bluuebunny/crossref_metadata_2025 huggingface dataset:
Venous Thromboembolism in Metastatic Uterine Leiomyosarcoma: A Case Report and Review of the Literature
Authors: Swisher Austin R. , Ornelas Denise , Ornelas Diana , Namazi Golnaz , Theodory Bassam , Chitkara Akshit , Desai Aditya , Sethi Prabhdeep
Published: October 2023

We report an unusual case of extensive deep vein thrombosis (DVT) and pulmonary embolism (PE) in the setting of metastatic uterine leiomyosarcoma. Recognition of the associated sequelae of this condition may improve short- and long-term outcomes. A 56-year-old black female with a history of uterine leiomyosarcoma diagnosed incidentally after total abdominal hysterectomy for fibroid uterus without initiation of chemoradiation treatment presented to the emergency department complaining of generalized weakness and progressively worsening stridor for 2 weeks. The patient was experiencing shortness of breath, dysphagia, and hoarseness. Physical exam was remarkable for rhonchi but was otherwise normal. Diagnostic imaging via CT of the abdomen, pelvis, and chest revealed DVTs of the left common and external iliac veins, the superior mesenteric artery, multiple pulmonary emboli of the right pulmonary artery, several nodular lesions within the lungs, and scattered peritoneal necrotic lesions, which were suspicious for metastatic disease. Additionally, CT of the neck showed an exophytic mass protruding into the airway from the subglottic region and thyromegaly with bilateral thyroid lobe nodules. The patient was subsequently started on Eliquis and chemotherapy. The rarity of this case is rooted in the extent of the patient’s DVTs and PEs secondary to hypercoagulability in metastatic cancer. This presentation should be further evaluated to exclude thrombophilias or underlying malignancies. Drawing from the lessons of this case will help guide future clinical management regarding the care of metastatic uterine leiomyosarcoma.
Altered Putamen Activation for Social Comparison-Related Feedback in Social Anxiety Disorder: A Pilot Study
Authors: Lin Huiyan , Bruchmann Maximilian , Straube Thomas
Published: October 2023

Introduction: Social anxiety disorder (SAD) is characterized by abnormal processing of performance-related social stimuli. Previous studies have shown altered emotional experiences and activations of different sub-regions of the striatum during processing of social stimuli in patients with SAD. However, whether and to what extent social comparisons affect behavioural and neural responses to feedback stimuli in patients with SAD is unknown. Materials and Methods: To address this issue, emotional ratings and functional magnetic resonance imaging (fMRI) responses were assessed while patients suffering from SAD and healthy controls (HC) were required to perform a choice task and received performance feedback (correct, incorrect, non-informative) that varied in relation to the performance of fictitious other participants (a few, half, or most of others had the same outcome). Results: Across all performance feedback conditions, fMRI analyses revealed reduced activations in bilateral putamen when feedback was assumed to be received by only a few compared to half of the other participants in patients with SAD. Nevertheless, analysis of rating data showed a similar modulation of valence and arousal ratings in patients with SAD and HC depending on social comparison-related feedback. Conclusions: This suggests altered neural processing of performance feedback depending on social comparisons in patients with SAD.
The Effects of Pifithrin-µ on Spermatogonial Stem Cell Viability and Pluripotency
Authors: Moghadasi Sara , Razeghian Ehsan , Shamsara Mehdi , Heidari Farid
Published: October 2023

Introduction: Spermatogonial stem cells (SSCs) offer remarkable competencies for animal reproduction and overcoming human disease as a result of their differentiation capability. We evaluated the effect of small molecule pifithrin-mu (PFT-µ), a well-known inhibitor of P53 on SSC biological processes such as viability, apoptosis, and gene expression pattern. Methods: The SSCs were isolated from the testes of adult NMRI mice and then cultured in DMEM/F12 medium containing 10% FBS. Then, they were characterized by the immunocytochemistry technique by high PLZF and low c-Kit expressions. SSC colony formation assay was carried out and their viability was estimated by methylthiazolyldiphenyl-tetrazolium bromide (MTT, or 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide) assay upon exposure to PFT-µ (0, 0.6, 1.2, 2.5, and 5 µm). The apoptosis percentages were also measured using FACS analysis, and finally, Oct4 and Stra8 expression at mRNA levels was assessed using real-time quantitative PCR. Results: The 0.6 and 1.2 µm PFT-µ improved the viability of SSC based on MTT assay results; however, 2.5 and 5 µm PFT-µ reduced SSC viability compared with the control group. Moreover, PFT-µ at lower concentrations enhanced the colony size of SSCs and diminished their apoptosis. As well, exposure to PFT-µ upregulated Oct4 expression while downregulating the meiotic entry marker, Stra8. Conclusion: Based on findings, optimized concentrations of PFT-µ can decrease SSC apoptosis, and conversely potentiate their pluripotency and self-renewal capacities in vitro.
Seroprevalence of Enterovirus D68 Infection among Humans: A Systematic Review and Meta-Analysis
Authors: Shi Yingying , Ran Qinqin , Wang Xiaochen , Shi Lu
Published: October 2023

Introduction: Human enterovirus D68 (EV-D68), which belongs to enteroviruses of the small RNA family, is a type of enterovirus that can cause acute respiratory tract infection and central nervous system diseases. This study systematically analysed and summarized EV-D68 antibody studies in databases and identified the seropositivity rates of different regions, ages, and sexes. Methods: Meta-analysis was performed using STATA 16.0 software. I2 and Q tests were used to analyse the heterogeneity of the included studies. Meta-regression analysis was performed for different groups, and Egger’s linear regression analysis was used to evaluate publication bias. Results: The results of multiple studies indicated that the serological prevalence range of EV-D68 antibody was 17.78–96.69%. The results of the meta-analysis showed that the seropositivity rate of EV-D68 antibody was 76% (95% confidence interval [CI]: 67–84%), among which that of the Chinese population was 74% (95% CI: 61–86%) and that of other countries was 79% (95% CI: 65–91%). At the same time, a subgroup analysis was conducted. The seroprevalence of EV-D68 antibody was related to age but not sex or region. Conclusion: The seropositivity rate was lower in the below 5-year age group; however, it gradually increased with age. The results of this study showed that EV-D68 infection was widespread in the population, and the current clinical infection situation could not reflect the actual epidemic situation of the virus, among which children under 5 years old were vulnerable to infection, which should be given greater attention for epidemic prevention and control.
Donor Evaluation of Living Kidney Transplantation in the Aging Society
Authors: Nishi Shinichi , Goto Shunsuke
Published: October 2023

Background: Because of the lack of organ donation, living kidney transplantation (LKT) is increasing worldwide. Recently, the number of elderly donors has been increasing, and the patients with end-stage kidney diseases are older than those in the previous decades. Due to the advanced ages, their glomerular filtration rates (GFR) decrease, and the comorbidities such as hypertension, diabetic condition, and obesity are common. The clinicians now have to give their unwilling consent to the LKT from the donors with expanded criteria. Summary: For the secure selection of donors, proper GFR measuring is essential. Although directly measured GFR (mGFR) was recommended in the guidelines, estimated GFR (eGFR) is used at the initial evaluation of donor renal function clinically. Many equations calculating eGFR have been published so far. In the selection of eGFR equations, the smaller difference between mGFR and eGFR and the closer relationship to the prevalence rates of comorbidities are requisite points. Therefore, we compared the specificity of the various eGFR equations. The eGFR calculated from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation showed approximate reliability with minimal difference between mGFR and eGFR and the closer relationships to the prevalence rates of comorbidities. Key Message: The CKD-EPI-eGFR presented optimal performance in the donor renal function evaluation. Therefore, eGFR from the CKD-EPI equation is highly recommended in evaluating renal function in LKT donors.
Effect of Lipid Levels on Tumor-Infiltrating Lymphocytes and Prognosis in Patients with Triple-Negative Breast Cancer
Authors: AiErken NiJiati , Shao Nan , Liu Yuhong , Shi Huijuan , Shi Yawei , Yuan Zhongyu , Lin Ying
Published: October 2023

Objective: Dyslipidemia can promote cell proliferation, malignant transformation, metastasis, and cancer recurrence. Moreover, it could also affect immune infiltration in the tumor microenvironment. Therefore, we aimed to explore the effects of lipid levels on tumor-infiltrating lymphocytes (TILs) and prognosis in patients with triple-negative breast cancer (TNBC). Methods: Samples from 222 patients with TNBC from July 2007 to December 2019 were obtained from the tissue specimen banks in 3 hospitals. The blood samples were used to detect the levels of lipid levels such as apolipoprotein B (Apo B), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C). The TILs in the 222 TNBC tissues were detected using hematoxylin and eosin (H&E) staining, and the relationship between the lipid levels, clinical characteristics, and prognosis was analyzed. Results: Among TNBC patients, the overall survival (OS) time and disease-free survival (DFS) time were lower in patients with high LDL-C levels than those with low LDL-C levels (p < 0.01, respectively). The DFS was shorter in patients with low stromal TIL (STIL) levels than those with moderate or high STIL levels (p = 0.023). Multifactor Cox regression analysis showed that LDL-C level, Apo B level, and lymphocyte-predominant breast cancer were independent risk factors for OS in TNBC patients. The number of positive lymph nodes, postoperative staging, and total amount of TILs were independent risk factors for DFS in TNBC patients. Conclusion: The LDL-C and STIL levels were correlated with survival and prognosis in patients with TNBC.
Hemolytic Uremic Syndrome-Induced Acute Kidney Injury Treated via Immunomodulation with the Selective Cytopheretic Device
Authors: Hambrick H. Rhodes , Short Kara , Askenazi David , Krallman Kelli , Pino Christopher , Yessayan Lenar , Westover Angela , Humes H. David , Goldstein Stuart L.
Published: October 2023

Introduction: Shiga-toxin associated-hemolytic uremic syndrome (STEC-HUS) is a severe cause of acute kidney injury (AKI) in children. Although most children recover, about 5% die and 30% develop chronic renal morbidity. HUS pathophysiology includes activated neutrophils damaging vascular endothelial cells. Therapeutic immunomodulation of activated neutrophils may alter the progression of disease. We present 3 pediatric patients treated with the selective cytopheretic device (SCD). Methods: We describe a 12 y.o. (patient 1) and two 2 y.o. twins (patients 2 and 3) with STEC-HUS requiring continuous renal replacement therapy (CRRT) who were enrolled in two separate studies of the SCD. Results: Patient 1 presented with STEC-HUS causing AKI and multisystem organ failure and received 7 days of SCD and CRRT treatment. After SCD initiation, the patient had gradual recovery of multi-organ dysfunction, with normal kidney and hematologic parameters at 60-day follow-up. Patients 2 and 3 presented with STEC-HUS with AKI requiring dialysis. Each received 24 h of SCD therapy. Thereafter, both gradually improved, with normalization (patient 2) and near-normalization (patient 3) of kidney function at 60-day follow-up. Conclusion: Immunomodulatory treatment with the SCD was associated with improvements in multisystem stigmata of STEC-HUS-induced AKI and was well-tolerated without any device-related adverse events.
A Rare Case of Pulmonary Adenocarcinoma in an 8-Year-Old Patient with Persistent Respiratory Manifestation: A Case Report Study
Authors: Shahkar Lobat , Bigdeli Noora , Mazandarani Mahdi , Lashkarbolouk Narges
Published: October 2023

Pulmonary adenocarcinoma is an extremely infrequent cancer in children. This cancer usually presents with unspecific manifestations that lead to delays in diagnosis. The treatment protocol for adenocarcinoma in children remains challenging due to its rarity. We presented an 8 years old with a chief complaint of a non-purulent cough, dyspnea, hemoptysis, and weight loss. Decreased lung sounds and wheezing in the left lung were heard during auscultation. The radiographic evaluation showed a mediastinal mass in the left middle upper. A biopsy was performed, and adenocarcinoma was reported. Based on being at stage 1, a lobectomy was the proper treatment for her. Although adenocarcinoma is rare in pediatrics, we suggested that physicians consider taking chest X-rays in patients with persistent respiratory manifestations, especially those with critical symptoms. Early detection leads to diagnosing patients in lower stages, which results in a good prognosis and better treatment outcomes.
Plunging Ranula Presenting as a Giant Anterior Cervical Cystic Mass: A Case Report and Literature Review
Authors: Jing Fangqi , Wu Fanglong , Wen Yuming , Gao Qinghong
Published: October 2023

Plunging ranula, a subtype of ranula, commonly presents as a submandibular or submental cystic mass without oral counterpart, and its clinical management remains challenging. Herein, the authors report an extremely rare case of 30-year-old female patient with plunging ranula involving the root of the left anterior neck.
The Ongoing Necessity of Sentinel Lymph Node Biopsy for cT1–2N0 Breast Cancer Patients
Authors: Jia Wenjun , Chen Xiao , Wang Xinyu , Zhang Jianzhong , Tang Tong , Shi Jianing
Published: October 2023

Background: Recent clinical trials attempt to determine whether it is appropriate to omit axillary lymph node surgery in patients with cT1–2N0 breast cancer. The study aimed to investigate the true extent of axillary node disease in patients with clinically negative nodes and explore the differences between negative axillary ultrasound (AUS-cN0) and suspicious axillary ultrasound with negative fine-needle aspiration (FNA-cN0). Methods: Pathologically identified T1–2 invasive breast cancer patients with clinically negative nodes were retrospectively analyzed at our center between January 2019 and December 2022. Patients who received any systematic treatment before surgery were excluded from this study. Results: A total of 538 patients were enrolled in this study. 134 (24.9%) patients had pathologically positive nodes, and 404 (75.1%) patients had negative nodes. Univariate analysis revealed that tumor size, T stage, Ki67 level, and vascular invasion (VI) were strongly associated with pathological axillary lymph node positivity. In multivariate analysis, VI was the only independent risk factor for node positivity in patients with cT1–2N0 disease (OR: 3.723, confidence interval [CI]: 2.380–5.824, p < 0.001). Otherwise, pathological node positivity was not significantly different between AUS-cN0 and FNA-cN0 groups (23.4% vs. 28.8%, p = 0.193). However, the rate of high nodal burden (≥3 positive nodes) was significantly higher in FNA-cN0 group. Further investigation revealed that FNA-cN0 and VI were independently associated with a high nodal burden (OR: 2.650, CI: 1.081–6.496, p = 0.033; OR: 3.521, CI: 1.249–9.931, p = 0.017, respectively). Conclusions: cT1–2 breast cancer patients with clinically negative axillary lymph nodes may have pathologically positive lymph nodes and even a high nodal burden. False negatives in AUS and AUS-guided FNA should not be ignored, and sentinel lymph node biopsy remains an ongoing necessity for cT1–2N0 breast cancer patients.
Pulmonary Spindle Cell Carcinoma Presenting Anaplastic Lymphoma Kinase Rearrangement
Authors: Sonehara Kei , Nozawa Shuhei , Suzuki Yusuke , Araki Taisuke , Komatsu Masamichi , Tateishi Kazunari , Hanaoka Masayuki
Published: October 2023

Pulmonary spindle cell carcinoma is a subtype of pulmonary sarcomatoid carcinoma and a very rare tumor type with a poor prognosis. A few case reports have documented patients with pulmonary sarcomatoid carcinoma with anaplastic lymphoma kinase rearrangement, and the efficacy and outcomes of anaplastic lymphoma kinase inhibitors remain unclear. Herein, we present the case of a 60-year-old woman with stage IVB disease who was diagnosed with a metastatic brain tumor. This patient showed high levels of programmed cell death ligand 1 expression and anaplastic lymphoma kinase rearrangement and received pembrolizumab as the first-line treatment. Three weeks later, pembrolizumab failed to reduce the size of the primary pulmonary tumor, and the patient’s general condition did not improve. The patient received alectinib as the second-line treatment. Two months later, multiple brain metastases were observed. Hence, whole-brain irradiation was performed as treatment for multiple brain metastases, while another anaplastic lymphoma kinase inhibitor was administered; however, both treatments remained ineffective. The patient eventually died 9 months after the initiation of first-line treatment. The present case report describes the therapeutic course of a patient with pulmonary spindle cell carcinoma with an anaplastic lymphoma kinase rearrangement.
The Role of Specificity Protein 1 (SP1) in Bladder Cancer Progression through PTEN-Mediated AKT/mTOR Pathway
Authors: Chen Zhiqiang
Published: October 2023

Introduction: The aim of the study was to investigate the potential mechanism of specificity protein 1 (SP1) in bladder cancer progression through the PTEN-mediated AKT/mTOR pathway. Methods: Human bladder cancer cell lines (HT-1197, HT-1376, and T24) and normal ureteral epithelial cell line SV-HUC-1 were used. SP1 expression was detected via quantitative real-time PCR and Western blotting. Cell viability, migration, invasion, and apoptosis were assessed using CCK-8, transwell, and flow cytometry assays, respectively. The involvement of the PTEN-mediated AKT/mTOR pathway was evaluated by Western blot. A mouse xenograft model was built, and immunohistochemical staining was applied to visualize SP1 and Ki67 expression in tumor tissues. Results: SP1 was overexpressed in bladder cancer cells. SP1 knockdown inhibited viability, migration, and invasion and promoted apoptosis in bladder cancer cells. PTEN intervention increased cell viability, migration, and invasion and decreased apoptosis, which was reversed by SP1 knockdown. The activation of the AKT/mTOR pathway resulting from PTEN knockdown was attenuated by SP1 knockdown. In vivo results showed that SP1 knockdown suppressed tumor growth, increased PTEN expression, and decreased AKT/mTOR pathway-related protein levels. Conclusion: SP1 promotes bladder cancer progression by inhibiting the PTEN-mediated AKT/mTOR pathway. Targeting SP1 may be a potential therapeutic strategy for treating bladder cancer.
Proposal of the Second Cutoff of Serum Carcinoembryonic Antigen Levels to Stratify Patients into Low, Intermediate, and High Risks at Recurrences after Curative Resection of Gastric Cancer
Authors: Sato Bin , Kanda Mitsuro , Ito Seiji , Mochizuki Yoshinari , Teramoto Hitoshi , Ishigure Kiyoshi , Murai Toshifumi , Asada Takahiro , Ishiyama Akiharu , Matsushita Hidenobu , Nakanishi Koki , Shimizu Dai , Tanaka Chie , Fujiwara Michitaka , Murotani Kenta , Kodera Yasuhiro
Published: October 2023

Introduction: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 are widely used for treating various cancers, with cutoff values of 5.0 ng/mL and 37.0 IU/mL, respectively. However, these cutoff values are not for specific diseases or purposes but are uniformly used for any disease and any purpose. It is also unclear as to whether patients are at equal risk of recurrence if they are below the cutoff values. This study aimed to investigate the optimal cutoff of serum tumor markers in the stratification of recurrence risk after curative resection of gastric cancer. Methods: We constructed a nine-center integrated database of patients who received gastrectomy between January 2010 and December 2014 with a 5-year follow-up period. We determined the cutoff value of preoperative serum tumor marker levels correlated with postoperative recurrences and evaluated its performance in risk stratification for recurrences in 948 patients with stage II/III gastric cancer who underwent radical resection. Results: The hazard ratio for postoperative recurrences increased at two points of preoperative CEA levels, 3.6 ng/mL and 5.0 ng/mL, which were set as cutoffs. These two cutoffs stratified relapse-free survival into three levels. Conclusions: By adding a second cutoff value for preoperative serum CEA, which was proposed specifically for the prediction of recurrences, patients can be stratified into low-, intermediate-, and high-risk recurrences after curative resection of gastric cancer.
Validation of an Automated Speech Analysis of Cognitive Tasks within a Semiautomated Phone Assessment
Authors: ter Huurne Daphne , Possemis Nina , Banning Leonie , Gruters Angélique , König Alexandra , Linz Nicklas , Tröger Johannes , Langel Kai , Verhey Frans , de Vugt Marjolein , Ramakers Inez
Published: October 2023

Introduction: We studied the accuracy of the automatic speech recognition (ASR) software by comparing ASR scores with manual scores from a verbal learning test (VLT) and a semantic verbal fluency (SVF) task in a semiautomated phone assessment in a memory clinic population. Furthermore, we examined the differentiating value of these tests between participants with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). We also investigated whether the automatically calculated speech and linguistic features had an additional value compared to the commonly used total scores in a semiautomated phone assessment. Methods: We included 94 participants from the memory clinic of the Maastricht University Medical Center+ (SCD N = 56 and MCI N = 38). The test leader guided the participant through a semiautomated phone assessment. The VLT and SVF were audio recorded and processed via a mobile application. The recall count and speech and linguistic features were automatically extracted. The diagnostic groups were classified by training machine learning classifiers to differentiate SCD and MCI participants. Results: The intraclass correlation for inter-rater reliability between the manual and the ASR total word count was 0.89 (95% CI 0.09–0.97) for the VLT immediate recall, 0.94 (95% CI 0.68–0.98) for the VLT delayed recall, and 0.93 (95% CI 0.56–0.97) for the SVF. The full model including the total word count and speech and linguistic features had an area under the curve of 0.81 and 0.77 for the VLT immediate and delayed recall, respectively, and 0.61 for the SVF. Conclusion: There was a high agreement between the ASR and manual scores, keeping the broad confidence intervals in mind. The phone-based VLT was able to differentiate between SCD and MCI and can have opportunities for clinical trial screening.
Life’s Essential 8 and Mortality in US Adults with Chronic Kidney Disease
Authors: Chen Hongyu , Tang Haoxian , Huang Jingtao , Luo Nan , Zhang Xuan , Wang Xin
Published: October 2023

Introduction: The current prevalence of chronic kidney disease (CKD) is substantial, and CKD individuals face a heightened risk of mortality, encompassing both all-cause and cause-specific outcomes. The current study aims to investigate the potential impact of adhering to Life’s Essential 8 (LE8) on reducing mortality among CKD individuals. Methods: Using the National Health and Nutrition Survey (NHANES) data from 2005 to 2018, we analyzed 22,420 US adults (≥20 years old). CKD is defined by urinary albumin-to-creatinine ratio (≥30 mg/g or 3 mg/mmol) and estimated glomerular filtration rate (<60 mL/min/1.73 m2). The components of LE8, including diet, physical activity (PA), nicotine exposure, sleep, body mass index, blood lipids, blood glucose, and blood pressure (BP), were measured and given a score of 0–100. The total LE8 score was the unweighted average of all components and was divided into low cardiovascular health (CVH) (0–49), moderate CVH (50–79), and high CVH (80–100). A Cox proportional hazards regression model was used to explore the associations of LE8 with all-cause, cardiovascular disease (CVD), and cancer mortality, which were followed prospectively by the National Center for Health Statistics until December 31, 2019. Results: In the overall population, individuals with moderate CVH had a 47% lower risk of CKD, while high CVH was linked to a 55% lower risk compared to low CVH. During a median follow-up of 7.58 years, CKD individuals had a 93% higher all-cause mortality rate and a 149% higher CVD mortality rate compared to those without CKD. Among the CKD individuals, every 10-point increase in the LE8 score was associated with reduced risks of 17% for all-cause mortality (especially PA, nicotine exposure, blood glucose, and BP), 18% for CVD mortality (especially PA), and 12% for cancer mortality (especially PA and sleep health). In additional and sensitivity analysis, the results remained significant after further consideration of potential confounding of renal function. Additionally, LE8 demonstrated superior risk stratification for CVD mortality among CKD patients compared with LS7. Interaction was observed between LE8 and age, education level, marital status, and drinking status. Conclusion: The current study demonstrates that adherence to higher LE8 levels within CKD individuals is associated with a reduced risk of both all-cause and cause-specific mortality.
Synthetic Inversion Image Generation using MP2RAGE T1 Mapping for Surgical Targeting in Deep Brain Stimulation and Lesioning
Authors: Middlebrooks Erik H. , Tao Shengzhen , Zhou Xiangzhi , Greco Elena , Westerhold Erin M. , Tipton Philip W. , Quinones-Hinojosa Alfredo , Grewal Sanjeet S. , Patel Vishal
Published: October 2023

Background: Advances in MRI technology have increased interest in direct targeting for deep brain stimulation (DBS). Various imaging sequences have been shown to provide increased contrast of numerous common DBS targets, such as T1-weighted, Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR), gray matter nulled, and Edge-Enhancing Gradient Echo (EDGE); however, the continual increase in the number of necessary sequences has led to an increase in imaging time, which is undesirable. Additionally, carefully timed inversion pulses can often lead to less-than-ideal contrast in some subjects, particularly in ultra-high field MRI, where B1+ field inhomogeneity can lead to substantial contrast variation. Objectives: This study proposes using 3D MP2RAGE-based T1 maps to retrospectively synthesize images of any desired inversion time, including T1-weighted, FGATIR, and EDGE contrasts, to visualize specific DBS targets at both 3T and 7T. Method: First, a systematic sequence optimization framework was applied to optimize MP2RAGE T1 mapping sequence parameters for the purpose of DBS planning. Next, we show that synthetic inversion-time images can be generated through a mathematical transformation of the T1 maps. The sequence was then applied to patients undergoing preoperative planning for DBS at 3T and 7T to generate synthetic contrasts used in surgical planning. Results: We show that synthetic image contrasts can be generated across a full range of inversion times at 3T and 7T, including commonly used sequences for DBS targeting, such as T1-weighted, FGATIR, and EDGE. Acquisition through a single sequence shortens scan time compared to acquiring the sequences independently without affecting image quality or contrast. Conclusions: The generation of synthetic images for DBS targeting allows faster acquisition of many key sequences, as well as the ability to optimize contrast properties post-acquisition to account for the variable B1+ effects present in ultra-high field MRI. The proposed approach has the potential to reduce imaging time and improve the accuracy of DBS targeting at 1.5T, 3T, and 7T.
Standardization of Nomenclature for the Mechanisms and Materials Utilized for Extracorporeal Blood Purification
Authors: Reis Thiago , Ronco Claudio , Soranno Danielle E. , Clark William , De Rosa Silvia , Forni Lui G. , Lorenzin Anna , Ricci Zaccaria , Villa Gianluca , Kellum John A. , Mehta Ravindra , Rosner Mitchell H. ,   on behalf of the Nomenclature Standardization Faculty
Published: October 2023

In order to develop a standardized nomenclature for the mechanisms and materials utilized during extracorporeal blood purification, a consensus expert conference was convened in November 2022. Standardized nomenclature serves as a common language for reporting research findings, new device development, and education. It is also critically important to support patient safety, allow comparisons between techniques, materials, and devices, and be essential for defining and naming innovative technologies and classifying devices for regulatory approval. The multidisciplinary conference developed detailed descriptions of the performance characteristics of devices (membranes, filters, and sorbents), solute and fluid transport mechanisms, flow parameters, and methods of treatment evaluation. In addition, nomenclature for adsorptive blood purification techniques was proposed. This report summarizes these activities and highlights the need for standardization of nomenclature in the future to harmonize research, education, and innovation in extracorporeal blood purification therapies.
Pathological Interplay and Clinical Complications between COVID-19 and Cardiovascular Diseases: An Overview in 2023
Authors: Zhou Sufeng , Zhang Anchen , Liao Hua , Liu Zhebo , Yang Feiyan
Published: October 2023

Background: The coronavirus disease 2019 (COVID-19) involves all organs of the body, of which the interaction with cardiovascular diseases is the most important. Summary: Numerous studies have reported that COVID-19 patients complicated with cardiovascular comorbidities (hypertension, coronary heart disease, chronic heart failure (HF), cerebrovascular disease) are more likely to develop into critical illness and have higher mortality. Conversely, COVID-19 may also cause myocardial injury in patients through various pathological mechanisms such as direct virus attack on cardiomyocytes, overactivation of immune response, microthrombus formation, which may lead to fatal acute ST-segment elevation myocardial infarction, arrhythmia, acute worsening of chronic HF, etc. In addition, the symptoms of the so-called long-COVID may remain in some patients who survived the acute viral infection. Positional tachycardia has been widely reported, and cardiovascular autonomic disorders are thought to play a pathogenic role. Key Message: The review summarizes the interaction between COVID-19 and cardiovascular disease in terms of pathological mechanism, clinical features, and sequelae. Therapeutic and rehabilitation programs after COVID-19 infection are compiled and need to be further standardized in the future.
Recurrence of Large-Vessel Vasculitis Induced by Multiple Types of Granulocyte Colony-Stimulating Factor Preparation in Patient with Large-Cell Neuroendocrine Lung Carcinoma: A Case Report
Authors: Seto Yurie , Yamada Tadaaki , Egami Masashi , Sugimoto Takumi , Sato Izumi , Tanaka Satomi , Chihara Yusuke , Morimoto Kenji , Iwasaku Masahiro , Tokuda Shinsaku , Kaneko Yoshiko , Takayama Koichi
Published: October 2023

With the increased use of granulocyte colony-stimulating factor (G-CSF) preparations, there is concern about the increase in G-CSF-associated large-vessel vasculitis; however, there have been no previous reports of vasculitis caused by multiple types of G-CSF preparations. We experienced a case of drug-induced large-vessel vasculitis caused by two different G-CSF products, which was difficult to diagnose. When treating patients with a history of large-vessel vasculitis caused by pegfilgrastim, we need to pay attention to its recurrence when using other G-CSF preparations.
A Chromosome 9p24.1 Amplification in Colorectal Cancer with Metastases to the Kidney and Adrenal Gland: A Case Report
Authors: Paric Ana , Karan-Krizanac Dragana , Saric Ivan , Vranic Semir
Published: October 2023

Colorectal cancer (CRC) is the third leading cause of mortality worldwide. The Food and Drug Administration recently designated pembrolizumab, an immune checkpoint inhibitor (ICI) against a programmed death-1 receptor, as a breakthrough drug for the treatment of patients with mCRC whose tumors have deficient mismatch-repair gene expression (as evidenced by microsatellite instability-high) and patients with solid tumors with a high tumor mutational burden with ≥10 mutations/megabase. We present a patient with metastatic CRC having renal and adrenal gland metastases. Comprehensive molecular profiling performed on a site of metastatic CRC in the kidney revealed multiple genomic alterations characteristic of CRC and rare chromosome 9p24.1 amplification, resulting in a co-amplification of the PDL1, PDL2, and JAK2 genes. Although this genomic alteration may predict the response to ICI, the lack of pembrolizumab prevented the patient from receiving targeted treatment and succumbing to the disease.
Atypical Presentation of Spitz Nevus: A Case Report
Authors: Araiza-Atanacio Isabel , Venegas-Andrade Andrea , Toussaint-Caire Sonia , Palacios López Carolina
Published: October 2023

Introduction: The Spitz nevus (SN) is an acquired melanocytic neoplasm composed of epithelioid and/or spindle cells, which tends to develop in childhood. In pediatric patients, it is usually located on the face and neck. Unusual locations have been found in the literature, such as the penis, mouth, and tongue, as well as 2 cases of ungual SN. Case Report: A 15-year-old male evaluated for dark brown-black longitudinal melanonychia that covered 40% of the nail, with pseudo-Hutchinson’s sign, of 1 year of evolution. Discussion: The SN accounts for 1% of the melanocytic neoplasms. In the present paper, we show the third case of ungual SN never previously disclosed, which presents a zigzag pattern reported in the literature for its association with the pediatric population.
Concurrent Cobalamin C and Plasminogen Deficiencies in a Patient with Chronic Thrombotic Microangiopathy
Authors: Dirim Ahmet Burak , Safak Seda , Balci Mehmet Cihan , Ozyavuz Pelin , Garayeva Nurane , Tiryaki Tarik Onur , Oto Ozgur Akin , Ozluk Yasemin , Kilicaslan Isin , Solakoglu Seyhun , Artan Ayse Serra , Yazici Halil , Turkmen Aydin , Ozturk Savas
Published: October 2023

Background: Although most patients with atypical hemolytic uremic syndrome (aHUS) have variants in genes participating in alternative complement pathways, rare variants in non-complement pathway-related genes, including DGKE, INF2, MMACHC, PLG, and THBD, have also been described. Case Presentation: We report an 18-year-old male patient with renal biopsy-proven chronic thrombotic microangiopathy that raised suspicion of aHUS. Whole-exome sequencing revealed a novel pathogenic homozygous MMACHC c.484G>T (p.Gly162Trp) variant. Subsequently, clinical and laboratory findings confirmed cobalamin C (Cbl C) deficiency. Also, homozygous missense c.1112C>T PLG (p.Thr371Ile) variant was detected (it had been reported as a variant of unknown significance). However, the low serum plasminogen (PLG) activity proved the pathogenicity of c.1112C>T. Hence, the patient was diagnosed with concurrent Cbl C and PLG deficiencies. Segregation analysis revealed that the mother and father had the same heterozygous PLG and MMACHC variants. PLG variants have generally been described in aHUS patients concomitant with complement gene variants in the literature; therefore, the association between aHUS and PLG variants is controversial. The possible contribution of PLG deficiency to thrombotic microangiopathy was also discussed in this case. Conclusion: Non-complement-mediated aHUS is an exceptional disorder. A limited number of genes are involved in this entity. To our knowledge, this is the first aHUS patient diagnosed with both Cbl C and PLG deficiencies in the literature.
Survival Outcome Analysis of Stereotactic Body Radiotherapy and Immunotherapy (SBRT-IO) versus SBRT-Alone in Unresectable Hepatocellular Carcinoma
Authors: Chiang Chi Leung , Lee Francis Ann Shing , Chan Kenneth Sik Kwan , Lee Venus Wan Yan , Chiu Keith Wan Hang , Ho Ryan Lok Man , Fong John Ka Shun , Wong Natalie Sean Man , Yip Winnie Wing Ling , Yeung Cynthia Sin Yu , Lau Vince Wing Hang , Man Kwan , Kong Feng-Ming Spring , Chan Albert Chi Yan
Published: October 2023

Introduction: While combination of stereotactic body radiotherapy (SBRT) and immunotherapy are promising, their efficacy and safety have not been compared with SBRT-alone in patients with unresectable hepatocellular carcinoma (HCC). Methods: This retrospective study included 100 patients with nonmetastatic, unresectable HCC in two hospitals. Eligible patients had tumor nodules ≤3 and Child-Pugh liver function score of A5 to B7. Seventy patients received SBRT-alone, and 30 patients underwent combined SBRT and immunotherapy (SBRT-IO). Overall survival (OS), time to progression (TTP), overall response rate (ORR), and toxicity were analyzed. We adjusted for the potential confounding factors using propensity score matching. Results: The median tumor size was 7.3 cm (range, 2.6–18 cm). Twenty-five (25%) of patients had vascular invasion. Before propensity score matching, the 1-year and 3-year OS rate was 89.9% and 59.8% in the SBRT-IO group and 75.7% and 42.3% in SBRT-alone group (p = 0.039). After propensity score matching (1:2), 25 and 50 patients were selected from the SBRT-IO and SBRT-alone group. The 1-year and 3-year OS was 92.0% and 63.9% in the SBRT-IO group versus 74.0% and 43.3% in the SBRT-alone group (p = 0.034). The 1-year and 3-year TTP was better in SBRT-IO group (1-year: 68.9% vs. 58.9% and 3-year: 61.3% vs. 32.5%, p = 0.057). The ORR of 88% (complete response [CR]: 56%, partial response [PR]: 22%) in SBRT-IO arm was significantly better than 50% (CR: 20%, PR: 30%) in the SBRT-alone arm (p = 0.006). Three patients (12%) developed ≥grade 3 immune-related treatment adverse events (n = 2 hepatitis, n = 1 dermatitis) leading to permanent treatment discontinuation. Conclusion: Adding immunotherapy to SBRT resulted in better survival with manageable toxicities. Prospective randomized trial is warranted.
A Case of Pneumothorax Required Surgical Treatment as a Complication of Paclitaxel with Bevacizumab Treatment
Authors: Moriya Yumi , Oshino Tomohiro , Hosoda Mitsuchika , Shikishima Karin , Miura Shun , Muto Jun , Kato Tatsuya , Takahashi Masato
Published: October 2023

A 63-year-old woman had a history of neoadjuvant chemotherapy, mastectomy, and adjuvant endocrine therapy for 5 years before being diagnosed with recurrent lesions involving the right anterior chest wall, multiple lymph nodes, and pulmonary metastases. The patient was subsequently initiated on a paclitaxel and bevacizumab regimen. During this treatment, the patient complained of palpitations and malaise. Chest radiography revealed a left pneumothorax. Despite attempts at conservative treatment, the pneumothorax did not improve and a thoracoscopic approach was required. One of the metastatic tumors in the left lower lobe appeared to rupture, and this area was estimated to be the cause of air leak. The tumor was covered with a tissue seal sheet, and the patient’s condition improved with no recurrence of pneumothorax. This case highlights the importance of early conversion to surgical treatment when conservative treatment for pneumothorax is unresponsive due to the potential side effects of bevacizumab. The findings of this case report may be of interest to oncologists, pulmonologists, and other healthcare professionals involved in the care of patients with breast cancer and pulmonary metastases who are undergoing bevacizumab chemotherapy.
First Female Patient with a Rare CIC-FOXO4-Translocated Sarcoma: A Case Report
Authors: Babkoff Aryeh , Berner-Wygoda Yael , Diment Judith , Kustanovich Anatoli , Zick Aviad , Katz Daniela , Grinshpun Albert
Published: October 2023

Small round cell sarcoma is a group of undifferentiated malignancies arising in the bone and soft tissue, notable for Ewing sarcoma. Recently, a new World Health Organization classification has been introduced, including an additional subset of these sarcomas, named CIC-rearranged sarcoma. Within this group, CIC-FOXO4 translocation is an exceedingly rare fusion that has been reported only 4 times in the literature. Herein, we report in-depth the pathological, clinical, and molecular features of a CIC-FOXO4 translocation-driven tumor in a 46-year-old woman.
An Asymptomatic Patient with Colonic Leiomyoma
Authors: Alkhowaiter Saad , Alsheikh Abdulmalik , Alotaibi Ammar
Published: October 2023

Subepithelial lesions (SELs) originating from muscularis mucosae of the colon are very rare findings on endoscopy. Appropriate management of SELs involves making a correct diagnosis and estimating their malignant potential. In this case study, a 58-year-old Saudi man presented with a small, 8-mm sigmoid polyp during screening colonoscopy. The polyp was removed by hot snare polypectomy and sent to pathology laboratory. Report showed an unremarkable colonic mucosa and underlying well-circumscribed submucosal lesion composed of monotonous spindle cells. Immunohistochemical (IHC) analysis ruled out CD117-/DOG1-positive GIST and confirmed the lesion as leiomyomatous polyp. Colonic leiomyomas are usually benign and often asymptomatic and discovered during CRC screening procedures. Diagnosis is made on histology/IHC analysis since endoscopically they might be indistinguishable from other SELs. Conventional polypectomy is an appropriate treatment for small colonic leiomyoma and these benign lesions typically do not recur.
Catheter-Related Bloodstream Infection in Hemodialysis Patient due to Atlantibacter hermannii
Authors: Hristova Preslava M. , Alexandrova Alexandra S. , Lukanov Martin , Hitkova Hristina Y. , Borisov Biser Kirilov
Published: October 2023

Atlantibacter hermannii, previously known as Escherichia hermannii, is a rare causative agent of human infections. Several reports testify that the most frequently infected patients are immunosuppressed, especially those undergoing hemodialysis. A 34-year-old man with an end-stage renal disease complained of chills, fever, and general fatigue at the end of a regular hemodialysis session. The echocardiographic examination showed vegetation located on the dialysis catheter in the right atrium. Empirical therapy was initiated with intravenous gentamicin, and after the isolation of the agent, the treatment was continued with intravenous imipenem/cilastatin. The blood cultures and the tip of the replaced catheter were positive for A. hermannii, identified by Vitek 2 Compact. Verification of the automated identification was performed using 16S sequencing. The 16S sequence product was used to query the NCBI bacterial database and revealed 99.75% identity to that of A. hermannii strain CIP 103176 16S ribosomal RNA in the NCBI GenBank database. The antimicrobial susceptibility results revealed resistance to aminopenicillins and susceptibility to all other tested antimicrobials. To our knowledge, this is the first report of catheter-related vegetation with echocardiographic confirmation and the successful eradication of A. hermannii infection in a patient undergoing hemodialysis with imipenem/cilastatin.
Mitochondrial Damage-Associated Molecular Patterns and Metabolism in the Regulation of Innate Immunity
Authors: Lyu Yanmin , Wang Tianyu , Huang Shuhong , Zhang Zhaoqiang
Published: October 2023

The innate immune system, as the host’s first line of defense against intruders, plays a critical role in recognizing, identifying, and reacting to a wide range of microbial intruders. There is increasing evidence that mitochondrial stress is a major initiator of innate immune responses. When mitochondria’s integrity is disrupted or dysfunction occurs, the mitochondria’s contents are released into the cytosol. These contents, like reactive oxygen species, mitochondrial DNA, and double-stranded RNA, among others, act as damage-related molecular patterns (DAMPs) that can bind to multiple innate immune sensors, particularly pattern recognition receptors, thereby leading to inflammation. To avoid the production of DAMPs, in addition to safeguarding organelles integrity and functionality, mitochondria may activate mitophagy or apoptosis. Moreover, mitochondrial components and specific metabolic regulations modify properties of innate immune cells. These include macrophages, dendritic cells, innate lymphoid cells, and so on, in steady state or in stimulation that are involved in processes ranging from the tricarboxylic acid cycle to oxidative phosphorylation and fatty acid metabolism. Here we provide a brief summary of mitochondrial DAMPs’ initiated and potentiated inflammatory response in the innate immune system. We also provide insights into how the state of activation, differentiation, and functional polarization of innate immune cells can be influenced by alteration to the metabolic pathways in mitochondria.
Percutaneous versus Open Fetal Surgical Intervention for Sacrococcygeal Teratomas: Is Less Really More?
Authors: Menchaca Alicia D. , Olutoye Oluyinka O. , Cass Darrell L. , Marwan Ahmed I.
Published: October 2023

Introduction: Sacrococcygeal teratomas (SCTs) may require in utero intervention for survival. Open surgical intervention (OSI) was first described, but increasing reports of percutaneous intervention (PI) with variable indications and outcomes exist. We reviewed the literature for all published cases of fetal SCT intervention and compared OSI to PI cohorts. Methods: A keyword search of PubMed was conducted. Inclusion criteria were as follows: data available per individual fetus including gestational age at intervention, type of intervention, primary indication, survival, gestational age at birth, and complications. Complications were grouped into categories: placenta/membrane, procedural, or hemorrhagic. Failure was defined as little/no improvement or recurrence of the primary indication. χ2 analysis was performed for solid tumor PI versus OSI to assess significant trends in these intervention groups. A meta-analysis was not feasible due to small numbers and heterogeneity. Results: Twenty-seven articles met inclusion criteria. In the PI group, 38 fetuses underwent intervention for solid tumors, 21 for cystic tumors, and 3 for solid and cystic tumor components. Among fetuses with solid tumors, OSI was associated with lower need for multiple interventions (0% vs. 31.6%, p = 0.01) and higher survival to discharge (50% vs. 39.5%, p = 0.02). A fetal intervention was performed in the absence of hydrops/early hydrops in 45% of fetuses receiving PI, compared to 21% receiving OSI. Failure to resolve the primary indication was higher in the PI group (55.9% vs. 11.1% OSI, p = 0.02). The overall complication rates were high in both groups (90% OSI, 87% PI), though bleeding was unique to the PI group (26.5%). Preemptive cyst drainage, for purely cystic tumors, was universally successful and associated with a low complication risk (18.2%). Conclusions: For solid tumors, OSI appears to be superior with regard to survival to discharge, fewer interventions, and lower failure rates. PIs to drain a cyst may facilitate delivery or preempt future complications, though consideration should be given to long-term oncologic outcomes.