: de Fátima Kirchner Luziane , de Jesus Dutra dos Reis Maria
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
Prevalence of multidrug-resistant and extended-spectrum beta-lactamase producing Gram-negative isolates from clinical samples in a tertiary care hospital of Nepal
Authors: Shilpakar Aryatara , Ansari Mehraj , Rai Kul Raj , Rai Ganesh , Rai Shiba Kumar
Published: March 2021

Background

The existence of multidrug-resistant organisms, including extended-spectrum beta-lactamases (ESBLs), is on rise across the globe and is becoming a severe problem. Knowledge of the prevalence and antibiogram profile of such isolates is essential to develop an appropriate treatment methodology. This study aimed to study the prevalence of Gram-negative isolates exhibiting ESBL at a tertiary care hospital and study their antibiogram profile.

Methods

A cross-sectional study was conducted at Shahid Gangalal National Heart Centre, Kathmandu, Nepal, from June 2018 to November 2018. A total of 770 clinical samples were collected and identified using the conventional biochemical tests following the Clinical and Laboratory Standard Institute (CLSI) guidelines. Antimicrobial susceptibility testing (AST) was performed using the standardized Kirby-Bauer disk diffusion method. The screening test for ESBL producers was performed as recommended by the CLSI and the confirmatory test was performed phenotypically using the E-test.

Results

Out of the 92 isolates, 84 (91.3%) were multidrug-resistant, and 47 (51.1%) were found to be potential ESBL producers. Of these, 16 isolates were confirmed ESBL producers by the E-test. Escherichia coli and Klebsiella pneumoniae were the predominant isolates and were also the major ESBL producers. Besides polymyxin B (100% sensitive), meropenem and imipenem showed high efficacy against the ESBL producers.

Conclusion

Multidrug resistance was very high; however, ESBL production was low. Polymyxin B and carbapenems are the choice of drugs against ESBL producers but should be used only as the last line drugs.
Screening of NKX2.5 gene in Moroccan Tetralogy of Fallot (TOF) patients: worldwide mutation rate comparisons show a significant association between R25C variant and TOF phenotype
Authors: EL Bouchikhi Ihssane , Belhassan Khadija , Moufid Fatima Zohra , Bouguenouch Laila , Samri Imane , Iraqui Houssaïni Mohammed , Ouldim Karim , Atmani Samir
Published: March 2021

Background

Tetralogy of Fallot is the most prevalent cyanotic congenital heart disease, occurring in 1/3 600 live births. This disorder comprises ventricular septal defect, right ventricular outflow obstruction, over-riding aorta, and right ventricular hypertrophy. The present study aims to reveal the spectrum of Nk2 homeobox 5 (NKX2-5) variants identified in a Moroccan non-syndromic tetralogy of Fallot cohort and to compare mutation rate with different studies from all over the world. Thirty-one patients with non-syndromic tetralogy of Fallot were recruited in this cross-sectional study. DNAs were extracted, and coding regions of NKX2.5 were PCR-amplified and sequenced. The obtained sequences were analyzed using different bioinformatics tools. Statistical comparisons were carried out using the R software.

Results

R25C mutation was found in two patients, in association with the E21E variant. The latter variant was frequently observed in the population and seems to have a potential altering effect on the splicing process. The NKX2.5 mutation rate in our tetralogy of Fallot population is around 6.4%, and no significant difference was noticed in comparison with previous studies. At the same time, a comparison of R25C mutation rate between atrial septal defect and tetralogy of Fallot worldwide populations shows a particular association of R25C mutation with tetralogy of Fallot phenotype.

Conclusions

This study reveals a consistency between our NKX2.5 mutation rate and those of different tetralogy of Fallot populations around the world. Our findings suggest a possible combined effect of R25C mutation and E21E variant on the carriers and emphasize particularly the significant association of R25C mutation with tetralogy of Fallot, which highlights the importance of an anticipative screening for TOF phenotype among the carriers’ offspring at the perinatal period.
Assessing COVID19-related anxiety in an Egyptian sample and correlating it to knowledge and stigma about the virus
Authors: Rabei Samah Hamed , El Fatah Wafaa Osman Abd
Published: March 2021

Background

COVID19 public health crisis has led to extensive anxiety regarding spread of virus. Aim of study is to assess COVID19-related anxiety in Egypt and correlate it to knowledge and stigma.

Results

Online questionnaire, 17–20 April 2020, had 218 Egyptian respondents to a socio-demographic questionnaire and Generalized Anxiety Disorder Scale (GAD-7). The present study revealed that 21.2% of the respondents were experiencing severe anxiety, 34.8% moderately severe anxiety, 25.2% moderate anxiety, and 18.8% mild anxiety. Women have more rates of severe anxiety. People who get online knowledge about COVID19 have least rates of severe anxiety. 51.8% think having the virus is stigmatizing. Knowledge and stigma are insignificantly inversely correlated to anxiety scores

Conclusion

Online scientific health education is necessary to reduce anxiety.
The role of MRI in comparison between benign and malignant chest wall masses in correlation with pathology
Authors: Kolta Marian Fayek Farid , El Rheem Nessma Kamal Abd , Ibrahim Amr Farouk , El-Mageed Mohammed Raafat Abd
Published: March 2021

Background

Tumors that arise from the chest wall (including bone structures such as the sternum, clavicle, scapula, and ribs) or from adjacent soft tissues are less common than other parts of the body, and so the resulting unfamiliarity can make it difficult to limit the number of possible diagnoses. These tumors have a wide range of possibilities, including primary chest wall tumors arising from the bone or soft tissue, which are subdivided into malignant and benign tumors, and the secondary metastatic deposits. The aim of the study is to investigate the ability of MRI with diffusion sequence in differentiation between benign and malignant chest wall masses, which is subsequently reflected in the management of chest wall masses patients.

Main body

MRI has superior soft-tissue resolution and value for local assessment of primary tumors and accurate tissue characterization and plays a key role in preoperative staging to assess for multi-spatial and multi-compartment involvement. ADC values were obtained in 31 patients, and the mean ADC values of benign (13 patients) chest wall masses were 1.31 ± 0.50 × 10−3 mm2/s while the mean ADC values of the malignant (18 patients) chest wall masses were 0.98 ± 0.36 × 10−3 mm2/s. There was a statistically significant difference between the ADC values obtained from the malignant and benign chest wall masses (P < 0.001).

Conclusion

This study demonstrates that diffusion-weighted MR imaging is a growing imaging modality to predict the histopathological differentiation of malignant from benign chest wall masses.
An observational study of the impact of COVID-19 and the rapid implementation of telehealth on community mental health center providers
Authors: Sklar Marisa , Reeder Kendal , Carandang Kristine , Ehrhart Mark G. , Aarons Gregory A.
Published: March 2021

Background

The COVID-19 pandemic has remarkably altered community mental health service delivery through the rapid implementation of telehealth. This study reports provider perspectives on the impact that COVID-19 and the transition to telehealth had on their work and their ability to deliver evidence-based practices (EBPs).

Methods

Providers (n = 93) completed online surveys with quantitative measures and open-ended items exploring their reactions to COVID-19 and to the transition to providing services via telehealth.

Results

Perceptions of personal risk and rumination around COVID-19 were low, while telehealth was viewed positively by providers. Three major themes emerged regarding the major impacts of COVID-19 on work: (1) the altered nature of interactions between patient/client and provider due to telehealth implementation, (2) changes in provider expectations regarding productivity, and (3) challenges maintaining work-life balance. In regard to the major impacts of COVID-19 on EBP delivery, three themes emerged: (1) increased difficulty delivering certain therapies via telehealth, (2) potential limitations to session confidentiality, and (3) challenge of engaging children in telehealth.

Conclusions

In the context of the COVID-19 pandemic, community mental health providers continued to engage with clients and deliver EBPs while navigating a number of changes related to the rapid transition to and implementation of telehealth. This study highlights the need for further work on what supports providers need to effectively engage with clients and deliver EBPs via telehealth, and has implications for how telehealth is sustained or de-implemented post-COVID-19.
Numerical modeling of multifrequency complex dielectric permittivity dispersion of sedimentary rocks
Authors: Posenato Garcia Artur , Heidari Zoya
Published: March 2021

The dielectric response of rocks results from electric double layer (EDL), Maxwell-Wagner (MW), and dipolar polarizations. The EDL polarization is a function of solid-fluid interfaces, pore water, and pore geometry. MW and dipolar polarizations are functions of charge accumulation at the interface between materials with contrasting impedances and the volumetric concentration of its constituents, respectively. However, conventional interpretation of dielectric measurements only accounts for volumetric concentrations of rock components and their permittivities, not interfacial properties such as wettability. Numerical simulations of the dielectric response of rocks provide an ideal framework to quantify the impact of wettability and water saturation ([Formula: see text]) on electric polarization mechanisms. Therefore, we have developed a numerical simulation method to compute pore-scale dielectric dispersion effects in the interval from 100 Hz to 1 GHz including effects of pore structure, [Formula: see text], and wettability on permittivity measurements. We solve the quasielectrostatic Maxwell’s equations in 3D pore-scale rock images in the frequency domain using the finite-volume method. Then, we verify simulation results for a spherical material by comparing to the corresponding analytical solution. Additionally, we introduce a technique to incorporate [Formula: see text]-polarization to the simulation and we verify it by comparing pore-scale simulation results to experimental measurements on a Berea sandstone sample. Finally, we quantify the impact of [Formula: see text] and wettability on broadband dielectric permittivity measurements through pore-scale numerical simulations. The numerical simulation results show that mixed-wet rocks are more sensitive than water-wet rocks to changes in [Formula: see text] at sub-MHz frequencies. Furthermore, permittivity and conductivity of mixed-wet rocks have weaker and stronger dispersive behaviors, respectively, when compared to water-wet rocks. Finally, numerical simulations indicate that conductivity of mixed-wet rocks can vary by three orders of magnitude from 100 Hz to 1 GHz. Therefore, Archie’s equation calibrated at the wrong frequency could lead to water saturation errors of up to 73%.
Estimating infiltration front depth using time-lapse multioffset gathers obtained from ground-penetrating-radar antenna array
Authors: Saito Hirotaka , Kuroda Seiichiro , Iwasaki Toshiki , Sala Jacopo , Fujimaki Haruyuki
Published: March 2021

Nondestructive and noninvasive visualization and quantification of dynamic subsurface hydrologic processes are needed. Using a ground-penetrating-radar (GPR) antenna array, time-lapse common-offset gather and common midpoint (CMP) data can be collected by fixing the antenna at a given location when scanning the subsurface. We have determined wetting front depths continuously during a field infiltration experiment by estimating electromagnetic (EM) wave velocities at given elapsed times using GPR antenna array data. A surface GPR antenna array system, consisting of 10 transmitters (Tx) and 11 receivers (Rx), that can scan each Tx-Rx combination in 10 s at a millisecond scale has been used to acquire all 110 Rx-Tx combinations in approximately 1.5 s. The field infiltration experiment has been conducted at an experimental field near the Tottori Sand Dunes in Japan. Using the estimated EM wave velocity from the CMP data, the depth to the wetting front is computed every minute. The estimated wetting front arrival time agrees with the time at which a sudden increase in the moisture sensor output is observed at a depth from 20 cm and below. We determine that time-lapsed CMP data collected with the GPR antenna array system could be used to estimate EM wave velocities continuously during the infiltration. The GPR antenna array is capable of accurate and quantitative tracking of the wetting front.
Improved hydrogeophysical imaging by structural coupling of 2D magnetic resonance and electrical resistivity tomography
Authors: Skibbe Nico , Günther Thomas , Müller-Petke Mike
Published: March 2021

Describing hydraulic properties in the subsurface in at least two dimensions is one of the main objectives in hydrogeophysics. However, due to the limited resolution and ambiguity of the individual methods, those images are often blurry. We have developed a methodology to combine two measuring methods, magnetic resonance tomography (MRT) and electrical resistivity tomography (ERT). To this end, we extend a structurally coupled cooperative inversion scheme to three parameters. It results in clearer images of the three main parameters: water content, relaxation time, and electrical resistivity; thus, there is a less ambiguous hydrogeophysical interpretation. Synthetic models demonstrate its effectiveness and show how the parameters of the coupling equation affect the images and how they can be chosen. Furthermore, we examine the influence of resistivity structures on the MRT kernel function. We apply the method to a roll-along MRT data set and a detailed ERT profile. As a final result, a hydraulic conductivity image is produced. Known ground-penetrating radar reflectors act as the ground truth and demonstrate that the obtained images are improved by the structural coupling.
Impact of Critical Material Attributes (CMAs)-Particle Shape on Miniature Pharmaceutical Unit Operations
Authors: Azad Mohammad A. , Capellades Gerard , Wang Allison B. , Klee David M. , Hammersmith Gregory , Rapp Kersten , Brancazio David , Myerson Allan S.
Published: March 2021

The U.S. Food and Drug Administration (FDA) emphasizes drug product development by Quality by Design (QbD). Critical material attributes (CMAs) are a QbD element that has an impact on pharmaceutical operations and product quality. Pharmaceutical drugs often crystallize as needle-shaped (a CMA) particles and affect the process due to poor flowability, low bulk density, and high compressibility, and eventually the product performance. In this study, the product obtained from crystallization was needle-shaped Ciprofloxacin HCl (CIPRO), formed lumps during drying, and compacted during processing through feeders. To delump small amounts of materials and break the needles, multiple available devices (mortar-pestle, Krups grinder) and custom-made grinder were assessed before formulation. The processed CIPRO powder was then used to make tablets in the miniature tablet manufacturing unit developed by the team at MIT. The critical quality attributes (CQA) of the tablets, set by the United States Pharmacopeia (USP), were then assessed for the drug powder processed with each of these devices. Powder properties comparable to commercial CIPRO were obtained when the custom MIT-designed grinder was used, leading to tablets that meet the USP criteria, with comparable dissolution profiles of those for marketed CIPRO tablets. This study demonstrates how needle-shaped crystals have an impact on pharmaceutical operations, even if it is on a miniature scale, and how proper shape and subsequent flow properties can be obtained by processing the particles through the MIT team-designed grinder.

Graphical Abstract
Serum Insulin-like Factor 3 Levels Are Reduced in Former Androgen Users, Suggesting Impaired Leydig Cell Capacity
Authors: Rasmussen Jon Jarløv , Albrethsen Jakob , Frandsen Mikkel Nicklas , Jørgensen Niels , Juul Anders , Kistorp Caroline
Published: March 2021

Context

Illicit use of anabolic androgenic steroids (AAS) is frequently observed in men and is associated with subsequent testosterone deficiency although the long-term effect on gonadal function is still unclear. Serum insulin-like factor 3 (INSL3) has been suggested to be a superior biomarker of Leydig cell secretory capacity compared to testosterone.

Objective

This study aimed to investigate serum INSL3 concentrations in AAS users.

Methods

This community-based, cross-sectional study included men aged 18 to 50 years, involved in recreational strength training and allocated to 1 of 3 groups: never-AAS users as controls (n = 44), current (n = 46), or former AAS users (n = 42) with an average duration since AAS cessation of 32 (23 ; 45) months.

Results

Serum INSL3 was lower in current AAS users and former AAS users than in controls, median (interquartile range), 0.04 µg/L (nondetectable [ND]-0.07 µg/L) and 0.39 µg/L (0.24-0.62 µg/L) vs 0.59 µg/L (0.45-0.72 µg/L), P less than .001. Former AAS users exhibited lower serum INSL3 levels than controls in a multivariable linear regression even after adjusting for serum total testosterone (TT) and other relevant confounders, (B) (95% CI), –0.16 µg/L (95% CI, –0.29 to –0.04 µg/L), P equal to .011. INSL3 and TT were not associated in the model, P equal to .821. Longer accumulated AAS duration (log2) was associated with lower serum INSL3 in former AAS users, (B) (95% CI), –0.08 (95% CI, –0.14 to –0.01), P equal to .022. Serum INSL3, but not inhibin B or testosterone, was associated with testicular size in a multivariate linear regression, (B) (95% CI); 4.7 (95% CI, 0.5 to 8.9), P equal to .030.

Conclusion

Serum INSL3 is reduced years following AAS cessation in men, independently of testosterone, suggesting persistently impaired Leydig cell capacity.
The Role for Metyrosine in the Treatment of Patients With Pheochromocytoma and Paraganglioma
Authors: Gruber Lucinda M , Jasim Sina , Ducharme-Smith Allison , Weingarten Toby , Young William F , Bancos Irina
Published: March 2021

Context

Treatment of pheochromocytoma and paraganglioma (PPGL) requires preintervention titration of alpha- and beta-adrenergic blockade, but patients may still be at risk for complications from catecholamine excess. Metyrosine decreases catecholamine production, making it an attractive therapeutic adjunct for select patients.

Evidence Acquisition

A systematic literature review was performed (Ovid Medline and Scopus databases) on December 17, 2019, including studies with humans and original data. Studies with 10 or more patients on metyrosine for PPGL were included. Studies were screened for overlapping populations, and the most comprehensive study was included. The references of included studies were reviewed for additional data. Patient data from our institution between 2000 and 2015 were also reviewed.

Evidence Synthesis

Metyrosine is well tolerated when used for a short course and can improve intraoperative outcomes in PPGL. Metyrosine should be considered when a difficult PPGL resection is expected (eg, pericardiac paraganglioma, abdominal paraganglioma with great vessel involvement), a large release of catecholamines is anticipated (eg, ablative therapy, chemotherapy), or when standard alpha- and beta-adrenergic blockade are not tolerated or cannot adequately control hypertension. Side effects are generally mild and self-limited, with sedation in a majority of patients. Extrapyramidal side effects are rare but can limit use of metyrosine. Because of its expense and limited availability, metyrosine use should be carefully planned and timed in relation to surgery.

Conclusions

Metyrosine is a safe addition to traditional alpha- and beta-adrenergic blockade and should be considered in those patients with PPGL at high risk for acute release of catecholamines.
Clinical Experience of the Efficacy and Safety of Low-dose Tolvaptan Therapy in a UK Tertiary Oncology Setting
Authors: Chatzimavridou-Grigoriadou Victoria , Al-Othman Sami , Brabant Georg , Kyriacou Angelos , King Jennifer , Blackhall Fiona , Trainer Peter J , Higham Claire E
Published: March 2021

Context

In patients with cancer, hyponatremia is associated with increased morbidity and mortality and can delay systemic therapy.

Objective

To assess the safety and efficacy of low-dose tolvaptan (7.5 mg) for hospitalized, adult patients with hyponatremia due to syndrome of inappropriate antidiuresis (SIAD), and coexisting malignancy.

Methods

Retrospective evaluation in a tertiary cancer center.

Results

Fifty-five patients with mean baseline serum sodium (sNa) 117.9 ± 4.6 mmol/L were included. In total, 90.9% had severe hyponatremia (sNa < 125 mmol/L). Mean age was 65.1 ± 9.3 years. Following an initial dose of tolvaptan 7.5 mg, median (range) increase in sNa observed at 24 hours was 9 (1-19) mmol/L. Within 1 week, 39 patients (70.9%) reached sNa ≥ 130 mmol/L and 48 (87.3%) had sNa rise of ≥5 mmol/L within 48 hours. No severe adverse events were reported. Thirty-three (60%) and 17 (30.9%) patients experienced sNa rise of ≥8 and ≥12 mmol/L/24 hours, respectively. The rate of sNa correction in the first 24 hours was significantly higher among participants that continued fluid restriction after tolvaptan administration (median [quantiles]: 14 [9-16] versus 8 [5-11] mmol/L, P = .036). Moreover, in the over-rapid correction cohort (≥12 mmol/L/24 hours) demeclocycline was appropriately discontinued only in 60% compared with 91.7% of the remaining participants (P = .047). Lower creatinine was predictive of higher sNa correction rate within 24 hours (P = .01).

Conclusion

In the largest series to date, although low-dose tolvaptan was demonstrated to be effective in correcting hyponatremia due to SIAD in cancer patients, a significant proportion experienced over-rapid correction. Concurrent administration of demeclocycline and/or fluid restriction must be avoided due to the increased risk of over-rapid correction.
Outcome Squares Integrating Efficacy and Safety, as Applied to Functioning Pituitary Adenoma Surgery
Authors: de Vries Friso , Lobatto Daniel J , Verstegen Marco J T , Schutte Pieter J , Notting Irene C , Kruit Mark C , Ahmed S Faisal , Pereira Alberto M , van Furth Wouter R , Biermasz Nienke R
Published: March 2021

Context

Transsphenoidal surgery is standard care in the treatment of hormone-secreting pituitary adenomas. Current clinician-reported surgical outcome measures are one-dimensional, typically focusing primarily on complete or partial resection, and secondarily on complication rates. However, outcomes are best reflected by the delicate balance of efficacy and complications at patient level.

Objective

This study proposes a novel way to classify and report outcomes, integrating efficacy and safety at the patient level.

Methods

Retrospective chart review of all pure endoscopic transsphenoidal surgical procedures for acromegaly, Cushing’s disease, and prolactinoma between 2010 and 2018 in a single tertiary referral center. We present our results in a classic (remission and complications separate) and in a novel outcome square integrating both outcomes, focusing on intended and adverse effects (long-term complications). This resulted in 4 outcome groups, ranging from good to poor. We use this approach to present these outcomes for several subgroups.

Results

A total of 198 surgical procedures were included (44 reoperations). Remission was achieved in 127 operations (64%). Good outcome was observed after 121 (61%), and poor outcome after 6 (3%) operations. When intended effect of surgery was applied (instead of remission), good outcome as intended was achieved after 148 of 198 surgeries (75%) and poor outcome after 4 (2%).

Conclusion

Quality of a surgical intervention can be presented in 4 simple categories, integrating both efficacy and safety with flexibility to adapt to the individualized situation at patient, disease, and surgical strategy and to the outcome of interest.
Vitamin D Supplementation for Prevention of Cancer: The D2d Cancer Outcomes (D2dCA) Ancillary Study
Authors: Chatterjee Ranee , Fuss Paul , Vickery Ellen M , LeBlanc Erin S , Sheehan Patricia R , Lewis Michael R , Dolor Rowena J , Johnson Karen C , Kashyap Sangeeta R , Nelson Jason , Pittas Anastassios G ,   D2d Research Group, Pittas Anastassios G , Brodsky Irwin , Ceglia Lisa , Chadha Chhavi , Chatterjee Ranee , Dawson-Hughes Bess , Desouza Cyrus , Dolor Rowena , Foreyt John , Ghazi Adline , Hsia Daniel S , Johnson Karen C , Kashyap Sangeeta R , Kim Sun , LeBlanc Erin S , Lewis Michael R , Liao Emilia , Malozowski Saul , Neff Lisa M , O’Neil Patrick , Park Jean , Peters Anne , Phillips Lawrence S , Pratley Richard , Raskin Philip , Rasouli Neda , Robbins David , Rosen Clifford , Reboussin Dave , Aroda Vanita R , Ware James H , Sheehan, Patricia , Staten Myrlene A , Knowler William C
Published: March 2021

Context

Observational studies suggest that low vitamin D status may be a risk factor for cancer.

Objective

In a population with prediabetes and overweight/obesity that is at higher risk of cancer than the general population, we sought to determine if vitamin D supplementation lowers the risk of cancer and precancers.

Methods

The Vitamin D and type 2 diabetes (D2d) cancer outcomes study (D2dCA) is an ancillary study to the D2d study, which was conducted at 22 academic medical centers in the United States. Participants had prediabetes and overweight/obesity and were free of cancer for the previous 5 years. Participants were randomized to receive vitamin D3 4000 IU daily or placebo. At scheduled study visits (4 times/year), cancer and precancer events were identified by questionnaires. Clinical data were collected and adjudicated for all reported events. Cox proportional hazard models compared the hazard ratio (HR) of incident cancers and precancers between groups.

Results

Over a median follow-up period of 2.9 years, among 2385 participants (mean age 60 years and 25-hydroxyvitamin D 28 ng/mL), there were 89 cases of cancer. The HR of incident cancer for vitamin D vs placebo was 1.07 (95% CI 0.70, 1.62). Of 241 participants with incident precancers, 239 had colorectal adenomatous polyps. The HR for colorectal polyps for vitamin D vs placebo was 0.83 (95% CI 0.64, 1.07).

Conclusion

In the D2d population of participants with prediabetes and overweight/obesity, not selected for vitamin D insufficiency, vitamin D supplementation did not have a significant effect on risk of incident cancer or colorectal polyps.
Antenatal Depression and Risk of Gestational Diabetes, Adverse Pregnancy Outcomes, and Postpartum Quality of Life
Authors: Minschart Caro , De Weerdt Kyara , Elegeert Astrid , Van Crombrugge Paul , Moyson Carolien , Verhaeghe Johan , Vandeginste Sofie , Verlaenen Hilde , Vercammen Chris , Maes Toon , Dufraimont Els , De Block Christophe , Jacquemyn Yves , Mekahli Farah , De Clippel Katrien , Van Den Bruel Annick , Loccufier Anne , Laenen Annouschka , Devlieger Roland , Mathieu Chantal , Benhalima Katrien
Published: March 2021

Aims

To determine the impact of depressive symptoms on pregnancy outcomes and postpartum quality of life in women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT).

Methods

1843 women from a prospective cohort study received universal GDM screening with an oral glucose tolerance test (OGTT). The Center for Epidemiologic Studies–Depression questionnaire was completed before GDM diagnosis was communicated and in GDM women in early postpartum. All participants completed the 36-Item Short Form Health Survey (SF-36) health survey postpartum.

Results

Women who developed GDM (231; 12.5%) had significantly more often depressive symptoms than NGT (1612; 87.5%) women [21.3% (48) vs 15.1% (239), odds ratio (OR) 1.52, 95% confidence interval (CI) (1.08-2.16), P = 0.017]. Compared to GDM women without depressive symptoms, depressed GDM women attended less often the postpartum OGTT [68.7% (33) vs 87.6% (155), P = 0.002], remained more often depressed [37.1% (13) vs 12.4% (19), P < 0.001], and had lower SF-36 scores postpartum. There were no significant differences in pregnancy outcomes between both groups. Rates of labor inductions were significantly higher in the NGT group with depressive symptoms compared to the nondepressed NGT group [31.7% (75) vs 24.7% (330), adjusted OR (aOR) 1.40, 95% CI (1.01-1.93), P = 0.041]. NGT women with depressive symptoms had lower SF-36 scores (P < 0.001) postpartum compared to nondepressed NGT women.

Conclusions

Women with antenatal symptoms of depression develop more often GDM. GDM women with depressive symptoms remain more often depressed postpartum with lower quality of life. NGT women with depressive symptoms have higher rates of labor inductions and lower quality of life postpartum compared to nondepressed NGT women.
Meta-analysis on the Effect of Mild Primary Hyperparathyroidism and Parathyroidectomy Upon Arterial Stiffness
Authors: Bernardi Stella , Giudici Fabiola , Barbato Vincenzo , Zanatta Lorenzo , Grillo Andrea , Fabris Bruno
Published: March 2021

Context

Current data about the cardiovascular manifestations of mild primary hyperparathyroidism (pHPT) are often conflicting. Pulse wave velocity (PWV) is the gold standard for assessing aortic stiffness, and it predicts cardiovascular morbidity and mortality.

Objective

Primary outcomes were to investigate if mild pHPT was associated with higher PWV and if parathyroidectomy (PTX) reduced PWV in mild pHPT. Secondary outcome was to investigate blood pressure changes after PTX.

Methods

Sources were PubMed, Google Scholar, SCOPUS, Web of Science, and the Cochrane Library. Eligible studies included reports of PWV in patients with mild pHPT and controls, or in patients with mild pHPT before and after PTX. Two investigators independently identified eligible studies and extracted data. Pooled mean difference (MD) was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Nine observational studies and one randomized clinical trial were selected, including 433 patients with mild pHPT, 171 of whom underwent PTX, and 407 controls. PWV was significantly higher in mild pHPT than in controls (MD = 1.18, 0.67 to 1.68, P < .0001). Seven studies evaluated the effect of PTX on PWV. PTX significantly reduced PWV (MD = –0.48, –0.88 to –0.07, P = .022).

Conclusion

Aortic stiffness is increased in patients with mild pHPT, supporting the notion that mild pHPT is also associated with adverse cardiovascular manifestations. PTX significantly reduced arterial stiffness in mild pHPT, indicating that the benefit of PTX over cardiovascular manifestations should not be dismissed but it deserves further studies.
Hepatic Fat in Participants With and Without Incident Diabetes in the Diabetes Prevention Program Outcome Study
Authors: Goldberg Ronald B , Tripputi Mark T , Boyko Edward J , Budoff Matthew , Chen Zsu-Zsu , Clark Jeanne M , Dabelea Dana M , Edelstein Sharon L , Gerszten Robert E , Horton Edward , Mather Kieren J , Perreault Leigh , Temprosa Marinella , Wallia Amisha , Watson Karol , Irfan Zeb
Published: March 2021

Context

There is little information about fatty liver in prediabetes as it transitions to early diabetes.

Objective

This study is aimed at evaluating the prevalence and determinants of fatty liver in the Diabetes Prevention Program (DPP).

Methods

We measured liver fat as liver attenuation (LA) in Hounsfield units (HU) in 1876 participants at ~14 years following randomization into the DPP, which tested the effects of lifestyle or metformin interventions versus standard care to prevent diabetes. LA was compared among intervention groups and in those with versus without diabetes, and associations with baseline and follow-up measurements of anthropometric and metabolic covariates were assessed.

Results

There were no differences in liver fat between treatment groups at 14 years of follow-up. Participants with diabetes had lower LA (mean ± SD: 46 ± 16 vs 51 ± 14 HU; P < 0.001) and a greater prevalence of fatty liver (LA < 40 HU) (34% vs 17%; P < 0.001). Severity of metabolic abnormalities at the time of LA evaluation was associated with lower LA categories in a graded manner and more strongly in those with diabetes. Averaged annual fasting insulin (an index of insulin resistance [OR, 95% CI 1.76, 1.41-2.20]) waist circumference (1.63, 1.17-2.26), and triglyceride (1.42, 1.13-1.78), but not glucose, were independently associated with LA < 40 HU prevalence.

Conclusion

Fatty liver is common in the early phases of diabetes development. The association of LA with insulin resistance, waist circumference, and triglyceride levels emphasizes the importance of these markers for hepatic steatosis in this population and that assessment of hepatic fat in early diabetes development is warranted.
Metabolic and Psychological Features are Associated with Weight Loss 12 Months After Sleeve Gastrectomy
Authors: Muraca Emanuele , Oltolini Alice , Binda Alberto , Pizzi Mattia , Ciardullo Stefano , Manzoni Giuseppina , Zerbini Francesca , Bianconi Eleonora , Cannistraci Rosa , Perra Silvia , Pizzi Pietro , Lattuada Guido , Perseghin Gianluca , Villa Matteo
Published: March 2021

Context

Laparoscopic sleeve gastrectomy (LSG) is a recognized effective procedure of bariatric surgery, but a poor response in weight loss may still represent a clinical problem. To date there are no validated predictors useful to better perform patient selection.

Objective

To establish the association of baseline anthropometric, metabolic, and psychologic features with the percent total weight loss (%TWL) and percent excess weight loss (%EWL) 12 months after surgery.

Design

Retrospective longitudinal analysis of a set of data about obese patients attending the outpatient service of a single obesity center from June 2016 to June 2019.

Patients

A total of 106 obese patients underwent LSG with presurgery evaluation and follow-up at 12 months after surgery.

Main outcome

Weight loss 12 months after LSG.

Results

Patients who achieved a %TWL higher than the observed median (≥34%) were younger, with a lower fasting plasma glucose and glycated hemoglobin, with a lower prevalence of hypertension and with a lower score in the impulsiveness scale, compared with patients with a %TWL < 34%. Similar findings were found when %EWL was considered. Multivariable stepwise regression analysis showed that younger age, lower impulsiveness, higher-than-normal urinary free cortisol, and lower HbA1c were associated with higher %TWL, explaining about 31.5% of the weight loss.

Conclusion

Metabolic and psychologic features at baseline were independently associated with weight loss and explained a non-negligible effect on the response to LSG. These data suggest that careful metabolic and psychologic profiling could help in sharper indications and personalized pre- and postsurgical follow-up protocols in candidates for LSG.
Vitamin D Regulates CXCL12/CXCR4 and Epithelial-to-Mesenchymal Transition in a Model of Breast Cancer Metastasis to Lung
Authors: Li Jiarong , Luco Aimée-Lee , Camirand Anne , St-Arnaud René , Kremer Richard
Published: March 2021

Vitamin D deficiency is associated with poor cancer outcome in humans, and administration of vitamin D or its analogs decreases tumor progression and metastasis in animal models. Using the mouse mammary tumor virus-polyoma middle T antigen (MMTV-PyMT) model of mammary cancer, we previously demonstrated a significant acceleration of carcinogenesis in animals on a low vitamin D diet and a reduction in spontaneous lung metastases when mice received vitamin D through perfusion. We investigate here the action mechanism for vitamin D in lung metastasis in the same non-immunodeficient model and demonstrate that it involves the control of epithelial to mesenchymal transition as well as interactions between chemokine C-X-C motif chemokine 12 (CXCL12) and its receptor C-X-C chemokine receptor type 4 (CXCR4). In vitro, 10−9M vitamin D treatment modifies the phenotype of MMTV-PyMT primary mammary tumor cells and significantly decreases their invasiveness and mammosphere formation capacity by 40% and 50%, respectively. Vitamin D treatment also inhibits phospho-signal transducer and activator of transcription 3 (p-STAT3), zinc finger E-box-binding homeobox 1 (Zeb1), and vimentin by 52%, 75%, and 77%, respectively, and increases E-cadherin by 87%. In vivo, dietary vitamin D deficiency maintains high levels of Zeb1 and p-STAT3 in cells from primary mammary tumors and increases CXCL12 expression in lung stroma by 64%. In lung metastases, vitamin D deficiency increases CXCL12/CXCR4 co-localization by a factor of 2.5. These findings indicate an involvement of vitamin D in mammary cancer ”seed” (primary tumor cell) and ”soil” (metastatic site) and link vitamin D deficiency to epithelial-to-mesenchymal transition (EMT), CXCL12/CXCR4 signaling, and accelerated metastasis, suggesting vitamin D repleteness in breast cancer patients could enhance the efficacy of co-administered therapies in preventing spread to distant organs.
Prolonged Low-Dose Dioxin Exposure Impairs Metabolic Adaptability to High-Fat Diet Feeding in Female but Not Male Mice
Authors: Matteo Geronimo , Hoyeck Myriam P , Blair Hannah L , Zebarth Julia , Rick Kayleigh R C , Williams Andrew , Gagné Rémi , Buick Julie K , Yauk Carole L , Bruin Jennifer E
Published: March 2021

Context

Human studies consistently show an association between exposure to persistent organic pollutants, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, aka “dioxin”), and increased diabetes risk. We previously showed that a single high-dose TCDD exposure (20 µg/kg) decreased plasma insulin levels in male and female mice in vivo, but effects on glucose homeostasis were sex-dependent.

Objective

The current study assessed whether prolonged exposure to a physiologically relevant low-dose of TCDD impacts glucose homeostasis and/or the islet phenotype in a sex-dependent manner in chow-fed or high-fat diet (HFD)-fed mice.

Methods

Male and female mice were exposed to 20 ng/kg/d TCDD 2×/week for 12 weeks and simultaneously fed standard chow or a 45% HFD. Glucose homeostasis was assessed by glucose and insulin tolerance tests, and glucose-induced plasma insulin levels were measured in vivo. Histological analysis was performed on pancreas from male and female mice, and islets were isolated from females for TempO-Seq transcriptomic analysis.

Results

Low-dose TCDD exposure did not lead to adverse metabolic consequences in chow-fed male or female mice, or in HFD-fed males. However, TCDD accelerated the onset of HFD-induced hyperglycemia and impaired glucose-induced plasma insulin levels in females. TCDD caused a modest increase in islet area in males but reduced the percent beta cell area within islets in females. TempO-Seq analysis suggested abnormal changes to endocrine and metabolic pathways in female TCDDHFD islets.

Conclusion

Our data suggest that prolonged low-dose TCDD exposure has minimal effects on glucose homeostasis and islet morphology in chow-fed male and female mice but promotes maladaptive metabolic responses in HFD-fed females.