bluuebunny/crossref_metadata_2025 huggingface dataset:
Cohort Profile Update: The Swiss Eosinophilic Esophagitis Cohort Study (SEECS)
Authors: Wakim El-Khoury Jeanine , Safroneeva Ekaterina , Saner Catherine , Rossel Jean-Benoit , Trelle Sven , Zwahlen Marcel , Biedermann Luc , Kreienbuehl Andrea , Greuter Thomas , Schreiner Philipp , Netzer Peter , Franke Annett , Brand Stephan , Hasler Chantal , Aepli Patrick , Burri Emanuel , Weber Achim , Sempoux Christine , Biral Ruggero , Jochum Wolfram , Diebold Joachim , Willi Niels , Straumann Alex , Schoepfer Alain M. ,   on behalf of the Swiss EoE Cohort Study Group
Published: August 2024

Introduction: The Swiss Eosinophilic Esophagitis Cohort Study (SEECS) is a national cohort that was established in 2015 with the aim of improving quality of care of affected adults with eosinophilic esophagitis (EoE). Between 2020 and 2022, paper questionnaires were gradually replaced by fully electronic data capture using Research Electronic Data Capture (REDCap®) software. We aim to provide an update of the SEECS 8 years after its launch. Methods: The SEECS prospectively includes adults (≥18 years of age) with EoE as well as patients with gastroesophageal reflux disease (GERD) and healthy control subjects (HC). Upon inclusion and follow-up (typically once every 12–18 months), patients and physicians complete REDCap® questionnaires, which are available in German, French, and English. Patient-reported outcomes (PROs) and biologic findings are assessed on the same day using validated instruments (EEsAI PRO for symptoms; EoE-QoL-A for QoL; EREFS for endoscopic activity; modified EoE-HSS for histologic activity). The SEECS biobank includes biosamples from patients with EoE, GERD, and HC. Results: As of July 2023, the SEECS included 778 patients (716 [92%] with EoE, 29 [3.8%] with GERD, and 33 [4.2%] HC; 559/778 [71.9%] were male). Mean age ± SD (years) at enrollment according to diagnosis was as follows: EoE 41.9 ± 12.9, GERD 53.6 ± 16.4, HC 51.7 ± 17.2. Concomitant GERD was found in 200 patients (27.9%) of the EoE cohort. Concomitant allergic disorders (asthma, rhinoconjunctivitis, eczema) were present in 500 EoE patients (74.4%). At inclusion, 686 (95.8%) of EoE patients were on ongoing treatment (orodispersible budesonide tablet [Jorveza®] in 281 patients [41%]; budesonide or fluticasone syrup or swallowed powder in 290 patients [42.3%]; proton-pump inhibitors in 162 patients [23.6%]; elimination diets in 103 patients [15%]; and esophageal dilation at last visit in 166 patients [24.2%]). A total of 8,698 biosamples were collected, of which 1,395 (16%) were used in the framework of translational research projects. Conclusion: SEECS continuously grows and is operational using fully electronic data capture. SEECS offers up-to-date epidemiologic and real-world clinical efficacy data on EoE and promotes clinical and translational research.
Multidisciplinary Treatment for Locally Advanced Mucinous Breast Cancer
Authors: Hayashi Masanori , Oura Shoji , Nishiguchi Haruka
Published: August 2024

Background: Due to its indolent biology and high estrogen receptor positivity of mucinous breast cancer, vast majority of locally advanced mucinous breast cancer (LABC) are treated with first-line endocrine therapy. Case Presentation: A 50-year-old woman was referred to our hospital for the treatment of her huge breast tumor. Computed tomography showed an oval solid tumor, 17 cm in size, and lymph node swelling in both the axilla and parasternum. Pathological study of the core needle biopsy specimen showed the tumor to be luminal mucinous carcinoma. After the failure of endocrine therapy aiming for tumor regression, the patient received sequential chemotherapy to get favorable local control, leading to marked tumor shrinkage. Axillar and parasternal lymph nodes, however, remained unchanged in size. The patient further underwent mastectomy and regional lymph node dissection including removal of the still enlarged parasternal lymph nodes followed by covering of the large skin defect with the latissimus dorsi musculocutaneous (LDMC) flap using a spindle skin island, 15 × 8 cm in size. Postoperative pathological study showed sparse cancer cell remnants with abundant mucus in both the primary tumor and the dissected lymph nodes. The patient has been well without any recurrences on endocrine therapy for 21 months. Conclusion: Breast oncologists should note that multidisciplinary treatment including preoperative chemotherapy and skin defect covering using LDMC flap can give favorable local control even to breast cancer patients with LABC.
New Perspectives in the Treatment of Inflammatory Myofibroblastic Tumor with ALK Translocation: Case Report
Authors: Benedetti Pedroza Johana , Carrasco García Irene , Martínez Bernal Gala , Miras Rodriguez Isabel
Published: August 2024

Introduction: Inflammatory myofibroblastic tumor (IMT) is a rare entity, classified within soft tissue sarcomas. It is an intermediate malignancy tumor, which seldom presents as metastatic disease. The treatment of choice is surgery, except in cases where surgery is not possible due to localization or if it presents with metastatic disease. Approximately 50% of IMTs will exhibit ALK translocation, providing a therapeutic target for these patients. Case Presentation: A case is presented of a patient with metastatic IMT in complete response to treatment with alectinib, maintained for over 4 years. Conclusion: This case showed a long time complete response in patient with IMT treated with alectinib.
Serum B-Cell Maturation Antigen Reflects Disease Status in a Patient Who Developed Nonsecretory Multiple Myeloma: A Case Report
Authors: Danis Ryan , Regidor Bernard , Bujarski Sean , Jew Scott , Goldwater Marissa-Skye , Swift Regina , Eades Benjamin Mark , Emamy-Sadr Marsiye , Del Dosso Ashley , Berenson James
Published: August 2024

Introduction: Multiple myeloma (MM) is an incurable bone marrow (BM)-based cancer involving clonal plasma cells. Most patients show elevated levels of serum monoclonal protein (sMP) and kappa or lambda serum free light chains (sFLCs) at diagnosis. However, around 1–2% of patients, termed nonsecretory, do not produce these biomarkers. As the disease progresses, more patients may become unevaluable using conventional markers, requiring invasive and expensive procedures like BM biopsies and positron emission tomography-computed tomography (PET-CT) scans for assessment and highlighting the need for alternative methods to monitor disease progression. Case Presentation: We present a case report of an MM patient who developed nonsecretory disease during his second line of treatment when he complained of new rib pain; progressive disease was then confirmed on a PET-CT scan. The patient showed an increase in his serum B-cell maturation antigen (sBCMA) levels whereas his conventional myeloma markers did not detect disease activity (sMP remained undetectable and involved sFLC level was normal). After starting a new treatment regimen, his rib pain disappeared, PET-CT scan improved, and sBCMA levels decreased. Upon relapse, he developed increased rib pain with a rising sBCMA level; his conventional myeloma markers did not detect disease activity. After changing to a new regimen, his rib pain improved, and this was accompanied by a decrease in his sBCMA levels. Conclusion: Thus, this case exemplifies the potential for sBCMA to provide a non-invasive method for monitoring MM patients who develop nonsecretory disease.
Construction and Validation of a Risk Prediction Model for Mild Cognitive Impairment in Non-Dialysis Chronic Kidney Disease Patient
Authors: Xu Wenbin , Yang Qin , Li Lin , Xiang Yuhe , Yang Qian
Published: August 2024

Introduction: The aims of this study are to explore the factors affecting mild cognitive impairment in patients with chronic kidney disease (CKD) who are not undergoing dialysis and to construct and validate a nomogram risk prediction model. Methods: Using a convenience sampling method, 383 non-dialysis CKD patients from two tertiary hospitals in Chengdu were selected between February 2023 and August 2023 to form the modeling group. The patients were divided into a mild cognitive impairment group (n = 192) and a non-mild cognitive impairment group (n = 191), and factors such as demographics, disease data, and sleep disorders were compared between the two groups. Univariate and multivariate binary logistic regression analyses were used to identify independent influencing factors, followed by collinearity testing, and construction of the regression model. The final risk prediction model was presented through a nomogram and an online calculator, with internal validation using Bootstrap sampling. For external validation, 137 non-dialysis CKD patients from another tertiary hospital in Chengdu were selected between October 2023 and December 2023. Results: In the modeling group, 192 (50.1%) of the non-dialysis CKD patients developed mild cognitive impairment, and in the validation group, 56 (40.9%) patients developed mild cognitive impairment, totaling 248 (47.7%) of all sampled non-dialysis CKD patients. Age, educational level, Occupation status, Use of smartphone, sleep disorders, hemoglobin, and platelet count were independent factors influencing the occurrence of mild cognitive impairment in non-dialysis CKD patients (all p < 0.05). The model evaluation showed an area under the ROC curve of 0.928, 95% CI (0.902, 0.953) in the modeling group, and 0.897, 95% CI (0.844, 0.950) in the validation group. The model's Youden index was 0.707, with an optimal cutoff value of 0.494, sensitivity of 0.853, and specificity of 0.854, indicating good predictive performance; calibration curves, Hosmer-Lemeshow test, and clinical decision curves indicated good calibration and clinical benefit. Internal validation results showed a consistency index (C-index) of 0.928, 95% CI (0.902, 0.953). Conclusion: The risk prediction model developed in this study shows excellent performance, demonstrating significant predictive potential for early screening of mild cognitive impairment in non-dialysis CKD patients. The application of this model will provide a reference for healthcare professionals, helping them formulate more targeted intervention strategies to optimize patient treatment and management outcomes.
Episodic Angle Closure after Visian™ Implantable Collamer Lens Implantation in a Patient Using Adderall®
Authors: Moshirfar Majid , Moin Kayvon A. , Jaafar Muhammed , Han Kenneth , Omidvarnia Soroush , Hoopes Phillip C.
Published: August 2024

Introduction: Amphetamine-based medications such as Adderall®, used for the treatment of attention deficit-hyperactivity disorder (ADHD), may theoretically elicit angle closure through their adrenergic mechanisms. The relationship between the use of implantable collamer lenses (ICLs) and angle closure has been extensively investigated based on appropriate vault and lens sizing and postoperative changes in the anterior chamber angle (ACA) and corneal morphology. This case reflects a synergistic impact from both Adderall® use and ICL implantation for the proposed mechanism of angle closure. Case Presentation: A 36-year-old myopic female with ADHD controlled with Adderall® underwent toric ICL implantation in the right eye after undergoing preoperative laser peripheral iridotomy. Shortly after, the patient developed episodic angle closure in the right eye, with episodes mainly occurring after taking an additional dose of Adderall® in a dimly lit environment. The patient later had an ICL exchange with a smaller sized EVO+ toric ICL in the right eye and remained asymptomatic after. Conclusion: Additive mechanisms from both the ICL and Adderall® were present in our patient. The ICL caused crowding of the ACA through a pseudophacomorphic mechanism, and the Adderall® caused increased iridotrabecular contact secondary to pharmacologic mydriasis. This resulted in episodic angle closure with subsequent spikes in the intraocular pressure. There are no current reports or studies in the current literature describing the combined mechanisms of ICL implantation and Adderall® use in the potential development of angle closure. Further studies may be done to assess interactions of such medications in patients after ICL implantation.
Finding the Balance: Venous Thromboembolism Prophylaxis during Hematochezia in Crohn’s Disease
Authors: Kim Kain , Llanos Danielle , Ramos Christopher , Shahnavaz Nikrad , Adhyaru Bhavin B.
Published: August 2024

Introduction: Despite heightened risk of venous thromboembolism (VTE) in hospitalized patients with inflammatory bowel disease (IBD), pharmacologic prophylaxis remains underutilized, particularly in those presenting with hematochezia. Although placement of retrievable inferior vena cava filters (rIVCF) may be considered in those with contraindications to anticoagulation and VTE risk, current recommendations from clinical guidelines are incongruent, leading to wide variation in practice. Case Presentation: This report highlights a case of rIVCF used in the management of recurrent VTEs in a patient hospitalized for persistent gastrointestinal bleeding. Conclusion: Our case demonstrates the need for a lower threshold for initiating VTE prophylaxis in patients with active IBD, even when hematochezia is the presenting symptom. A small group of patients with recurrent VTE and clear contraindications to anticoagulation may require IVCFs, necessitating close follow-up and monitoring for filter complications.
Case Study of a Refractory Idiopathic Peptic Ulcer in Which 24-h Intragastric pH Monitoring Contributed to Its Pathophysiological Analysis
Authors: Iwano Tomoyo , Takeda Tsutomu , Oki Shotaro , Uemura Yasuko , Yamamoto Momoko , Uchida Ryota , Utsunomiya Hisanori , Abe Daiki , Suzuki Nobuyuki , Ikeda Atsushi , Akazawa Yoichi , Ueda Kumiko , Ueyama Hiroya , Hojo Mariko , Nagahara Akihito
Published: August 2024

Introduction: In recent years, the frequency of idiopathic peptic ulcers (IPUs) has increased. However, the clinicopathological characteristics of IPU have not been fully elucidated and treatment methods for recurrent and refractory cases have not yet been established. Case Presentation: A man in his forties complained of epigastric discomfort. Esophagogastroduodenoscopy revealed a gastric ulcer in the lesser curvature of the gastric angle. After Helicobacter pylori was eradicated, the gastric ulcer recurred despite the administration of a potassium competitive acid blocker (PCAB), and a diagnosis of IPU was made. Twenty-four-hour intragastric pH monitoring revealed insufficient gastric acid suppression. Misoprostol was added to the patient’s treatment. Subsequently, the ulcer healed and recurrence was not observed. Conclusion: For refractory IPU, the evaluation of pathophysiological function through 24-h gastric pH monitoring may lead to the selection of an appropriate treatment. If a proton pump inhibitor and PCAB do not improve the IPU, combination treatment with misoprostol may be considered as an option.
Presumptive Cytomegalovirus Retinitis as a Complication of Dyskeratosis Congenita: A Case Report
Authors: Du Yuxi , Dang Yalong
Published: August 2024

Introduction: Dyskeratosis congenita is a rare genetic disorder characterized by abnormalities of the skin, nails, and oral mucosa. Retinal involvement in this condition is uncommon. Here, we present a case of a young male patient diagnosed with presumptive cytomegalovirus retinitis, ultimately found to be concomitant with dyskeratosis congenita. Case Presentation: A non-HIV-infected young male with recurrent infections, including aspergillus pneumonia and pneumocystis pneumonia, presented with presumptive cytomegalovirus retinitis in both eyes. Systemic manifestations included cutaneous hyperpigmentation, nail dystrophy, and oral mucosal leukoplakia. Genetic testing revealed a mutation in the DKC1 gene. The final diagnosis was dyskeratosis congenita complicated by presumptive cytomegalovirus retinitis. Conclusion: Cytomegalovirus retinitis can serve as an ocular complication of dyskeratosis congenita. When a patient presents with cytomegalovirus retinitis, a comprehensive systematic examination should be conducted as it indicates severe immunodeficiency.
Burden of Disease of Bullous Pemphigoid: A Targeted Literature Review
Authors: Bahloul Donia , Dubucq Hugo , Thomas Ryan B. , Ajith Athira , Boss Jennifer , Fotheringham Iain , Kumichel Alexandra
Published: August 2024

Background: Bullous pemphigoid (BP) is a rare, chronic, autoimmune, blistering disease characterized by heterogenous lesions including the formation of fluid-filled blisters on frequently flexed areas of the skin and involvement of the mucosa in 10–25% of patients. BP mainly affects older patients and is associated with increased morbidity and mortality. The aim of the targeted literature review was to assess the clinical, humanistic, and economic burden associated with BP. Summary: Targeted searches were conducted in Embase and MEDLINE for studies published in English up to November 2022 that reported burden of illness of BP. A total of 42 publications on the clinical (n = 37), humanistic (n = 6), and economic (n = 8) burden of BP were identified. BP was associated with a high mortality rate (27–72%) and an increased risk of death compared to matched controls. The majority of patients had at least one comorbidity, including hypertension, diabetes mellitus, stroke, and neurological disorders, and showed severe symptoms such as itching and pain. BP was associated with a negative impact on BP- and pruritus-related quality of life and mental health, with 31% and 38% of patients with BP experiencing depression and anxiety in the “borderline/abnormal” range, respectively. BP was further associated with high economic burden, reflected by increased healthcare resource utilization, such as longer hospital stays (7.3 days in patients with BP vs. 4.7 days in those without BP), and direct disease-related costs. Key Messages: This review provides a detailed assessment of the evidence base for BP, characterizing key aspects of the disease burden including clinical, humanistic, and economic burden. The results emphasize that this rare disease is associated with a substantial burden to patients and have implications for clinical practice in the management of BP.
Dysthyroid Optic Neuropathy Complicated by Neuromyelitis Optica Spectrum Disorder: A Case Report
Authors: Tokuhisa Teruaki , Hayashi Takaaki , Omoto Shusaku , Kozaki Ai , Inoue Toshu , Nakano Tadashi
Published: August 2024

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder that principally targets the central nervous system, specifically the spinal cord and optic nerves. NMOSD is often associated with thyroid pathologies such as Graves’ disease or Hashimoto’s thyroiditis. Thyroid eye disease (TED) is an autoimmune condition characterized by inflammation and hypertrophy of the extraocular muscles. Dysthyroid optic neuropathy (DON), a critical complication of TED, may lead to irreversible visual loss. We report a case of DON complicated by NMOSD. Case Presentation: We report a case of an autoimmune disease presenting as DON in a 44-year-old Japanese woman with a history of Graves’ disease, who experienced reduced visual acuity and orbital pain. Brain magnetic resonance imaging disclosed hypertrophy of the rectus muscles, compressing the optic nerve bilaterally. Consequently, she was diagnosed with DON and underwent three courses of steroid semi-pulse therapy and left orbital decompression surgery, alleviating optic nerve compression. Nevertheless, the visual prognosis remained poor. A subsequent serological test showed positive for aquaporin-4 antibody. Treatment with satralizumab, an interleukin-6 receptor monoclonal antibody, was initiated in conjunction with steroids to suppress the autoimmune response and reduce NMOSD relapse risk. Following this treatment, no NMOSD recurrences were reported. Conclusion: This case highlights the necessity of considering the possible coexistence of DON and NMOSD in patients with autoimmune diseases.
Cardiopulmonary Response to Acute Exercise before Hemodialysis: A Pilot Study
Authors: Hsiao Ching-Chung , Chou Chuan-Yi , Fang Ji-Tseng , Chang Shih-Chieh , Liu Kuo-Cheng , Huang Shu-Chun
Published: August 2024

Introduction: Disparities in physical fitness between immediately before dialysis (pre-D) and the day following dialysis (non-D) have not been investigated despite potential adverse factors such as fluid status, uremia, and electrolyte levels in the pre-dialysis period. The effect of acute exercise immediately before hemodialysis (HD) on HD-related hypotension remains unclear. We hypothesized that cardiopulmonary performance and muscular strength would be inferior in the immediate pre-D period compared to those non-D. Methods: Twenty patients receiving chronic HD treatments underwent symptom-limited incremental cardiopulmonary exercise testing (CPET) and isokinetic testing both 1–2 h prior to dialysis (pre-D) and non-D. This investigation was a sub-study of a clinical trial assessing the efficacy of a pre-D exercise training program. Blood pressure profiles during HD post-CPET and pre-D exercise training were compared with those during usual HD sessions. Results: No adverse events were observed during the 80 exercise tests. Prior to dialysis, the nadir of the ventilatory equivalent of CO2 was slightly elevated, the resting heart rate was lower, and the peak systolic blood pressure was higher than those non-D. Contrary to our hypothesis, peak V˙O2 and quadriceps peak torque showed no differences. Blood pressure profiles during HD post-exercise were similar to those during sessions without prior exercise, except for a lower resting systolic blood pressure at the beginning of HD. Conclusion: Cardiopulmonary response and muscular strength in the 1–2 h prior to HD were comparable with those on the day following HD, with only minor clinically insignificant differences. Acute exercise prior to HD did not affect the magnitude of hypotension during HD. This study suggests a potential alternative timing for exercise training or testing in patients undergoing chronic HD.
Prognostic and Clinical Significance of the Proliferation Marker MCM7 in Breast Cancer
Authors: Lashen Ayat G. , Toss Michael S. , Rutland Catrin S. , Green Andrew R. , Mongan Nigel P. , Rakha Emad
Published: August 2024

Introduction: Minichromosome maintenance complex component 7 (MCM7) plays an essential role in proliferation and DNA replication of cancer cells. However, the expression and prognostic significance of MCM7 in breast cancer (BC) remain to be defined. In this study, we aimed to evaluate the role of MCM7 in BC. Methods: We conducted immunohistochemistry staining of MCM7 in 1,156 operable early-stage BC samples and assessed MCM7 at the transcriptomic levels using publicly available cohorts (n = 13,430). MCM7 expression was evaluated and correlated with clinicopathological parameters including Ki67 labelling index and patient outcome. Results: At the transcriptomic level, there was a significant association between high MCM7 mRNA levels and shorter patient survival in the whole cohort and in luminal BC class but not in the basal-like molecular subtype. High MCM7 protein expression was detected in 43% of patients and was significantly associated with parameters characteristic of aggressive tumour behaviour. MCM7 was independently associated with shorter survival, particularly in oestrogen receptor-positive (luminal) BC. MCM7 stratified luminal tumours with aggressive clinicopathological features into distinct prognostic groups. In endocrine therapy-treated BC patients, high MCM7 was associated with poor outcome, but such association disappeared with administration of adjuvant chemotherapy. Patients with high expression of Ki67 and MCM7 showed worst survival, while patients with double low expression BC showed the best outcome compared with single expression groups. Conclusion: The current findings indicate that MCM7 expression has a prognostic value in BC and can be used to identify luminal BC patients who can benefit from adjuvant chemotherapy.
Obstruktive Schlafapnoe: Pneumothorax nach Implantation eines Zungenschrittmachers – häufiger als gedacht!
Authors: Keymel Stefanie
Published: August 2024

Objective: There have been case reports of adverse events of hypoglossal nerve stimulator (HNS) implantation not seen in previous clinical trials, including pneumothorax and pleural effusion. The purpose of this study was to determine the rates of these complications and potential risk factors. Study Design: Retrospective case-control study during 2014 to 2021. Setting: Twenty-five health care organizations across the United States. Methods: The TriNetX Research Network was queried by using disease codes to retrospectively identify patients with obstructive sleep apnea who underwent HNS implantation. Rates of pneumothorax, pleural effusion, other complications, and need for revision/replacement or explant were determined. Results: We identified 1813 patients from 25 health care organizations who underwent HNS implantation. The average age was 60 years, and there were 68% males and 32% females. Of the cohort, 2.4% (n = 44 from 7 implant centers) experienced a pneumothorax, and 0.6% (n = 11) were diagnosed with a pleural effusion on the day of surgery. Patients who experienced pneumothorax were more likely to have a history of chronic lower respiratory diseases when compared with those who did not (odds ratio, 2.2; 95% CI, 1.1–4.1; P = .02).
Intestinal ultrasonography diagnostic performance and feasibility in IBD during pregnancy: a systematic review and narrative synthesis.
Authors: Pillet Julie , Voirol-Perrin Julia , Martel Myriam , Kherad Omar , Restellini Sophie
Published: August 2024

Introduction: Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC) are associated to poor maternal and foetal outcomes during pregnancy, requiring a strict monitoring of the disease activity, preferably with non-invasive modalities. There are numerous data confirming intestinal ultrasonography (IUS) accuracy and efficacy for the detection of IBD disease activity and complications, but data in pregnant IBD patients are scarce. We aimed to evaluate the diagnostic performance and feasibility of IUS to monitor IBD activity throughout pregnancy.

Methods: A systematic literature review has been performed identifying studies the use of ultrasound modality in pregnant inflammatory bowel disease women from date of inception until April 2024 using MEDLINE, Cochrane library, EMBASE and ISI Web of Science databases, with keywords including 1) ultrasound/ultrasonography2) pregnancy, and 3) IBD (CD and UC). Additional relevant studies were identified from cross-referencing and hand-searches of references of the retrieved articles. We included fully published observational studies and abstracts.

Results: Overall, five studies have been selected from 264 citations. All studies were highly heterogeneous in the definition of disease activity as reference standard, IUS protocols, and outcomes. Two of them used a cut off value of fecal calprotectin (FCP) >100 [ug/g]. In one of them, clinical scores were used when FCP value was ≥100-249 [ug/g] and FCP ≥ 250 [ug/g] was considered as an active disease independently of clinical scores. Only one study used a single reference standard with a Harvey Bradshaw Index (HBI) >4. Across these 3 studies, results suggest a relatively good specificity (range 83%-98%) but low sensitivity (range 33%-84%) to detect disease’s activity. Only 1 study analysed IUS performance in detecting remission with a sensitivity of 80% and a specificity of 92% compared to the reference standard. The size of the uterus limits the visualization of the terminal ileum and the sigmoid from the second trimester and the third trimester respectively. The evaluation of the rectum remains limited.

Conclusion: IUS appears to offer a practical, readily available and non-invasive means of monitoring disease activity in IBD pregnant women. However, existing literature on IUS accuracy is limited and further studies with standardized reference comparator are needed.
Blue Dye-Assisted Intraoperative Optical Coherence Tomography for Macular Surgery
Authors: Pellegrini Marco , Adamo Ginevra , Sarti Laura , Talli Pietro Maria , Nasini Francesco , Mura Marco
Published: August 2024

Introduction: The purpose of this study was to evaluate whether vital blue dyes could enhance the contrast of intraoperative optical coherence tomography (OCT) during macular surgery. Methods: Consecutive patients undergoing elective pars plana vitrectomy for vitreomacular interface disorders were enrolled. Intraoperative OCT was performed with the Artevo 800 microscope (Carl Zeiss Meditec AG, Jena, Germany) before and after injection of 0.2 mL of Trypan Blue and Brilliant Blue G Ophthalmic Solution. The OCT contrast ratio was measured with ImageJ, while the overall scan quality was subjectively classified using a 4-point scale. Results: Ten eyes of 10 patients were enrolled in the study. The OCT contrast ratio was 9.39 ± 5.35 without blue dye and significantly improved to 14.31 ± 10.50 after blue dye injection (p = 0.027). The percentage of patients with a grade 4 scan quality also significantly improved (from 40% without blue dye to 90% with blue dye injection; p = 0.012). Conclusion: The use of blue dyes during intraoperative OCT is an effective strategy for improving contrast and scan quality without affecting the surgical time and workflow.
An Overlap of Anticoagulant-Related and IgA Nephropathy: A Case Report
Authors: Galloway Mercedes , Sim John J. , Slater Andrew , Bray Christopher , Bishev Daniel , Walker Patrick
Published: August 2024

Introduction: Anticoagulant-related nephropathy (ARN) is an increasingly recognized cause of acute kidney injury (AKI), initially associated with warfarin use. Supratherapeutic warfarin levels were implicated in kidney toxicity. With the widespread adoption of direct oral anticoagulants (DOACs), it becomes imperative to understand their potential risk for ARN and its clinical presentation. Case Presentation: We report a case of a 64-year-old male prescribed DOAC for paroxysmal atrial fibrillation management, presenting with heart failure and worsening AKI. Hematuria and mild proteinuria were also observed. Despite management attempts, AKI persisted, prompting a kidney biopsy. Histopathological examination revealed acute tubular injury with numerous intratubular red blood cell casts consistent with ARN. Additionally, findings indicative of IgA nephropathy (IgAN), including mesangial hypercellularity and IgA dominant deposition, were noted. Conclusion: This case underscores the emerging risk of ARN associated with DOACs and emphasizes the potential exacerbation of ARN in the presence of underlying glomerular diseases such as IgAN. Clinicians should maintain a high index of suspicion for ARN in patients on anticoagulation therapy, particularly DOACs, who present with AKI and urinary abnormalities, as early recognition and intervention are crucial in preventing further renal damage.
Sustained Reduction of Elevated Intact Parathyroid Hormone Concentrations with Extended-Release Calcifediol Slows Chronic Kidney Disease Progression in Secondary Hyperparathyroidism Patients
Authors: Bishop Charles W. , Ashfaq Akhtar , Strugnell Stephen A. , Choe John , Patel Nilay , Norris Keith C. , Sprague Stuart M.
Published: August 2024

Introduction: Chronic kidney disease (CKD) drives onerous human and healthcare costs, underscoring an urgent need to avert disease progression. Secondary hyperparathyroidism (SHPT) develops as CKD advances, and persistently elevated parathyroid hormone (PTH) may be nephrotoxic and associated with earlier dialysis onset. This study examines, for the first time, the hypothesis that sustained reduction of elevated intact PTH (iPTH) with extended-release calcifediol (ERC) reduces the nephrotoxic impact of SHPT and forestalls renal decline. Methods: Changes in estimated glomerular filtration rate (eGFR) were analyzed post hoc in 126 adults with SHPT, stage 3–4 CKD, and low serum 25-hydroxyvitamin D (25D) treated for 1 year with ERC in pivotal trials. ERC was administered at 30 μg/day increasing, as needed, to 60 μg/day to achieve ≥30% reductions in iPTH. Calcium, phosphorus, 25D, 1,25-dihydroxyvitamin D (1,25D), iPTH, eGFR, fibroblast growth factor-23 (FGF23), bone turnover markers (BTMs), and urine albumin-to-creatinine ratio (uACR) were measured at baseline and regular intervals. Participants were categorized by achievement (or not) of sustained ≥30% iPTH reductions over the last 2 quarters of treatment to evaluate differences in eGFR decline. Results: For all participants, 25D increased 58.5 ± 2.3 (SE) ng/mL (p < 0.001) by the end of treatment (EOT), 1,25D increased 10.1 ± 1.8 pg/mL (p < 0.001), iPTH decreased from 143.8 ± 5.8 pg/mL to 108.8 ± 7.2 (p < 0.001), BTMs improved (p < 0.01), and eGFR declined 2.2 ± 0.5 mL/min/1.73 m2 (p < 0.001). The rate of eGFR decline was >5-fold higher (p = 0.014) in participants who did not achieve sustained iPTH reductions of ≥30% (3.2 ± 0.7; 12.7 ± 2.2%) than in those who did (0.6 ± 0.8; 2.9 ± 2.4%). It was highest in the 30 participants who did not exhibit an iPTH lowering response in both of the last 2 quarters of treatment (5.4 ± 0.9; 20.9 ± 3.4%). Duration of iPTH reduction had no impact on safety parameters. Degree of iPTH reduction at EOT was also associated with slower CKD progression. Conclusion: Sustained reduction of elevated iPTH with ERC treatment was associated with slower rates of eGFR decline in patients with SHPT and stage 3–4 CKD without raising safety concerns. A prospective trial is warranted to confirm this finding.
Symmetric Dimethylarginine Predicts Previously Undetected Atrial Fibrillation in Patients With Ischemic Stroke
Authors: Hannemann Juliane , Wasser Katrin , Mileva Yoana , Kleinsang Fiona , Schubert Mario , Schwedhelm Edzard , Guan Kaomei , Wachter Rolf , Böger Rainer
Published: August 2024

Background

Atrial fibrillation (AF) is a stroke risk factor that often remains undetected at hospital admission. Long‐term Holter monitoring helps to identify patients with previously unrecognized AF. Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are elevated in AF in cross‐sectional studies. We analyzed ADMA, SDMA, and other L‐arginine metabolites to assess their association with AF in the Find‐AF trial.

Methods and Results

We included 280 patients presenting with acute cerebral ischemia. Patients presenting in sinus rhythm received 7‐day Holter‐ECG. Biomarkers were quantified by ultra‐performance liquid chromatography–tandem mass spectrometry. We also analyzed protein methylation and L‐arginine‐related metabolites in human induced pluripotent stem cell‐derived cardiomyocytes in vitro. ADMA and SDMA were elevated in 44 patients who presented with AF. SDMA, but not ADMA, was significantly elevated in patients newly diagnosed with AF in Holter‐ECG as compared with those in sinus rhythm. SDMA plasma concentration >0.571 μmol/L significantly predicted presence of AF in Holter‐ECG (area under the curve=0.676 [0.530–0.822];
P
=0.029; sensitivity 0.786, specificity 0.572). SDMA levels further increased in patients with AF during the first 24 hours in hospital, and ADMA levels remained stable. In vitro, induced pluripotent stem cell‐derived cardiomyocytes showed increased symmetric protein methylation and elevated SDMA during rapid pacing (2.0 Hz versus 0.5 Hz), whereas asymmetric protein methylation and ADMA were unchanged.

Conclusions

SDMA at admission was significantly elevated in stroke patients presenting with AF and showed a moderate but significant prospective association with previously unrecognized AF. Thus, stroke patients with elevated SDMA concentration at admission may specifically benefit from extended Holter‐ECG monitoring.
Reduced Fetuin‐A Levels Are Associated With Exercise Intolerance and Predict the Risk of Adverse Outcomes in Patients With Heart Failure: The Role of Cardiac–Hepatic–Peripheral Interaction
Authors: Tomita Yusuke , Misaka Tomofumi , Sugawara Yukiko , Ichijo Yasuhiro , Anzai Fumiya , Sato Yu , Kimishima Yusuke , Yokokawa Tetsuro , Sato Takamasa , Oikawa Masayoshi , Kobayashi Atsushi , Yoshihisa Akiomi , Takeishi Yasuchika
Published: August 2024

Background

Exercise intolerance in heart failure arises from multifactorial pathophysiological mechanisms. Hepatokines, liver‐synthesized molecules, regulate systemic metabolisms in peripheral tissues. We previously identified the hepatokine fetuin‐A as being linked to liver hypoperfusion in heart failure. Here, we investigated the role of fetuin‐A in connecting cardiac–hepatic–peripheral interaction.

Methods and Results

We conducted a prospective study involving 202 consecutive hospitalized patients (mean age, 56.8 years; 76.2% men) with heart failure who underwent cardiopulmonary exercise testing. We measured the serum concentration of fetuin‐A by ELISA. Correlation analysis revealed a negative association between fetuin‐A levels and the ratio of minimum minute ventilation to carbon dioxide production, its slope, and a tendency toward a positive correlation with peak oxygen uptake. Patients with impaired exercise tolerance exhibited lower fetuin‐A levels. During a median follow‐up of 1045 days, 18.3% experienced cardiac events, including 4 cardiac deaths and 33 cases of worsening heart failure. Classification and regression tree analysis identified a high‐risk subgroup with lower fetuin‐A (<24.3 mg/L) and impaired exercise tolerance (peak oxygen uptake<14.2 mL/kg per min). Kaplan–Meier analysis revealed that this subgroup had the highest risk of cardiac events. In a multivariable Cox proportional hazard model, the combination of lower fetuin‐A and exercise intolerance was independently associated with increased risks of cardiac events.

Conclusions

Reduced circulating fetuin‐A levels were associated with exercise intolerance in heart failure patients. Fetuin‐A could emerge as a target implicated in exercise capacity connecting cardiac–hepatic–peripheral interaction and as a valuable biomarker for predicting prognosis when combined with peak oxygen uptake.
Ultra‐Processed Food Consumption and Risk of Incident Hypertension in US Middle‐Aged Adults
Authors: Rivera Nikolaos , Du Shutong , Bernard Lauren , Kim Hyunju , Matsushita Kunihiro , Rebholz Casey M.
Published: August 2024

Background

Consumption of ultra‐processed food, which is manufactured food that is high in additives and sparse in intact foods, is adversely associated with cardiovascular health, primarily in non‐US study populations. We aimed to estimate the association between ultra‐processed food consumption and incident hypertension in middle‐aged adults in the United States.

Methods and Results

We included 8923 ARIC (Atherosclerosis Risk in Communities) study participants who were hypertension free at baseline and had complete dietary, covariate, and hypertension data from visit 1 (1987–1989). Over a median (25th, 75th percentile) follow‐up of 13 (6–21) years, 79% of participants developed hypertension. Participants in the highest quartile of ultra‐processed food consumption had 15% higher risk of incident hypertension than those in the lowest quartile (hazard ratio [HR], 1.15 [95% CI, 1.08–1.23]). Participants in the highest quartile of consumption of sugar‐sweetened beverages, red and processed meat, and margarine had 16% (HR, 1.16 [95% CI, 1.08–1.24]; p‐trend <0.001), 10% (HR, 1.10 [95% CI, 1.03–1.19];
P
trend = 0.005), and 6% (HR, 1.06 [95% CI, 0.99, 1.45];
P
trend = 0.045) higher risk of incident hypertension, respectively, when compared with the lowest quartiles of consumption. Each additional serving of minimally or unprocessed food was associated with a 2% lower risk of incident hypertension (HR, 0.98 [95% CI, 0.98, 0.99],
P
<0.001).

Conclusions

High consumption of ultra‐processed foods, specifically of sugar‐sweetened beverages, red and processed meat, and margarine, was associated with a higher incidence of hypertension, whereas minimally or unprocessed food consumption was associated with lower hypertension risk.
Using Machine Learning to Predict Outcomes Following Transfemoral Carotid Artery Stenting
Authors: Li Ben , Eisenberg Naomi , Beaton Derek , Lee Douglas S. , Al‐Omran Leen , Wijeysundera Duminda N. , Hussain Mohamad A. , Rotstein Ori D. , de Mestral Charles , Mamdani Muhammad , Roche‐Nagle Graham , Al‐Omran Mohammed
Published: August 2024

Background

Transfemoral carotid artery stenting (TFCAS) carries important perioperative risks. Outcome prediction tools may help guide clinical decision‐making but remain limited. We developed machine learning algorithms that predict 1‐year stroke or death following TFCAS.

Methods and Results

The VQI (Vascular Quality Initiative) database was used to identify patients who underwent TFCAS for carotid artery stenosis between 2005 and 2024. We identified 112 features from the index hospitalization (82 preoperative [demographic/clinical], 13 intraoperative [procedural], and 17 postoperative [in‐hospital course/complications]). The primary outcome was 1‐year postprocedural stroke or death. The data were divided into training (70%) and test (30%) sets. Six machine learning models were trained using preoperative features with 10‐fold cross‐validation. The primary model evaluation metric was area under the receiver operating characteristic curve. The algorithm with the best performance was further trained using intra‐ and postoperative features. Model robustness was assessed using calibration plots and Brier scores. Overall, 35 214 patients underwent TFCAS during the study period and 3257 (9.2%) developed 1‐year stroke or death. The best preoperative prediction model was extreme gradient boosting, achieving an area under the receiver operating characteristic curve of 0.94 (95% CI, 0.93–0.95). In comparison, logistic regression had an AUROC of 0.65 (95% CI, 0.63–0.67). The extreme gradient boosting model maintained excellent performance at the intra‐ and postoperative stages, with area under the receiver operating characteristic curve values of 0.94 (95% CI, 0.93–0.95) and 0.98 (95% CI, 0.97–0.99), respectively. Calibration plots showed good agreement between predicted/observed event probabilities with Brier scores of 0.11 (preoperative), 0.11 (intraoperative), and 0.09 (postoperative).

Conclusions

Machine learning can accurately predict 1‐year stroke or death following TFCAS, performing better than logistic regression.
From Imminent Threat to Metaphor: Gog and Magog in Modern Sunnī Sources
Authors: Polinsky Sheridan
Published: August 2024

Gog and Magog are portrayed in the Quran as two malevolent forces that once wreaked havoc on earth and will reappear near the end of time. Hadiths elaborate their natures and actions and served as the principal source for premodern Muslim treatment of the two. In the modern period, Gog and Magog have, besides remaining objects of Quran exegesis, received considerable attention from apocalyptic writers. This article contributes to current scholarship on the modern Muslim discourse on Gog and Magog by examining the views of some notable Sunnī Quran commentators, which have thus far been almost entirely neglected. I show that they adopt either a literal interpretation, whereby Gog and Magog are understood as certain humans, or a metaphorical interpretation, whereby they are conceived as symbols of various phenomena. I also survey, in contrast to most previous researchers, the ideas of several non-Arab writers, especially the Trinidadian Imran Nazar Hosein (b. 1942), author of several apocalyptic works, including a book on Gog and Magog and their dominance in today’s world. My discussion highlights the remarkable diversity of perspectives among Muslim scholars as well as the tendency to demythologize Gog and Magog by either avoiding hadiths or understanding them in light of contemporary circumstances.
International Criminal Law, Complementarity and Amnesty Within the Context of Transitional Justice: Lessons from Uganda
Authors: Kirabira Tonny Raymond
Published: August 2024

The article explores the domestic implementation of international criminal law and complementarity, when operating alongside parallel transitional justice approaches. International criminal justice in Uganda is best understood as part of the broader lens of transitional justice, in response to a two-decade war in the Northern part of the country. Besides a doctrinal analysis of the relevant legal regime and cases, the article benefits from the author’s personal insights working in Uganda and The Hague, the two sites of international justice that inform this article. Specifically, the International Crimes Division (icd) which is the specialised court dealing with war crimes and crimes against humanity and the International Criminal Court (icc). The article highlights critical paradoxes of the icd and trial of former rebel Thomas Kwoyelo, putting this domesticated International Criminal Justice regime in a dilemma, also suggesting pathways for reforms.
Review of the genus Chirodisca Emeljanov, 1996 (Hemiptera: Fulgoroidea: Caliscelidae)
Authors: GNEZDILOV VLADIMIR M.
Published: August 2024

The caliscelid genus, Chirodisca Emeljanov, 1996 (Caliscelinae, Caliscelini), is reviewed. Adults and 5th instar nymph of Chirodisca astyages (Dlabola, 1982) and adults of Ch. eximia (Stål, 1859) are described and illustrated on the basis of type specimens and other material examined. Caliscelis macbridei Fernando, 1960 is synonymised with Ch. eximia (Stål, 1859). The composition and distribution of the genus are revised and discussed, and new records from the Palaearctic, Oriental and Afrotropical Realms are given for both species.
The Response of Tropopause-Overshooting Convection over North America to Climate Change
Authors: Tinney Emily N. , Homeyer Cameron R. , Bedka Kristopher M. , Scarino Benjamin R.
Published: August 2024

Recent field campaigns, observational studies, and modeling work have demonstrated that extratropical tropopause-overshooting convection has a substantial and previously underestimated impact on stratospheric water vapor concentrations. This necessitates improved understanding of how tropopause-overshooting convection will respond to a warming climate. A growing body of research indicates that environments conducive to severe thunderstorms will occur more often and be increasingly unstable in the future, but no study has examined how this may be related to increased overshooting. To rectify this, this study leverages an existing pseudo–global warming (PGW) experiment to evaluate potential future changes in tropopause-overshooting convection over North America. We examine two 10-yr simulations consisting of 1) a retrospective period (2003–12) forced by ERA-Interim initial and boundary conditions (the control simulation) and 2) the same retrospective period with CMIP5 ensemble-mean high-end emission scenario climate changes added to the initial and boundary conditions (the PGW simulation). Tropopause-overshooting convection in the control simulation is validated against observed overshoots from both ground-based radar observations in the United States and GOES observations over North America. The model is shown to effectively simulate the observed regional distribution, annual cycle, and diurnal cycle of tropopause-overshooting convection. In the PGW simulation, tropopause-overshooting convection is found to increase more than 250% across the model domain, and the projected seasonal period of frequent tropopause-overshooting convection is shown to extend into late summer. Additionally, tropopause-overshooting convection with extreme tropopause-relative heights (>4 km) is more frequent in a warmed climate scenario.