bluuebunny/crossref_metadata_2025 huggingface dataset:
Fasting Blood Glucose: A Mediator of the Association between Estimated Glomerular Filtration Rate and Arterial Stiffness in Japanese Population with Decreased Kidney Function
Authors: Wu Liling , Yang Zhichen , Wu Xiaodan , Chen Xinglin , Cao Wei , Hu Haofei , Wan Qijun
Published: August 2024

Introduction: Low estimated glomerular filtration rate (eGFR) is associated with an increased risk of arterial stiffness in participants with kidney damage. It is uncertain whether this association is due to eGFR itself or is mediated by the eGFR-associated increases in fasting blood glucose (FBG). Method: The cross-sectional study included 865 Japanese participants with decreased kidney function, whose eGFR was less than 90 mL/min/1.73 m2, and recruited individuals who received medical healthcare. The mediating variable was FBG, with eGFR as the independent variable and brachial-ankle pulse wave velocity (baPWV) as the dependent variable. A mediation analysis was used to evaluate the mediating effect of FBG on the association between eGFR and arterial stiffness. Results: The mean age of the participants was 51.69 ± 9.25 years old, with 65.90% individuals being male. The mean values for FBG, eGFR, and baPWV were 5.46 ± 0.79 mmol/L, 68.83 ± 10.05 mL/min/1.73 m2, and 1,423.50 ± 247.78 cm/s, respectively. The mediation analysis revealed that eGFR had a significant direct effect on baPWV (β = −25.68 95% CI: −46.42, −7.45), and that FBG played a partial mediating role in the indirect effect of eGFR on baPWV (β = −3.54 95% CI: −11.88, −0.079). Mediation analysis showed that 12.10% of the effect of eGFR on risk of arterial stiffness was mediated through FBG. Conclusion: The study indicated that there is a mediating relationship between eGFR and FBG in people with decreased kidney function, which is associated with the risk of arterial stiffness. Therefore, the importance of FBG as a mediator should be acknowledged and taken into consideration.
Detailed Phenotype Supports Pathogenicity of Hypomorphic Variant in ABCC6-Associated Pattern Dystrophy
Authors: Tsui Jonathan C. , Aleman Tomas S. , Tapino Paul J. , Kim Benjamin J.
Published: August 2024

Introduction: We report a case of pseudoxanthoma elasticum (PXE) with an atypical phenotype likely related to a hypomorphic variant in ABCC6. Case Presentation: A 66-year-old Caucasian female with a history of a maculopathy interpreted as either age-related macular degeneration or a pattern dystrophy underwent a detailed ophthalmic evaluation. Visual acuities were 20/25, OD, and 20/20, OS. Spectral domain optical coherence and fluorescein angiography demonstrated outer retinal disruptions and breaks in retinal pigment epithelium (RPE)/Bruch’s membrane bilaterally, consistent with angioid streaks. A large area of hypo- and hyperautofluorescence extending from the central retina into the peripapillary retina was documented with short-wavelength excitation autofluorescence. The area of hypoautofluorescence, which was much larger on near-infrared excitation, spared the temporal retina. Two-color dark-adapted perimetries documented severe rod sensitivity losses and less severe cone sensitivity abnormalities co-localizing with the RPE abnormalities. No obvious skin findings were observed, and initial dermatologic biopsy was negative. Gene screening identified a pathogenic ABCC6 gene variant c.1552C>T and a previously reported variant of uncertain significance c.1171A>G. A second dermatologic biopsy demonstrated positive findings consistent with PXE. Conclusion: Although this patient had minimal skin findings, this patient had characteristic structural and functional abnormalities of a pattern dystrophy with angioid streaks and histologic evidence of PXE, suggesting compound heterozygous variants involving the hypomorphic ABCC6 c.1171A>G variant. These findings support the pathogenic role of both variants.
Challenges and Opportunities for the Clinical Translation of Spatial Transcriptomics Technologies
Authors: Smith Kelly D. , Prince David K. , MacDonald James W. , Bammler Theo K. , Akilesh Shreeram
Published: August 2024

Background: The first spatially resolved transcriptomics platforms, GeoMx (Nanostring) and Visium (10x Genomics) were launched in 2019 and were recognized as the method of the year by Nature Methods in 2020. The subsequent refinement and expansion of these and other technologies to increase -plex, work with formalin-fixed paraffin-embedded tissue, and analyze protein in addition to gene expression have only added to their significance and impact on the biomedical sciences. In this perspective, we focus on two platforms for spatial transcriptomics, GeoMx and Visium, and how these platforms have been used to provide novel insight into kidney disease. The choice of platform will depend largely on experimental questions and design. The application of these technologies to clinically sourced biopsies presents the opportunity to identify specific tissue biomarkers that help define disease etiology and more precisely target therapeutic interventions in the future. Summary: In this review, we provide a description of the existing and emerging technologies that can be used to capture spatially resolved gene and protein expression data from tissue. These technologies have provided new insight into the spatial heterogeneity of diseases, how reactions to disease are distributed within a tissue, which cells are affected, and molecular pathways that predict disease and response to therapy. Key Message: The upcoming years will see intense use of spatial transcriptomics technologies to better define the pathophysiology of kidney diseases and develop novel diagnostic tests to guide personalized treatments for patients.
A New Sarcoma Shortly after Treatment for High-Grade Glioma with Adjuvant Chemoradiation: A Case Report
Authors: Madkhali Abdossalam M. , Alaluan Hasah F. , Alnajeim Mohammed H. , Al Saeed Eyad F. , Ajlan Abdulrazag M. , Abdelwarith Ahmed , Abduh Ali , Albanyan Saleh , Alqurashi Ashwag , Alkhalidi Hisham
Published: August 2024

Introduction: High-grade gliomas are central nervous system tumors conventionally treated with surgery followed by adjuvant chemoradiotherapy. Secondary cancer due to radiation therapy is a rare yet established phenomenon that typically occurs years after radiation therapy. Case Presentation: In this case, we discuss an early presentation of a second cancer adjacent to the radiation field. This case report is of a 52-year-old male who developed a new scalp sarcoma at the site of primary surgery 8 months after radiation therapy. Genetic testing revealed a heterozygous missense variant in the NF1 gene, a variant of uncertain significance. The report highlights that this case does not conform to the expected criteria for postradiation sarcoma in terms of timing. Conclusion: Secondary cancers may arise earlier than expected, even in phenotypically normal patients, as they may have unmanifested variants of relevant mutations. The question of pre-radiotherapy screening for radiosensitivity syndromes and diseases requires further study, as current data are limited and do not provide enough insight into the significance of different genetic variants.
Bilateral Late-Onset Pigment Dispersion Syndrome following Implantable Collamer Lens Surgery: A Case Report
Authors: Katsimpris Andreas , Kumarasamy Manjula
Published: August 2024

Introduction: We report a case of bilateral pigment dispersion syndrome after 13 years of uncomplicated implantable collamer lens (ICL) surgery. Case Presentation: A 53-year-old woman was referred from her optometrist to our glaucoma clinic due to early superonasal visual field loss in both eyes. She was asymptomatic with no changes in visual acuity and had undergone bilateral ICL implantation 13 years ago to correct her high myopia. Clinical examination revealed pigment deposition on the corneal endothelium, iris transillumination defects, and iris vaulting at the areas of contact with the ICL. Gonioscopy showed open angles with significant pigmentation of the trabecular meshwork. The diagnosis of pigment dispersion syndrome secondary to ICL implantation was made, and subsequent follow-up visits demonstrated normal intraocular pressure IOP and stable visual fields. Conclusion: Pigmentary dispersion syndrome can occur several years after ICL implantation. This case report emphasizes the need for long-term follow-up and monitoring after ICL surgery.
A Case of Inflammatory Juvenile Conjunctival Nevus with a Rare Histopathological Type
Authors: Iwata Chihiro , Asahina Yuichi , Ono Takashi , Taketani Yukako , Kimakura Mikiko , Toyono Tetsuya , Tanaka Mariko , Aihara Makoto , Miyai Takashi
Published: August 2024

Introduction: Inflammatory juvenile conjunctival nevus (IJCN) is a rare condition affecting both children and adolescents. It has misleading clinical and histopathological features; therefore, careful assessment is necessary. We present a case of IJCN with a rare pathological type and misleading histopathological features. Case Presentation: A 13-year-old girl with IJCN in the right eye was treated with antiallergic and steroid eye drops but showed no response and was referred to our hospital for excisional biopsy. Slit-lamp examination revealed a nonpigmented juxtalimbal tumor in the right eye. Histopathologically, nevus cells with mild nuclear atypia proliferated within the conjunctival epithelium. Confluent growth of junctional nests, conjunctival cysts, and prominent inflammatory infiltration were also observed. Considering the young age of the patient and immunohistochemical characteristics (HMB-45, SOX10, p16 and Ki-67), the patient was finally diagnosed with IJCN. IJCN has three pathological subtypes – compound, subepithelial, and junctional – depending on the location of the nevus cells. This case was diagnosed as a rare junctional type, as most of the examined sections only showed lesions within the epithelium; no lesions were clearly identified extending beneath the epithelium. Conclusion: The pathological diagnosis of IJCN is difficult because some features of IJCN suggest malignancy. Detailed microscopic examination, immunohistochemical staining, and the patient’s young age helped render a final diagnosis.
Cytomegalovirus Retinitis in an Eye with Unilateral Retinoblastoma: A Case Report
Authors: Meller Leo , Jagadeesh Vasan , Oca Michael , Wilson Katherine , Zuraski Connor , Koretz Zachary A. , Chevez-Barrios Patricia , Liu Catherine , Berry Jesse L. , Scott Nathan L.
Published: August 2024

Introduction: Cytomegalovirus (CMV) retinitis in the setting of pediatric retinoblastoma is exceedingly unusual. Here, we present the first reported case of CMV retinitis in an enucleated eye with retinoblastoma after chemotherapy in the western hemisphere. Case Presentation: A 2-year-old Hispanic male without a family history of retinoblastoma presented with a 3-month history of right eye exotropia and squinting. Clinical examination revealed dense white vitreous opacities in the right eye. Ocular oncology evaluation unveiled an exudative retinal detachment with vitreous seeds, subretinal seeding, and a tumor emanating from the retina in the superonasal quadrant of the right eye. The patient was diagnosed with unilateral Group D retinoblastoma, and RB1 sequencing revealed a pathogenic variant with mosaicism. Treatment involved systemic chemotherapy, intravitreal chemotherapy, and cryotherapy. However, the patient developed a rhegmatogenous retinal detachment with diffuse vitreous hemorrhage and ultimately underwent right eye enucleation. Interestingly, histopathological analysis of the enucleated eye revealed concomitant CMV retinitis alongside retinoblastoma. After consultation with infectious disease, antiviral treatment was not initiated as the patient remained asymptomatic and maintained a recovered immune system. Repeat CMV PCR confirmed viral clearance. The patient received a prosthetic eye and continues to be monitored for retinoblastoma recurrence. Conclusion: Clinicians should be aware of the potential for CMV retinitis to develop in retinoblastoma patients receiving chemotherapy, which may complicate clinical decision-making and management. Timely identification of CMV retinitis in this setting may improve patient ocular outcomes and overall prognosis.
Case Report of a Benign Granular Cell Tumor Resembling Breast Carcinoma in a Young Woman: A Diagnostic Challenge
Authors: Akbari Atieh , Behravan Parisa , Moradi Afshin , Akbari Mohammad Esmaeil
Published: August 2024

Introduction: Granular cell tumors (GCTs) are uncommon, low-grade Schwann cell tumors found in the skin, soft tissue, and mucosal surfaces of the oral, gastrointestinal, and respiratory tracts. One in 1,000 breast cancer cases is GCT. Just 1–2% of GCTs are malignant GCTs. Case Presentation: This case report presents the clinical details and outcomes of a 34-year-old woman with a main concern of a palpable mass and pain in her right breast. In the clinical examination, we found a 1.5 × 2-cm palpable mass in her right breast with no axillary lymph node detection. The primary diagnosis was a benign GCT mimicking carcinoma of the breast. Upon evaluation, the mass was confirmed to be a benign GCT through pathology. The patient underwent breast-conserving surgery and sentinel lymph node dissection at the Cancer Research Center of Shahid Beheshti University of Medical Sciences on November 30, 2022. The surgical margins were found to be free of tumors, and there was no involvement of skin or axillary lymph nodes. The patient had a positive postoperative outcome, with no complications observed. Conclusion: The case highlights the importance of accurate diagnosis and appropriate surgical planning to avoid invasive procedures and unnecessary radical surgeries in cases of benign GCT mimicking carcinoma of the breast.
Janus Kinase Inhibitors as Successful Treatment Alternative in Dupilumab-Induced Psoriasis
Authors: Weiss Lina , Marbet Corinne Punsap , Branca Lorenzo Barino , Mühleisen Beda , Navarini Alexander
Published: August 2024

Introduction: After the introduction of dupilumab as systemic treatment for atopic dermatitis, an increasing number of patients have been successfully treated. However, reports of patients developing psoriasis as a secondary skin condition have been accumulating. The most likely reason is assumed to be an immune shift from Th2- to Th1-mediated auto-inflammatory processes. Case Presentation: Our patient is a 38-year-old male suffering from head-neck type atopic dermatitis since childhood. As one of the first patients in Switzerland, he received dupilumab in 2018 leading to a significant improvement of his skin lesions. One year later he developed progressing circular erythematous-squamous plaques which correlated histologically with psoriasis. In 2021, 3 years after initiating dupilumab, we switched systemic therapy to baricitinib. Three months after initiation, his psoriatic lesions were completely healed, while the atopic lesions remained stable with low inflammatory activity. Conclusion: In patients treated with dupilumab for atopic dermatitis immune shift needs to be considered in case of newly appearing skin lesions. With a growing number of described cases, we conclude that baricitinib is a good alternative treatment for atopic dermatitis in patients suffering from biologic-induced psoriasis.
Changes in Exhaled Carbon Dioxide during the Menstrual Cycle and Menopause
Authors: Cramer Tomer , Yeshurun Shlomo , Mor Merav
Published: August 2024

Introduction: The menstrual cycle (MC) reflects multifaceted hormonal changes influencing women’s metabolism, making it a key aspect of women’s health. Changes in hormonal levels throughout the MC have been demonstrated to influence various physiological parameters, including exhaled carbon dioxide (CO2). Lumen is a small handheld device that measures metabolic fuel usage via exhaled CO2. This study leverages exhaled CO2 patterns measured by the Lumen device to elucidate metabolic variations during the MC, which may hold significance for fertility management. Additionally, CO2 changes are explored in menopausal women with and without hormonal replacement therapy (HRT). Methods: This retrospective cohort study analyzed exhaled CO2 data from 3,981 Lumen users, including eumenorrheal women and menopausal women with and without HRT. Linear mixed models assessed both CO2 changes of eumenorrheal women during the MC phases and compared between menopausal women with or without HRT. Results: Eumenorrheic women displayed cyclical CO2 patterns during the MC, characterized by elevated levels during the menstrual, estrogenic and ovulation phases and decreased levels during post-ovulation and pre-menstrual phases. Notably, despite variations in cycle length affecting the timing of maximum and minimum CO2 levels within a cycle, the overall pattern remained consistent. Furthermore, CO2 levels in menopausal women without HRT differed significantly from those with HRT, which showed lower levels. Conclusion: This study reveals distinct CO2 patterns across MC phases, providing insights into hormonal influences on metabolic activity. Menopausal women exhibit altered CO2 profiles in relation to the use or absence of HRT. CO2 monitoring emerges as a potential tool for tracking the MC and understanding metabolic changes during menopause.
Disseminated Carcinomatosis of the Bone Marrow from Castration-Resistant Prostate Cancer Revealed by Choline Positron Emission Tomography-Computed Tomography
Authors: Kitajima Kazuhiro , Yamamoto Shingo , Kanematsu Akihiro , Tomono Masato , Nishimoto Sayuri , Wada Reona , Hirayama Miyu , Kitamoto Jyunpei , Takagaki Kiyoshi , Kuroda Norihiro , Kihara Takako , Yamakado Koichiro
Published: August 2024

Introduction: Disseminated carcinomatosis of the bone marrow is caused by cancer metastasis to the bone marrow and is the diagnosis is very difficult by imaging. Case Presentation: We report a 75-year-old male with disseminated carcinomatosis of the bone marrow from castration-resistant prostate cancer revealed by 11C-choline positron emission tomography-computed tomography (PET/CT). Although he already received radiotherapy to the prostate, combined androgen blockade, enzalutamide and apalutamide, and external beam radiotherapy for the pelvic bone metastases, serum prostate-specific antigen (PSA) value rapidly increased from 32 ng/mL to 104 ng/mL in recent 1 month. Bone scintigraphy showed almost no abnormal uptake in the whole body, whereas 11C-choline PET/CT showed diffuse bone marrow 11C-choline uptake. The disseminated carcinomatosis of the bone marrow was diagnosed from the discordant findings between bone scintigraphy and 11C-choline PET/CT examinations and confirmed pathologically by iliac marrow biopsy pathologically. Although docetaxel therapy was started, PSA value continued rising and he died after 4 months of the diagnosis. Conclusion: The discordant findings of choline PET/CT and bone scintigraphy can diagnose disseminated carcinomatosis of the bone marrow from prostate cancer.
Exposure to Caper Spurge (Euphorbia lathyris) Sap: A Case of Ocular and Periorbital Toxicity
Authors: Kok Li Teng , Bizrah Mukhtar , Cordeiro M. Francesca , Din Nizar
Published: August 2024

Introduction: We aimed to describe a case of bilateral keratoconjunctivitis after exposure to the toxic sap of Euphorbia lathyris. Case Report: A 76-year-old gentleman presented after exposure to E. lathyris whilst he was gardening. He had 6/12 visual acuity in his right eye, and 6/4 in his left. Examination revealed marked periocular dermatitis, conjunctival injection and corneal oedema in the right eye with diffuse punctate epithelial staining. He was treated with ocular irrigation, topical steroids, antibiotics, cycloplegics and lubricants. Over 48 h, his left eye started to become symptomatic. He developed bilateral corneal epithelial defects and anterior chamber inflammation. His visual acuity worsened to 6/36 right and 6/24 left. At his 3-week follow-up, there was marked improvement in the resolution of the toxic keratoconjunctivitis in both eyes. Conclusion: Toxic sap from E. lathyris can cause severe keratoconjunctivitis. Irrigation of both eyes despite unilateral symptoms and early follow-up should be considered signs of toxicity may only become evident after 24–48 h.
Severe Bradycardia Associated with the Use of Terlipressin: A Case Report
Authors: Yartsev Alex , Nguyen Jessica T.
Published: August 2024

Introduction: Although terlipressin is known to cause bradycardia, this adverse effect is usually described in association with hypertension and is considered a benign compensatory response mediated by arterial baroreceptors. Cardiac monitoring for patients receiving terlipressin is not routinely recommended. Case Presentation: A 77-year-old female patient with no history of coronary artery disease and no other coexisting risk factors for cardiac arrhythmias or conduction disturbances was admitted to intensive care unit with severe cholangitis, complicated by variceal bleeding. She developed severe sinus bradycardia following the use of terlipressin, which was associated with significant hypotension that required the infusion of norepinephrine. The bradycardia occurred again when terlipressin therapy was reattempted. Conclusion: Vasopressin is known to sensitize baroreceptor reflexes by a central mechanism though its actions on V1a receptors in the area postrema, and we speculate that vasopressin analogues such as terlipressin may act in the same manner. That this effect is not widely described in terlipressin safety literature may be due to the overall younger age range of the trial population. This raises the possibility that cardiac monitoring may be warranted for elderly patients receiving terlipressin.
Status Epilepticus and Low-Grade Glioma in the Pregnant State: Case Report and Ethical Considerations
Authors: Waack Andrew L. , Lucarelli Vito M. , Marellapudi Amulya , Gega Alisa , Zillgitt Andrew J. , Staudt Michael D.
Published: August 2024

Introduction: The pregnant state may cause or exacerbate existing neurological disease. Gliomas appear to be influenced by the physiological changes that occur during pregnancy. The pregnant state may also cause seizures, including status epilepticus. There are currently no defined treatment guidelines to direct clinical decision making, and many of the commonly employed therapies are contraindicated during pregnancy. Case Presentation: The current article describes the case of a 40-year-old G3P1101 female at 10 weeks’ gestation, who sought medical care for recurrent left hemifacial twitching, eventually leading to nonconvulsive status epilepticus. Intubation and sedation were required to achieve seizure cessation. Imaging revealed a lobulated cystic mass in the right parietal lobe, suspicious for low-grade glioma. Despite thorough explanation of the potential risks, the patient adamantly wished to pursue surgical intervention. An uneventful craniotomy was performed for resection of a low-grade glioma. No patient or fetal complications were encountered, and the patient has not had any reported seizures since surgery. Discussion: Managing complex neurosurgical diseases in pregnant patients provides both clinical and ethical quandaries. We describe the successful management of a patient presenting with status epilepticus caused by an underlying glioma during pregnancy. Although challenging, favorable neurosurgical outcomes are possible during pregnancy.
An Algorithm for Automated Measurement of Kinetic Tremor Magnitude Using Digital Spiral Drawings
Authors: Longardner Katherine , Shen Qian , Tang Bin , Wright Brenton A. , Kundu Prantik , Nahab Fatta B.
Published: August 2024

Introduction: Essential tremor is a common movement disorder. Numerous validated clinical rating scales exist to quantify essential tremor severity by employing rater-dependent visual observation but have limitations, including the need for trained human raters and the lack of precision and sensitivity compared to technology-based objective measures. Other continuous objective methods to quantify tremor amplitude have been developed, but frequently provide unitless measures (e.g., tremor power), limiting real-world interpretability. We propose a novel algorithm to measure kinetic tremor amplitude using digital spiral drawings, applying the V3 framework (sensor verification, analytical validation, and clinical validation) to establish reliability and clinical utility. Methods: Archimedes spiral drawings were recorded on a digitizing tablet from participants (n = 7) enrolled in a randomized placebo control double-blinded crossover pilot trial evaluating the efficacy of oral cannabinoids in reducing essential tremor. We developed an algorithm to calculate the mean and maximum tremor amplitude derived from the spiral tracings. We compared the digitally measured tremor amplitudes to manual measurement to evaluate sensor reliability, determined the test-retest reliability of the digital output across two short-interval repeated measures, and compared the digital measure to kinetic tremor severity graded using The Essential Tremor Rating Assessment Scale (TETRAS) score for spiral drawings. Results: This algorithm for automated assessment of kinetic tremor amplitude from digital spiral tracings demonstrated a high correlation with manual spot measures of tremor amplitude, excellent test-retest reliability, and a high correlation with human ratings of the TETRAS score for spiral drawing severity when the tremor severity was rated “slight tremor” or worse. Discussion: This digital measure provides a simple and clinically relevant evaluation of kinetic tremor amplitude that shows promise as a potential future endpoint for use in clinical trials of essential tremor.
Long-Term Survival in Hepatocellular Carcinoma following Second-Line Tumor Treating Fields Therapy and Sorafenib: A Case Report
Authors: Torres Velasco Marisa , Álvarez Gallego Rafael , Peinado Paloma , Muñoz Gregorio Cesar , Ugidos Lisardo , García Morillo Marcial , Vicente Emilio , Quijano Yolanda , Prados Susana , de la Fuente Enrique , Cubillo Gracián Antonio
Published: August 2024

Introduction: Hepatocellular carcinoma (HCC) is an aggressive solid tumor associated with high mortality. Surgery is the main treatment consideration for early disease, but patients who present with locally advanced or metastatic HCC at diagnosis have limited treatment options. There has been great progress in locoregional, immunotherapy, and targeted treatments for advanced HCC. Standard of care for HCC has changed due to results demonstrating safety and efficacy in phase 3 studies, namely, for atezolizumab concomitant with bevacizumab. Nonetheless, additional therapeutic approaches are still warranted to further increase overall survival in HCC. A first-in-class treatment option investigated in patients with HCC is Tumor Treating Fields (TTFields) therapy, which is delivered locoregionally to the tumor site from a portable medical device. TTFields are electric fields that interfere with critical cancer cell processes, hindering tumor progression. Case Presentation: Here, we report on a case study of a 62-year-old male patient with HCC receiving TTFields concomitant with sorafenib as second-line therapy. Although the patient experienced adverse events with previous nivolumab, they achieved a complete response and continued on treatment for 51 months until disease progression, which led to treatment cessation. We report that during 39 months of subsequent treatment with TTFields therapy and sorafenib, the patient experienced a good quality of life, low systemic toxicity, and stable disease following a partial response. Conclusions: These promising findings, along with those of the pilot phase 2 HEPANOVA clinical study, warrant further investigation of TTFields therapy in HCC.
Diagnostic and Therapeutic Challenges of Rare Concurrent Intracranial Meningioma and Oligodendroglioma
Authors: Shoushtari Ali , Robinson Lorraina , Mao Qinwen , Shah Lubdha M. , Salzman Karen L. , Menacho Sarah T.
Published: August 2024

Introduction: Concurrent primary brain tumors are rare clinical entities, with a prevalence ranging from 0.1 to 0.5% of all diagnosed brain tumors. The co-occurrence of meningioma and oligodendroglioma is particularly uncommon, posing unique diagnostic and therapeutic challenges. We describe the case of a patient diagnosed with concurrent meningioma and oligodendroglioma and review the existing literature on this rare phenomenon. Case Presentation: A 55-year-old female patient with a history of seizures presented to the emergency department with worsening headaches, nausea, and vomiting. She had a known right frontoparietal intracranial mass but had previously declined surgery. Magnetic resonance imaging revealed extensive fluid-attenuated inversion recovery /T2 hyperintensity around the lesion, which had slowly increased over 5 years; the growth of the lesion was producing a mass effect with a significant midline shift. The patient underwent urgent hemicraniectomy with subsequent resection. Clinical evaluation, imaging studies, and histopathological examination were conducted to confirm the diagnosis. Genetic and molecular analyses were also performed to explore potential underlying mechanisms. Histopathological findings confirmed a diagnosis of an isocitrate dehydrogenase-mutated World Health Organization Grade II oligodendroglioma with 1p/19q codeletion, along with a Grade I meningioma. Conclusion: The coexistence of meningioma and oligodendroglioma represents a rare clinical event. Surgical management remains the cornerstone of treatment. Further investigation into the genetic and environmental factors that contribute to the co-occurrence of such tumors could pave the way for more targeted therapeutic strategies.
Urinary SIRT2 Reflects Kidney Injury in Type 2 Diabetes
Authors: Dai Yali , Li Dan , Peng Juan , Luo Yanfang , Xiong Lianlian , Wu Su , Liao Xiangyu , Yi Bin
Published: August 2024

Introduction: The early diagnosis of kidney injury in type 2 diabetes (T2DM) is important to prevent the long-term damaging effects of kidney loss and is decisive for patient outcomes. While SIRT2 is implicated in diabetes pathogenesis, its correlation with diabetic nephropathy remains unexplored. This study was designed to evaluate the association of urine SIRT2 levels with diabetic kidney injury, as well as potential underlying mechanisms. Methods: In T2DM patients, db/db mice, and high glucose plus palmitic acid treated HK2 cell models, ELISA, Immunoturbidimetry, Immunohistochemistry, Western blot, and Quantitative real-time polymerase chain reaction were used to detect SIRT2 levels and kidney damage. According to urinary albumin/creatinine ratio (UACR), 163 T2DM patients were divided into three groups. Spearman correlation analysis was used to investigate the relationship between urinary sirtuin2/creatinine ratio (USCR) and biomarkers of kidney injury. The influencing factors of albuminuria in T2DM patients were analyzed by logistic regression model. Results: In our findings, the Macro group exhibited the highest USCR levels as UACR increased. There was a positive association between USCR and UACR, α1-microglobulin/creatinine ratio (UαCR), β2-microglobulin/creatinine ratio (UβCR), and retinol-binding protein/creatinine ratio (URCR), with a negative correlation observed with eGFR. Logistic ordered multiclassification regression analysis, adjusting for confounding variables, confirmed that USCR remained a significant risk factor for the severity of albuminuria in T2DM patients. In the db/db mice kidney SIRT2 protein level increased significantly. Increased SIRT2 protein levels were also observed in renal tubular epithelial cells treated with high glucose plus palmitic acid. Moreover, SIRT2 promotes the expression of proinflammatory factors TNF-α and IL-6 by modulating the phosphorylation of p38 MAPK and p-JNK in renal tubular cells induced by high glucose and palmitic acid. Conclusion: Urinary SIRT2 is closely related to eGFR, renal tubule injury, and urinary albumin excretion in T2DM patients, which is expected to be an important indicator to comprehensively reflect renal injury.
RRAGD-Associated Autosomal Dominant Kidney Hypomagnesemia with Cardiomyopathy: A Review on the Clinical Manifestations and Therapeutic Options
Authors: Trepiccione Francesco , Sambri Irene , Ruggiero Barbara , Emma Francesco , Ballabio Andrea , Florio Giulia , Vanderheyden Ines , Iervolino Anna , Jouret François
Published: August 2024

Background: A hereditary condition primarily affecting the kidneys and heart has newly been identified: the RRAGD-associated autosomal dominant kidney hypomagnesemia with cardiomyopathy (ADKH-RRAGD). This disorder is characterized by renal loss of magnesium and potassium, coupled with varying degrees of cardiac dysfunction. These range from arrhythmias to severe dilated cardiomyopathy, which may require heart transplantation. Mutations associated with RRAGD significantly disrupt the non-canonical branch of the mechanistic target of rapamycin complex 1 pathway. This disruption hinders the nuclear translocation and transcriptional activity of the transcription factor EB a crucial regulator of lysosomal and autophagic function. Summary: All identified RRAGD variants compromise kidney function, leading to hypomagnesemia and hypokalemia of various severity. The renal phenotype for most of the variants (i.e., S76L, I221K, P119R, P119L) typically manifests in the second decade of life occasionally preceded by childhood symptoms of dilated cardiomyopathy. In contrast, the P88L variant is associated to dilated cardiomyopathy manifesting in adulthood. To date, the T97P variant has not been linked to cardiac involvement. The most severe manifestations of ADKH-RRAGD, particularly concerning electrolyte imbalance and heart dysfunction requiring transplantation in childhood appear to be associated with the S76L, I221K, P119R variants. Key Messages: This review aimed to provide an overview of the clinical presentation for ADKH-RRAGD, aiming to enhance awareness, promote early diagnosis, and facilitate proper treatment. It also reports on the limited experience in patient management with diuretics, magnesium and potassium supplements, metformin, or calcineurin and SGLT2 inhibitors.
Fluorescein Angiogram Causing Cutaneous Venous Staining: A Rare Self-Resolving Phenomenon
Authors: Angus Zachary George , Ong Daini , Wickremasinghe Sanjeewa S.
Published: August 2024

Introduction: Fluorescein angiography (FA) is a useful investigation in the diagnosis and treatment of retinal and choroidal disease. FA has well-reported adverse effects, most being mild. Very few cases have reported cutaneous venous staining following FA. Case Presentation: Two cases are reported. Case 1 was a 90-year-old female with bilateral neovascular age-related macular degeneration. In the few minutes following her routine FA, she developed cutaneous fluorescein staining ascending along the superficial forearm veins proximal to the cannula in situ at the dorsal wrist. Case 2 was a 50-year-old male with diabetic macular oedema. In the minutes following his FA, he developed cutaneous fluorescein staining descending along the dorsal forearm veins distal to the cannula in situ at the cubital fossa. Both patients were managed conservatively with the stain resolving in the next few days. Conclusion: Cutaneous fluorescein staining around superficial vasculature is a rare phenomenon. Despite this, it seems to be self-limiting and does not require any treatment.
Physical Exercise in Kidney Renal Recipients: Where Have We Come?
Authors: Mosconi Giovanni , Totti Valentina , Sella Gianluigi , Roi Giulio Sergio , Costa Alessandro Nanni , Bellis Lia , Cardillo Massimo
Published: August 2024

Background: Kidney transplantation constitutes the most effective therapeutic option for patients suffering from end-stage renal disease but remains burdened by a high incidence of cardiovascular disease. To date, exercise is an important preventive strategy that has been underestimated; in kidney transplant patients, exercise programs lead to an improvement in cardiorespiratory performance, muscle strength, arterial stiffness, and patients’ quality of life perception. Summary: The nephrology and transplant community have moved from generic suggestions to specific indications regarding frequency, intensity, time, type, volume, and progression of physical exercise both in the pre- and posttransplant phase. The latest guidelines from the World Health Organization for patients with chronic conditions propose a combination of aerobic, muscle-strengthening, and multicomponent exercises (e.g., balance) to improve health. Based on recent evidence, a combined exercise program (aerobic and strength exercise) is largely proposed to kidney transplant recipients. Aerobic exercise should be performed at an intensity >60% of theoretical maximum heart rate or maximum oxygen uptake possibly every day, and strength training should be performed at a >60% the estimate single maximum repetition, at least 2 times per week. Key Messages: Physical exercise should be personalized in relation to the patient’s baseline performance; increases must be progressive and gradual. Regular physical activity should also be recommended to patients awaiting for a transplant. Eventually, organizational models based on a network of nephrology units, transplant centers, sports medicine centers, and fitness center or outdoor gym are essential elements for overcoming the logistical barriers for prescribing and carrying out regular physical activity.
Enfortumab Vedotin-Induced Febrile Neutropenia and Hyperglycemia Successfully Treated with Multidisciplinary Treatment Including Continuous Hemodialysis Filtration and Insulin Injection in a Patient with Chemo-Resistant Metastatic Urothelial Carcinoma: A Case Report
Authors: Otsuka Ayatsugu , Sawada Norifumi , Suda Ryosuke , Yano Fumiakira , Osada Takuya , Otake Yuko , Shimura Hiroshi , Mochizuki Takanori , Harada Daiki , Goto Junko , Watanabe Tomomi , Hosokawa Tadatsugu , Kira Satoru , Tsuchiya Kyoichiro , Moriguchi Takeshi , Mitsui Takahiko
Published: August 2024

Introduction: Enfortumab vedotin (EV) is an antibody-drug conjugate combining a monoclonal antibody targeting nectin-4 with a highly potent microtubule disrupting agent. EV is expected to be a candidate for the third-line treatment for urothelial carcinoma previously treated with platinum-based chemotherapy and PD-1/PD-L1 inhibitors. Very few cases of patients experienced hyperglycemia of unknown cause. Case Presentation: We describe a 72-year-old Asian man with mild obesity, type 2 diabetes, hyperlipidemia, hypertension, and chemo-resistant metastatic urothelial carcinoma. He developed hyperglycemia and febrile neutropenia after 3 doses of EV. He had hyperglycemia of 489 mg/dL and was started on continuous intravenous insulin infusion (CVII). The patient’s intravenous insulin requirements peaked at 316 units per day. He also developed febrile neutropenia and consequent sepsis caused acute kidney injury. Continuous hemodialysis filtration (CHDF) together with antibiotics were started to treat the septic condition. The blood glucose level gradually decreased after CHDF treatment and CHDF was continued for 14 days. The timing of liberation from CHDF correlated with the elimination half-life of EV of 3.4 days. CVII was treated for 26 days and the patient was finally released from the intensive care unit. Conclusion: This case indicates that the uncontrollable hyperglycemia induced by EV during metastatic urothelial carcinoma treatment is effectively managed with CVII and CHDF until the elimination of the adverse effect of EV.
Parathyroid Hormone-Related Protein-Producing Adenocarcinoma Suspicious of Lung Cancer: A Case Report
Authors: Hirabayashi Masahiro , Koizumi Tomonobu , Nakajima Daichi , Azegami Shuko , Midorikawa Hajime , Kitagawa Nami , Hamano Hideaki , Chino Tatsunori , Ohya Maki
Published: August 2024

Introduction: Lung adenocarcinoma with parathyroid hormone (PTH)-related hypercalcemia is uncommon. Case Presentation: A 69-year-old man was admitted to our hospital due to anorexia and fatigue. Serum calcium (15.0 mg/dL) and carcinoembryonic antigen (361.7 ng/mL) were extremely high, and PTH-related protein (PTH-rP) also elevated (16.7 pmol/L). Systemic computed tomography revealed multiple enlarged lymph nodes and disseminated peritoneal nodules, with irregularly shaped nodules in the upper lobe in the left lung. Ultrasound-guided biopsy from the axillary lymph node revealed adenocarcinoma. Immunohistological staining showed the tumor cells to be positive for cytokeratin 7 and PTH-rP and negative for cytokeratin 20 and thyroid transcription factor-1. Although the primary origin remains undetermined despite detailed examinations, possible primary tumor was considered to be lung adenocarcinoma in the present case. The serum calcium level was reduced by denosumab, but the patient died 20 days after admission. Conclusion: The present case demonstrated the importance of considering oncological emergency, such as hypercalcemia and/or PTH-rP-producing hypercalcemia, in patients with adenocarcinoma.
The Effects of Atoh8 on Postnatal Murine Neurogenesis
Authors: Cuhalik Dilek , Gellisch Morris , Morosan-Puopolo Gabriela , Saberi Darius
Published: August 2024

Introduction: Basic helix-loop-helix (bHLH) transcription factors are expressed in various organs and are involved in diverse developmental processes. The mouse atonal homolog 8 (Atoh8), a bHLH transcription factor, plays a crucial role in various developmental processes, especially as a regulator of neurogenesis in the retina. Besides, Atoh8 expression has been observed in the central nervous system. The function of Atoh8 during the postnatal neurogenesis is still unclear. Methods: This study focuses on elucidating the impact of Atoh8 on postnatal neurogenesis in the brain, particularly in selected regions: the subventricular zone (SVZ), rostral migratory stream (RMS), and olfactory bulb (OB), across different life stages, using male homozygous Atoh8-knockout (M6KO) mice. Our morphometric analysis is based on immunohistochemically labeled markers for neuroblasts (doublecortin) and proliferation (phospho-histone H3, PHH3) as well as pan neuronal markers. Results: In Atoh8−/− mice, alteration in the postnatal neurogenesis can be observed. Immunohistochemical analysis revealed a significant reduction in doublecortin-positive neuroblasts within the SVZ of neonatal M6KO mice compared to wild-type mice. Interestingly, no differences in cell number and distribution were observed in the subsequent migration of neuroblasts through the RMS to the OB. Proliferating PHH3-positive neuronal progenitor cells were significantly diminished in the proliferation rate in both the SVZ and RMS of neonatal and young M6KO mice. Furthermore, in the glomerular layer of the OB, significantly fewer neurons were detected in the neonatal stage. Conclusion: In conclusion, Atoh8 emerges as a positive regulator of postnatal neurogenesis in the brain. Its role encompasses the promotion of neuroblast formation, modulation of proliferation rates, differentiation, and maintenance of mature neurons. Understanding the intricacies of Atoh8 function provides valuable insights into the complex regulatory mechanisms governing neurogenesis.
Bilateral Endogenous Bacterial Endophthalmitis with Asynchrony for 14 Months due to Klebsiella pneumoniae: A Case Report
Authors: Nuova Pedro Javier
Published: August 2024

Introduction: The aim of this study was to describe a very rare case of endogenous bacterial endophthalmitis caused by Klebsiella pneumoniae in both eyes with a difference in the onset of symptoms of 14 months in an immunocompetent patient. Case Presentation: A 66-year-old immunocompetent man presented with asynchronous bilateral endogenous endophthalmitis produced by the K. pneumoniae bacterium at the starting point of a liver abscess after cholecystectomy surgery, causing endophthalmitis 1 year and 2 months apart between an eye and another. The first was diffuse anteroposterior endophthalmitis in the left eye that ended in visual loss and phthisis bulbi due to delayed initial diagnosis and established treatment, and the second was focal endophthalmitis in the right eye that preserved the organ and resulted in a vision of 20/20 due to early suspected diagnosis and rapid instituted treatment. Conclusion: To our knowledge, this is the first published case of a long asynchronous bilateral endogenous bacterial endophthalmitis caused by K. pneumoniae with a prolonged difference of 14 months in the onset of symptoms between one eye and another. This case is a vision-threatening ophthalmologic emergency that can be associated with life-threatening systemic morbidities. The early diagnosis of infection represents a challenge for clinicians, ophthalmologists, and microbiologists.
Reconsidering Neurogenetic Indication in the Human Brain: Broad Expression of Doublecortin Transcript in the Hippocampal and Cortical Cell Populations
Authors: Cho Tae-Hyeon , Kim Miri , Kim Shin Hyung , Lee Jong Eun , Kim Se Hoon , Kim Hyun Jung , Hong Ju-Eun , Yeo In-Seung , Yang Hun-Mu
Published: August 2024

Introduction: Neurogenesis in the adult brain may play an important role in memory and cognition; however, knowledge of neurogenic markers in the human brain remains limited. We compared the single-nucleus transcriptome of the hippocampus with that of other cortical regions to identify hippocampus-specific neurogenic markers. Methods: We analyzed 26,189 nuclei from four human brains collected within 16 h of death. Clustering and annotation were performed to examine differential expression, gene ontology, and intercellular communication. DCX expression was validated by ddPCR. Results: Immature markers such as DCX, CALB2, NES, SOX2, PAX6, DPYSL3, and TUBB3 were expressed in both hippocampus and prefrontal cortex, with higher levels in the prefrontal cortex. ddPCR confirmed higher expression of DCX in the prefrontal cortex. DCX was involved in both neurogenesis and neuroprotection pathways. Conclusion: Neurogenic markers are not definitive indicators of adult neurogenesis as their roles are more complex than previously understood.
Terreiros tombados em São Paulo: laudos e reflexões sobre a patrimonialização de bens afro-brasileiros
Authors:   Universidade de São Paulo. Faculdade de Filosofia, Letras e Ciências Humanas, Silva Vagner Gonçalves da
Published: August 2024

São Paulo é o estado brasileiro que possui a maior população negra do país em números absolutos. Entretanto, por conta de um certo imaginário decorrente da migração europeia, da modernização e do suposto cosmopolitismo de suas cidades, a cultura negra local não desfruta da mesma visibilidade que possui em outros estados e cidades do nordeste, por exemplo. No território paulista, porém, essa presença negra existe e insiste. Entre essas presenças estão as comunidades religiosas afro-paulistas, imprescindíveis vetores de africanidades que há décadas vêm se mantendo contra os inúmeros fatores que desafiam sua reprodução no ambiente urbano: especulação imobiliária, ausência crescente de espaços de culto na natureza, ameaças ao espólio material religioso nos casos de falecimento das lideranças sacerdotais e o recrudescimento da intolerância e racismo religiosos. Esta obra busca apresentar as bases e estratégias de tombamento de terreiros como bens patrimoniados.