bluuebunny/crossref_metadata_2025 huggingface dataset:
The Predictors of Seizures in Patients with Encephalocele: An 11-Year Experience from a Tertiary Hospital
Authors: Nejat Amirhosein , Berchi Kankam Samuel , Heidari Vahid , Tayebi Meybodi Keyvan , Habibi Zohreh , Karami Sajedeh , Nejat Farideh
Published: October 2023

Introduction: The aim of the study was to investigate and identify the predictors associated with the incidence of seizures in patients with encephalocele (EC). Methods: A retrospective analysis was undertaken of patients treated for EC at a tertiary medical center in Tehran between 2010 and 2021. Data including age at presentation, gender, location, size, and content of EC, ventriculomegaly, hydrocephalus, associated anomalies, and neurodevelopmental delay (NDD) were evaluated for their prognostic value. In addition, univariate and multivariate analyses were performed to identify the correlation between independent predictors and seizure incidence. Results: One hundred and two cases of EC were identified. Seventy-one ECs (69.6%) were posterior ECs, while 31 (30.4%) were anterior. Neural tissue was found in 43 (42.2%) of the ECs. Thirty-three patients (32.4%) had ventriculomegaly, of which 90.9% underwent shunt placement for progressive or symptomatic hydrocephalus. Seizure was found in 26 (25.5%) patients. On univariate analysis, presence of other anomalies, postoperative infections, and NDD were associated with seizures (p < 0.05). When the anomalies were categorized into intracranial and extracranial groups in univariate analysis, none was associated with statistically significant increase in seizure (p values of 0.09 and 0.61, respectively). Although according to multivariate analysis, only the association between other associated anomalies and seizure was near significant (OR: 2.0, 95% CI: 0.95–4.2, p = 0.049). Children with NDD and postoperative infection were, respectively, 3.04 and 1.3 times more at risk to experience seizures compared to other patients. Conclusion: We found a rate of 25.5% risk of seizure in patients with EC. This study could not find any significant predictors of seizure in children with EC. However, pediatric patients with postoperative infections including sepsis, wound infection, and NDD require more consideration to reduce the risk of seizure.
A Role for Sodium-Glucose Cotransporter 2 Inhibitors in the Treatment of Chronic Kidney Disease: A Mini Review
Authors: Song Jinfang , Li Xia , Ni Jiang
Published: October 2023

Background: Sodium-glucose cotransport protein 2 (SGLT2) inhibitors, a new type of glucose-lowering drug, have been well proved in several clinical studies for their glucose-lowering and nephroprotective effects, and the nephroprotective effects include both indirect effects of metabolic improvement and direct effects, independent of glucose-lowering effects. Summary: In patients with diabetic kidney disease (DKD), several studies have demonstrated the potential nephroprotective mechanisms of SGLT2 inhibitors, and evidence of nephroprotective mechanisms in the non-DKD population is accumulating. Although the nephroprotective mechanism of SGLT2 inhibitors has not been fully elucidated, several laboratory studies have illustrated the mechanism underlying the effects of SGLT2 inhibitors at various aspects. Key Messages: The purpose of this article is to review the mechanism of nephroprotective effect of SGLT2 inhibitors and to look forward to promising research in the future.
Risk Factors and Drug Efficacy for Severe Illness in Hemodialysis Patients Infected with the Omicron Variant of COVID-19
Authors: Wu Yan , He Lingling , Guo Yongping , Wang Niansong
Published: October 2023

Introduction: The Omicron variant of the novel coronavirus (COVID-19) has been spreading more rapidly and is more infectious, posing a higher risk of death and treatment difficulty for patients undergoing hemodialysis. This study aims to explore the severity rate and risk factors for hemodialysis patients infected with the Omicron variant and to conduct a preliminary analysis of the clinical efficacy of drugs. Methods: Clinical and biochemical indicators of 219 hemodialysis patients infected with the Omicron variant were statistically analyzed. The patients were divided into two groups based on whether they were severely ill or not, and multiple regression analysis was conducted to determine the risk factors for severe illness. The severely ill patients were then grouped based on discharge or death, and the treatment drugs were included as influencing factors for multiple regression analysis to determine the risk factors and protective factors for death of severely ill patients, and drug efficacy analysis was conducted. Results: Analysis showed that diabetes, low oxygen saturation, and high C-reactive protein (CRP) were independent risk factors for severe illness in hemodialysis patients infected with the Omicron variant. A history of diabetes and high C-reactive significantly increased the risk of severe illness in patients (aOR: 1.450; aOR: 1.011), while a high oxygen saturation level can reduce this risk (aOR: 0.871). In addition, respiratory distress was an independent risk factor for death in severely patients, significantly reducing the probability of discharge for patients (aOR: 0.152). The drugs thymalfasin and Tanreqing significantly increased the probability of discharge for patients (aOR: 1.472; aOR: 3.104), with the latter having a higher correlation, but with a relatively longer effective course. Conclusion: Hemodialysis patients infected with the Omicron variant of COVID-19 should pay special attention to their history of diabetes, CRP, and oxygen saturation levels, as well as respiratory distress symptoms, to reduce the risk of severe illness and death. In addition, thymalfasin and Tanreqing may be considered in treatment.
Three-Dimensional Graphene Promotes the Proliferation of Cholinergic Neurons
Authors: Jiang Ziyun , Zhou Linhong , Xiao Miao , Ma Sancheng , Cheng Guosheng
Published: October 2023

Introduction: An early substantial loss of basal forebrain cholinergic neurons (BFCNs) is a common property of Alzheimer’s disease and the degeneration of functional BFCNs is related to learning and memory deficits. As a biocompatible and conductive scaffold for growth of neural stem cells, three-dimensional graphene foam (3D-GF) supports applications in tissue engineering and regenerative medicine. Although its effects on differentiation have been demonstrated, the effect of 3D-GF scaffold on the generation of BFCNs still remains unknown. Methods: In this study, we used 3D-GF as a culture substrate for neural progenitor cells (NPCs) and demonstrated that this scaffold material promotes the differentiation of BFCNs while maintaining excellent cell viability and proliferation. Results: Immunofluorescence analysis, real-time polymerase chain reaction, Western blotting, and ELISA revealed that the proportion of BFCNs at 21 days of differentiation reached approximately 30.5% on 3D-GF compared with TCPS group that only presented 9.7%. Furthermore, a cell adhesion study suggested that 3D-GF scaffold enhances the expression of adhesion proteins including vinculin, integrin, and N-cadherin. These findings indicate that 3D-GF scaffold materials are preferable candidates for the differentiation of BFCNs from NPCs. Conclusions: These results suggest new opportunities for the application of 3D-GF scaffold as a neural scaffold for cholinergic neurons therapies based on NPCs.
Postinfectious Inflammation, Autoimmunity, and Obsessive-Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection, and Pediatric Acute-Onset Neuropsychiatric Disorder
Authors: Vreeland Allison , Calaprice Denise , Or-Geva Noga , Frye Richard E. , Agalliu Dritan , Lachman Herbert M. , Pittenger Christopher , Pallanti Stefano , Williams Kyle , Ma Meiqian , Thienemann Margo , Gagliano Antonella , Mellins Elizabeth , Frankovich Jennifer
Published: October 2023

Postinfectious neuroinflammation has been implicated in multiple models of acute-onset obsessive-compulsive disorder including Sydenham chorea (SC), pediatric acute-onset neuropsychiatric syndrome (PANS), and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). These conditions are associated with a range of autoantibodies which are thought to be triggered by infections, most notably group A streptococci (GAS). Based on animal models using huma sera, these autoantibodies are thought to cross-react with neural antigens in the basal ganglia and modulate neuronal activity and behavior. As is true for many childhood neuroinflammatory diseases and rheumatological diseases, SC, PANS, and PANDAS lack clinically available, rigorous diagnostic biomarkers and randomized clinical trials. In this review article, we outline the accumulating evidence supporting the role neuroinflammation plays in these disorders. We describe work with animal models including patient-derived anti-neuronal autoantibodies, and we outline imaging studies that show alterations in the basal ganglia. In addition, we present research on metabolites, which are helpful in deciphering functional phenotypes, and on the implication of sleep in these disorders. Finally, we encourage future researchers to collaborate across medical specialties (e.g., pediatrics, psychiatry, rheumatology, immunology, and infectious disease) in order to further research on clinical syndromes presenting with neuropsychiatric manifestations.
Prurigo nodularis: Dupilumab zeigt als erste zugelassene Systemtherapie große Wirksamkeit
Authors: Schadelbauer Eva
Published: October 2023

Prurigo nodularis (PN) is a chronic inflammatory skin disease with intensely pruritic nodules. The LIBERTY-PN PRIME and PRIME2 phase 3 trials enrolled adults with PN with ≥20 nodules and severe itch uncontrolled with topical therapies. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13. Patients were randomized 1:1 to 300 mg dupilumab or placebo subcutaneously every 2 weeks for 24 weeks. The primary endpoint was pruritus improvement, measured by proportion of patients with a ≥4-point reduction in Worst Itch Numeric Rating Scale (WI-NRS) from baseline at week 24 (PRIME) or week 12 (PRIME2). Key secondary endpoints included nodule number reduction to ≤5 at week 24. PRIME and PRIME2 enrolled 151 and 160 patients, respectively. Both trials met all the pre-specified primary and key secondary endpoints. A ≥4-point WI-NRS reduction at week 24 in the dupilumab and placebo arms was achieved by 60.0% and 18.4% of patients, respectively, in PRIME (95% confidence interval (CI), 27.8-57.7 for the difference, P < 0.001) and at week 12 by 37.2% and 22.0% of patients, respectively, in PRIME2 (95% CI, 2.3-31.2; P = 0.022). Dupilumab demonstrated clinically meaningful and statistically significant improvements in itch and skin lesions versus placebo in PN. Safety was consistent with the known dupilumab safety profile.ClinicalTrials.gov identifiers: NCT04183335 and NCT04202679 .
Verbal Learning Impairment in Parkinson’s Disease: Role of the Frontostriatal System in Working and Strategic Memory
Authors: Cocuzza Alessandro , Difonzo Teresa , Aiello Edoardo Nicolò , Sbrissa Luca Pietro Ernesto , Zago Stefano , Gendarini Claudia , Sirtori Martina Andrea , Poletti Barbara , Ticozzi Nicola , Franco Giulia , Di Fonzo Alessio , Comi Giacomo Pietro , Saetti Maria Cristina
Published: October 2023

Introduction: Learning is a long-term memory process, influenced by working memory control processes, including recognition of semantic properties of items by which subjects generate a semantic structure of engrams. The aim of the study was to investigate the verbal learning strategies of individuals with Parkinson’s disease (PD). Methods: Thirty individuals with idiopathic PD and healthy control (HC) subjects were tested with a multi-trial word list learning, under two conditions: without cue and then with an explicit cue suggesting the categories in the list, respectively. Results: In comparison to HC subjects, individuals with PD recalled fewer words and achieved a reduced number of categorical clusters; the strategical cue did not improve their performance. Conclusion: This suggests, besides a difficulty in identifying the correct learning strategy, a deficit in working memory, which undermines the strategy implementation.
Autonomic Nervous System Dysfunction in Peritoneal Dialysis Patients: An Underrecognized Cardiovascular Risk Factor?
Authors: Faitatzidou Danai , Karagiannidis Artemios G. , Theodorakopoulou Marieta P. , Xanthopoulos Andrew , Triposkiadis Filippos , Sarafidis Pantelis A.
Published: October 2023

Background: In patients with end-stage kidney disease (ESKD) receiving peritoneal dialysis (PD), cardiovascular events represent the predominant cause of morbidity and mortality, with cardiac arrhythmias and sudden death being the leading causes of death in this population. Autonomic nervous system (ANS) dysfunction is listed among the non-traditional risk factors accounting for the observed high cardiovascular burden, with a plethora of complex and not yet fully understood pathophysiologic mechanisms being involved. Summary: In recent years, preliminary studies have investigated and confirmed the presence of ANS dysfunction in PD patients, while relevant results from cohort studies have linked ANS dysfunction with adverse clinical outcomes in these patients. In light of these findings, ANS dysfunction has been recently receiving wider consideration as an independent cardiovascular risk factor in PD patients. The aim of this review was to describe the mechanisms involved in the pathogenesis of ANS dysfunction in ESKD and particularly PD patients and to summarize the existing studies evaluating ANS dysfunction in PD patients. Key Messages: ANS dysfunction in PD patients is related to multiple complex mechanisms that impair the balance between SNS/PNS, and this disruption represents a crucial intermediator of cardiovascular morbidity and mortality in this population.
Shear Bond Strength of Adhesives Placed following Selective Removal of Red-Fluorescing Carious Dentine in vitro
Authors: Lennon Áine M. , Reich Nina Sophie , Ferstl Gerlinde , Ebensberger Helga , Hiller Karl-Anton , Buchalla Wolfgang
Published: October 2023

Red-fluorescing dentine indicates bacterial contamination [Caries Res 2002; 36: 315–319]. We investigated effect of removal of red fluorescent dentine caries on shear bond strength and fracture mode of 4 adhesive approaches. Sixty-five carious teeth and 50 noncarious controls were distributed into 4 groups: Clearfil™ self-etch (CSE), OptiBond™ FL total etch (OTE), Scotchbond™ Universal total etch (STE) and self-etch (SSE). Samples were excited at 405 nm and viewed through 530 nm filter. Carious samples were ground flat exposing strongly red-fluorescing (StrongRF) dentine, on which a composite cylinder was placed, using one of 4 adhesives. After 22 h in water, shear bond strength and fracture mode were analysed. StrongRF was removed; composite cylinders were placed on weakly red-fluorescing (WeakRF) dentine and tested as described above. Finally, red-fluorescing dentine was removed, and composite cylinders were placed on non-fluorescing (NonRF) dentine and tested. Composites were placed at 3 corresponding heights in controls. After 22 h in water, shear bond strength testing and fracture mode analysis were performed. Differences were tested using Mann-Whitney or Wilcoxon tests (p ≤0.05). Median (Q1, Q3) shear bond strength on StrongRF was SSE 14.4 (9.2, 18.2) MPa >CSE 10.2 (6.4, 17.3) MPa >STE 9.1 (6.9, 11.2) MPa >OTE 6.8 (4.0, 10.8) MPa. Shear bond strength increased statistically significantly for all adhesives on WeakRF: SSE 19.8 (13.6, 24.3) MPa >STE 19.5 (12.7, 23.1) MPa >CSE 17.5 (12.0, 22.5) MPa >OTE 15.8 (11.9, 20.9) MPa. Only STE 25.6 (22.4, 29.1) MPa and CSE 22.1 (17.6, 24.6) MPa were significantly different on NonRF compared to WeakRF. For controls tested at corresponding depths, superficial shear bond strength was OTE 18.7 (16.0, 22.1) MPa >STE 18.4 (12.0, 25.9) MPa >CSE 18.1 (12.7, 20.7) MPa >SSE 13.0 (9.6, 17.8) MPa. This was significantly higher compared to StrongRF except for SSE. Central shear bond strength was not significantly different to WeakRF, deep shear bond strength was significantly lower for SSE and CSE but higher for OTE compared to carious. Conclusion: StrongRF dentine should be removed for higher shear bond strength, but WeakRF dentine can often be preserved without compromising adhesive bond strength.
Baló Concentric Sclerosis Mimicking Encephalitis with Seizures and Progressive Aphasia in a 26-Year-Old Woman: A Challenging Diagnostic Dilemma
Authors: Shala Nexhmedin , Tolaj Ilir , Jashari Fisnik , Malazogu Edita , Shala Argjend , Bajraktari Gentiant , Ahmetgjekaj Ilir , Dreshaj Shemsedin
Published: October 2023

Introduction: Baló’s concentric sclerosis (BCS) is a rare subtype of multiple sclerosis characterized by inflammatory demyelination within the central nervous system. Case Presentation: This case report presents a challenging diagnostic scenario involving a 26-year-old woman diagnosed with BCS. Despite treatment, her condition did not ameliorate, and magnetic resonance imaging (MRI) findings remained unchanged. A subsequent stereotactic biopsy revealed tumefactive Balo disease, highlighting the intricate diagnostic and therapeutic issues surrounding BCS. Conclusion: The juxtacortical location of the BCS lesion, as observed in our case, suggests an unfavourable prognosis due to treatment-resistant seizures.
Effects of Exercise during Chemo- or Radiotherapy on Immune Markers: A Systematic Review
Authors: de Hoop Anne M.S. , Valkenet Karin , Dronkers Jaap J. , Krul Cyrille A.M. , Ruurda Jelle P. , Veenhof Cindy , Pieters Raymond H.H.
Published: October 2023

Introduction: Patients with cancer receiving radio- or chemotherapy undergo many immunological stressors. Chronic regular exercise has been shown to positively influence the immune system in several populations, while exercise overload may have negative effects. Exercise is currently recommended for all patients with cancer. However, knowledge regarding the effects of exercise on immune markers in patients undergoing chemo- or radiotherapy is limited. The aim of this study is to systematically review the effects of moderate- and high-intensity exercise interventions in patients with cancer during chemotherapy or radiotherapy on immune markers. Methods: For this review, a search was performed in PubMed and EMBASE, until March 2023. Methodological quality was assessed with the PEDro tool and best-evidence syntheses were performed both per immune marker and for the inflammatory profile. Results: Methodological quality of the 15 included articles was rated fair to good. The majority of markers were unaltered, but observed effects included a suppressive effect of exercise during radiotherapy on some pro-inflammatory markers, a preserving effect of exercise during chemotherapy on NK cell degranulation and cytotoxicity, a protective effect on the decrease in thrombocytes during chemotherapy, and a positive effect of exercise during chemotherapy on IgA. Conclusion: Although exercise only influenced a few markers, the results are promising. Exercise did not negatively influence immune markers, and some were positively affected since suppressed inflammation might have positive clinical implications. For future research, consensus is needed regarding a set of markers that are most responsive to exercise. Next, differential effects of training types and intensities on these markers should be further investigated, as well as their clinical implications.
Techniques to Assess the Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Blood Volume in Patients with Diabetic Kidney Disease
Authors: Vinje Vårin , Bomholt Tobias , Rossing Peter , Lundby Carsten , Oturai Peter , Hornum Mads
Published: October 2023

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert a kidney protective effect in patients with diabetic kidney disease. Several mechanisms have been proposed, but why precisely SGLT2 inhibition has a kidney protective effect is incompletely understood. Clinical trials using SGLT2 inhibitors have found them to induce a rapid weight loss likely due to loss of sodium and subsequently fluid. While SGLT2 inhibitors are reported to increase hematocrit, it remains unknown whether the natriuretic and aquaretic effect reduces patient’s blood volume and whether this could partly explain its kidney protective effects. A blood volume reduction could induce several beneficial effects with reduction in arterial and venous blood pressure as two central mechanisms. The aim of this paper was to review current techniques for assessing patient blood volume that could enhance our understanding of SGLT2 inhibitors’ physiological effects. Summary: Changes induced by SGLT2 inhibitors on erythrocyte volume and plasma volume can be assessed by tracer dilution techniques that include radioisotopes, indocyanine green (ICG) dye, or carbon monoxide (CO). Techniques with radioisotopes can provide direct estimates of both erythrocyte volume and plasma volume but are cumbersome procedures and the radiation exposure is a limitation for repeated measures in clinical studies. Methods more suitable for repeated assessment of erythrocyte and plasma volume include dilution of injected ICG dye or dilution of inhaled CO. ICG dye requires higher precision with timed blood samples and provides only a direct estimate of plasma volume wherefrom erythrocyte volume is estimated. Inhalation of CO is a time-effective and automated method that provides measure of the total hemoglobin mass wherefrom erythrocyte and plasma volumes are estimated. Key Messages: A kidney protective effect has been observed in clinical trials with SGLT2 inhibitors, but the underlying mechanisms are not fully understood. Significant weight loss within weeks has been reported in the SGLT2 inhibitor trials and could be related to a reduction in blood volume secondary to increased natriuresis and aquaresis. Alterations in blood volume compartments can be quantified by tracer dilution techniques and further improve our understanding of kidney protection from SGLT2 inhibitors.
Predictors of Hyporesponsiveness to Erythropoiesis-Stimulating Agents in Patients with Non-Dialysis-Dependent Chronic Kidney Disease (RADIANCE-CKD Study)
Authors: Mase Kaori , Yamagata Kunihiro , Yamamoto Hiroyasu , Tsuruya Kazuhiko , Hase Hiroki , Nishi Shinichi , Nangaku Masaomi , Wada Takashi , Hayashi Terumasa , Uemura Yukari , Hirakata Hideki
Published: October 2023

Introduction: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) has been associated with increased mortality and cardiovascular events in patients with chronic kidney disease. We hypothesized that the prediction of ESA resistance during ESA administration would be very useful in deciding on a treatment plan. Methods: Patients enrolled in a randomized controlled trial to evaluate renal prognosis in anemic patients with non-dialysis-dependent chronic kidney disease with hyporesponsiveness to ESA were included; the patients had different target hemoglobin levels. A landmark analysis was performed at 3 months into the study. To construct a predictive model for the severe ESA hypo-responder group, in which there was no increase in hemoglobin even with active treatment, background factors and serum test items that affect anemia at study entry were included in a logistic regression model, the area under the curve (AUC) and 95% confidence intervals (CI) were estimated, and sensitivity and specificity were calculated. This study was a post hoc sub-analysis of a randomized controlled trial. Results: The AUC for the 19 existing risk factors as predictors was 0.783 (95% CI: 0.711–0.855). Among the 19 risk factors, the combination of six factors (hemoglobin level, systolic blood pressure, weight, gender, smoking status, and hypertensive retinopathy) with the largest χ2 statistics were selected by multiple logistics regression. The AUC for these 6 predictors was 0.716 (95% CI: 0.634–0.799). To the six existing risk factors, five serum test items that affect anemia (vitamin B12, vitamin B6, folic acid, parathyroid hormone, and 25-hydroxyvitamin D) were added, for a total of 11 risk factors, with a similar AUC of 0.736 (95% CI: 0.655–0.817), sufficient to predict ESA resistance. Conclusions: Our results suggest that existing risk factors and serum test items can be used to predict ESA resistance in patients with non-dialysis-dependent chronic kidney disease on ESA.
Real-World Data on Short-Term and Long-Term Treatment Results of Ustekinumab in Patients with Steroid-Resistant/Dependent Ulcerative Colitis
Authors: Komeda Yoriaki , Tribonias George , Kono Masashi , Handa Kohei , Omoto Shunsuke , Takenaka Mamoru , Hagiwara Satoru , Tsuji Naoko , Nishida Naoshi , Kashida Hiroshi , Kudo Masatoshi
Published: October 2023

Introduction: Ustekinumab is an IgG1 kappa monoclonal antibody directed against the common p40 subunit of interleukin-12 and interleukin-23, which activate Th1- and Th17-mediated immune responses, respectively. It has proven efficacy for the treatment of moderate to severe ulcerative colitis (UC) in the UNIFI phase III clinical trial; however, data on its efficacy in the real world are limited. In this study, we aimed to assess the real-world efficacy of ustekinumab. Methods: This observational study included 30 patients with UC who received ustekinumab from April 2020 to April 2022. We examined demographic information, disease type and activity (Mayo score, partial Mayo score [PMS]), use of biologics, concomitant use of predonisolone (PSL), 8-week ustekinumab clinical response rate, remission induction rate, 44- and 152-week remission maintenance rate, continuation rate, and 44-week steroid-free remission rate. The primary outcomes were the short- and long-term efficacy of ustekinumab. Results: Included patients (53% women; mean age: 41.2 years [16–80 years]) had an average disease duration of 86 weeks. The Mayo score (median) was 7.4 and the PMS was 5.4. Two (7%), 24 (80%), and four (13%) patients had a Mayo endoscopic subscore (MES) of MES1, MES2, and MES3, respectively. The median serum CRP was 1.0 mg/dL. Five patients had no history of biotherapy (naive), while eight and 17 had a history of one and two or more biologic agents, respectively. Eight patients were PSL-resistant and 22 were PSL-dependent. The 8-week clinical response rate was 73% and the clinical remission induction rate was 70%. The remission maintenance rates at 44 and 152 weeks were 67% and 63%, respectively. The ustekinumab retention rate was 67% (86-week mean follow-up period). Regarding biologic failure cases, the clinical response rate in the failure group with up to one biologic agent (including naive cases) was 84.6%, which was higher than the 58.0% rate in the failure group with two or more biologic agents (p = 0.06). Steroid-free remission rates at 44 and 152 weeks were 63% each. In the logistic regression analysis parameters for discontinuation of ustekinumab, only PMS remained significant after multivariate analysis (p = 0.018). Conclusion: Our study showed short-term and long-term ustekinumab effectiveness, especially with comparative low disease activity.
Simultaneous Tumor Shrinkage and Bronchial Perforation Induced by Nivolumab plus Cabozantinib Combination Therapy in a Patient with Collecting Duct Carcinoma
Authors: Okumura Hiroki , Murase Kyoko , Oka Suguru , Kizawa Rika , Yamaguchi Takeshi , Tanabe Yuko , Suyama Koichi , Sakaguchi Kazushige , Urakami Shinji , Miura Yuji
Published: October 2023

Vascular endothelial growth factor receptor tyrosine kinase inhibitors are known to cause perforation as one of their severe side effects, and postoperative and postradiation therapy are known risk factors. However, there are few studies on perforation following tumor shrinkage. A 78-year-old woman with postoperative recurring left collecting duct carcinoma of the right hilar lymph nodes and mediastinum underwent eight courses of nivolumab plus cabozantinib, resulting in tumor shrinkage. Three days after the last administration, she developed fever and cough and was hospitalized for right lobar pneumonia. The patient received long-term antibiotics for bronchial fistula with the destruction of the bronchial wall and secondary lung abscess. When using nivolumab plus cabozantinib combination therapy for a tumor with bronchial invasion, physicians should be aware of bronchial perforation as the tumor shrinks.
Sex Difference in the Association between Depression and Adherence to Recommended Dilated Eye Examinations among Patients with Diabetes: Findings from National Health and Nutrition Examination Survey
Authors: Zhong Zhe , Lin Yaying , Zhong Li , Yu Xi , Xie Aihong
Published: October 2023

Introduction: The relationship between depression and adherence to regular dilated fundus examination (DFE) in patients with diabetes remains unclear. This study aimed to assess the association between depression and adherence to annual or biennial DFE among individuals with diabetes. Methods: In this cross-sectional study, we used the National Health and Nutrition Examination Survey database from 2005 to 2016 which contains information on demographics, clinical characteristics, health-related factors, and the time since last DFE. Participants were classified as having depression based on a score of >9 on the Patient Health Questionnaire-9. The main outcomes were the association between depression and the adherence of patients with diabetes to annual or biennial DFE. The second objective was to explore the potential influence of gender in this association. The independent association of depression with DFE compliance was explored by a series of multivariate logistic regression analyses (overall sample and then stratified by sex). Results: In total, 3,656 eligible participants were identified. The adherence rates to annual or biennial DFE were all higher for participants without depression than those with depression (64.8% vs. 56.1% and 80.3% vs. 69.7%, respectively). In the multivariate analyses, depression was neither independently associated with the adherence to annual DFE nor biennial DFE in the overall sample. An interaction was observed between depression and gender for the adherence to annual or biennial DFE (p = 0.017 and p = 0.026, respectively). When analyses were stratified by sex, female patients with diabetes and depression had a significantly increased odds ratio (OR) of being nonadherent to annual and biennial DFE (OR = 1.52, 95% confidence interval [CI]: 1.02–2.25, p = 0.039; OR = 1.55, 95% CI: 1.02–2.35, p = 0.039, respectively). However, this relationship was not evident in men with diabetes. Conclusions: The independent association between depression and DFE compliance varied by sex, that is, only female patients with diabetes and depression were at a higher risk of nonadherence to annual or biennial DFE compared to those without depression.
Efficacy and Safety of Ferric Citrate on Hyperphosphatemia among Chinese Patients with Chronic Kidney Disease Undergoing Hemodialysis: A Phase III Multicenter Randomized Open-Label Active-Drug-Controlled Study
Authors: Wang Yong , Chen Xiangmei , Zhu Hanyu , Guo Zhiyong , Yang Yibin , Luo Ping , He Yani , Xu Yan , Ji Daxi , Gao Xinlu , Sun Xiuli , Xing Changying , Wang Yu , Wang Xiaohui , Zhao Shuping , Guan Yan , Lin Hongli , Zhong Aimin , Shui Hua , Shao Fengmin , Lv Lu , Yan Yuehong , Sun Xiaokun , Zhang Lei
Published: October 2023

Introduction: Hyperphosphatemia in chronic kidney disease (CKD) patients is positively associated with mortality. Ferric citrate is a potent phosphorus binder that lowers serum phosphorus level and improves iron metabolism. We compared its efficacy and safety with active drugs in Chinese CKD patients with hemodialysis. Methods: Chinese patients undergoing hemodialysis were randomized into two treatment groups in a 1:1 ratio, receiving either ferric citrate or sevelamer carbonate, respectively, for 12 weeks. Serum phosphorus levels, calcium concentration, and iron metabolism parameters were evaluated every 2 weeks. Frequency and severity of adverse events were recorded. Results: 217 (90.4%) patients completed the study with balanced demographic and baseline characteristics between two groups. Ferric citrate decreased the serum phosphorus level to 0.59 ± 0.54 mmol/L, comparable to 0.56 ± 0.62 mmol/L by sevelamer carbonate. There was no significant difference between two groups (p > 0.05) in the proportion of patients with serum phosphorus levels reaching the target range, the response rate to the study drug, and the changes of corrected serum calcium concentrations, and intact-PTH levels at the end of treatment. The change of iron metabolism indicators in the ferric citrate group was significantly higher than those in the sevelamer carbonate group. There are 47 (40.5%) patients in the ferric citrate group, and 26 (21.3%) patients in the sevelamer carbonate group experienced drug-related treatment emergent adverse events (TEAEs); most were mild and tolerable. Common drug-related TEAEs were gastrointestinal disorders, including diarrhea (12.9 vs. 2.5%), fecal discoloration (14.7 vs. 0%), and constipation (1.7 vs. 7.4%) in ferric citrate and sevelamer carbonate group. Conclusion: Ferric citrate capsules have good efficacy and safety in the control of hyperphosphatemia in adult patients with CKD undergoing hemodialysis. Efficacy is not inferior to sevelamer carbonate. The TEAEs were mostly mild and tolerated by the patients.
Urinary Fetuin-A Fragments Predict Progressive Estimated Glomerular Filtration Rate Decline in Two Independent Type 2 Diabetes Cohorts of Different Ethnicities
Authors: Chuang Gwo-Tsann , Kremer Daan , Huang Chi-Hsuan , Alkaff Firas F. , Lin Chih-Hung , Tseng Tzu-Ling , Laverman Gozewijn D. , Bakker Stephan J. L. , Chuang Lee-Ming
Published: October 2023

Introduction: There is a great clinical need for novel markers to predict kidney function decline in patients with type 2 diabetes. We explored the potential of posttranslationally modified fetuin-A fragments in urine (uPTM-FetA) as such a marker. Methods: We included patients with type 2 diabetes from two independent, nonoverlapping prospective cohort studies. A cut-off for uPTM-FetA, measured via ELISA method, was determined using the Youden index in the primary cohort of patients with type 2 diabetes from Taiwan. Kidney endpoint was defined as an estimated glomerular filtration rate (eGFR) decline ≥30% from baseline, reaching of an eGFR <15 mL/min/1.73 m2, or a need of renal replacement therapy. Prospective associations were assessed in Cox regression models. All analyses were replicated in a cohort of patients with type 2 diabetes from the Netherlands. Results: In total, 294 patients with type 2 diabetes (age 61 ± 10 years, 55% male, eGFR 88 ± 16 mL/min/1.73 m2) were included in the primary cohort. During a follow-up of median 4.6 years, 42 participants (14%) experienced the kidney endpoint. Using the defined cut-off, a high uPTM-FetA was associated with a higher risk of renal function decline (Plog-rank < 0.0001). This association was similar in subgroups depending on albuminuria. This association remained, independent of age, sex, baseline eGFR, albuminuria, HbA1c, and other potential confounders (HR: 9.94; 95% CI: 2.96–33.40; p < 0.001 in the final model). Analyses in the validation cohort (376 patients with type 2 diabetes, age 64 ± 11 years, 66% male, eGFR 76 ± 24 mL/min/1.73 m2) using the same cut-off yielded similar results. Conclusion: uPTM-FetA was independently associated with kidney function decline in patients with type 2 diabetes validated in a 2-cohort study. The significant additive predictive power of this biomarker from conventional risk factors suggests its clinical use for renal function progression in patients with type 2 diabetes.
Possibility of PD-1/PD-L1 Inhibitors for the Treatment of Patients with Chronic Hepatitis B Infection
Authors: Su Menghan , Ye Ting , Wu Wei , Shu Zheyue , Xia Qi
Published: October 2023

Background: Chronic hepatitis B (CHB) infection is still a major global public health problem, with nearly two billion patients. Although current antiviral drugs can inhibit viral replication and reduce hepatitis B virus (HBV) related complications, it is difficult to achieve clinical endpoints due to drug resistance. Summary: Immune checkpoint inhibitors (ICIs) are an important strategy to reverse T-cell exhaustion, and rebuilding an effective functional T-cell response is a promising immunomodulatory approach for CHB patients. However, ICIs may lead to viral reactivation or immune-related adverse effects. There are still many controversies in the application of ICIs in treating patients with CHB. Key Messages: This article reviews the research progress of ICIs in CHB infection and related issues. The goal of this paper was to summarize the possible impact of new therapies for CHB with the aim of reducing potential clinical risks.
Abstract 005: Renal Macrophages From Losartan Treated Mice Transfer The Hypertension
Authors: Araos Patricio A , Cortés Sut'yam , Campos Rafael , Reyes Javier , Figueroa Stefanny , Guzman Eduardo , Fuenzalida María José , Pacheco Rodrigo , Amador Cristián A
Published: October 2023

The immune system participates in the Angiotensin II (AngII)-dependent hypertension (HTN). Dendritic Cells (DCs)-CD11c
+
and macrophages (Mo) are abundant in the kidney. However, new subpopulations of CD11c
+
cells with Mo characteristics (F4/80
+
) have been described. Recently, studies have shown that type-1 AngII receptor (AT
1
R) in CD11c
+
cells could have a protective effect on HTN in contrast to the pro-hypertensive effects of AT
1
R activation in other cells. Here, our goal was to evaluate whether renal Mo (rMo) modify their phenotype during AngII-induced inflammatory kidney damage, and whether their transfer to normotensive animals promotes HTN in an AT
1
R-dependent manner.

Male C57BI/6 mice (10 weeks, n=6) were infused with AngII (490 ng/kg/min), AngII+Losartan (LOS; 20mg/kg/d, in drinking water), or vehicle (Vh) for 14-days. Systolic blood pressure (SBP) was measured by plethysmography. Renal DCs (rDCs, CD11c
+
F4/80
-
) and rMo (CD11c
+
F4/80
+
) were evaluated by flow cytometry and isolated at 14-days for the transfer to normotensive mice, which were followed for 7-days (n=4-5). Finally, rDCs and rMo were stimulated
in vitro
with AngII (100nM, 24h) to analyze the mRNAs abundance of AT
1
R. All data are presented by mean±standard deviation.LOS prevented the SBP rise (AngII+LOS=110.3±11.1
vs.
AngII=134.7±6.9 mmHg; p<0.01) and the increase of rDCs population (AngII+LOS=12.8±2.0%
vs.
AngII=16.5±0.6%; p<0.01) induced by AngII, without changing rMo population. The rMo transfer from AngII mice did not induce HTN in normotensive animals after 24h (basal=106.8±2.3
vs.
112.4±4.9 mmHg; ns), compared to rDCs (Basal=110.0±8.3
vs.
132.0±14.3 mmHg; p<0.05). However, the rMo from AngII+LOS mice increased SBP in healthy animals compared to their baseline (basal=109±5.6
vs.
123±8.0 mmHg; p<0.05). This effect was not observed by rDCs transfer (basal=109±2.9
vs.
113±7.0 mmHg; ns). Finally, the rMo from AngII mice showed an increase in the AT
1
R mRNA abundance (p<0.05), compared to Vh rMo, however, AngII
in vitro
treatment did not modify the mRNA levels.The
in vivo
AT
1
R antagonism may have a differential effect on rMo, transferring HTN to normotensive mice. These findings suggest that subpopulations of renal CD11c
+
cells have a differential role in HTN.Fondecyt 1231909
Abstract 008: Sex-dependency Of T Cell-induced Salt-sensitive Hypertension And Kidney Damage
Authors: Abais-Battad Justine M , Dasinger John H , Burns Emily C , Walton Samuel D , Cherian-Shaw Mary , Mattson David L
Published: October 2023

We have previously demonstrated that female Dahl Salt-Sensitive (SS) rats are protected from salt-induced hypertension and renal injury compared to males. There is an immunological component to this sex difference, since genetic deletion of T cells via mutation of the CD247 gene on the Dahl SS genetic background (CD247-/-) normalizes sex differences in blood pressure, though females are still protected from salt-sensitive renal damage compared to males. The current study hypothesized that sex of the T cell is an important factor in determining the severity of salt-sensitivity. We tested the hypothesis via a sex-specific splenocyte transfer by freshly isolating 10
7
male or female splenocytes and injecting them i.p. on postnatal day 5 into either male or female CD247-/- recipients. At 9 weeks of age, rats underwent a 3 week high salt challenge (HS, 4.0% NaCl, AIN-76A), with blood pressure measured continuously by telemetry and overnight urine collected weekly to assess renal damage. All data presented are from HS day 21. Transfer of either male or female donor splenocytes into CD247-/- recipient males exacerbated salt-induced hypertension compared to PBS vehicle controls (+PBS: 143.7±2.9, +Male: 152.8±5.2, +Female: 151.8±3.9 mmHg, n=11-14, p<0.05). Similarly reflected in proteinuria, splenocyte transfer, regardless of sex, also worsened kidney damage in male CD247-/- recipients (+PBS: 191.9±26.7, +Male: 304.6±51.3, +Female: 283.9±37.1 mg/day, n=12-16, p<0.05). In CD247-/- female recipients, there was an exacerbation in blood pressure with the transfer of male splenocytes (+PBS: 144.8±6.1, +Male: 151.5±3.9 mmHg, n=6-13, p<0.05), but no significant change with the transfer of female splenocytes (+Female: 145.3±2.6 mmHg). There was a trend for male splenocytes to worsen proteinuria in CD247-/- female recipients (+PBS: 103.9±11.1, +Male: 157.7±21.2 mg/day, n=6-14, p=0.056), but there was a significant reduction in the transfer of female versus male splenocytes (+Female: 113.2±15.7, p<0.05). Through flow cytometry, we confirmed similar extent of T cell reconstitution in both male and female CD247-/- recipients. These data demonstrate that salt-sensitive hypertension and renal damage are amplified if the sex of the T cell or the recipient are male.
Abstract 012: Diagnosis Of Salt Sensitivity Of Blood Pressure Using Circulating Monocyte Isolevuglandin-CXCL/CCL Signaling In Response To Elevated Sodium
In Vitro
Authors: Jamison Sydney , Pitzer Ashley , Kirabo Annet
Published: October 2023

Salt sensitivity of blood pressure (SSBP) is when blood pressure changes parallel to salt loading/ depletion and is an independent risk factor for cardiovascular disease. Despite its importance, there is no feasible diagnosis, which limits investigational studies to identify therapeutic targets. Our studies indicate that changes in production of isolevuglandins (IsoLGs) in antigen presenting cells (APCs) parallel changes in blood pressure following salt-loading and depletion in humans and this is associated with chemokine signaling. We hypothesized that
in vivo
responses to salt-loading/depletion leading to IsoLG production in APCs are mirrored
in vitro
. To test this hypothesis, we isolated peripheral blood mononuclear cells from known salt-sensitive and salt-resistant people and treated them with either normal salt (140 mmoL) or high salt (190 mmoL) for 24 hours
in vitro
. Using flow cytometry, we found that classical monocytes from salt sensitive but not salt resistant people had a significant increase in IsoLGs (25.15 ± 7.41 vs 14.52 ± 8.60, p = 0.0022) after 24 hours of high salt treatment. To determine mechanisms, we also performed bulk RNAseq on
in vitro
high salt treated monocytes and CITEseq on PBMCs following the salt-loading/depletion protocol. We found that salt-loading/depletion was associated with parallel changes in the expression of various chemokines in the CXCL and CC families both
in vitro
and
in vivo
. Specifically, the changes in levels of CXCL8 (p = 0.01553, r = 0.8067) , CXCL16 (p = 0.004697, r = -0.8725), and CCL2 (p = 0.002292, r = -0.9004) correlated with changes in diastolic and systolic blood pressure from salt loading to depletion. Moreover, changes in systolic blood pressure significantly correlated with changes in CCL2 (p= 0.008878, r= -0.6302) and CCL4 (p= 0.03209, r = -0.5367) from salt loading to salt depletion. These data suggest that
in vitro
responses of IsoLGs and chemokine production to salt treatment could serve as a feasible diagnosis for salt sensitivity of blood pressure in the clinic.
Abstract 013: Hippocampal Neuroinflammation Occurs After Focal Cerebral Ischemic Stroke That May Contribute To Post-Stroke Memory Loss
Authors: Krant Nick W , Tremble Sarah , Johnson Abbie C
Published: October 2023

Chronic hypertension is a leading risk factor for ischemic stroke. Post-stroke dementia occurs in up to 80% of stroke survivors, and its prevalence is increasing due to an aging population. Memory is impaired in rodent models of transient middle cerebral artery occlusion (tMCAO). However, the impact of cerebral ischemia on brain regions involved in memory that are distant from the ischemic site, such as the hippocampus, remains unclear, but may involve neuroinflammation that is known to disrupt memory. We tested the hypothesis that neuroinflammation occurs in the hippocampus after tMCAO, contributing to memory dysfunction, and is more severe during chronic hypertension. Adult normotensive male Wistar rats and spontaneously hypertensive rats (SHR) underwent 45 minutes of ischemia induced using the intravascular filament method of tMCAO and seven days of reperfusion (or sham; n=6-8/group). A novel object recognition task was used days 5-7 post-tMCAO, and recognition index calculated to assess long-term memory function. Neuroinflammation in the hippocampal CA1 region of ipsi- and contralesional hemispheres was assessed immunohistochemically: microglial activation using Iba1 staining and neuronal expression of tumor necrosis factor alpha (TNFα). Data are mean ± SEM and comparisons made via a two-way ANOVA to determine the interaction between hypertension and stroke with a post-hoc Tukey test. Sham operated SHR and Wistar rats performed similarly well in the memory task and had recognition indices 0.65-0.70. However, memory was impaired in rats that had tMCAO, with recognition indices decreasing to 0.52±0.02 in Wistar rats and 0.52±0.03 in SHR (F
1,24
=21.60; p<0.01). Ischemia increased the number of TNFα expressing neurons regardless of hypertensive status in hippocampus of ipsi- (F
1,25
=7.87; p<0.01) and contra-lesional hemispheres (F
1,25
=4.22; p<0.05). There was a significant effect of ischemia on microglial activation in the hippocampus of both SHR and Wistar rats that only occurred ipsi-lesionally (F
1,24
=5.48; p<0.05). These findings demonstrate that hippocampal neuroinflammation is present seven days after transient focal cerebral ischemia that may contribute to post-stroke memory impairment.