bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of genetic polymorphism of NUDT15, TPMT and ITPA gene in the toxicity and efficacy of azathioprine-based regimen in Egyptian inflammatory bowel disease patients
Authors: Eltantawy Nashwa , El-Zayyadi Islam Abd El-Hamid , Elberry Ahmed A. , Salah Layla M. , Abdelrahim Mohamed E. A. , Kassem Amira B. 
Published: January 2023

AbstractBackgroundInflammatory Bowel disease (IBD) is a chronic progressive condition that prompts generous physical and mental morbidity. Choosing the best kind of management and medication dosage prevents new episodes of high disease activity during therapy because of adverse drug reactions (ADRs). This can lead to cessation or inefficacy of the treatment, or complete non-responsiveness to specific medications. Pharmacogenetics (PGx) is a well-established aspect in IBD. One of the exemplary instances of PGx is thiopurines, which are frequently utilized as IBD therapy. This study aimed to evaluate specific gene polymorphism involved in the toxicity and efficacy of Azathioprine (AZA) use in the management in Egyptian patients and to find the correlation between the polymorphism of Nudix Hydrolase15 (NUDT15) gene (rs116855232), The Thiopurine methyltransferase (TPMT) gene (rs1800460) and Inosine Triphosphatase (ITPA) gene (rs1127354) which are involved in the metabolism of the medications utilized in IBD management.MethodsThis prospective study was performed in 150 patients with IBD. All patients were treated with 2 mg/kg per day AZA (Imuran, GlaxoSmithKline®) for at least 3 months at therapeutic doses to induce remission. Subsequent treatment of AZA. The minimum follow-up period for those who did not experience ADR was one year. Among the studied patients, one hundred twenty-nine patients were treated with combination regimen of steroids (oral prednisone 1 mg/kg/day).Also, treatment failure was considered among the patients who could not tolerate AZA side effects, or there was no improvement after dose modification.ResultsThe most identifiable adverse effect among the studied population was anemia followed by leukopenia and myelosuppression. SNPs genotype TPMT (rs1800460) and ITPA gene (rs1127354) were significantly related to adverse effects among IBD patients receiving Azathioprine treatment. There was a lack of any variants in the NUDT15 genotype among the Egyptian population.ConclusionFurther research is required in to clarify the relationship between NUDT15 PGx and AZA-ADRs. The effect of NUDT15 PGx on toxicity and ADRs as yet necessitates to be elucidated. Studies with a larger sample size and involving different ethnicities are also necessary.
The awareness and knowledge of dysphagia among health care practitioners in Egypt
Authors: Hady Aisha Fawzy Abdel , Farag Heba Mahmoud , Sheikhany Ayatallah Raouf 
Published: January 2023

Abstract
Background
There is a lack of research relating to awareness associated with dysphagia-specific knowledge of health care practitioners in Egypt. The study aimed at determining the level of awareness and knowledge of dysphagia among health care practitioners in Egypt to detect the pitfalls to be addressed through awareness-raising programs.

Methods
A questionnaire was distributed online to be filled in by health care practitioners apart from those with the highest knowledge about dysphagia as otolaryngologists, phoniatricians, and gastroenterologists. It consists of 4 sections including sociodemographic data, the participants’ level of awareness and knowledge about dysphagia through questions about dysphagia identification, symptoms and signs, and complications, data about the practice of dysphagia in their hospitals, and their level of awareness and knowledge of the role played by the phoniatricians in dysphagia management in addition to the availability of this specialty in their centers.

Results
Forty-seven percent of the participants rated themselves as having moderate to high contract with dysphagia cases. Sixty-six percent of the participants did not receive training in dysphagia. Only 18.1% of the participants indicated the presence of a dysphagia clinic in their institute. Forty percent of the participants refer dysphagia cases to GIT followed by 37.8% of the participants refer to ENT then 18.6% of them refer to Phoniatrics. Forty-six percent of the participants do not know the investigations work-up for dysphagia.

Conclusion
Egyptian health care practitioners in the Greater Cairo area encountered in this study differ in their knowledge and awareness level about dysphagia according to their specialties and their degree of contact with dysphagia cases. Minimal awareness was found in specialties with low contact. Fair awareness was found in specialties with moderate to high contact with dysphagia cases. There was insufficient knowledge about non-overt symptoms and signs of dysphagia, the widely used investigations, and the role of phoniatricians in dealing with dysphagia cases. Neurology was the specialty with a relatively higher awareness.
Evaluation of myocardial performance by serial speckle tracking echocardiography in diagnosis and follow-up of a patient with eosinophilic myocarditis
Authors: Sharifkazemi Mohammadbagher , Rezaian Gholamreza , Lotfi Mehrzad 
Published: January 2023

Abstract
Background
Speckle tracking echocardiography (STE) has been used as an adjunct diagnostic modality in patients with eosinophilic myocarditis. Its serial dynamic nature, however, has never been reported before.

Case presentation
A 17-year-old boy presented in cardiogenic shock state. His full blood count revealed an absolute eosinophilic count of 11.18 × 103/μL. An emergency 2D echocardiogram (2DE) showed global left ventricular hypokinesia with LVEF = 9.0% by Simpson’s method and a large amount of pericardial effusion. STE showed a global longitudinal strain (GLS) of − 4.1%. Because of his poor clinical status and presence of marked hypereosinophilia and the possibility of eosinophilic myocarditis (EM), parenteral pulse therapy with methylprednisolone and inotropes was started with subsequent improvement within the next 48 h. Over the next few days, he had his first cardiovascular magnetic resonance imaging (CMR), which showed late gadolinium enhancement (LGE) in different cardiac regions. After two weeks of therapy, he left the hospital in a stable condition, with LVEF = 38.0%, and GLS = − 13.9%. He did well during his two months of outpatient follow-ups and was found to have an absolute eosinophil count of 0.0% on several occasions. Unfortunately, he was re-admitted because of treatment non-compliance with almost the same, albeit milder, symptoms. The WBC count was 18.1 × 103 per microliter, and the eosinophilic count was 5.04 × 103/μL (28%). Heart failure treatment and high-dose prednisolone were started. After 15 days of admission, he got better and was discharged. During both hospital admissions and several months of follow-up, he had multiple 2DEs, STE, and two CMR studies. None of his STEs were identical to the prior studies and were dynamic with frequent wax and wanes throughout the admissions and follow-ups. Thus a single admission-time STE study was not sufficient enough to properly predict the patient’s outcome. Follow-up STEs showed new sites of myocardial involvement despite the absence of eosinophilia.

Conclusion
The use of STE in this patient, proved to have an added value in the evaluation and stratification of the left ventricular function in patients with EM and can be used as a diagnostic adjunct to CMR for diagnosis of EM.
Mutational heterogeneity of imatinib resistance and efficacy of ripretinib vs sunitinib in patients with gastrointestinal stromal tumor: ctDNA analysis from INTRIGUE.
Authors: Bauer Sebastian , Jones Robin Lewis , George Suzanne , Gelderblom Hans , Schöffski Patrick , von Mehren Margaret , Zalcberg John Raymond , Kang Yoon-Koo , Abdul Razak Albiruni Ryan , Trent Jonathan C. , Attia Steven , Le Cesne Axel , Reichmann William , Sprott Kam , Achour Haroun , Sherman Matthew L. , Ruiz-Soto Rodrigo , Blay Jean-Yves , Heinrich Michael C. 
Published: January 2023

397784 Background: Ripretinib, a switch-control tyrosine kinase inhibitor (TKI), is indicated for patients (pts) with gastrointestinal stromal tumor (GIST) who received prior treatment with ≥3 TKIs, including imatinib. Sunitinib is approved for advanced GIST after imatinib failure. Circulating tumor DNA (ctDNA) analysis may provide insight into the efficacy of these agents in second-line advanced GIST. Here, we present exploratory baseline ctDNA results from INTRIGUE. Methods: INTRIGUE is an open-label, phase 3 study that enrolled adult pts with advanced GIST who progressed on or had intolerance to imatinib (NCT03673501). Randomization was 1:1 to ripretinib 150 mg once daily (QD) or sunitinib 50 mg QD (4 wks on/2 wks off). Baseline peripheral whole blood was analyzed by Guardant360, a 74-gene ctDNA next-generation sequencing (NGS)-based assay. Only KIT mutations are reported here. Results: Of 453 pts in the overall intent-to-treat (ITT) population, 362 (80%) samples were analyzed. ctDNA was detected in 280/362 (77%), with KIT mutations detected in 213/280 (76%). Common resistance mutations were in the KIT activation loop (AL; exons 17/18; 89/213, 42%) and ATP-binding pocket (ATP-BP; exons 13/14; 81/213, 38%). Efficacy in pts with detectable ctDNA in the KIT exon 11 and overall ITT populations was consistent with the primary analysis based on tumor data used for randomization. Pts with KIT exon 11 + 17/18 (−9/13/14) mutations had superior progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) with ripretinib vs sunitinib, whereas pts with exon 11 + 13/14 (−9/17/18) mutations had better PFS, ORR, and OS with sunitinib vs ripretinib (Table). Subgroup safety profiles were consistent with the primary analysis. Conclusions: While KIT ATP-BP mutations predicted clinical benefit from sunitinib vs ripretinib, pts harboring resistance mutations in the KIT AL derived meaningful clinical benefit from ripretinib but not sunitinib. This study demonstrates the value of ctDNA NGS-based sequencing of the complex landscape of KIT mutations to predict the clinical benefit of ripretinib or sunitinib as second-line therapy in pts with advanced GIST. Clinical trial information: NCT03673501 . [Table: see text]
Radioactive Iodine Therapy Decreases the Recurrence of Intermediate-Risk PTC With Low Thyroglobulin Levels
Authors: Tian Tian , Qi Zhibing , Huang Shuhui , Wang Hongxi , Huang Rui 
Published: January 2023

Abstract

Context
Whether radioactive iodine therapy (RAIT) is necessary for intermediate-risk papillary thyroid cancer (PTC) after total thyroidectomy is still lacking reliable evidence, especially for patients with low postoperative thyroglobulin (Tg) levels.

Objective
This study conducted a propensity score matching (PSM) analysis to investigate whether RAIT is effective in reducing the recurrence of intermediate-risk PTC with low Tg levels.

Methods
In total, 1487 patients with intermediate-risk PTC with unstimulated Tg ≤ 1 ng/mL or stimulated Tg ≤ 10 ng/mL after total thyroidectomy were enrolled retrospectively. The clinicopathological characteristics were compared between the non-RAIT and RAIT groups before and after PSM (1:4 matching). The impact of RAIT on biochemical recurrence and structural recurrence was evaluated.

Results
Overall, 1349 (90.7%) patients underwent RAIT, and 138 (9.3%) did not. After a median follow-up time of 51 months, 30 patients presented with recurrence, including 11 structural and 19 biochemical recurrences. After PSM, the non-RAIT group had a higher rate of structural recurrence (5/138 vs 5/552, P = .046) and biochemical recurrence (6/138 vs 4/552, P = .005) than the RAIT group. Multivariate analysis showed that not receiving RAIT was an independent risk factor for structural recurrence (hazard ratio [HR] 10.572, 95% CI 2.439-45.843, P = .002) and biochemical recurrence (HR 16.568, 95% CI 3.670-74.803, P &lt; .001). Kaplan–Meier analysis showed that the non-RAIT group had more unfavorable recurrence-free survival (structural and biochemical, all P &lt; .05).

Conclusion
RAIT could decrease the recurrence risk of intermediate-risk PTC in patients with unstimulated Tg ≤ 1 ng/mL or stimulated Tg ≤ 10 ng/mL. Further prospective randomized studies are needed to confirm these findings.
Deep Brain Stimulation of the Centromedian Nucleus of the Thalamus for Lennox-Gastaut Syndrome: A Systematic Review and Individual Patient Data Analysis
Authors: Shlobin Nathan A. , Hofmann Katherine , Cohen Nathan T. , Koubeissi Mohamad Z. , Gaillard William D. , Oluigbo Chima O. 
Published: January 2023

BACKGROUND:
Lennox-Gastaut syndrome (LGS) is a severe childhood-onset pharmacoresistant epilepsy. Deep brain stimulation (DBS) of the centromedian nucleus of the thalamus (CMN) has been utilized.

OBJECTIVE:
To conduct a systematic review and individual patient data (IPD) analysis to characterize outcomes of DBS of CMN in LGS.

METHODS:
PubMed, Embase, and Scopus were searched per Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Articles were screened by title/abstract then full text. Included articles were reviewed for bibliographic, demographic, and outcome data. IPD were extracted from studies providing IPD for all patients.

RESULTS:
Of 72 resultant articles, 10 studies (114 patients) were included. Six of 7 studies reporting the outcome of ≥50% seizure reduction indicated that ≥50% of patients achieved this, with improved functional ability. Seizure freedom rate was generally <10%. Six studies with 47 patients provided IPD. The mean ages at epilepsy onset and CMN DBS were 3.9 ± 4.5 years and 17.4 ± 8.8 years, respectively. Nineteen of 41 (46.3%) patients had positive MRI findings. Seizure types included atypical absence in 39 (83.0%) patients, generalized tonic-clonic in 32 (68.1%), tonic in 22 (46.8%), and atonic in 20 (42.6%). Thirty-eight (80.9%) patients experienced ≥50% reduction in seizure frequency, and only 3 (6.4%) experienced seizure freedom. The mean seizure reduction was 62.9% ± 31.2% overall. Quality of life improved in 30/34 (88.2%) and was unchanged in the remainder (11.8%). The complication rate was 2/41 (4.9%). The mean length of follow-up was 19.8 ± 26.1 months (IQR: 4-18 months).

CONCLUSION:
Limited data indicate that DBS of the CMN may be effective and safe for people with LGS.
Stimulation of the Presupplementary Motor Area Cluster of the Subthalamic Nucleus Predicts More Consistent Clinical Outcomes
Authors: Kähkölä Johannes , Lahtinen Maija , Keinänen Tuija , Katisko Jani 
Published: January 2023

BACKGROUND:
The development of diffusion tensor imaging and tractography has raised increasing interest in the functional targeting of deep brain stimulation of the subthalamic nucleus (STN) in Parkinson disease.

OBJECTIVE:
To study, using deterministic tractography, the functional subdivisions of the STN and hyperdirect white matter connections located between the STN and the medial frontal cortex, especially the presupplementary motor area (preSMA), SMA, primary motor area (M1), and dorsolateral premotor cortex, and to study retrospectively whether this information correlates with clinical outcome.

METHODS:
Twenty-two patients with Parkinson disease who underwent STN deep brain stimulation were analyzed. Using 3 T MR images, the medial frontal cortex was manually segmented into preSMA, SMA, M1, and dorsolateral premotor cortex, which were then used to determine the functional subdivisions of the lateral border of the STN. The intersectional quantities of the volume of activated tissue (VAT) and the hyperdirect white matter connections were calculated. The results were combined with clinical data including unilateral 12-month postoperative motor outcome and levodopa equivalent daily dose.

RESULTS:
Stimulated clusters of the STN were connected mostly to the cortical SMA and preSMA regions. Patients with primarily preSMA cluster stimulation (presmaVAT% ≥ 50%) had good responses to the treatment with unilateral motor improvement over 40% and levodopa equivalent daily dose reduction over 60%. Larger VAT was not found to correlate with better patient outcomes.

CONCLUSION:
Our study is the first to suggest that stimulating, predominantly, the STN cluster where preSMA hyperdirect pathways are located, could be predictive of more consistent treatment results.
Surgical Management in Herpes Simplex Encephalitis: Illustrative Case Report and Systematic Review of the Literature
Authors: Bhave Varun M. , Bernstock Joshua D. , Carlson Julia M. , Kappel Ari D. , Torio Erickson F. , Chen Jason A. , Essayed Walid Ibn , Gawelek Kara L. , DiToro Daniel F. , Izzy Saef , Cosgrove G. Rees 
Published: January 2023

BACKGROUND:
Herpes simplex virus (HSV) is a common cause of viral encephalitis and can result in refractory seizures. Although HSV encephalitis (HSVE) is treated primarily with acyclovir, surgery can play a role in medically intractable cases.

OBJECTIVE:
To systematically review cases describing surgery for the treatment of severe HSVE. We also present an illustrative case of anterior temporal lobectomy (ATL) for refractory status epilepticus in a patient with unilateral HSVE. This case demonstrates one clinical context in which surgery can be a useful adjunct.

METHODS:
We performed a systematic review using PubMed and Google Scholar, including case reports and series describing surgical interventions for HSVE. Clinical data were extracted from 54 publications that incorporated 67 patient cases.

RESULTS:
Surgical decompression occurred at a wide range of times after the onset of illness, although most patients were operated on 4 or more days after HSVE symptoms began. Numerous reports indicated that decompressive craniectomy, temporal lobectomy, and hematoma removal could treat intractably elevated intracranial pressure because of HSVE with favorable long-term outcomes. We describe an additional case in which a 52-year-old woman with HSVE developed refractory right temporal lobe seizures. After ATL, the seizures resolved with significant clinical improvement.

CONCLUSION:
Surgical treatment can be a useful adjunct for treatment of HSVE. There is substantial variability in the timing of surgical decompression in patients with HSVE, which can be necessary up to approximately 3 weeks after illness onset. ATL should be considered for refractory status epilepticus in HSVE with a unilateral seizure focus.
Correlation of Pituitary Descent and Diabetes Insipidus After Transsphenoidal Pituitary Macroadenoma Resection
Authors: Ma Josh , Gooderham Peter , Akagami Ryojo , Makarenko Serge 
Published: January 2023

BACKGROUND:
Endoscopic transsphenoidal surgery remains the technique of choice for resection of pituitary adenoma. Postoperative diabetes insipidus (DI) is most often transient and observed in 1.6% to 34% of patients, whereas permanent DI has been reported in 0% to 2.7% of patients. The proposed mechanism was the transduction of traction forces exerted by the surgeon on the descended diaphragma sellae and through the pituitary stalk.

OBJECTIVE:
To quantify and correlate the degree of pituitary gland descent with postoperative DI.

METHODS:
Of 374 patients who underwent transsphenoidal resection of a pituitary adenoma between 2010 and 2020 at our institution, we report a cohort of 30 patients (Group A) DI. We also report a matched cohort by tumor volume of 30 patients who did not develop DI (Group B). We quantified the tension on the pituitary stalk by calculating pituitary descent interval (PDI) by comparing preoperative and postoperative position of the pituitary gland and using Pythagoras' formula where

, with craniocaudal (CC) and anterior–posterior (AP) representing measurements of pituitary translation in respective directions after resection.

RESULTS:
Patients who developed DI had significantly greater pituitary gland translations in the craniocaudal (23.0 vs 16.3 mm, P = .0015) and anteroposterior (2.4 vs 1.5 mm, P = .0168) directions. Furthermore, Group A had a statistically greater PDI, which was associated with development of DI (23.2 vs 16.6 mm, P = .0017).

CONCLUSION:
We were able to quantify pituitary descent and subsequent tension on the pituitary stalk, while also associating it with development of postoperative DI after pituitary adenoma resection.
Anatomic Depth Estimation and Three-Dimensional Reconstruction of Microsurgical Anatomy Using Monoscopic High-Definition Photogrammetry and Machine Learning
Authors: Gonzalez-Romo Nicolas I. , Hanalioglu Sahin , Mignucci-Jiménez Giancarlo , Abramov Irakliy , Xu Yuan , Preul Mark C. 
Published: January 2023

BACKGROUND:
Immersive anatomic environments offer an alternative when anatomic laboratory access is limited, but current three-dimensional (3D) renderings are not able to simulate the anatomic detail and surgical perspectives needed for microsurgical education.

OBJECTIVE:
To perform a proof-of-concept study of a novel photogrammetry 3D reconstruction technique, converting high-definition (monoscopic) microsurgical images into a navigable, interactive, immersive anatomy simulation.

METHODS:
Images were acquired from cadaveric dissections and from an open-access comprehensive online microsurgical anatomic image database. A pretrained neural network capable of depth estimation from a single image was used to create depth maps (pixelated images containing distance information that could be used for spatial reprojection and 3D rendering). Virtual reality (VR) experience was assessed using a VR headset, and augmented reality was assessed using a quick response code–based application and a tablet camera.

RESULTS:
Significant correlation was found between processed image depth estimations and neuronavigation-defined coordinates at different levels of magnification. Immersive anatomic models were created from dissection images captured in the authors' laboratory and from images retrieved from the Rhoton Collection. Interactive visualization and magnification allowed multiple perspectives for an enhanced experience in VR. The quick response code offered a convenient method for importing anatomic models into the real world for rehearsal and for comparing other anatomic preparations side by side.

CONCLUSION:
This proof-of-concept study validated the use of machine learning to render 3D reconstructions from 2-dimensional microsurgical images through depth estimation. This spatial information can be used to develop convenient, realistic, and immersive anatomy image models.