bluuebunny/crossref_metadata_2025 huggingface dataset:
Arabic version of the SF‐Qualiveen: cross-cultural adaptation, translation, and validation of urinary disorder‐specific instruments in patients with spinal cord injury
Authors: Khadour Younes A. , Ebrahem Bashar , Khadour Fater A.
Published: January 2024

Background

The Short-Form Qualiveen (SF-Qualiveen) questionnaire assesses the effect of bladder and urinary symptoms on patients' quality of life (QoL) with urological impairment caused by neurological diseases. There is no validated SF-Qualiveen questionnaire in Arabic, so this study aims to provide a translated and validated version of the SF-Qualiveen questionnaire among Arabic patients experiencing spinal cord injury (SCI).

Methods

Psychometric features such as content and construct validity, test–retest reliability, and internal consistency were analyzed. Construct validity was evaluated by contrasting the SF-Qualiveen with the Neurogenic Bladder Symptom Score Short-Form (NBSS-SF) questionnaire. Internal consistency was measured using Cronbach's alpha, whereas the intraclass correlation coefficient (ICC) was employed to assess the test–retest reliability. Factorial validity was established by principal component analysis (PCA).

Results

The internal consistency of the total SF-Qualiveen and the domains “Bother with limitations,” “Fear,” “Feeling,” and “Frequency of limitations” showed good internal consistency (Cronbach's alpha of > 0.7). ICC was 0.90 for the total score, 0.83 for the bother with limitations, 0.80 for fears, 0.84 for feeling, and 0.81 for frequency of limitations. The correlation analysis revealed a positive association between the total scores on the NBSS-SF and the domains of the SF-Qualiveen, comprising bother with limitations (r = 0.53, p = 0.02), fears (r = 0.44, p = 0.03), feelings (r = 0.49, p = 0.04), and frequency of limitations (r = 0.46, p = 0.02). The best-fit four-factor model for confirming overall item communalities ranged from 0.552 to 0.814, which indicates moderate to high communalities, and confirms the homogeneity of the SF-Qualiveen using PCA.

Conclusions

The findings of this validation study revealed that the SF-Qualiveen is a reliable and valid instrument appropriate for Arabic-speaking patients with SCI in both research and clinical practices.
Fine-scale monitoring of insecticide resistance in Aedes aegypti (Diptera: Culicidae) from Sri Lanka and modeling the phenotypic resistance using rational approximation
Authors: Mendis B. A. N. , Peiris V. , Harshani W. A. K. , Fernando H. S. D. , de Silva B. G. D. N. K.
Published: January 2024

Background

The unplanned and intensified use of insecticides to control mosquito-borne diseases has led to an upsurge of resistance to commonly used insecticides. Aedes aegypti, the main vector of dengue, chikungunya, and Zika virus, is primarily controlled through the application of adulticides (pyrethroid insecticides) and larvicides (temephos). Fine spatial-scale analysis of resistance may reveal important resistance-related patterns, and the application of mathematical models to determine the phenotypic resistance status lessens the cost and usage of resources, thus resulting in an enhanced and successful control program.

Methods

The phenotypic resistance for permethrin, deltamethrin, and malathion was monitored in the Ae. aegypti populations using the World Health Organization (WHO) adult bioassay method. Mosquitoes' resistance to permethrin and deltamethrin was evaluated for the commonly occurring base substitutions in the voltage-gated sodium channel (vgsc) gene. Rational functions were used to determine the relationship between the kdr alleles and the phenotypic resistant percentage of Ae. aegypti in Sri Lanka.

Results

The results of the bioassays revealed highly resistant Ae. aegypti populations for the two pyrethroid insecticides (permethrin and deltamethrin) tested. All populations were susceptible to 5% malathion insecticide. The study also revealed high frequencies of C1534 and G1016 in all the populations studied. The highest haplotype frequency was detected for the haplotype CC/VV, followed by FC/VV and CC/VG. Of the seven models obtained, this study suggests the prediction models using rational approximation considering the C allele frequencies and the total of C, G, and P allele frequencies and phenotypic resistance as the best fits for the area concerned.

Conclusions

This is the first study to our knowledge to provide a model to predict phenotypic resistance using rational functions considering kdr alleles. The flexible nature of the rational functions has revealed the most suitable association among them. Thus, a general evaluation of kdr alleles prior to insecticide applications would unveil the phenotypic resistance percentage of the wild mosquito population. A site-specific strategy is recommended for monitoring resistance with a mathematical approach and management of insecticide applications for the vector population.

Graphical Abstract
Genomic and transcriptomic analysis of breast cancer identifies novel signatures associated with response to neoadjuvant chemotherapy
Authors: Yin Gengshen , Liu Liyuan , Yu Ting , Yu Lixiang , Feng Man , Zhou Chengjun , Wang Xiaoying , Teng Guoxin , Ma Zhongbing , Zhou Wenzhong , Ye Chunmiao , Zhang Jialin , Ji Changhua , Zhao Linfeng , Zhou Peng , Guo Yaxun , Meng Xingchen , Fu Qinye , Zhang Qiang , Li Liang , Zhou Fei , Zheng Chao , Xiang Yujuan , Guo Mingming , Wang Yongjiu , Wang Fei , Huang Shuya , Yu Zhigang
Published: January 2024

Background

Neoadjuvant chemotherapy (NAC) has become a standard treatment strategy for breast cancer (BC). However, owing to the high heterogeneity of these tumors, it is unclear which patient population most likely benefit from NAC. Multi-omics offer an improved approach to uncovering genomic and transcriptomic changes before and after NAC in BC and to identifying molecular features associated with NAC sensitivity.

Methods

We performed whole-exome and RNA sequencing on 233 samples (including matched pre- and post-treatment tumors) from 50 BC patients with rigorously defined responses to NAC and analyzed changes in the multi-omics landscape. Molecular features associated with NAC response were identified and validated in a larger internal, and two external validation cohorts, as well as in vitro experiments.

Results

The most frequently altered genes were TP53, TTN, and MUC16 in both pre- and post-treatment tumors. In comparison with pre-treatment tumors, there was a significant decrease in C > A transversion mutations in post-treatment tumors (P = 0.020). NAC significantly decreased the mutation rate (P = 0.006) of the DNA repair pathway and gene expression levels (FDR = 0.007) in this pathway. NAC also significantly changed the expression level of immune checkpoint genes and the abundance of tumor-infiltrating immune and stroma cells, including B cells, activated dendritic cells, γδT cells, M2 macrophages and endothelial cells. Furthermore, there was a higher rate of C > T substitutions in NAC nonresponsive tumors than responsive ones, especially when the substitution site was flanked by C and G. Importantly, there was a unique amplified region at 8p11.23 (containing ADGRA2 and ADRB3) and a deleted region at 3p13 (harboring FOXP1) in NAC nonresponsive and responsive tumors, respectively. Particularly, the CDKAL1 missense variant P409L (p.Pro409Leu, c.1226C > T) decreased BC cell sensitivity to docetaxel, and ADGRA2 or ADRB3 gene amplifications were associated with worse NAC response and poor prognosis in BC patients.

Conclusions

Our study has revealed genomic and transcriptomic landscape changes following NAC in BC, and identified novel biomarkers (CDKAL1P409L, ADGRA2 and ADRB3) underlying chemotherapy resistance and poor prognosis, which could guide the development of personalized treatments for BC.
Insulin resistance-related features are associated with cognitive decline: a cross-sectional study in adult patients with type 1 diabetes
Authors: Ji Xiaolin , Zou Wenjing , Fan Li , Zhou Zhiguang , Zhu Xiongzhao , Li Xia
Published: January 2024

Background

To investigate the associations between insulin resistance (IR)-related features and cognitive function in type 1 diabetes (T1D).

Methods

A total of 117 adult patients with T1D were recruited in this cross-sectional study. IR-related features include overweight/obesity/central obesity, hypertension, atherogenic dyslipidemia, and decreased estimated insulin sensitivity (eIS). The Wechsler Memory Scale-Chinese Revision, Wisconsin Card Sorting Test, and Sustained Attention to Response Task was used to assess memory, executive function and sustained attention, respectively. A z-score was generated from each test, and a composite measure of global cognitive performance was calculated by averaging the z-scores of all tests. Cognitive differences were measured between T1D patients with and without IR-related features. The associations between IR-related features and and cognitive performance were analyzed using: logistic regression, partial correlation, and multivariate linear regression analysis.

Results

A total of 53 (45.3%) T1D patients were defined as having IR-related features. Individuals with IR-related features displayed worse overall cognitive scores compared to those without and had a 4-fold increase in the risk for having global cognitive z-score < 0. Among the IR-related features, higher triglyceride (TG) and lower eIS showed linear correlation with lower global cognitive performance. And the subsequent regression analysis identified eIS as the factor independently associated with global cognitive performance.

Conclusions

We have provided evidence linking IR-related features to deteriorated cognitive function in adult patients with T1D. And eIS showed an independent positive correlation with global cognitive performance. Although no causal relationship can be drawn, IR emerges as an important factor reflecting cognitive function.

Trial registration

ClinicalTrials.gov NCT03610984.
Sleep patterns and risks of incident cardiovascular disease and mortality among people with type 2 diabetes: a prospective study of the UK Biobank
Authors: Hu Jinxia , Wang Xuanyang , Cheng Licheng , Dang Keke , Ming Zhu , Tao Xinmiao , Xu Xiaoqing , Sarker Shuvan Kumar , Li Ying
Published: January 2024

Background

To explore the relationship between sleep patterns and cardiovascular disease (CVD) incidence and mortality risk in a population with type 2 diabetes through a UK Biobank sample.

Methods

A total of 6860 patients with type 2 diabetes were included in this study. Five sleep factors (including Chronotype, sleep duration, insomnia, daytime sleepiness, and snoring) were collected as a questionnaire. The calculation generates a sleep score of 0–5, and then three sleep patterns were defined based on the sleep scores: poor sleep pattern (0–2), Intermediate sleep pattern (3–4), and healthy sleep pattern (5). HRs and 95% confidence intervals were calculated by multivariate COX proportional risk model adjustment. Restricted cubic splines were used to validate linear associations between sleep scores CVD events.

Results

Our results found a reduced risk of CVD events in individuals with healthy sleep patterns compared to participants with poor sleep patterns. CVD Mortality (HR, 0.690; 95% CI 0.519–0.916), ASCVD (Atherosclerosis CVD) (HR, 0.784; 95% CI 0.671–0.915), CAD (Coronary Artery Disease) (HR, 0.737; 95% CI 0.618–0.879), PAD (Peripheral Arterial Disease) (HR, 0.612; 95% CI 0.418–0.896), Heart Failure (HR, 0.653; 95% CI 0.488–0.875). Restricted cubic spline responded to a negative linear correlation between sleep scores and CVD Mortality, ASCVD, CAD, PAD, and Heart Failure.

Conclusions

Healthy sleep patterns are significantly associated with a reduced risk of CVD Mortality, ASCVD, CAD, PAD, and Heart Failure in the diabetes population.
Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status
Authors: Reas Emilie T. , Triebswetter Curtis , Banks Sarah J. , McEvoy Linda K.
Published: January 2024

Background

APOE4is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD), whereasAPOE2confers protection. However, effects ofAPOEon neurodegeneration in cognitively intact individuals, and how these associations evolve with cognitive decline, are unclear. Furthermore, few studies have evaluated whether effects ofAPOEon neurodegenerative changes are modified by other AD key risk factors including age and sex.

Methods

Participants included older adults (57% women; 77 ± 7 years) from the Rancho Bernardo Study of Health Aging and the University of California San Diego Alzheimer’s Disease Research Center, including 192 cognitively normal (CN) individuals and 33 with mild cognitive impairment. Participants underwent diffusion MRI, and multicompartment restriction spectrum imaging (RSI) metrics were computed in white matter, gray matter, and subcortical regions of interest. Participants were classified asAPOE4carriers,APOE2carriers, andAPOE3homozygotes. Analysis of covariance among CN (adjusting for age, sex, and scanner) assessed differences in brain microstructure byAPOE, as well as interactions betweenAPOEand sex. Analyses across all participants examined interactions betweenAPOE4and cognitive status. Linear regressions assessedAPOEby age interactions.

Results

Among CN,APOE4carriers showed lower entorhinal cortex neurite density than non-carriers, whereasAPOE2carriers showed lower cingulum neurite density than non-carriers. Differences in entorhinal microstructure byAPOE4and in entorhinal and cingulum microstructure byAPOE2were present for women only. Age correlated with lower entorhinal restricted isotropic diffusion amongAPOE4non-carriers, whereas age correlated with lower putamen restricted isotropic diffusion amongAPOE4carriers. Differences in microstructure between cognitively normal and impaired participants were stronger forAPOE4-carriers in medial temporal regions, thalamus, and global gray matter, but stronger for non-carriers in caudate.

Conclusions

The entorhinal cortex may be an early target of neurodegenerative changes associated withAPOE4in presymptomatic individuals, whereasAPOE2may support beneficial white matter and entorhinal microstructure, with potential sex differences that warrant further investigation.APOEmodifies microstructural patterns associated with aging and cognitive impairment, which may advance the development of biomarkers to distinguish microstructural changes characteristic of normal brain aging,APOE-dependent pathways, and non-AD etiologies.
How Germany is phasing out lignite: insights from the Coal Commission and local communities
Authors: Radtke Jörg , David Martin
Published: January 2024

Background

This article asks the following question: how well are coal regions, affected by phase-out plans, represented in mediating commissions, to what extent do local communities participate in the decision-making process and how are the political negotiations perceived by the communities? We look at the case of the German lignite phase-out from a procedural justice perspective. Informed by literature on sociotechnical decline and procedural justice in energy transitions, we focus first on aspects of representation, participation and recognition within the German Commission on Growth, Structural Change and Employment (“Coal Commission”). Second, we analyze how to exnovate coal in two regions closely tied to the coal- and lignite-based energy history in Germany: Lusatia and the Rhenish Mining District.

Results

Based on interview series in both regions, we connect insights from local communities with strategies for structural change and participation programs in the regions. We find significant differences between the two regions, which is primarily an effect of the challenging historical experiences in Lusatia. Participation within existing arrangements is not sufficient to solve these problems; they require a comprehensive strategy for the future of the regions.

Conclusions

We conclude that the first phase-out process was a lost opportunity to initiate a community-inclusive sustainable transition process. As the phase-out process is not yet concluded, additional efforts and new strategies are needed to resolve the wicked problem of lignite phase-out.
Solar-assisted poultry production in small-scale farms: a case study in the Bekaa semi-arid region, Lebanon
Authors: Sleem Sara T. , Salam Darine A. , Ghaddar Nesreen , Abou Ghali Kamel , Chehab Ghassan , Daghir Nuhad , Doughan Youssef , Haddad Nicolas
Published: January 2024

Background

In Lebanon, poultry production is one of the major components of the agricultural sector; however, it suffers from increasing energy costs necessary to cover poultry heating requirements. This affects the profits of brooding farms, namely, small-scale farms in rural areas. Few studies have addressed the use of renewable energy in the poultry industry in Lebanon, with most having focused on modelling ventilation and air quality requirements in poultry houses. Therefore, there is a need to investigate the efficiency of renewable energy sources in providing heating requirements for poultry production. Accordingly, this study evaluates the performance of a solar-assisted, localized heating system in providing heat requirements for chicks in a renovated green poultry house in the Bekaa semi-arid rural region in Lebanon. For this aim, two brooding cycles were conducted during the warm and cold seasons in a greenhouse and were later replicated in a conventional poultry house.

Results

The energy inputs in the green and conventional houses, respectively, were 33,995.39 and 40,656.97 MJ (1000 birds)−1 in the warm season, and 37,058.25 and 45,770.05 MJ (1000 birds)−1 in the cold season. Calculated energy efficiency values for the green and conventional poultry houses were, respectively, 0.58 and 0.50 in the warm season, and 0.46 and 0.41 in the cold season. The net return was negative for both systems and the benefit-to-cost ratio from broiler production was calculated to be 0.49 and 0.50 in the green and conventional houses, respectively. Life cycle cost analysis showed that adopting the green heating system in the studied farm would entail an 18.89% increase in cost over a period of 20 years as compared to the conventional system.

Conclusion

It was concluded that poultry production is not profitable in small-scale farms in the studied area in Lebanon. The use of renewable energy might be more suited for large-scale broiler operations to achieve their purpose in reducing overall production costs. Optimization of the green system to fully satisfy the poultry energy requirements would render it more economically competitive.
Phytoplankton ecology in the early years of a boreal oil sands end pit lake
Authors: Furgason Chantel C. , Smirnova Angela V. , Dacks Joel B. , Dunfield Peter F.
Published: January 2024

Background

Base Mine Lake (BML) is the first full-scale end pit lake for the oil sands mining industry in Canada. BML sequesters oil sands tailings under a freshwater cap and is intended to develop into a functional ecosystem that can be integrated into the local watershed. The first stage of successful reclamation requires the development of a phytoplankton community supporting a typical boreal lake food web. To assess the diversity and dynamics of the phytoplankton community in BML at this reclamation stage and to set a baseline for future monitoring, we examined the phytoplankton community in BML from 2016 through 2021 using molecular methods (targeting the 23S, 18S, and 16S rRNA genes) and microscopic methods. Nearby water bodies were used as controls for a freshwater environment and an active tailings pond.

Results

The phytoplankton community was made up of diverse bacteria and eukaryotes typical of a boreal lake. Microscopy and molecular data both identified a phytoplankton community comparable at the phylum level to that of natural boreal lakes, dominated by Chlorophyta, Cryptophyta, and Cyanophyta, with some Bacillariophyta, Ochrophyta, and Euglenophyta. Although many of the same genera were prominent in both BML and the control freshwater reservoir, there were differences at the species or ASV level. Total diversity in BML was also consistently lower than the control freshwater site, but consistently higher than the control tailings pond. The phytoplankton community composition in BML changed over the 5-year study period. Some taxa present in 2016–2019 (e.g., Choricystis) were no longer detected in 2021, while some dinophytes and haptophytes became detectable in small quantities starting in 2019–2021. Different quantification methods (qPCR analysis of 23S rRNA genes, and microscopic estimates of populations and total biomass) did not show a consistent directional trend in total phytoplankton over the 5-year study, nor was there any consistent increase in phytoplankton species diversity. The 5-year period was likely an insufficient time frame for detecting community trends, as phytoplankton communities are highly variable at the genus and species level.

Conclusions

BML supports a phytoplankton community composition somewhat unique from control sites (active tailings and freshwater lake) and is still changing over time. However, the most abundant genera are typical of natural boreal lakes and have the potential to support a complex aquatic food web, with many of its identified major phytoplankton constituents known to be primary producers in boreal lake environments.
A hybrid neuro fuzzy decision-making approach to the participants of derivatives market for fintech investors in emerging economies
Authors: Rahadian Dadan , Firli Anisah , Dinçer Hasan , Yüksel Serhat , Mikhaylov Alexey , Ecer Fatih
Published: January 2024

The risk profiles of investors play an important role in the success of derivative products investments. It is also necessary to determine the appropriate investor profile according to the conditions of a country. This protects investors from major losses. Therefore, there is a strong need for a new study that analyzes the risk profiles of derivative products in emerging economies. This study aims to identify the most appropriate investor risk profile for derivative instruments in emerging economies. It constructs a novel decision-making model. In this model, the facial action coding system, quantum theory, spherical fuzzy sets, and multi-stepwise weight assessment ratio analysis (M-SWARA) methodology are integrated to minimize uncertainty in this process. First, three main participants of derivatives for financial technology investors are evaluated using the quantum spherical fuzzy M-SWARA technique. After that, seven emerging economies are ranked based on this performance using quantum spherical fuzzy technique for order of preference by similarity to ideal solution. The main contribution is that an appropriate investor profile is identified for financial derivative investments in emerging economies. One of the important originalities of this study is the development of a new technique called M-SWARA by making some improvements to the classical stepwise weight assessment ratio analysis method. It is concluded that hedging is the most appropriate purpose for making investments in derivative products in emerging economies. It is also identified that China has the greatest performance among the seven emerging economies regarding the appropriate purpose for making derivative investments. For the effective management of this problem in these countries, it is recommended to prevent the speculative use of derivative products with legal regulations.
Phenolic-rich fraction of green tea attenuates histamine-mediated cardiopulmonary toxicity by inhibiting Cox-2/NF-κB signaling pathway and regulating oxidant/antioxidant balance
Authors: Hassanen Eman I. , Kamel Shaimaa , Issa Marwa Y. , Mohamed Wafaa A. , Mansour Hayam A. , Mahmoud Mahmoud A.
Published: January 2024

Background

Histamine (HIS) has a substantial impact on the development of numerous allergic disorders including asthma. Antihistamines mostly target histamine receptor-1 alone, so it is not entirely effective in the treatment of allergic diseases. In the current investigation, we examine the growing evidence for novel therapeutic strategies that aim to treat histamine-mediated cardiopulmonary toxicity with the phenolic-rich fraction of green tea (PRFGT).

Results

Our findings demonstrated that weekly ingestion of HIS to rats induced oxidant/antioxidant imbalance in both lung and heart homogenates. The histopathological examination demonstrated extensive interstitial pneumonia with progressive alveolar and bronchial damage in HIS receiving groups. Heart sections showed severe myocardial necrosis and hemorrhage. All lesions were confirmed by the immunohistochemical staining that demonstrated strong caspase-3, cyclooxygenase-2 (Cox-2), and tumor necrosis factor-α (TNF-α) protein expressions along with upregulation of the pulmonary m-RNA expression of TNF-α, nuclear factor kappa-B (NF-κB), and interleukin-1β (IL-1β) genes and cardiac levels of many apoptotic genes. Otherwise, the pretreatment of rats with PRFGT had the ability to alleviate all the aforementioned toxicological parameters and return the microscopic picture of both lung and heart sections to normal histology.

Conclusions

We concluded that PRFGT’s powerful antioxidant, anti-inflammatory, and anti-apoptotic properties can reduce cardiopulmonary toxicity caused by HIS. We recommended daily intake of green tea as a beverage or adding it to foods containing elevated levels of HIS to prevent its possible toxicity.
In vitro and in vivo evaluation of nanoliposomes loading quercetin and 3-bromopyruvate against glioma
Authors: Soriano-Ursúa Marvin Antonio , Vega-García Angélica , Buzoianu-Anguiano Vinnitsa , Ocampo-Nestor Ana Lilia , Manjarrez-Marmolejo Joaquín , Feria-Romero Iris Angélica
Published: January 2024

Background

Diffuse astrocytoma (a type of glioma) and its prevalence are matters of concern worldwide. Patients with this type of tumour have a poor prognosis because after surgical treatment, radiotherapy and/or chemotherapy, these tumours eventually regrow or progress. To date, there is no effective treatment that can cure affected patients. Quercetin and 3-bromopyruvate are chemical compounds that have been proven to have antitumour effects alone or in combination with other compounds. Nevertheless, combination treatments including these agents are not used for treating diffuse astrocytoma.

Methods

The use of nanoliposomes loaded with quercetin and 3-bromopyruvate as combination therapy was evaluated by treating C6 cells in vitro and in vivo (in Sprague–Dawley rat brain).

Results

The 0.5 mg/mL quercetin + 0.75 mg/mL 3-bromopyruvate combination treatment decreased the expression of the biomarkers Annexin V and Caspase-3 and inhibited tumour growth; this was consistent with the in vivo results that revealed the administration of this treatment resulted in improved animal survival.

Conclusions

The observations in the present study support the further exploration of this combination of active agents in the treatment of high-grade diffuse astrocytoma, especially in cases for which wide resection is possible.
O-04 A diagnostic riddle of an adrenal incidentaloma
Authors: Sane Riikka , Viukari Marianna , Matikainen Niina , Jäntti Camilla Schalin
Published: January 2024

Clinical case

A 78-year-old male underwent preoperative CT as transcatheter aortic valve implantation was planned. In addition to a 6 cm incidental mass in the right adrenal, it also revealed unspecific pulmonary nodules. The patient was referred to the Endocrine unit. Non-contrast adrenal CT demonstrated a heterogenous 6 cm tumor, < 10 HU.

The patient had a history of psoriasis, type 2 diabetes mellitus, hypertension, chronic kidney disease, atrial fibrillation, peripheral artery disease, aortic stenosis and coronary artery disease. Clinical examination revealed no signs of Cushing's syndrome.

First, normal blood metanephrine/normetanephrine concentrations confirmed that pheochromocytoma was ruled out. The possibility of a metastatic tumor mass was investigated by tumor biopsy, histopathology was compatible with an adrenocortical neoplasm, Ki67 2%.

Further laboratory work-up is given in Table 1.

How should the laboratory findings be interpreted?

Primary aldosteronism was ruled out. Cortisol was not suppressed on 1mg DST, in contrast to perfectly normal 24h urinary free cortisol.

Late night salivary cortisol (LNSC) was markedly increased, 1210 nmol/l and low ACTH concentration further suggested true hypercortisolism.

Does the patient suffer from hypercortisolism?

The patient had no clinical signs of Cushing syndrome, albeit cardiometabolic diseases. False positive DST and LNSC results were suspected. Indeed, the patient was using 1% hydrocortisone lip lotion. On repeat screening after discontinuation of hydrocortisone, LNSC was 3.8 nmol/l, and DST remained positive (258nmol). The patient was diagnosed with autonomous cortisol excess (MACS) (1).

Should the patient undergo surgery for the right adrenal mass?

MACS in combination with relevant co-morbidities and large tumor size indicated surgery (1), which the patient consented to. After surgery, cortisol concentrations remained suppressed which prompted hydrocortisone replacement therapy. Final pathology review classified the tumor as an adenoma, Weiss Score 0/9 and Ki-67 2%.

Conclusion

False positive cortisol screening tests are common and must be ruled out before surgery. For DST, common explanations are exogenous glucocorticoid use, drugs that accelerate dexamethasone metabolism and estrogen induced increase in CBG. The most common pitfalls for LNSC are deranged circadian rhythm and exogenous hydrocortisone.

Reference (1). Fassnacht el al. European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas. European Journal of Endocrinology,2023; 189(1): G1–G42.Table 1
P-05 Malignant pheochromocytoma with a negative biomarker hormonal assay: A case report
Authors: Mohammed Adel Gassab , Hassan Muteib Ahmed Abul , Sajit Assad Hussein , Alwaeli Dheyaa Kadhim
Published: January 2024

Description

Malignant pheochromocytoma is a rare, predominantly sporadic, but also familial disease, with a malignancy frequency of about 10%.

Clinical Case

A 25-year-old male was referred to us by the general surgeon after he had a hypertensive crisis during the appendectomy surgery and then accidentally discovered a left adrenal gland mass by CT scan. Assessment of the patient done by physical examination, the height 168cm, weight 53 kg and the BMI 19 kg/m2 and the vital sign was Bp 200/110, and PR 87 b/min. Investigations: normal renal function test and negative metanephrines, normetanephrine and aldosterone, renin and aldosterone renin ratio also normal serum electrolytes. Imaging abdomen CT shows a mass measuring 4.8 X3.7X6.2 cm in its (AP, TS&CC dimension) in the left adrenal gland (encircle), density 40-50 HU. with central hypo density represented cystic necrosis. Right adrenal is normal limbs following intravenous contrast, the left adrenal mass enhances brightly (130-140HU) with central cystic necrosis … consisting with typical features of pheochromocytoma. The patient referred to expert surgeon and there was some preoperative preparation inform of the patient received phenoxybenzamine (alpha blocker) the receive propranolol to control reflux tachycardia and normalized the blood pressure, resection of left adrenal mass was done and the gross tissue biopsy was sent to histopathologist, and the result revealed a diagnosis of malignant pheochromocytoma, after two weeks from operation CT images post operatively after total resection of left adrenal mass revealed clear bed no residual SOL with surgical clips seen.

Conclusion

Marker-negative Pheochromocytomas are an uncommon form of the illness. Even more dangerous forms, malignant pheochromocytomas typically release metabolites. However, a doctor must be alert to patients with negative markers who exhibit typical symptoms and must make a diagnosis using a combination of clinical, radiologic, and biochemical testing. When choosing patients for presurgical alpha blockade, this is extremely important.

Table 1
P-11 Case report of Primary Hyperparathyroidism and Pulmonary Embolism
Authors: Mashayekhi Yashar , Baba-Aissa Sara , Al-Qaysi Amina Adil , Owles Henry , Panourgia Maria , Ahmed Mohamed H
Published: January 2024

Introduction

Primary hyperparathyroidism (PHPT) is a disorder characterized by excessive parathyroid hormone secretion, resulting in hypercalcaemia. Patients with PHPT are believed to be in a hypercoagulable state due to the role of calcium in the platelet function and the coagulation pathway.

Clinical Case

An 82-year-old male with a background history of deep vein thrombosis twelve years ago, was admitted with left leg pain following a fall, he was found to have an intra-capsular left neck of femur fracture for which he underwent left hip hemiarthroplasty at a later stage during his admission. He was also found to have adjusted calcium of 2.9 mmol/L at admission, parathyroid hormone of 15.2 pmol/L, raised urine calcium-creatinine ratio of 0.39 and he was vitamin D replete (vitamin D 50.3 nmol/L). He was treated for delirium and a urinary tract infection and his inflammatory markers continued to worsen, this triggered performing a CT scan of the chest, abdomen and pelvis, which revealed a right parathyroid nodule and an acute pulmonary embolism (PE). He was commenced on prophylactic dose of low molecular weight heparin at admission, it was changed to a therapeutic dose of low molecular weight heparin after the PE diagnosis and then to Apixaban for three months. The patient was assessed to not be suitable for parathyroidectomy, the decision was made to manage the PHPT medically and he is going to be followed up locally at the Endocrinology Clinic.

Conclusion

There have been few case reports suggesting a correlation between the hypercalcaemic PHPT and the risk of venous thromboembolism. Ionised calcium is necessary for thrombin formation, platelet activation and aggregation, as well as activation of various clotting factors, such as factor VII and factor X. Studies have also shown that these patients have increased protein S activity and fibrinogen levels. This case, among other cases that we have observed in our hospital, highlights that the hypercalcaemia could pose an additional hypercoagulability risk in the presence of other risk factors.
P-19 A case of Birt Hogg Dube syndrome presented with parathyroid carcinoma
Authors: Bektaş Mustafa , Yavuz Dilek Gogas
Published: January 2024

Introduction

The Birt Hogg Dube syndrome is an autosomal dominant genodermatosis caused by a mutation in the folliculin gene. It is characterized by benign lung cysts with spontaneous pneumothorax, kidney tumors, and hair follicle tumors. Other solid tumors may accompany. Our case is a man with Birt Hogg Dube Syndrome who has parathyroid cancer.

Clinical Case

A 50-year-old male was referred to our clinic for treatment of hypercalcemia and elevated parathormone; he complained of weakness, muscle, and joint discomfort. His previous medical history included Renal Cell Carcinoma, Coronary artery by-pass graft, pulmonary thromboembolism, hypertension, nephrolithiasis, and stage 4 chronic kidney disease.

There was a familial history of colon cancer, with both his aunt and uncle having been diagnosed. The systemic evaluation revealed the presence of constipation, polyuria, pollakiuria. A palpable 3 cm nodular lesion was discovered in the inferior lobe of the patient's left thyroid, and the patient's vital signs were stable. There were lesions on the inner surface of the right thigh and the skull. The biopsies obtained from the lesions on the skin revealed a lipoma on the cranium and a fibrofolliculoma on the thigh upon pathological examination. Regarding laboratory exams, both the hemogram and transaminase levels were within normal limits. Serum albumin was measured at 4.9 g/L creatinine at 2.5 mg/dl, calcium at 12 mg/dl, ionized calcium at 5.9 mg/dl, phosphorus at 2.4 mg/dl, parathormone at 373 ng/dL, and 25-OH Vitamin D at 32 ng/ml. Alkaline phosphatase was determined to be 66 U/L, and 24-hour calcium output was 60 mg/day. The thyroid function test results were euthyroid, while the anterior pituitary panel was normal.

The patient underwent a left inferior parathyroidectomy after thyroid ultrasonography and parathyroid scintigraphy revealed a parathyroid adenoma. The parathyroid carcinoma is identified in the pathology report. The ultrasound-observed nodule on the isthmus of the thyroid has been identified as thyroid papillary carcinoma.

Bone mineral density was normal. A previously performed CT scan of the thorax for dyspnea revealed the presence of multiple cystic structures in the lungs. Taking into account the patient's history of multiple malignancies, an 18-FDG-PET CT scan was performed, revealing a significant FDG uptake (SUV Max: 22) in the patient's sigmoid colon. Pathology analysis of the removed lesion confirmed that it was a tubulovillous adenoma with high-grade dysplasia.

The patient, who showed heterozygosity for the Folliculin gene, was identified as having Birt-Hogg-Dube syndrome after further genetic panel testing.

Conclusion

According to the most recent literature evaluation, our patient is the first Birt Hogg Dube individual to present with parathyroid carcinoma. There is some evidence in the published literature linking somatic mutation of the Folliculin gene to the development of parathyroid cancer.
P-23 Insulin autoimmune syndrome possibly induced by Alpha-Lipoic acid
Authors: Uysal Serhat , Yılmaz Efekan , Damci Taner
Published: January 2024

Introduction

Insulin autoimmune syndrome (IAS) is a relative rare cause of hypoglycemia due to the presence of extremely high circulating insulin levels and elevated serum concentrations of autoantibodies to human insulin despite no prior exposure to exogenous insulin, insulin analogues or oral hypoglycemic agents. It is characterized by repeated fasting hypoglycemia or episodes of hypoglycemia late after meals in non-diabetic, non-acutely ill patients. Increasing the titer of insulin autoantibodies and immune reactive insulin occurs owing to both genetic influences and environmental triggers such as medication, genetic instability and other factors. It is associated with the use of drugs comprising sulfhydryl groups, such as methimazole, clopidogrel and alpha lipoic acid, mostly. Insulin autoantibodies appear a few weeks after the exposure of sulfhydryl radicals. Here, we summarize the case of IAS caused by drug administration.

Clinical Case

A 60-year-old female patient who has a history of migraine for 30 years was referred to our hospital for feeling of hunger, dizziness, sweating, tremor, and palpitations for 1 month. These symptoms had commenced episodically, soon after starting 600 mg/day of alpha lipoic acid. She was diagnosed with hypoglycemia based on a plasma glucose concentration of 31 mg/dL. There was no personal or family history of diabetes mellitus, or previous use of oral hypoglycemic drugs such as sulfonylureas or exogenous insulin. No abnormality was detected in the systemic examination. She had no smoking and alcohol abuse. Her regular medication was tricyclic antidepressant (amitriptyline). Laboratory results are presented in Table 1. On our evalution, the serum levels of insulin, C-peptide, and anti-insulin antibody titers were inappropriately elevated in the presence of hypoglycemia, confirming the diagnosis of hyperinsulinemic hypoglycemia. Thyroid function, human growth hormone, insulin growth factor-1 (IGF-1), and cortisol result were within normal limits. Screening for antinuclear factor, serum protein electrophoresis, serology for viral hepatitis, and other autoimmune diseases were negative. Insulinoma was excluded with computed tomography. In light of the above results, a diagnosis of IAS was made with possible alpha lipoic acid. Because, alpha lipoic acid was the only medication being taken associated with a sulfhydryl group. The patient was prescribed oral methylprednisolone (32 mg once daily), alpha lipoic acid was withdrawn. Hypoglycemia did not occur after methylprednisolone treatment of follow-up. Methylprednisolone treatment was tapered to 4 mg once daily within 2 months. The insulin, and anti-insulin antibody titers had decreased.

Conclusion

We report a rare case of IAS. Sulfhydryl group containing drugs such as alpha lipoic acid might induce or exacerbate hypoglycemia in patients with a history of IAS. For this reason, the use of alpha lipoic acid should be questioned in patients with IAS.

Table 1. Laboratory test results
O-16 Never too late: Delayed diagnosis of Prader-Willi syndrome
Authors: Baş Aksu Özge , Canpolat Asena Gökçay , Leblebici Can Berk , Karabulut Halil Gürhan , Çorapçıoğlu Demet
Published: January 2024

Introduction

Prader-Willi syndrome (PWS) is the leading inherited cause of severe childhood obesity. The aim of this case report is to describe a case of delayed diagnosis of PWS and to emphasize the importance of early diagnosis of PWS.

Clinical Case

A 24-year-old young woman with a history of hyperphagia, severe obesity, and cognitive impairment was admitted to our department for glycemic control due to newly diagnosed type 2 diabetes mellitus. She also had obstructive sleep apnea, daytime sleepiness, scoliosis, short stature (148 cm), and impaired speech articulation. Central obesity (BMI:54.7 kg/m2, waist circumference 147 cm), cognitive impairment, and characteristic body and facial features (narrow bifrontal diameter, almond-shaped palpebral fissures, small hands and feet, strabismus) suggested a genetic disorder. Test results showed growth hormone 0.07 ng/mL (0-3.5) and IGF-1 46 ng/mL (191-478). Cytogenetic analysis was performed on GTG-banded metaphases obtained from peripheral blood lymphocyte culture. t(3;16)(p21;p13) was observed in the patient. Cytogenetic analysis of the parents showed that this translocation was of paternal origin. The SNRPN gene was amplified from the patient's genomic DNA by PCR using methylation-specific primers after bisulfite modification. PCR products were visualized by agarose gel electrophoresis. The methylation pattern was found to be consistent with PWS. Hypocaloric diet (1400 Kcal/day) metformin 2 g/day, liraglutide (dose gradually increased to 2.4 mg/day), and dapagliflozin 10 mg/day were started. During hospitalization, glycemic regulation was achieved and 5.4 kilograms of weight loss occurred.

Conclusion

Obesity-related complications (e.g. sleep apnea, type 2 diabetes) and behavioral problems contribute significantly to morbidity and mortality in individuals with PWS. Prevention and treatment of morbid obesity and related conditions in individuals with PWS and management of maladaptive behaviors are key goals that require long-term follow-up and attention to managing the process. In these adults with compulsive eating behaviors who lack the ability to make informed decisions, it is very challenging to ensure compliance with treatments such as obesity treatment and the use of assistive devices for sleep apnea, which require the patient's consent and compliance. The complexity of this multisystemic disease increases with age, and we emphasize the need for early diagnosis to reduce the morbidity and mortality associated with PWS.Figure 1.Used with the patient's and family's consent.
P-47 Rare case of acromegaly due to plurihormonal pituitary adenoma and ACTH-independent Cushing syndrome
Authors: Elfekih Hamza , Abdessalem Fatma Ben , Bnina Molka Ben , Gorchene Asma , Ach Koussay , Hasni Yosra , Chaieb Molka
Published: January 2024

Introduction

The concurrence of acromegaly and Cushing syndrome is infrequent. Pituitary adenomas are responsible for acromegaly and for Cushing syndrome in about 95% and 80% of cases respectively. Except adrenal adenoma, the other causes of Cushing syndrome remain rare. We here describe a case of a Tunisian patient with acromegaly due to plurihormonal pituitary adenoma and ACTH-independent Cushing syndrome with bilateral macronodules.

Clinical Case

A 35-year-old male patient was diagnosed with acromegaly by acrofacial dysmorphia. He had a family history of type 2 diabetes mellitus and hypertension but no endocrine diseases. He has diabetes mellitus for 15 years, hypertension and obstructive sleep apnea. Physical examination showed multiple blue nevi in the trunk. IGF-1 was elevated (1680ng/mL) and GH levels were not suppressed after an oral glucose load (nadir 78ng/mL). He had hypogonadotropic hypogonadism with normal prolactin (9,66ng/mL). Basal cortisol, FT4 and TSH levels were in the normal ranges. Pituitary MRI showed pituitary macroadenoma of 25×20.7 mm, invading both cavernous sinuses and compression of optic chiasma. He underwent transsphenoidal resection with histology confirming a prolactin, GH and LH co-secretory pituitary adenoma. He received postoperatively somatostatin analogue and cabergoline, in addition to external radiotherapy. Ultrasonography found infracentimetric EU-TIRADS 2 left nodule and multiple colloid cysts of the thyroid, testicles microlithiasis and no cardiac myxomas. Nine years after the diagnosis of acromegaly, bilateral adrenal adenomas (left:14 mm, right: 9 mm) were incidentally discovered by CT-scan done for abdominal pain. Low dose dexamethasone suppression test was carried out showing no suppression of cortisol and the low ACTH level confirmed ACTH-independent Cushing syndrome.

Conclusion

In our patient, at least two endocrine syndromes deserve to be mentioned. The first syndrome is Multiple Endocrine Neoplasia Type 1 but calcium and PTH levels were normal and there was no sign for neuroendocrine tumors. The second one is Carney's complex since our patient has acromegaly and multiple blue nevi which are two major criteria confirming the diagnosis. Cushing syndrome in Carney's complex is related to primary pigmented nodular adrenal disease characterized by micronodular hyperplasia. However, bilateral macronodules could be found in up to 30% of cases.