bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytokine, Anti-SARS-CoV-2 Antibody, and Neutralizing Antibody Levels in Conventional Blood Donors Who Have Recovered from COVID-19
Authors: Maličev Elvira , Žiberna Klemen , Jazbec Katerina , Kolenc Ana , Mali Polonca , Rahne Potokar Urška , Rožman Primož
Published: October 2023

Background: At the beginning of the pandemic, COVID-19 convalescent plasma (CCP) containing anti-SARS-CoV-2 antibodies was suggested as a source of therapy. In the last 3 years, many trials have demonstrated the limited usefulness of CCP therapy. This led us to the hypothesis that CCP could contain other elements, along with the desired neutralizing antibodies, which could potentially prevent it from having a therapeutic effect, among them cytokines, chemokines, growth factors, clotting factors, and autoantibodies. Methods: In total, 39 cytokines were analyzed in the plasma of 190 blood donors, and further research focused on the levels of 23 different cytokines in CCP (sCD40L, eotaxin, FGF-2, FLT-3L, ractalkine, GRO-α, IFNα2, IL-1β, IL-1RA, IL-5, IL-6, IL-8, IL-12, IL-13, IL-15, IL-17E, IP-10, MCP-1, MIP-1b, PDGF-AA, TGFα, TNFα, and TRAIL). Anti-SARS-CoV-2 antibodies and neutralizing antibodies were detected in CCP. Results: We found no significant differences between CCP taken within a maximum of 180 days from the onset of the first COVID-19 symptoms and the controls. We also made a comparison of the cytokine levels between the low neutralizing antibodies (<160) group and the high neutralizing antibodies (≥160) group and found there were no differences between the groups. Our research also showed no correlation either to levels of anti-SARS-CoV-2 IgG Ab or to the levels of neutralizing antibodies. There were also no significant changes in cytokine levels based on the period after the start of COVID-19 symptoms. Conclusions: No elements which could potentially be responsible for preventing CCP from having a therapeutic effect were found.
Higher House Dust Mite-Specific IgE Levels among Chronic Spontaneous Urticaria Patients May Implicate Higher Basophil Reactivity
Authors: Liang Gaopeng , Zhou Jie , Jiang Lanlan , Wang Wenwen , Wu Qijun , Gao Cuie , Liu Wenying , Li Shifei , Feng Shujing , Song Zhiqiang
Published: October 2023

Introduction: Allergen-specific IgE (sIgE) sensitization exists in a considerable fraction of chronic spontaneous urticaria (CSU) patients. Basophils have been implicated in the pathogenesis of CSU. This paper aimed to explore the relationship between allergic sensitization and basophil reactivity in CSU and the possible underlying mechanism. Methods: Basophil-enriched leukocytes were isolated from the peripheral blood of 76 CSU patients and 9 healthy controls. Basophil CD63 and FcεRIα (the alpha subunit of the high-affinity IgE receptor) expression in the blood samples with various house dust mite (HDM)-sIgE levels were determined by flow cytometry. Basophil reactivity and SHIP-1 (a molecule related to the IgE/FcεRI signaling pathway) expression were analyzed after stimulation with an HDM allergen or other stimuli. Results: HDM-sIgEstrong positive (≥3.5 kU/L) CSU patients had a significantly higher mean percentage of basophil CD63 and higher baseline levels of FcεRIα expressed by basophils than HDM-sIgEnormal (<0.35 kU/L) CSU patients and healthy controls; the same went for total serum IgE. After stimulation with Dermatophagoides pteronyssinus peptidase 1 (Derp1) alone or together with Derp1-sIgE, the stimulation index of CD63 and levels of FcεRIα expressed by basophils in HDM-sIgEstrong positive CSU patients were significantly higher than those in HDM-sIgEnormal CSU patients and healthy controls. Significantly more SHIP-1 mRNA expression in HDM-sIgEstrong positive CSU patients was induced after the combined stimulation in comparison to other subjects. Conclusion: CSU patients with higher HDM-sIgE levels (≥3.5 kU/L) may have higher CD63 and FcεRIα expression on peripheral blood basophils. Peripheral blood basophils in these CSU patients are more responsive to HDM allergen stimulation. Higher HDM-sIgE levels among CSU patients may implicate higher basophil reactivity.
Maternal Dietary Vitamin D Intake during Pregnancy Is Associated with Allergic Disease Symptoms in Children at 3 Years Old: The Japan Environment and Children’s Study
Authors: Shimizu Muneyuki , Kato Taisuke , Adachi Yuichi , Wada Takuya , Murakami Shokei , Ito Yasunori , Itazawa Toshiko , Adachi Yoko S. , Tsuchida Akiko , Matsumura Kenta , Hamazaki Kei , Inadera Hidekuni ,   the Japan Environment and Children’s Study Group
Published: October 2023

Introduction: Vitamin D plays an important role in the immune system, and postnatal vitamin D insufficiency is one of the risk factors for the development of allergic disease. However, the effects of women’s vitamin D intake during pregnancy on the prevalence of allergic disease in their children remain controversial. Methods: From the Japan Environment and Children’s Study, an ongoing nationwide birth cohort study, we obtained information on maternal dietary vitamin D intake determined using a food frequency questionnaire and parent-reported allergic disease symptoms based on the ISAAC questionnaire in children at 3 years of age. Results: From the full dataset of 103,060 pregnancies, we analyzed complete data for 73,309 mother-child pairs. The prevalence of current wheeze, current rhinitis, current rhino-conjunctivitis, current eczema, ever asthma, ever pollinosis, and ever atopic dermatitis in the children was 17.2%, 29.7%, 3.8%, 15.2%, 9.6%, 3.7%, and 11.0%, respectively. The ORs for current rhinitis were significantly lower in the 3rd, 4th, and 5th quintiles than in the 1st quintile after adjustment for various covariates and showed a linear association. The ORs for ever pollinosis were significantly lower in the 2nd, 3rd, and 4th quintiles than in the 1st quintile, showing a U-shaped curve. There was no clear association between mothers’ dietary vitamin D intake and symptoms of asthma or atopic dermatitis in their 3-year-old children. Conclusion: Maternal dietary vitamin D intake during pregnancy is associated with the ORs for nasal allergies in children at the age of 3 years. Further studies are warranted to evaluate the appropriate intake dose of vitamin D for pregnant women to prevent the development of nasal allergies in their children.
Prevalence of Trimethoprim-Sulfamethoxazole Adverse Reaction Mislabelling in Australia
Authors: Lam Lydia , Jiang Melinda , Bacchi Stephen , Kovoor Joshua , Inglis Joshua M. , Shakib Sepehr , Yuson Carlo , Smith William
Published: October 2023

Introduction: Trimethoprim-sulfamethoxazole (TMP-SMX) is an important antibiotic, with the most compelling indications for Pneumocystis jirovecii pneumonia prophylaxis and methicillin-resistant Staphylococcus aureus treatment. Previous adverse reactions (AR) to TMP-SMX may limit the usability of TMP-SMX. Electronic medical record (EMR) of AR for other antibiotics has previously been shown to be inaccurate; however, the extent to which this occurs for TMP-SMX is unknown. Methods: A multi-centre retrospective observational study was conducted for consecutive inpatient admissions over a 2.5-year period commencing 2020. Adverse reactions to TMP-SMX recorded in the EMR were collected and reviewed by two independent medical officers using pre-defined expert criteria for the classification of allergies and intolerances. Results: TMP-SMX AR were present in the EMR of 759 individuals (prevalence 0.6%). The majority were labelled as allergy (725, 95.5%) rather than intolerance (34, 4.5%). Most common AR were rash, vomiting, and swelling. When classified against the gold-standard expert criteria, there were 437 allergies (57.6%) and 159 intolerances (21.0%). Overall, the number of incorrect EMR AR labels was 133/759 (17.5%). Both medical and surgical specialties had significant numbers of patients with TMP-SMX AR labels and incorrectly classified EMR AR labels. Conclusion: TMP-SMX AR labels affect inpatients admitted under multiple specialty units. The user-entered categorization as allergy or intolerance labels in EMRs are frequently used incorrectly. These incorrect labels may inappropriately contraindicate the use of TMP-SMX, and formal evaluation of TMP-SMX ARs with immunological assessment and relabelling where appropriate may increase the use of this agent.
Emodin Inhibits the Indoxyl Sulfate-Induced trans-Differentiation of Vascular Smooth Muscle Cells through Upregulating Thrombospondin-1
Authors: Zhang Weidong , Chen Jing , Tan Xiao , Zhang Pan , Xu Xialian , Ding Xiaoqiang , Zhao Shuan , Jin Shi
Published: October 2023

Background: Indoxyl sulfate (IS) is a protein-bound uremic toxin with vascular toxicity. The primary cause of death in uremic patients on maintenance hemodialysis is vascular disease, and it had been reported that vascular smooth muscle cells (VSMCs) trans-differentiation (VT) plays a vital role in the context of vascular diseases, but the underlying mechanisms remain obscure. Thrombospondin-1 (TSP-1) participates in vascular calcification by keeping the balance of extracellular matrix, but its role in IS-induced VT is unclear. Methods: In this study, clinical specimens, animal models, and in vitro VSMCs were used to investigate the role of TSP-1 in IS induced VT and the potential therapeutic methods. Results: We found that TSP-1 was significantly decreased in arterial samples from uremic patients, animal models, and in VSMCs after IS treatment. Downregulation of TSP-1 sufficiently induced the trans-differentiation genotypes of VSMCs. Conclusion: Emodin, the main monomer extracted from rhubarb, could alleviate IS-induced VT in vitro by upregulating TSP-1. Taken together, IS induces VT by downregulating TSP-1. Emodin might be a candidate drug to alleviate VT under IS treatment.
Sjögren’s Syndrome Caused by PD-1 Inhibition in a Lung Cancer Patient
Authors: Caeyman Aaron , Vandekerckhove Olivia , Pat Karin , Wynants Jokke , Weytjens Karolien , De Wergifosse Isabelle , Cuppens Kristof
Published: October 2023

In this report, we present a patient with metastatic non-small cell lung cancer who developed Sjögren’s syndrome secondary to immune checkpoint inhibition. This patient had a typical clinical presentation as well as biochemical signature, developing only 18 months after the start of treatment with PD-1 inhibition (pembrolizumab).
Cardiorenal Outcomes with Finerenone in Asian Patients with Chronic Kidney Disease and Type 2 Diabetes: A FIDELIO-DKD post hoc Analysis
Authors: Koya Daisuke , Anker Stefan D. , Ruilope Luis M. , Rossing Peter , Liu ZhiHong , Lee Byung Wan , Lee Chien-Te , Scott Charlie , Kolkhof Peter , Lawatscheck Robert , Wang Lili , Joseph Amer , Pitt Bertram ,   on behalf of the FIDELIO-DKD Investigators
Published: October 2023

Introduction: In FIDELIO-DKD, finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease and type 2 diabetes (T2D). This post hoc analysis explores finerenone in patients from the Asian region. Methods: In FIDELIO-DKD, 5,674 patients with T2D and urine albumin-to-creatinine ratio (UACR) ≥30–<300 mg/g and estimated glomerular filtration rate (eGFR) ≥25–<60 mL/min/1.73 m2 or UACR ≥300–≤5,000 mg/g and eGFR ≥25–<75 mL/min/1.73 m2, treated with optimized renin-angiotensin system blockade, were randomized 1:1 to finerenone or placebo. Efficacy outcomes included a primary kidney composite (time to kidney failure, sustained decrease of ≥40% in eGFR from baseline, and death from renal causes) and secondary cardiovascular (CV) (time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure) and kidney (time to kidney failure, sustained decrease of ≥57% in eGFR from baseline, and death from renal causes) composites. Results: Of 1,327 patients in the Asian subgroup, 665 received finerenone. Finerenone reduced the ≥40% and ≥57% eGFR kidney and CV composite outcomes versus placebo in the Asian subgroup (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.56–0.87, HR: 0.73; 95% CI: 0.55–0.97, and HR: 0.85; 95% CI: 0.59–1.21, respectively), with no apparent differences versus patients from the rest of the world (HR: 0.88; 95% CI: 0.77–1.02; p interaction 0.09, HR: 0.78; 95% CI: 0.64–0.95; p interaction 0.71, and HR: 0.86; 95% CI: 0.74–1.00; p interaction 0.95, respectively). The safety profile of finerenone was similar across subgroups. Conclusion: Finerenone produces similar cardiorenal benefits in Asian and non-Asian patients.
Efficient Chimeric Antigen Receptor T-Cell Generation Starting with Leukoreduction System Chambers of Thrombocyte Apheresis Sets
Authors: Xhaxho Stefani , Chen-Wichmann Linping , Kreissig Sophie , Windisch Roland , Gottschlich Adrian , Nandi Sayantan , Schabernack Sophie , Kohler Irmgard , Kellner Christian , Kobold Sebastian , Humpe Andreas , Wichmann Christian
Published: October 2023

Introduction: Primary human blood cells represent an essential model system to study physiology and disease. However, human blood is a limited resource. During healthy donor plateletpheresis, the leukoreduction system chamber (LRSC) reduces the leukocyte amount within the subsequent platelet concentrate through saturated, fluidized, particle bed filtration technology. Normally, the LRSC is discarded after apheresis is completed. Compared to peripheral blood, LRSC yields 10-fold mononuclear cell concentration. Methods: To explore if those retained leukocytes are attractive for research purposes, we isolated CD3+ T cells from the usually discarded LRSCs via density gradient centrifugation in order to manufacture CD19-targeted chimeric antigen receptor (CAR) T cells. Results: Immunophenotypic characterization revealed viable and normal CD4+ and CD8+ T-cell populations within LRSC, with low CD19+ B cell counts. Magnetic-activated cell sorting (MACS) purified CD3+ T cells were transduced with CD19 CAR-encoding lentiviral self-inactivating vectors using concentrated viral supernatants. Robust CD19 CAR cell surface expression on transduced T cells was confirmed by flow cytometry. CD19 CAR T cells were further enriched through anti-CAR MACS, yielding 80% CAR+ T-cell populations. In vitro CAR T cell expansion to clinically relevant numbers was achieved. To prove functionality, CAR T cells were co-incubated with the human CD19+ B cell precursor leukemia cell line Nalm6. Compared to unmodified T cells, CD19 CAR T cells effectively eradicated Nalm6 cells. Conclusion: Taken together, we can show that lymphocytes isolated from LRSCs of plateletpheresis sets can be efficiently used for the generation of functional CAR T cells for experimental purposes.
New Findings in the Multidisciplinary Management of a Fetal Intrapericardial Teratoma: A Case Report
Authors: Carosso Marco , Carosso Andrea Roberto , Bertschy Gianluca , Sdei Simona , Marozio Luca , Sciarrone Andrea , Benedetto Chiara
Published: October 2023

Introduction: Fetal intrapericardial teratoma is a rare tumor that can be diagnosed by antenatal ultrasonography early in pregnancy. Case Presentation: A fetal intrapericardial teratoma was detected on routine ultrasonography in the second trimester of pregnancy. At 31 weeks gestation, a marked increase in tumor size, fetal ascites, and pericardial effusion were observed, indicating that preterm delivery would be inevitable. Corticosteroid prophylaxis (24 mg of betamethasone in two doses of 12 mg 24 h apart) initiated for prophylaxis of respiratory distress syndrome led to a reduction in fetal ascites and pericardial effusion. Betamethasone therapy (4 mg/per day) was continued with the aim to postpone the expected date of delivery. Gestation was extended for more than 2 weeks. At 33 weeks and 5 days gestation, the neonate was delivered by elective cesarean section with ex utero intrapartum treatment and immediately submitted to fetal cardiac surgery. The infant was discharged from the hospital in good health about 4 months later. Conclusion: The present report draws attention to improvement in fetal status and extension of gestation achieved with maternal low-dose corticosteroid therapy on antenatal ultrasound finding of fetal ascites and pericardial effusion due to intrapericardial teratoma.
A New Measure of Posterior Morphology in Sagittal Craniosynostosis: The Occipital Bullet Index
Authors: Bins Griffin  P. , Cull Deborah , Layton Ryan G. , Kogan Samuel , Zhou Larry , Dunson Blake , David Lisa R. , Runyan Christopher M.
Published: October 2023

Introduction: Sagittal craniosynostosis (SC) is associated with scaphocephaly, an elongated narrow head shape. Assessment of regional severity in the scaphocephalic head is limited by the use of serial computed tomographic (CT) imaging or complex computer programing. Three-dimensional measurements of cranial surface morphology provide a radiation-free alternative for assessing cranial shape. This study describes the creation of an occipital bulleting index (OBI), a novel tool using surface morphology to assess the regional severity in patients with SC. Methods: Surface imaging from CT scans or 3D photographs of 360 individuals with SC and 221 normocephalic individuals were compared to identify differences in morphology. Cartesian grids were created on each individual’s surface mesh using equidistant axial and sagittal planes. Area under the curve (AUC) analyses were performed to identify trends in regional morphology and create measures capturing population differences. Results: The largest differences were located in the medial regions posteriorly. Using these population trends, a measure was created to maximize AUC. The OBI has an AUC of 0.72 with a sensitivity of 74% and a specificity of 61%. When the frontal bossing index is applied in tandem, the two have a sensitivity of 94.7% and a specificity of 93.1%. Correlation between the two scores in individuals with SC was found to be negligible with an intraclass correlation coefficient of 0.018. Severity was found to be independent of age under 24 months, sex, and imaging modality. Conclusions: This index creates a tool for differentiating control head shapes from those with SC and has the potential to allow for objective evaluation of the regional severity, outcomes of different surgical techniques, and tracking shape changes in individuals over time, without the need for radiation.
A 4-Variable Model to Predict Cardio-Kidney Events and Mortality in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study
Authors: Mendonça Luís , Bigotte Vieira Miguel , Neves João Sérgio , Castro Chaves Paulo , Ferreira Joao Pedro
Published: October 2023

Introduction: Current prognostic models for chronic kidney disease (CKD) are complex and were designed to predict a single outcome. We aimed to develop and validate a simple and parsimonious prognostic model to predict cardio-kidney events and mortality. Methods: Patients from the CRIC Study (n = 3,718) were randomly divided into derivation (n = 2,478) and validation (n = 1,240) cohorts. Twenty-nine candidate variables were preselected. Multivariable Cox regression models were developed using stepwise selection for various cardio-kidney endpoints, namely, (i) the primary composite outcome of 50% decline in estimated glomerular filtration rate (eGFR) from baseline, end-stage renal disease, or cardiovascular (CV) mortality; (ii) hospitalization for heart failure (HHF) or CV mortality; (iii) 3-point major CV endpoints (3P-MACE); (iv) all-cause death. Results: During a median follow-up of 9 years, the primary outcome occurred in 977 patients of the derivation cohort and 501 patients of the validation cohort. Log-transformed N-terminal pro-B-type natriuretic peptide (NT-proBNP), log-transformed high-sensitive cardiac troponin T (hs-cTnT), log-transformed albuminuria, and eGFR were the dominant predictors. The primary outcome risk score discriminated well (c-statistic = 0.83) with a proportion of events of 11.4% in the lowest tertile of risk and 91.5% in the highest tertile at 10 years. The risk model presented good discrimination for HHF or CV mortality, 3P-MACE, and all-cause death (c-statistics = 0.80, 0.75, and 0.75, respectively). The 4-variable risk model achieved similar c-statistics for all tested outcomes in the validation cohort. The discrimination of the 4-variable risk model was mostly superior to that of published models. Conclusion: The combination of NT-proBNP, hs-cTnT, albuminuria, and eGFR in a single 4-variable model provides a unique individual prognostic assessment of multiple cardio-kidney outcomes in CKD.
Favorable Impact of Serum TERT C228T for Prognosis after Surgical Resection for Liver Cancer
Authors: Akuta Norio , Kawamura Yusuke , Fujiyama Shunichiro , Sezaki Hitomi , Hosaka Tetsuya , Saitoh Satoshi , Kobayashi Mariko , Arase Yasuji , Ikeda Kenji , Suzuki Yoshiyuki , Kumada Hiromitsu , Suzuki Fumitaka
Published: October 2023

Introduction: Personalized medicine and molecular therapies with the diagnosis of somatic genetic alterations are expected to be developed for liver cancer. Nevertheless, it is unknown whether a mutation in the telomere reverse transcriptase promoter (TERT C228T) in serum cfDNA might be useful for making prognostic predictions after surgical resection for primary liver cancer. Methods: This cohort study retrospectively investigated 111 patients who had undergone surgical resection of liver cancer for the first time. We investigated the differences between clinicopathological features and prognosis according to classification of three tumor markers, including AFP, PIVKAII, and TERT C228T. Results: Multivariate analysis identified etiology (fatty liver disease vs. HBV odds ratio [OR] 6.853) and fibrosis stage (2–4, OR: 0.137) as determinants of TERT C228T-positive liver cancer with normal levels of AFP and PIVKAII (TERT single positive liver cancer). TERT single positive (Yes, OR: 0.301), fibrosis (FIB)-4 index (≥3.25, OR: 2.038), Child-Pugh classification (B, OR: 4.975), and number of tumors (≥2, OR: 4.098) were identified as determinants of the recurrence of liver cancer. TERT single positive (Yes, OR: 3.311), FIB-4 index (≥3.25, OR: 0.433), and number of tumors (≥2, OR: 0.262) were identified as determinants of disease-free survival. Conclusions: Our results highlight the impact of classification of prognostic tumor markers. TERT single positive is one predictor of favorable prognosis after surgical resection for liver cancer.
Point-of-Care Ultrasound versus Chest X-Ray for Determining Lung Expansion Based on Rib Count in High-Frequency Oscillatory Ventilation
Authors: Sahin Ozlem , Colak Derya , Tasar Sevinc , Yavanoglu Atay Funda , Guran Omer , Mungan Akin Ilke
Published: October 2023

Introduction: Chest X-ray (CXR) is the most prevalent method for evaluating lung expansion in high-frequency oscillatory ventilation (HFOV). The purpose of this study was to compare the accuracy of chest radiography with point-of-care ultrasound (POCUS) in determining lung expansion. Methods: This prospective study included newborns who required HFOV and were monitored in a neonatal intensive care unit. A single neonatologist assessed lung expansion with CXR and POCUS to measure the costal level of the right hemidiaphragm and compared the results. Results: A neonatologist performed 55 measurements in 28 newborns with a gestational age of 32 (23.2–39.4) weeks, followed by HFOV. The rib counts obtained from anterior chest ultrasonography and posterior CXR showed a statistically high concordance (r = 0.913, p < 0.001). Conclusion: Lung ultrasonography is a reliable method for the evaluation of lung expansion based on rib count in patients with HFOV.
Impact of Normal and Overweight Pregnancy in GLUT4 and Glucose-Dependent Vascular Contractility
Authors: Juarez Cortés Esther , López y López Gustavo , Perez Muñoz Eduardo I. , Rodriguez Reyes Betzabel , Madrigal-Aguilar Damian A. , Bobadilla-Lugo Rosa A.
Published: October 2023

Introduction: Obesity during pregnancy can contribute to hypertensive complications through changes in glucose utilization. We investigated the impact of vascular glucose uptake, GLUT4 density, and endothelium on agonist-induced vasoconstriction in the aortas of overweight pregnant rats. Methods: Isolated aortic rings with or without endothelium from pregnant or nonpregnant rats fed a standard (SD) or hypercaloric diet (HD) were contracted with phenylephrine or serotonin (10−9 to 10−4M) using standard (11 mm) or without (0 mm) glucose Krebs solution. GLUT4 density in the aortas was measured using the en face method. Results: Aortas from overweight pregnant animals (PHD) showed increased Phe-induced vasoconstriction (p < 0.05 vs. pregnant standard diet [PSD]), which was endothelium-independent. The contraction decreased significantly in the absence of glucose. In contrast, vessels from pregnant SD rats maintained their contraction in glucose-free Krebs solution. 5-HT increases PHD aortic contraction only in the absence of glucose. The fetal aortas from PHD mothers showed blunted vasoconstriction. Overweight significantly reduced GLUT4 expression in maternal and fetal aortas (p < 0.05 vs. PSD). Conclusions: Aortic contractility is independent of glucose uptake during healthy pregnancy. In contrast, overweight pregnancy increases contractility. This increase depends directly on smooth muscle glucose uptake and inversely on GLUT-4 density. The increased contraction observed in the vasculature of overweight mothers was inverted in the fetal aortas.
Esophageal Motility Disorders: Diagnosis and Treatment Strategies
Authors: Hoshikawa Yoshimasa , Iwakiri Katsuhiko
Published: October 2023

Background: Esophageal motility disorders (EMDs) are caused by the impaired relaxation of the upper/lower esophageal sphincter and/or defective esophageal peristaltic contractions, resulting in dysphagia and noncardiac chest pain. High-resolution manometry (HRM) is essential for the diagnosis of primary EMD; however, the recognition of EMD and HRM by general practitioners in Japan is limited. This review summarizes the diagnosis of and treatment strategies for EMD. Summary: HRM is a specific test for the diagnosis of EMD, whereas endoscopy and barium swallow as screening tests provide characteristic findings (i.e., esophageal rosette and bird’s beak sign) in some cases. It is important to note that manometric diagnoses apart from achalasia are often clinically irrelevant; therefore, the recently updated guidelines suggest additional manometric maneuvers, such as the rapid drink challenge, and further testing, including functional lumen imaging, for a more accurate diagnosis before invasive treatment. Endoscopic/surgical myotomy, pneumatic dilation, and botulinum toxin injections need to be considered for patients with achalasia and clinically relevant esophagogastric junction outflow obstruction. Key Message: Since the detailed pathophysiology of EMD remains unclear, their diagnosis needs to be cautiously established prior to the initiation of invasive treatment.
Considerations for Colorectal Neoplasia Detection in Inflammatory Bowel Disease Clinical Trials
Authors: Yang Mira M. , Usiskin Keith , Ahmad Harris A. , Ather Shabana , Sreih Antoine , Canavan James B. , Farraye Francis A. , Ma Christopher
Published: October 2023

Background: High-quality colonoscopic surveillance can lead to earlier and increased detection of colorectal neoplasia in patients with inflammatory bowel disease (IBD). In IBD clinical trials, endoscopy is used to assess mucosal disease activity before and after treatment but also provides an opportunity to surveil for colorectal neoplasia during follow-up. Summary: Best practices for colorectal cancer identification in IBD clinical trials require engagement and collaboration between the clinical trial sponsor, site endoscopist and/or principal investigator, and central read team. Each team member has unique responsibilities for maximizing dysplasia detection in IBD trials. Key Messages: Sponsors should work in accordance with scientific guidelines to standardize imaging procedures, design the protocol to ensure the trial population is safeguarded, and oversee trial conduct. The site endoscopist should remain updated on best practices to tailor sponsor protocol-required procedures to patient needs, examine the mucosa for disease activity and potential dysplasia during all procedures, and provide optimal procedure videos for central read analysis. Central readers may detect dysplasia or colorectal cancer and a framework to report these findings to trial sponsors is essential. Synergistic relationships between all team members in IBD clinical trials provide an important opportunity for extended endoscopic evaluation and colorectal neoplasia identification.
Allostatic Load in Children and Adolescents: A Systematic Review
Authors: Lucente Marcella , Guidi Jenny
Published: October 2023

Introduction: The concept of allostatic load encompasses the cumulative effects of both ordinary daily life events as well as major challenges, and also includes related health-damaging behavior. Allostatic overload ensues when environmental challenges exceed the individual’s ability to cope. Identification of allostatic load is carried out through the use of biomarkers and clinimetric criteria. Studies are increasingly reported on allostatic load in younger populations, yet a systematic review is missing. Objective: The aim of the present systematic review was to summarize the current knowledge on allostatic load/overload among children and adolescents. Methods: PubMed, PsycINFO, Web of Science, and the Cochrane Library were searched from inception to April 2023. A manual search of the literature was also performed. We considered only studies in which allostatic load or overload were adequately described and assessed in either clinical or non-clinical populations younger than 18 years. Results: A total of 38 original investigations were included in this systematic review. Studies reported an association between allostatic load and sociodemographic characteristics (e.g., poverty, ethnicity, perceived discrimination, adverse childhood experiences) and environmental factors, as well as consequences of allostatic load on both physical and mental health among children and adolescents. Conclusions: The findings indicate that greater allostatic load is associated with poorer health outcomes in both clinical and non-clinical pediatric populations, with possible enduring effects. The results support the clinical utility of the transdiagnostic identification of allostatic load and overload in children and adolescents across a variety of settings, with a number of potential clinical implications.
Diagnostic Endoscopic Ultrasound in Pancreatology: Focus on Normal Variants and Pancreatic Masses
Authors: Vitali Francesco , Zundler Sebastian , Jesper Daniel , Wildner Dane , Strobel Deike , Frulloni Luca , Neurath Markus F.
Published: October 2023

Background: Endoscopic ultrasound (EUS) is a main tool in gastroenterology for both diagnosis and exclusion of pancreatic pathology. It allows minimally invasive assessment of various diseases or anatomic variations affecting the pancreas also with the help of new Doppler technologies, elastography, contrast-enhanced imaging including post hoc image processing with quantification analyses, three-dimensional reconstruction, and artificial intelligence. EUS also allows interventional direct access to the pancreatic parenchyma and the retroperitoneal space, to the pancreatic duct, pancreatic masses, cysts, and vascular structures. Summary: This review aimed to summarize new developments of EUS in the field of pancreatology. We highlight the role of EUS in evaluating pancreatic pathology by describing normal anatomic variants like pancreas divisum, pancreatic lipomatosis, pancreatic fibrosis in the elderly and characterizing pancreatic masses, both in the context of chronic pancreatitis and within healthy pancreatic parenchyma. EUS is considered the optimal imaging modality for pancreatic masses of uncertain dignity and allows both cytological diagnosis and histology, which is essential not only for neoplastic conditions but also for tailoring therapy for benign inflammatory conditions. Key Messages: EUS plays an indispensable role in pancreatology and the development of new diagnostic and interventional approaches to the retroperitoneal space and the pancreas exponentially increased over the last years. The development of computer-aided diagnosis and artificial intelligence algorithms hold the potential to overcome the obstacles associated with interobserver variability and will most likely support decision-making in the management of pancreatic disease.
Endoscopic Ultrasound in Pancreatology: Focus on Inflammatory Diseases and Interventions
Authors: Vitali Francesco , Zundler Sebastian , Jesper Daniel , Strobel Deike , Wildner Dane , de Pretis Nicoló , Frulloni Luca , Crinó Stefano Francesco , Neurath Markus F.
Published: October 2023

Background: Endoscopic ultrasound (EUS) is a main tool in pancreatology for both diagnosis and therapy. It allows minimally invasive differentiation of various diseases, with a minimal degree of inflammation or anatomic variations. EUS also enables interventional direct access to the pancreatic parenchyma and the retroperitoneal space, the pancreatic duct, the pancreatic masses, cysts, vascular structures for diagnostic and therapeutic purposes. Summary: This review aimed to summarize the new developments of EUS in the field of pancreatology, with special interest on inflammation and interventions. EUS enables way to perform pseudocyst drainage, necrosectomy, transenteral drainage and transenteric access of the main pancreatic duct, or the direct visualization or therapy of vascular structures adjacent to the pancreas. Key Messages: EUS has a deep impact on pancreatology, and the development of new diagnostic and interventional approaches to the retroperitoneal space and the pancreas has increased in the last years exponentially, allowing minimal invasive diagnostics and therapy and avoiding surgery and percutaneous therapy.
Evaluation of the Neonatal Sequential Organ Failure Assessment and Mortality Risk in Neonates with Early-Onset Infection
Authors: Yeo Kee Thai , Goh Guan Lin , Park Woo Yeon , Wynn James L. , Aziz Khyzer B.
Published: October 2023

Background: The discriminative utility of the neonatal sequential organ failure assessment (nSOFA) for early-onset sepsis (EOS) mortality in the neonatal intensive care unit (NICU) is unknown. Objectives: The objective of the study was to determine the utility of nSOFA for EOS mortality. Methods: Multicenter, retrospective cohort study of NICU patients with EOS between 2012 and 2023. nSOFA scores of survivors and non-survivors were compared, and area under the receiver operating characteristics curve (AUROC) for mortality was calculated. Results: 104 subjects were identified (88 lived, 16 died). AUROC at blood culture collection (T0), 6 h after collection (T6), and the maximum nSOFA at T0 or T6 (T0–6max) were 0.76 (95% CI: 0.62, 0.91), 0.89 (0.80, 0.99), and 0.87 (0.77, 0.97), respectively. Analyses restricted to birthweight (<1.5, <1 kg) or gestational age (<32, <29 week) cutoffs revealed AUROC ranges of 0.86–0.92 for T6 and 0.82–0.84 for T0–6max. Conclusions: The nSOFA showed good-to-excellent discrimination of mortality among infants with EOS in the NICU.
Characteristics of Severe Asthma Patients and Predictors of Asthma Control in the Swiss Severe Asthma Registry
Authors: Jaun Fabienne , Tröster Lydia Marie , Giezendanne Stéphanie , Bridevaux Pierre-Olivier , Charbonnier Florian , Clarenbach Christian , Gianella Pietro , Jochmann Anja , Kern Lukas , Miedinger David , Pavlov Nikolay , Rothe Thomas , Steurer-Stey Claudia , von Garnier Christophe , Leuppi Jorg D.
Published: October 2023

Background: Asthma is a chronic airway disease, affecting over 300 million people worldwide. 5–10% of patients suffer from severe asthma and account for 50% of asthma-related financial burden. Availability of real-life data about the clinical course of severe asthma is insufficient. Objectives: The aims of this study were to characterize patients with severe asthma in Switzerland, enrolled in the Swiss Severe Asthma Registry (SSAR), and evaluate predictors for asthma control. Method: A descriptive characterisation of 278 patients was performed, who were prospectively enrolled in the registry until January 2022. Socio-demographic variables, comorbidities, diagnostic values, asthma treatment, and healthcare utilisation were evaluated. Groups of controlled and uncontrolled asthma according to the asthma control test were compared. Results: Forty-eight percent of patients were female and the mean age was 55.8 years (range 13–87). The mean body mass index (BMI) was 27.4 kg/m2 (±6). 10.8% of patients were current smokers. Allergic comorbidities occurred in 54.3% of patients, followed by chronic rhinosinusitis (46.4%) and nasal polyps (34.1%). According to the ACT score, 54.7% had well controlled, 16.2% partly controlled and 25.9% uncontrolled asthma. The most common inhalation therapy was combined inhaled corticosteroids/long-acting β2-agonists (78.8%). Biologics were administered to 81.7% of patients and 19.1% received oral steroids. The multivariable analysis indicated that treatment with biologics was positively associated with asthma control whereas higher BMI, oral steroids, exacerbations, and COPD were negative predictors for asthma control. Conclusion: Biologics are associated with improved control in severe asthma. Further studies are required to complete the picture of severe asthma in order to provide improved care for those patients.
Risk of Reintervention or Postoperative Bleeding after Laparoscopy for Benign Gynecological Disease: A Clinical Prediction Model
Authors: Šalamun Vesna , Riemma Gaetano , Pavec Manca , Laganà Antonio Simone , Ban Frangež Helena
Published: October 2023

Objective: The objective of the study was to develop a clinically applicable prediction tool to early seek for postoperative major complications after laparoscopic surgery for benign pathologies. Design: Retrospective analysis of prospectively collected data was performed. Setting: The study was conducted at Tertiary Care University Hospital. Participants: The participants of this study were reproductive-aged women undergoing laparoscopy for benign conditions. Methods: Anamnestic, intraoperative, and postoperative characteristics from January 2019 to December 2021 were retrospectively reviewed. Patients with postoperative complications (reintervention or postoperative bleeding) were matched in a 1:2 ratio with women with same surgical indications without complications. Cases and controls were matched for preoperative hemoglobin, hematocrit, weight, height, body mass index, age, and blood volume. A prediction model was created by inserting multiple independent modifying factors through logistic regression. The receiver operating characteristic (ROC) curve was used to evaluate the predictive accuracy of the model, and the Hosmer-Lemeshow (H-L) test was carried out to evaluate the goodness-of-fit, and a calibration curve was drawn to confirm the predictive performance. A nomogram was depicted to visualize the prediction model. Results: Thirty-nine complicated procedures were matched with 78 uncomplicated controls. According to the multivariate logistic regression analysis findings, the prediction model was developed using C-reactive protein (CRP), intraoperative blood loss, and 24 h postoperative urinary volume, therefore a nomogram was generated. The area under the ROC curve of the prediction model was 0.879, depicting good accuracy, the sensitivity was 60.00%, while specificity reached 93.59%. The H-L test (χ2 = 4.45, p = 0.931) and the calibration curve indicated a good goodness-of-fit and prediction stability. Limitations: The retrospective design, moderate sensitivity, and study population limit the generalization of the findings, requiring additional research. Conclusions: This prediction model based on CRP, intraoperative blood loss, and 24 h postoperative urinary volume might be a potentially useful tool for predicting reintervention and postoperative bleeding in patients undergoing planned gynecological laparoscopy.
Inhibition of Piezo1 Ameliorates Intestinal Inflammation and Limits the Activation of Group 3 Innate Lymphoid Cells in Experimental Colitis
Authors: Liu Chang , Xia Yanan , Fu Shichen , Meng Fanyi , Feng Bingcheng , Xu Leiqi , Li Lixiang , Zuo Xiuli
Published: October 2023

Piezo1, the mechanosensory ion channel, has attracted increasing attention for its essential roles in various inflammatory responses and immune-related diseases. Although most of the key immune cells in inflammatory bowel disease (IBD) have been reported to be regulated by Piezo1, the specific role of Piezo1 in colitis has yet to be intensively studied. The present study investigated the impact of pharmacological inhibition of Piezo1 on dextran sulfate sodium (DSS)-induced colitis and explored the role of Piezo1 in intestinal immune cells in the context of colitis. We observed upregulated expression of Piezo1 in the colon tissue of mice with DSS-induced colitis. Pharmacological inhibition of Piezo1 by GsMTx4 diminished the severity of colitis. Piezo1 inhibition downregulated the expression of pro-inflammatory mediators Il1b, Il6, and Ptgs2 in colonic tissue and suppressed the production of IL-6 from macrophages and dendritic cells without altering the balance of T helper (Th) cells. In particular, Piezo1 did not affect cell viability but regulated cell proliferation and production of IL-17A in group 3 innate lymphoid cells (ILC3s), which is dependent on the PI3K-Akt-mTOR signaling pathway. Our findings uncover Piezo1 as an effective regulator of gut inflammation. Targeting Piezo1 could be a promising strategy to modulate intestinal immunity in IBD.
A Global, Regional, and National Survey on Burden and Quality of Care Index of Multiple Sclerosis: Global Burden of Disease Systematic Analysis 1990–2019
Authors: Maroufi Seyed Farzad , Shobeiri Parnian , Mohammadi Esmaeil , Azadnajafabad Sina , Malekpour Mohammad-Reza , Ghasemi Erfan , Rashidi Mohammad-Mahdi , Saeedi Moghaddam Sahar , Rezaei Nazila , Sharifnejad Tehrani Yeganeh , Mohammadi Fateh Sahar , Ahmadi Naser , Farzi Yosef , Rezaei Negar , Larijani Bagher
Published: October 2023

Background: Multiple sclerosis (MS) is a common neurologic autoimmune disorder. We have used a newly introduced measure, Quality of Care Index (QCI), which is associated with the efficacy of care given to patients suffering from MS. Objectives: The aims of the study were to report and compare the quality of care given to MS patients in different regions and country. Methods: Primary measures were retrieved from Global Burden of Disease (GBD) from 1990 to 2019. Secondary measures (mortality-to-incidence ratio, DALY-to-prevalence ratio, prevalence-to-incidence ratio, and YLL-to-YLD ratio) were combined using principal component analysis, to form an essential component (QCI) (0–100 index with higher values representing better condition). Results: In 2019, there were 59,345 (95% UI: 51,818–66,943) new MS incident cases globally. Global QCI of 88.4 was calculated for 2019. At national level, Qatar had the highest quality of care (100) followed by Kuwait (98.5) and Greenland (98.1). The lowest QCI was observed in Kiribati (13.5), Nauru (31.5), and Seychelles (36.3), respectively. Most countries have reached gender equity during the 30 years. Also, QCI was lowest in ages from 55 to 80 in global scale. Conclusion: MS QCI is better among those countries of higher socioeconomic status, possibly due to better healthcare access and early detection in these regions. Countries could benefit from adopting the introduced QCI to evaluate the quality of care given to MS patients at national and global level.
Topic and Content of Personal Narratives of Children from Three East Asian Cultures and Three English-Speaking Cultures: A Collaborative Qualitative Analysis
Authors: Westby Carol E. , Chen Kai-Mei , Lee Jisun P. , Wong Anita Mei-Yin
Published: October 2023

Purpose/Introduction: Narrative language skills are critical for effective social interactions and academic success. Consequently, narratives are regularly an aspect of assessment and intervention for children with communication impairments, supporting the need for information about typical development from children across cultures. Development of coherent personal narratives is associated with growth of both one’s individual identity and cultural identity which are linked to psychological well-being. The topics and contents of children’s personal stories can provide insight into cultural influences on what children consider important, how they interpret experiences, and their values and beliefs, which in turn contribute to their developing individual and cultural self-identity. The purpose of this study was to investigate the topics and content of personal narratives told by typically developing 10-year-old children from East Asian and Western English-speaking cultures. Methods: There were 20 children in each of three East Asian language groups – Mandarin, Cantonese, and Korean; and 62 children in the English-speaking groups (22 in the USA and 20 each in the Australian and New Zealand groups). In each group, half were boys and half were girls. Children responded to prompts from the Global TALES protocol to elicit personal narratives. All language samples were transcribed, translated, and coded for topic choices using qualitative content analysis in collaborative discussions by the four authors, who included an English-speaking author from the USA (C.E.W.), and three authors, who are native speakers of the three East Asian languages, Mandarin (K.-M.C.), Cantonese (A.M.-Y.W.), and Korean (J.P.L.). Results: Results on topics in stories from East Asian and Western English-speaking cultures are described in relation to literature on anthropology. English-speaking children and East Asian children in this study talked about similar topics in their personal narratives, but the frequency of these topics within their stories varied. Possible explanations for differences in story topics are discussed within a framework on cultural dimensions. Conclusion: Evaluation of the topics of children’s personal narratives provides insight into what is important to the children and the way they view their worlds. This information may inform clinical approaches to assessment and intervention with children with communication impairments, encouraging clinicians to go beyond analysis of language structure to consider multiple factors that influence communicative competence.