bluuebunny/crossref_metadata_2025 huggingface dataset:
Chimeric antigen receptor-engineered NK cells: new weapons of cancer immunotherapy with great potential
Authors: Wang Xiao , Yang Xuejiao , Yuan Xiang , Wang Wenbo , Wang Yueying
Published: November 2022

Chimeric antigen receptor (CAR)-engineered T (CAR-T) cells have obtained prominent achievement in the clinical immunotherapy of hematological malignant tumors, leading to a rapid development of cellular immunotherapy in cancer treatment. Scientists are also aware of the prospective advantages of CAR engineering in cellular immunotherapy. Due to various limitations such as the serious side effects of CAR-T therapy, researchers began to investigate other immune cells for CAR modification. Natural killer (NK) cells are critical innate immune cells with the characteristic of non-specifically recognizing target cells and with the potential to become “off-the-shelf” products. In recent years, many preclinical studies on CAR-engineered NK (CAR-NK) cells have shown their remarkable efficacy in cancer therapy and their superiority over autologous CAR-T cells. In this review, we summarize the generation, mechanisms of anti-tumor activity and unique advantages of CAR-NK cells, and then analyze some challenges and recent clinical trials about CAR-NK cells therapy. We believe that CAR-NK therapy is a promising prospect for cancer immunotherapy in the future.
Target-enriched long-read sequencing (TELSeq) contextualizes antimicrobial resistance genes in metagenomes
Authors: Slizovskiy Ilya B. , Oliva Marco , Settle Jonathen K. , Zyskina Lidiya V. , Prosperi Mattia , Boucher Christina , Noyes Noelle R.
Published: November 2022

Background

Metagenomic data can be used to profile high-importance genes within microbiomes. However, current metagenomic workflows produce data that suffer from low sensitivity and an inability to accurately reconstruct partial or full genomes, particularly those in low abundance. These limitations preclude colocalization analysis, i.e., characterizing the genomic context of genes and functions within a metagenomic sample. Genomic context is especially crucial for functions associated with horizontal gene transfer (HGT) via mobile genetic elements (MGEs), for example antimicrobial resistance (AMR). To overcome this current limitation of metagenomics, we present a method for comprehensive and accurate reconstruction of antimicrobial resistance genes (ARGs) and MGEs from metagenomic DNA, termed target-enriched long-read sequencing (TELSeq).

Results

Using technical replicates of diverse sample types, we compared TELSeq performance to that of non-enriched PacBio and short-read Illumina sequencing. TELSeq achieved much higher ARG recovery (>1,000-fold) and sensitivity than the other methods across diverse metagenomes, revealing an extensive resistome profile comprising many low-abundance ARGs, including some with public health importance. Using the long reads generated by TELSeq, we identified numerous MGEs and cargo genes flanking the low-abundance ARGs, indicating that these ARGs could be transferred across bacterial taxa via HGT.

Conclusions

TELSeq can provide a nuanced view of the genomic context of microbial resistomes and thus has wide-ranging applications in public, animal, and human health, as well as environmental surveillance and monitoring of AMR. Thus, this technique represents a fundamental advancement for microbiome research and application.
Combined, sequential dye analysis and radiocarbon dating of single ancient textile yarns from a Nazca tunic
Authors: Smith Gregory D. , Chen Victor J. , Holden Amanda , Haghipour Negar , Hendriks Laura
Published: November 2022

The accessioning of ancient textiles into museum collections often requires objective information regarding the object’s appropriateness and authenticity before purchase or gift acceptance. In the case of colored fabrics, the identification of dyestuffs consistent with the attributed time period and culture builds confidence and reduces the chances of the object being a simple forgery or fake produced using modern materials. Moreover, this information adds to the technical, cultural, and conservation knowledge regarding the object. Increasingly, chronometric age estimates in the form of radiocarbon dating are also needed to establish the object’s age or to further prove the materials match the purported date range of the textile. Each of these analyses consumes a small sample of the object, and typically they are conducted separately by different laboratories on individual sample yarns. This report demonstrates for the first time the sequential, combined analysis of dyes by liquid chromatography-diode array detection-mass spectrometry and radiocarbon dating of the same residual dye-extracted sample. The chemicals and solvents used in various dye extraction protocols are shown not to contaminate the extracted yarns for radiocarbon dating purposes. The approach was used in the authentication study of an ancient Nazca tunic made from natural fibers (wool) and dyes (indigoids, anthraquinones, and flavonoids) shown to have most likely been produced between 595 and 665 CE.
Progress on the earthquake early warning and shakemaps system using low-cost sensors in Taiwan
Authors: Mittal Himanshu , Yang Benjamin M. , Wu Yih-Min
Published: November 2022

Building an earthquake early warning (EEW) network requires the installation of seismic instruments around the seismogenic zone. Using low-cost sensors to build a seismic network for EEW and to generate shakemaps is a cost-effective way in the field of seismology. The National Taiwan University (NTU) network employing 762 P-Alert low-cost sensors based on micro-electro-mechanical systems (MEMS) technology is operational for almost the last 10 years in Taiwan. This instrumentation is capable of recording the strong ground motions of up to ± 2 g and is dense enough to record the near-field ground motion. The NTU system has shown its importance during various earthquakes that caused damage in Taiwan. Although the system is capable of acting as a regional as well as an onsite warning system, it is particularly useful for onsite warning. Using real-time seismic signals, each P-Alert device provided a 2–8 s warning time for the near-source earthquake regions situated in the blind zone of the Central Weather Bureau (CWB) regional EEW system, during the 2016 $${{{M}}}_{{{w}}}$$

M
w

6.4 Meinong and 2018 $${{{M}}}_{{{w}}}$$

M
w

6.4 Hualien earthquakes. The shakemaps plotted by the P-Alert dense network help to assess the damage pattern and act as key features in the risk mitigation process. These shakemaps are delivered to the intended users, including the disaster mitigation authorities, for possible relief purposes. Currently, the P-Alert network can provide peak ground acceleration (PGA), peak ground velocity (PGV), spectral acceleration ($${S}_{a}$$

S
a

) at different periods, and CWB intensity shakemaps. Using shakemaps, it is found that PGV is a better indicator of damage detection than PGA. Encouraged by the performance of the P-Alert network, more instruments are installed in Asia-Pacific countries.
Q-value customized versus wavefront-optimized ablation in femtosecond laser-assisted LASIK for myopia and myopic astigmatism: a prospective contralateral comparative study
Authors: Mostafa Magdi Mohammad , Abdelmotaal Hazem , Abdelazeem Khaled , Goda Islam , Abdel-Radi Mahmoud
Published: November 2022

Background

Corneal refractive surgery for myopia results in an oblate shift with increased postoperative aberrations inversely affecting the quality of vision. Aspheric ablation profiles have been introduced to minimize such a problem. The aim of this study was to compare changes in corneal asphericity, central and mid-peripheral pachymetry between the Q-value customized and the wavefront-optimized (WFO) ablation profiles.

Methods

A prospective, comparative non-randomized fellow eye study was conducted. Eighty eyes of 40 eligible patients underwent femtosecond laser-assisted laser in situ keratomileusis for myopia and myopic astigmatism. In each patient, the more myopic eye was included in the custom-Q ablation experimental group and the other less myopic eye was included in the WFO control group. For the custom-Q group, the target asphericity was set to the preoperative Q-value. Corneal asphericity, central and mid-peripheral pachymetric changes and the root mean square of corneal higher-order aberrations (RMSh) were assessed 6 months following surgery. Visual and refractive outcomes were also evaluated in both platforms 6 months postoperatively.

Results

The mean preoperative refractive spherical equivalent was significantly more myopic in the custom-Q group than in the WFO group (P = 0.001). The mean Q-value changed from − 0.2 ± 0.1 to 0.6 ± 0.7 and from − 0.2 ± 0.1 to 0.4 ± 0.5 in the custom-Q and WFO groups, respectively. The oblate shift in corneal asphericity was not significantly different between both treatment groups (P = 0.094). The mean ablation depth at the pupillary center was significantly greater in the custom-Q group (P = 0.011), while there was no significant difference at the mid-peripheral pachymetry (P = 0.256). The RMSh significantly increased in both treatment profiles (P < 0.001) with no significant difference between the two groups (P = 0.06). The uncorrected distance visual acuity (UDVA) and the manifest refraction spherical equivalents (MRSE) significantly improved in both treatment groups (P < 0.001).

Conclusions

The custom-Q treatment profile with target asphericity set at the preoperative Q-value achieved comparable outcomes vs. the WFO profile in terms of postoperative corneal asphericity and mid-peripheral pachymetry despite the greater amount of ablation, the smaller optical zone, and the resulting increase in postoperative corneal flattening in the custom-Q group.

Trial registration (Clinicaltrials.gov): NCT04738903, 4 February 2021- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04738903
Frequency of occurrence and habitat selection shape the spatial variation in the antibiotic resistome in riverine ecosystems in eastern China
Authors: Jiang Chunxia , Chen Haiyang , Grossart Hans-Peter , Zhang Quanfa , Stoks Robby , Zhao Yi , Ju Feng , Liu Wenzhi , Yang Yuyi
Published: November 2022

Background

Riverine ecosystems are one of the most important reservoirs of antibiotic resistance genes (ARGs) in the environment, but the occurrence and controlling factors of ARG distribution in different habitats of riverine ecosystems remain poorly understood. In this study, a metagenomic approach was used to characterize ARG types and their abundance in different habitats (rhizosphere soil, surface bulk soil, bottom bulk soil, and sediment) of riverine ecosystems in eastern China. Sampling sites were located along different rivers of eastern China, which are geographically isolated. Differences in bacterial communities, mobile genetic elements (MGEs), pattern and intensity of human activities, climate, and other environmental factors at the sampling sites and habitats were expected to affect ARG occurrence.

Results

ARGs were observed with high variations in diversity (44–206 subtypes) and abundance (6.85–105.68 ×/Gb). There were significant south-north differences in ARG occurrence in the same habitat, except for surface bulk soil. And the significant difference was found in ARGs among four southern habitats. South–north differences in ARGs of the same habitat were mainly attributed to the combination of different occurrence frequencies and habitat selections of ARGs. Differences in ARG profiles among the four habitats in the south and the north were both mainly attributed to the different occurrence frequencies of ARGs. Bacterial communities and MGEs (Mobile genetic elements) could account for the observed variance in the resistome of riverine ecosystems across eastern China. The co-occurrences of specific ARGs with bacterial communities and MGEs were more frequent at the northern sampling sites than in the south, and co-occurrence patterns (i.e. ARGs and bacterial communities or ARGs and MGEs) varied between the habitats. Moreover, building land in all habitats, except bulk soils, showed significant positive correlations with ARG abundance.

Conclusion

This study reveals a high variance in the resistome of riverine ecosystems in eastern China and its controlling factors. We appeal to the importance of assessment of ARGs in the riverine ecosystem and the need for future prevention and intervention of ARG spread.
Are flipped classrooms less stressful and more successful? An experimental study on college students
Authors: Aydin Betul , Demirer Veysel
Published: November 2022

The flipped classroom model, which is a technology-supported model that employs active learning strategies, has been studied many times. However, the effect of the model on psychological variables has not been adequately questioned. In this context, this study aims to investigate the effects of flipped classroom model on the students’ assignment stress and academic achievement. For this purpose, a quasi-experimental study was designed; the pre- and post-test control group model was used. The study was conducted with the participation of 44 undergraduate pre-service teachers for 11-week period in Material Design and Use in Education course. Students' assignment stress was measured with a scale, while their academic achievement was evaluated by considering course success and material development scores. Also, students’ opinions were investigated in the process. The experimental group students followed the courses outside the class through interactive videos, and they completed the given assignments in-class with the group collaboration. On the other hand, the control group students followed the lessons in-class (face-to-face), and they completed the given assignments outside of the class with the group collaboration. Consequently, it was found that the assignment stress of the students in the experimental group decreased more than the students in the control group. In addition, the course success of the students in the experimental group increased more than the students in the control group. However, there was no significant difference between the material development scores of groups. Finally, a significant portion of the students’ who experienced the flipped classroom model, reported positive opinions about the model.
Consolidating food safety measures against COVID-19: a review
Authors: Abolmaaty Assem , Amin Dina H. , Abd El-kader Reham M. M. , ELsayed Alaa F. , Soliman Basma S. M. , Elbahnasawy Amr S. , Sitohy Mahmoud
Published: November 2022

Background

The world is facing an extraordinarily unprecedented threat from the COVID-19 pandemic triggered by the SARS-CoV-2 virus. Global life has turned upside down, and that several countries closed their borders, simultaneously with the blockage of life cycle as a result of the shutdown of the majority of workplaces except the food stores and some few industries.

Main body

In this review, we are casting light on the nature of COVID-19 infection and spread, the persistence of SARS-CoV-2 virus in food products, and revealing the threats arising from the transmission of COVID-19 in food environment between stakeholders and even customers. Furthermore, we are exploring and identifying some practical aspects that must be followed to minimize infection and maintain a safe food environment. We also present and discuss some World Health Organization (WHO) guidelines-based regulations in food safety codes, destined to sustain the health safety of all professionals working in the food industry under this current pandemic.

Conclusion

The information compiled in this manuscript is supporting and consolidating the safety attributes in food environment, for a prospective positive impact on consumer confidence in food safety and the citizens’ public health in society. Some research is suggested on evaluating the use and potentiality of native and chemical modified basic proteins as possible practices aiming at protecting food from bacterial and viral contamination including COVID-19.
Prevalence, psychosocial correlates of youths’ suicidal behaviors and perspectives on the phenomena at Zagazig University: a mixed-methods study
Authors: Abozaid Mai Mohammed ElSayed , Aboserea Mona Mostafa , Metwally Safaa Mohammed , AbElkhalek Hanem Ahmed
Published: November 2022

Background

Suicidal behaviors are major public health concerns that affect large numbers of youth, leaving not only the youth but also their parents, family, friends, and peers in constant wailing. This study aimed to investigate the prevalence, psychosocial correlates, and perspectives of youths’ suicidal behaviors. A concurrent mixed-methods descriptive study was used in carrying out this study. This study was conducted at Zagazig University, Al Sharkia Governorate. A stratified multi-stage cluster sampling technique was used to enroll 364 youths. Four tools were used to collect quantitative data. They were as follows: The Youth Profile Questionnaire, composed of two parts (socio-demographic data and youth characteristics), the Suicide Behaviors Questionnaire-Revised (SBQ-R), Social Problem-Solving Inventory-Revised Short Form (SPSI-R-SF), and the Short Version of the World Health Organization Quality of Life (WHOQOL-BREF). For the qualitative part, focus group discussions were conducted to explore youths’ perspectives on the phenomenon of suicidal behaviors.

Results

Quantitative findings revealed that 25% of the youth participants had a significant risk for suicidal behaviors. Being female, in the first years of practical faculties and having no friends are significantly correlated with suicidal behaviors. Further, the quality of life had a statistically significant negative correlation with suicidal behaviors. Qualitative findings were discussed under one main category: youths’ perspectives about suicidal behaviors (pressure/escaping tool, seeking help/ending pain, attention-grabbing behavior, and stain for life).

Conclusions

According to this mixed-methods study, youths’ suicidal behaviors are prevalent multifaceted phenomena that certain factors have been correlated with. It is suggested that female sex, having no friends, and academic stressors are risk factors for suicidal behaviors. Also, the quality of life was introduced as a protective factor against suicidal behaviors. Therefore, it is recommended to implement prevention and management approaches to realize the complexity of the phenomena of suicidal behaviors among youth; these approaches target the youths themselves (mental health promotion and strategies for coping with stress) and the population (careful media coverage, limit access to suicidal methods, and raise the awareness about mental illness).
The Impact of Intensified CNS-Directed Therapy on Neurocognitive Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia Treated Without Cranial Irradiation
Authors: Jacola Lisa M. , Conklin Heather M. , Krull Kevin R. , Pei Deqing , Cheng Cheng , Reddick Wilburn E. , Pui Ching-Hon , Jeha Sima
Published: November 2022

PURPOSE

Findings from St Jude Total Therapy Study 16 (Total 16) showed early intensification of triple intrathecal therapy (ITT) improved CNS disease control for children with newly diagnosed acute lymphoblastic leukemia (ALL) at the greatest risk of CNS relapse. We examined the impact of this treatment on end-of-therapy neurocognitive outcomes.

METHODS

Between 2007 and 2017, 400 (83.5%) of 479 eligible patients treated with Total 16 risk-directed chemotherapy completed protocol-directed neurocognitive testing at the end of therapy. Intensified ITT was defined as ≥ 21 cumulative doses for patients with low-risk ALL (n = 70/194) and ≥ 27 doses for those with standard-to-high risk ALL (n = 81/206).

RESULTS

Compared with age-normative expectations, the overall group had significantly lower estimated intelligence quotient ( P < .0001), attention ( P = .0051), working memory ( P = .0001), processing speed ( P = .0002), fine motor speed ( P = .0001), and math ( P = .0087). Caregiver ratings of patient functioning showed elevated risk for problems in attention ( P = .0173), executive function ( P = .0001), and adaptive skills ( P = .0001). Among the low-risk treatment group, there were no significant differences between patients treated with or without intensified ITT (all P's >.10). Among patients with standard-to-high risk ALL, those treated with intensified ITT had poorer working memory ( P = .0328) and fine motor speed ( P = .0403), and elevated ratings of inattention ( P = .0189) and executive dysfunction ( P = .0245). In the standard-to-high risk group, females treated with intensified ITT had lower working memory scores. Public insurance status was associated with worse neurocognitive outcomes in both treatment groups.

CONCLUSION

Standard-to-high risk patients treated with intensified ITT are at moderately increased risk for neurocognitive problems. The findings suggest a threshold effect for ITT exposure, which can inform the design of future clinical trials and approaches to neurocognitive monitoring and intervention.
LBODP011 Pembrolizumab Induced Hypophysitis And Resultant Isolated ACTH Deficiency Presenting As Secondary Adrenal Insufficiency.
Authors: Arora Gunjan , Lising Jannell
Published: November 2022

Introduction

Pembrolizumab is a novel human immunotherapeutic monoclonal antibody directed against PD-1 (programmed death receptor 1). It has been approved by the FDA for treatment of many malignancies including breast cancer. Although it has improved survival for many oncological conditions, it has been linked to a variety of endocrinopathies. We present a case of Pembrolizumab induced hypophysitis with isolated ACTH deficiency presenting as secondary adrenal insufficiency.

Case presentation

A 36 year old female with a history of breast cancer treated with chemotherapy and surgery, presented with intractable nausea and vomiting. She reported not being able to keep anything down for 4-5 days and had experienced multiple episodes of non-bilious, non-bloody emesis. She endorsed dizziness, but denied fever, chills, shortness of breath, abdominal pain, or problems with urination/bowel movements. She had been treated with Pembrolizumab with the last dose being 4 months prior to presentation. On arrival, vitals included temperature 98.4 F, BP 104/62 mm Hg, Heart rate 104 bpm, RR 16 with SpO2 100%. Labs were significant for WBC count 3.65 K/uL (3.81 - 8.94), Eosinophils 10.4% (0.1 - 6; she was noted to have eosinophilia prior to presentation), Hemoglobin 11.6 g/dL (11 - 14.9), Sodium 140 mmol/L (136-145), Potassium 3.4 mmol/L (3.4 - 5.1), Glucose 57 mg/dL (70 - 100), Lactate 0.7 mmol/L (0.2 -2), Lipase 23 U/L (13 - 60), Urine HCG negative, Urinalysis negative for nitrites and leukocyte esterase, TSH 1.22 uIU. ml (0.5 -5.7) and AM cortisol 0.4 ug/dL (6 - 18.4). Endocrinology was consulted and further work up was sought: ACTH <5 pg/ml (7.2 - 63) and Cortisol 30 - 60 minutes after cosyntropin stimulation 3.6 ug/dL. Prolactin, free T4, FSH and LH were within normal limits. MRI brain showed a prominent pituitary gland with enhancement and interval loss of posterior pituitary bright spot representing lymphocytic hypophysitis. She was started on Solu-Cortef and her symptoms resolved. She was discharged on hydrocortisone with education on sick day rules for secondary adrenal insufficiency.

Discussion

Adrenal insufficiency secondary to immunotherapy is a rare, emergent and dangerous condition. The key to successful management is early recognition. In patients treated with immunotherapy agents, non-specific symptoms such as nausea, vomiting, fatigue (which are common adverse effects of chemotherapy) should prompt urgent evaluation with hormonal workup. Evidence suggests that eosinophilia may be an early indicator before the onset of symptoms which was evident in our case. Radio-graphic imaging is helpful for diagnosis. Treatment entails high dose corticosteroids for acute crisis followed by physiological maintenance dosing. Patients should be educated on sick day rules for adrenal insufficiency.

Presentation: No date and time listed
ODP312 Giant Silent Corticotroph Adenoma: Presentation of 3 Cases
Authors: Oliveira Miriam C , Corso Eduardo Raul B , Pereira-Lima Ana Paula S , Rech Carolina GSL , Pereira-Lima Julia Fernanda S , Nesello Alberto C
Published: November 2022

Introduction

Silent corticotroph adenoma (SCA) is a T-pit lineage cells-derived tumor without clinical presentation of Cushing's disease and normal cortisol dynamics (totally silent) or elevated ACTH/abnormal cortisol dynamics (clinically silent). SCAs account for 10-20% of silent pituitary adenomas. Giant SCAs (GSCAs), adenomas with a diameter of 4cm or more, are rare cases of pituitary adenomas.

Objective

Present the experience of a tertiary center with GSCAs.

Methods

We conducted a retrospective search of cases with a diagnosis of GSCA in the medical records of a cohort of patients with pituitary adenomas.

Results

We present three patients (two women, with 57 and 65 years) and a man (44 years) diagnosed with GSCA. They presented with macroadenoma associated with mass-related symptoms without clinical stigmas of hormonal dysfunction. Tumors had 4.3-5.1cm in the longest axis. In two cases, the superior tumor growth extended to the third ventricle and in only one there was a cavernous sinus invasion. The cortisol level was in the normal range in all cases; however, dynamic tests were not assessed. One patient had mild hyperprolactinemia, one had central hypothyroidism, and all cases had hypogonadism, and GH deficiency The most prevalent comorbidity was diabetes mellitus. The patients underwent transsphenoidal surgery and, in one case, two re interventions . One patient underwent radiotherapy. One patient was lost to follow-up after surgery and the other cases were followed for 39 and 53 months. At the last visit, one patient showed a 3,5cm lesion persistence and the other had a recurrent giant lesion.

Conclusions

Giant SCAs have severe implications depending on their size and invasiveness, difficult total removal, greater risk of complications, significant incidence of pituitary apoplexy, short time to progression and/or higher recurrence rates after surgery, different therapies requirement including adjuvant radiotherapy, and the possibility to evolve into Cushing disease after years of inactivity. Handling this situation requires a multidisciplinary team of expert professionals, personalized decisions for each patient to minimize damage, and advances in new therapeutic agents.

Presentation: No date and time listed
ODP313 Glucagon-Stimulated Copeptin Measurements in the Differential Diagnosis of Diabetes Insipidus: A Double-Blind Randomized Placebo-Controlled Study
Authors: Atila Cihan , Christ-Crain Mirjam , Gaisl Odile , Szinnai Gabor , Vogt Deborah , Werlen Laura
Published: November 2022

Background

The differential diagnosis of diabetes insipidus and primary polydipsia is challenging. To date, the most reliable approaches are copeptin measurement after hypertonic saline infusion or arginine, which is a known growth hormone secretagogue but has recently also been shown to stimulate the neurohypophysis. Similar to arginine, glucagon is also known to stimulate growth hormone release, but its effect on the neurohypophysis unknown.

Methods

In this double-blind, randomized, placebo-controlled trial, we enrolled 22 healthy participants, 10 patients with central diabetes insipidus and 10 patients with primary polydipsia at the University Hospital Basel. Each participant underwent the glucagon test, i. e., subcutaneous injection of 1mg glucagon, and placebo test, i. e., subcutaneous injection of 1 ml 0.9% sodium. Plasma copeptin levels were measured at baseline and 30, 60, 90, 120, 150, 180 minutes after injection. The primary objective was to determine whether glucagon stimulates copeptin and to explore whether the copeptin response differentiates between diabetes insipidus and primary polydipsia. Findings: The median (IQR) age of all participants was 27 years (23; 32), 59% were female. In healthy participants, glucagon injection stimulated copeptin with a median (IQR) increase of 7.56 (2.38; 28. 03) pmol/l, while placebo had no effect (0.10pmol/l (-0.70; 0.68); difference: 7.67 (1.98, 27. 09) pmol/l, p < 0. 001). In patients with central diabetes insipidus, copeptin showed no relevant increase after glucagon injection, with an increase of 0.55pmol/l (0.21; 1.65), whereas copeptin was stimulated in patients with primary polydipsia with an increase of 15.70 (5.99; 24.39) pmol/l. Using a copeptin cutoff level of 4.6pmol/l had a sensitivity of 100% (95%CI 100-100) and a specificity of 90% (95%CI 70-100) to discriminate between diabetes insipidus and primary polydipsia. Interpretation: Glucagon stimulates the neurohypophysis, and glucagon-stimulated plasma copeptin has the potential to be used for a safe, novel, and precise test in the differential diagnosis of polyuria-polydipsia syndrome.

Presentation: No date and time listed
ODP322 Impact of Mifepristone on Liver Function and Resolution of Liver Steatosis in Patients with Cushing Syndrome – A Case Study
Authors: East Honey E , Moraitis Andreas G , Belanoff Joseph K
Published: November 2022

Background

Hypercortisolism is a recognized cause of non-alcoholic fatty liver disease (NAFLD). Mifepristone (Korlym®, Corcept Therapeutics), a glucocorticoid receptor (GR) antagonist, is FDA-approved for the treatment of hyperglycemia in patients with endogenous Cushing syndrome (CS). Mifepristone has also shown beneficial effects in preclinical models of fatty liver disease, including reduced liver injury, improved insulin sensitivity, and increased plasma adiponectin concentrations. Here, we report the case of a patient with CS and liver steatosis who was treated intermittently with mifepristone.

Clinical Case

A 36-year-old woman with CS associated with uncontrolled type 2 diabetes mellitus, obesity, major depressive disorder, hyperlipidemia, hypertension, and liver steatosis was intermittently treated with mifepristone for 3 years. Abdominal imaging was performed several times for abdominal pain. Before treatment with mifepristone was initiated, the patient had a body weight of 198 lbs, BMI of 32kg/m 2, HbA1c of 11.5%, and liver steatosis as noted on abdominal imaging with normal liver function tests (ALT: 40 U/L [normal: 6-42 U/L], AST: 30 U/L [normal: 8-36 U/L]). After 16 months, treatment with mifepristone was discontinued secondary to abnormal uterine bleeding. Imaging performed around the time of discontinuation showed resolution of liver steatosis, which was accompanied by significant reductions in LFTs to levels typically seen in healthy volunteers without liver steatosis (ALT: 10 U/L, AST: 17 U/L). The patient's HbA1c had decreased to 6.8%. Imaging performed 7months after mifepristone discontinuation showed recurrence of liver steatosis, LFTs had returned to pre-treatment values (ALT: 42 U/L, AST: 31U/L), and HbA1c had increased to 9.3%. The patient underwent hysterectomy and restarted mifepristone treatment. One year after resumption of mifepristone, imaging showed that liver steatosis had resolved once again, along with a similar reduction in LFTs as observed before (ALT: 16 U/L, AST: 12 U/L). Fourteen months after restart, mifepristone was discontinued again. Labs and imaging performed 10 months after discontinuation showed, as previously, recurrence of liver steatosis along with elevated LFTs (ALT: 100 U/L, AST: 56 U/L). Data from mifepristone's prospective pivotal study (SEISMIC, NCT00569582) of 50 patients with CS also showed a similar reduction in ALT throughout the study, which was reversed during the 6-week discontinuation follow-up phase of the study. This was followed by a repeat reduction when mifepristone was restarted in the extension study (NCT00936741).

Conclusion

These results suggest that mifepristone is effective in improving liver function and decreasing liver steatosis in patients with endogenous CS, a trend that is also accompanied by improvement in insulin resistance and glycemic control.

Presentation: No date and time listed
ODP326 Isolated Abducens Palsy as a Presenting Feature of Pituitary Apoplexy
Authors: Alam Mustafa , Alam Mustafa , Abdelrahim Baha , Alam Mahad , Horani Mohamed Hosam
Published: November 2022

Case Presentation

A 27-year-old female with a history of T1DM presented to the ED for continued visual changes onset the past 10 days. The patient states that she was driving from Wisconsin to Arizona when she developed blurry vision localized to her right eye. She was previously evaluated by outpatient ophthalmology where she was diagnosed with R abducens palsy with no evidence of retinopathy. Associated symptoms included nausea, dizziness, and right sided HA localized behind her right eye and the base of her head. This HA was not relieved by Excedrin or Tylenol. Over the past 3 months, her menstrual periods have been lighter and irregular. Additionally, she has been lactating ever since the birth of her child 2.5 years ago. Hospital Course: Pt had stable vitals: T: 36.4 C, HR: 97, BP: 130/76, RR: 23, SPO2: 100%. Physical exam was WNL other than CN6 palsy. Lab workup was notable for: Na: 138, Cr: 1. 02. FT4 0.94, TSH 3.281, AM Cortisol 8.5, Random Cortisol 7.5, FSH 3.4, FG Glucose 329, and Prolactin 60.4. An MR Brain with and without contrast revealed an enlarged pituitary with a posterior 7mm lesion with small amount of hemorrhage given the high T1 signal. The patient was admitted for concerns of apoplexy and started on Hydrocortisone 50mg IV q12 x2 followed by Hydrocortisone 15mg qAM and 5mg qPM. 18 units of Lantus were started q24 hours along with Cabergoline 0.5mg tabs qhs Wednesday and Sunday.

Discussion

Pituitary Apoplexy is an endocrine emergency characterized by cortisol levels insufficient for normal body homeostasis. However, not all presentations of Apoplexy are typical. This case highlights isolated abducens palsy as the presenting feature of pituitary apoplexy. Due to the nature of the anatomy of the cavernous sinus, ocular palsies can be a simple physical findings that may have important clinical correlates that should be investigated further.

Presentation: No date and time listed
ODP334 Must we Wait for the Development of Metastasis to be Able to Distinguish Dopamine Resistant Aggressive Prolactinoma from Prolactin Producing Pituitary Carcinomas? Case Report and Literature Review
Authors: Rios Paola , Iragorry Corina , Jara Mark , Hannoush Zeina
Published: November 2022

Background

Prolactinomas, the most prevalent type of neuroendocrine disease, account for approximately 40% of all pituitary adenomas. In the vast majority of cases, these are benign tumors with excellent clinical response to medical therapy with dopamine agonist agents such as bromocriptine and cabergoline. Rarely medical treatment fails to normalize prolactin levels and/or decrease the size of the tumor, posing a challenge to the clinician.

Case presentation

40-year-old man who underwent resection of a 7.4 cm pituitary prolactinoma via frontal craniotomy followed by radiotherapy. He developed panhypopituitarism and was placed on chronic hormonal replacement therapy plus high dose cabergoline. Two years later he presented with recurrence of his disease and was diagnosed with an unresectable 4.9 cm pituitary adenoma showing cortical breakthrough of the sellar floor, invasion into the optic chiasm, erosion of the posterior sphenoid walls, extension into the sphenoid sinuses and posteriorly into the pons, midbrain and third ventricle, as well as complete encasement of the distal, superior cerebellar and posterior cerebral arteries. The patient underwent endoscopic trans sphenoidal partial tumor resection and CSF leak repair. Pathology revealed a pituitary prolactinoma with Ki-67 of up to 8% and positive p53 immunostaining. His cabergoline dose was adjusted to 0.5 mg PO daily and he was also started on Sandostatin 20 mg IM monthly as well as appropriate hormonal replacement of the other deficient pituitary hormonal axes. Follow up imaging revealed stability of the lesion. The patient continues to do clinically well and actively follows with endocrinology and neurosurgery with serial brain MRIs and laboratory workup.

Discussion

The histological and biochemical characteristics of aggressive prolactin secreting tumors has been reported to be of minimal utility in distinguishing benign from malignant lesions. Tumors can only be diagnosed as carcinomas after they have metastasized and they can only be classified as aggressive after treatment failure or unusual growth, which creates a disadvantage for the prognosis and management of these patients. Clinicians are in need of better guidelines that can help them identify the rare cases that might warrant more aggressive clinical interventions beyond dopamine agonists such as surgery, radiation, temozolomide, somatostatin receptor agonists and others, with the hope of delaying or preventing the development of metastasis. Case reports of atypical presentations of aggressive prolactinomas such as the one here presented, can help broaden our understanding of the predictable signs of poor prognosis.

Presentation: No date and time listed
ODP341 Pachydermia lesions identified on imaging in a cohort of acromegaly patients
Authors: Roque Joao , Marques Pedro
Published: November 2022

Introduction

Pachydermia is a clinical term derived from the former taxonomic order of mammals pachydermata, and it corresponds to a benign thickening and furrowing of the skin. It is classically associated with pachydermoperiostosis, but it can emerge in another conditions, including in acromegaly. These lesions may be distributed throughout the body. When they are mainly located to the scalp and forehead, resembling cerebral gyri, they receive the designation of cutis verticis gyrata (CVG). These are seldomly reported in acromegaly patients. Therefore, with this study we aimed to assess the prevalence of these pachydermia lesions in the patients with acromegaly followed at our center.

Materials and methods

We retrospectively reviewed the head magnetic resonance imaging (MRI) of 42 patients with acromegaly followed at our center. We inspected the composition, thickness and shape of the scalp, and those cases with more than 1 unequivocal furrow on the skin/connective tissue of the scalp region visible on the MRI were considered as a patient displaying pachydermia lesions. Demographic data and IGF-I levels at diagnosis were also registered.

Results

Six out of the 42 (14%) acromegaly patients displayed pachydermia lesions identifiable on MRI. Of the 6 patients, 4 had pachydermia lesions in the parietal area, while the occipital and the temporo-occipital regions were each involved in 1 patient. The mean age of these six patients were 51±10yr, and there were 4 males and 2 females. Their serum IGF-1 levels at the diagnosis of acromegaly were 1125±326ng/mL (minimum and maximum IGF-1 levels were respectively 517 and 1358), and 5 of the six patients were identified with a pituitary macroadenoma at diagnosis, while only one patient had a microadenoma.

Discussion

Pachydermia lesions are uncommonly reported in patients with acromegaly, although their prevalence might be significant in this setting, particularly in male patients, as demonstrated in this study. Pachydermia lesions may be depicted on imaging studies, thus clinical examination together with careful inspection of the scalp and skin on radiological studies may be important to identify such lesions, which in turn may contribute for an earlier diagnosis of acromegaly or facilitate the investigation of other etiologies.

Presentation: No date and time listed
OR08-4 Endocrine Mechanisms of an Orphan G Protein-Coupled Receptor Regulating Metabolic Homeostasis
Authors: Ren Hongxia
Published: November 2022

G protein-coupled receptors (GPCRs) are the largest protein family and amenable for pharmacological manipulation. GPCRs in the neuroendocrine and enteroendocrine systems respond to various biological cues and in turn exert crucial roles in maintaining whole body metabolic homeostasis. For example, GPCRs in the gastrointestinal tract are involved in maintaining glucose and energy homeostasis by regulating the release of gut hormones in response to luminal dietary nutrients as well as microbial metabolites. We recently identified that an orphan GPCR, Gpr17, was co-expressed in glucagon-like peptide-1 (GLP-1)-expressing EECs in human and rodent intestinal epithelium. We reported that acute genetic ablation of Gpr17 in intestinal epithelium (iKO) improved oral glucose tolerance and glucose-stimulated insulin secretion (GSIS) in female and male mice through increased secretion of incretin hormone in response to nutrient ingestion (Cell Reports, 2022). In the neuroendocrine system, we previously identified Gpr17 as the transcription target of Forkhead box protein O1 (FoxO1) in the hypothalamus and generated hypothalamic neuron specific Gpr17 knockout animals (Cell, 2012). Our results demonstrated that agouti-related peptide (AgRP) neuron Gpr17 knockout mice had increased satiety during fasting-refeeding challenge (Diabetes, 2015) and that proopiomelanocortin (POMC) neuron Gpr17 knockout mice had increased alpha-melanocyte stimulating hormone (aMSH) processing and increased firing of POMC neurons (Nutrition & Diabetes, 2019). However, how Gpr17 may regulate energy balance especially regarding leptin hormone signaling is unclear. To address this question, we used genetic knockout approach to generate Gpr17 conditional knockout in leptin receptor expressing neurons in the brain. We found Gpr17 deficiency in leptin receptor expressing neurons increased leptin sensitivity in animals and resulted in reduced food intake, which corresponded with reduced inflammatory response in the hypothalamus. Moreover, male Gpr17 whole body knockout mice have improved intraperitoneal glucose tolerance, and increased insulin sensitivity in hyperinsulinemic-euglycemic clamp studies. In conclusion, our collective body of work showed that ablation of Gpr17 signaling in the neuroendocrine and enteroendocrine systems led to improved neurohormonal regulation to maintain metabolic homeostasis, indicating functionally targeting this GPCR may lead to better therapeutic outcome of diabetes and obesity.

Presentation: Saturday, June 11, 2022 12:15 p.m. - 12:30 p.m.
ODP030 Autoimmune Adrenalitis Following mRNA Covid- 19 Immunization In A Patient Without A Known Diagnosis Of Adrenal Insufficiency.
Authors: Jamal Yusra , Camacho Yudi , Mullally Jamie
Published: November 2022

A 45-year-old female with a past medical history of Hashimoto thyroiditis and celiac disease presented after a syncopal episode that resulted in a motor vehicle accident. The patient had symptoms of fatigue, nausea, and anorexia for three weeks following the second dose of the Pfizer-BioNTech COVID-19 Vaccine. Initial laboratory tests revealed hyponatremia with serum sodium (Na) of 123mEq/L that worsened to 111mEq/L after receiving the normal saline infusion. Serum potassium was 3.4mEq/l, Thyroid-stimulating hormone level was 6.350mIU/l, free thyroxine level was 1.1 ng/dl and glucose were 85mg/dl. The PCR test for COVID-19 was negative. Vitals were unremarkable except for a low blood pressure of 90/60. On physical examination, the patient was alert and communicative and there was no hyperpigmentation of the skin. The patient denied personal and family history of adrenal insufficiency. She denied prior use of any steroid medications. Her prior outpatient serum Na levels were normal (138-140 mEq/L). The patient was admitted to the ICU for severe hyponatremia, where she was treated with fluid restriction and hypertonic saline. However, she remained hypotensive, and serum sodium failed to improve above 118mEq/l. Serum cortisol at 8: 00 am and 10: 00 am were 4.5 and 5.8 mcg/dl, respectively. She was started on stress doses of hydrocortisone 100 mg intravenous (IV) followed by hydrocortisone 50 mg IV every 8 hours and serum Na improved to 130m Eq/l. Steroids were tapered gradually to physiological doses. The levothyroxine dose was also increased from the home dose of 75mcg to 88 mcg daily due to the elevated TSH. Hormonal workup showed aldosterone of 0.3ng/dl, plasma renin activity of 20, and adrenocorticotropic hormone(ACTH) levels of >1250pg/ml. Gonadotropins, insulin-like growth factor-1, and prolactin were within normal limits. Cosyntropin stimulation test after holding steroids for 24 hours was abnormal, with pre-cosyntropin cortisol level 7. 0mcg/dl, and the 60-minute post-cosyntropin cortisol level 7.1mcg/dl. The diagnosis of autoimmune adrenalitis was confirmed with a positive 21-hydroxylase antibody test. The patient had an uneventful recovery and was discharged on oral hydrocortisone.

Presentation: No date and time listed
PMON155 Intraoperative, confocal laser endomicroscopy in pituitary surgery
Authors: Schlaffer Sven-Martin , Buchfelder Michael , Coras Roland
Published: November 2022

Introduction

Fluorescence imaging, such as confocal laser endomicroscopy (CLE) is a fast modality of image acquisition, which offers the possibility of early intraoperatively diagnosis and may be used to improve surgical decision making.

Objective

Within a 3-month prospective trail we used the Zeiss CONVIVO CLE in transspehnoidal surgery for different sellar pathologies. CLE is a miniaturized portable, handheld, fiber optic-based, confocal laser scanning microscope used in conjunction with a 488-nm excitable fluorophore. During the trial period we investigated feasibility, diagnostic accuracy and usability in terms of differential diagnosis in transsphenoidal surgeries of various pituitary tumours (15 pituitary adenomas, 2 craniopharyngiomas, 1 sellar metastasis).

Method: Patients were randomly selected. Inclusion criteria were a pituitary macroadenoma or a sellar mass lesion exceeding 10 mm in diameter. A transsphenoidal approach was used and fluorescin was injected upon opening the sellar floor. CLE was carried out immediately after dural opening and during tumour resection, whenever possible. Additionally, the microprobe was used ex vivo with the resected tumor material. Histopathologic features of CLE images and H&E-stained permanent sections were assessed and compared postoperatively.

Result: We were able to obtain CLE in-vivo images in all cases. Using the microscopic approach, no problems occurred regarding space for the microprobe. To obtain in-vivo images we had to rest the probe within a mount. Wiggling of the surgeon's hand, pulse synchronous movements of the mass and mild intraoperative venous bleeding led to inexact images. To overcome these problems, we used CLE as early as possible at the beginning of tumor resection to avoid bleeding interferences.

Additionally we investigated resected tumor specimens ex-vivo within the OR. Since no bleeding and no interference with movements occurred image quality and acquisition time improved.

Histopathologic features of CLE images and H&E-stained permanent sections showed, that except for the sellar metastasis, a diagnosis could be made on the basis of the intraoperative CLE images, whereas the ex-vivo images were more precise.

Conclusion

CLE is a potential imaging modality for transnasal assessment of skull base and pituitary lesions. It may help to establish an early diagnosis, to identify pituitary microadenomas, especially in cushing´s disease and to distinguish the various sellar pathologies.

CLE is a fascinating possibility to verify a suspected diagnoses already intraoperatively.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.