The Latest Evidence on Bempedoic Acid: Meta-Analysis of Safety and Efficacy in High Cardiovascular Risk Patients With Hypercholesterolemia⋆.

Background: Bempedoic Acid (BA) is a novel drug that has a potential to serve as an alternative to statins to decrease lipid levels and improve cardiovascular disease (CVD) outcomes, particularly for statin-intolerant individuals. However, insufficient statistical power has limited our understanding of the efficacy and safety of BA. This meta-analysis utilizes the latest data to improve our knowledge of BA's effects on lipids and CVD with increased statistical power. Methods: MEDLINE, Embase, Cochrane Central, Clinicaltrials.gov, abstracts of national and international conferences, and reference lists of studies were searched for relevant studies. Rayyan was used to screen the search results, and Revman 5.3 was used for the meta-analysis and sensitivity analysis. Results: Our final analysis included seven randomized control trials (RCTs) with 17,782 participants, 53.6 % in the BA group (n = 9535) and 46.4 % in the placebo group (n = 8247). BA significantly decreased major adverse cardiovascular events (MACE) (OR: 0.86; 95 % CI 0.78-0.95; p = 0.03), non-fatal myocardial infarction (OR 0.72; 95 % CI 0.61-0.85; p = 0.0001), and new onset/worsening diabetes (OR:0.55; 95 % CI 0.30-0.98, p = 0.04), while reducing low-density lipoprotein cholesterol (LDL-C) levels by 22.5 % (MD: -22.53 %; 95 % CI -25.54 to -19.52, p < 0.00001). Conclusion: The findings of this meta-analysis suggest that BA is a promising and effective alternative to statin therapy, particularly for statin-intolerant and high CVD-risk patients. However, further studies with diverse populations are needed to quantify the long-term efficacy and safety endpoints.

A rare occurrence of isolated superior mesenteric artery dissection, a case image report.

Isolated spontaneous superior mesenteric artery (SMA) dissection is relatively rare. Often found incidentally on cross-sectional imaging, often managed non-operatively. We present a patient who presented with chest pain and was found to have a SMA dissection.

Impact of pathologic re-review on grade, clinical stage, and risk stratification for patients with nonmuscle invasive bladder cancer.

OBJECTIVES: Pathologic re-review of transurethral resection of bladder tumor (TURBT) specimen is a common practice at our tertiary care center, but its impact on disease risk stratification remains unknown. We sought to determine how pathologic re-review of specimen initially read at an outside institution changed grade, clinical T (cT) stage, and AUA non-muscle-invasive bladder cancer (NMIBC) risk stratification. METHODS AND MATERIALS: The laboratory information system was searched for patients who underwent TURBT from 2021 to 2022, yielding 561 records. 173 patients met inclusion criteria: 113 with

Clinical Upstaging After Neoadjuvant Chemotherapy Impacting Eligibility for Vaginal-sparing Cystectomy: Identifying Bladder Cancer Patients Who May Benefit From Interim Imaging.

OBJECTIVE: Limited data exist on the frequency with which clinical progression during neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) impacts eligibility for a vaginal-sparing surgical approach or on the utility of interim imaging assessment. We sought to evaluate the incidence of clinical upstaging following NAC that would render a patient ineligible for a vaginal-sparing cystectomy. METHODS: Eighty-nine female patients with non-metastatic MIBC treated with NAC and radical cystectomy (RC) (2012-2023) were retrospectively reviewed. Tumor location(s) was determined from transurethral resection of bladder tumor operative reports. Pre- and post-NAC clinical staging was determined from imaging. Outcomes of interest included clinical upstaging and upstaging to vaginal invasion after NAC. RESULTS: 75/89 patients had pre- and post-NAC imaging. Fifty-five had no change in clinical staging, 6 patients were upstaged (4 cT2→cT3, 2 cT3→cT4), and 14 patients were downstaged (13 cT3→cT2, 1 cT4→cT2). Of the 75 patients with pre- and post-NAC imaging, 39 had trigone tumors. Of these, 28 had no change in clinical staging, 2 were upstaged (1 cT2→cT3, 1 cT3→cT4) and 9 were downstaged (8 cT3→cT2, 1 cT4→cT2). Overall, 6/75 (8%) of patients demonstrated clinical upstaging after NAC. 2/39 (5%) of patients with trigone tumors clinically progressed after NAC and both had vaginal invasion (pT4) on final pathology. CONCLUSION: Although clinical upstaging after NAC was infrequent, 5% of patients with trigonal MIBC were rendered ineligible for vaginal-sparing cystectomy following NAC due to progression. Interim imaging assessment may identify non-responders and preserve eligibility for vaginal-sparing RC.

Emergence of the brain-border immune niches and their contribution to the development of neurodegenerative diseases.

Historically, the central nervous system (CNS) was regarded as 'immune-privileged', possessing its own distinct immune cell population. This immune privilege was thought to be established by a tight blood-brain barrier (BBB) and blood-cerebrospinal-fluid barrier (BCSFB), which prevented the crossing of peripheral immune cells and their secreted factors into the CNS parenchyma. However, recent studies have revealed the presence of peripheral immune cells in proximity to various brain-border niches such as the choroid plexus, cranial bone marrow (CBM), meninges, and perivascular spaces. Furthermore, emerging evidence suggests that peripheral immune cells may be able to infiltrate the brain through these sites and play significant roles in driving neuronal cell death and pathology progression in neurodegenerative disease. Thus, in this review, we explore how the brain-border immune niches may contribute to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). We then discuss several emerging options for harnessing the neuroimmune potential of these niches to improve the prognosis and treatment of these debilitative disorders using novel insights from recent studies.

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2024.

Introduction: Each year the interdisciplinary AGO (Arbeitsgemeinschaft Gynäkologische Onkologie, German Gynecological Oncology Group) Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer. Methods: The updated evidence-based treatment recommendations for early and metastatic breast cancer have been released in March 2024. Results and Conclusion: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter.

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2024.

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2024 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer.

App-based support for breast cancer patients to reduce psychological distress during therapy and survivorship - a multicentric randomized controlled trial.

Introduction: The negative impact of unmanaged psychological distress on quality of life and outcome in breast cancer survivors has been demonstrated. Fortunately, studies indicate that distress can effectively be addressed and even prevented using evidence-based interventions. In Germany prescription-based mobile health apps, known as DiGAs (digital health applications), that are fully reimbursed by health insurances, were introduced in 2020. In this study, the effectiveness of an approved breast cancer DiGA was investigated: The personalized coaching app PINK! Coach supports and accompanies breast cancer patients during therapy and follow-up. Methods: PINK! Coach was specifically designed for breast cancer (BC) patients from the day of diagnosis to the time of Follow-up (aftercare). The app offers individualized, evidence-based therapy and side-effect management, mindfulness-based stress reduction, nutritional and psychological education, physical activity tracking, and motivational exercises to implement lifestyle changes sustainably in daily routine. A prospective, intraindividual RCT (DRKS00028699) was performed with n = 434 patients recruited in 7 German breast cancer centers from September 2022 until January 2023. Patients with BC were included independent of their stage of diseases, type of therapy and molecular characteristics of the tumor. Patients were randomized into one of two groups: The intervention group got access to PINK! over 12 weeks; the control group served as a waiting-list comparison to "standard of care." The primary endpoint was psychological distress objectified by means of Patient Health Questionnaire-9 (PHQ-9). Subgroups were defined to investigate the app's effect on several patient groups such as MBC vs. EBC patients, patients on therapy vs. in aftercare, patients who received a chemotherapy vs. patients who did not. Results: Efficacy analysis of the primary endpoint revealed a significant reduction in psychological distress (least squares estimate -1.62, 95% confidence interval [1.03; 2.21]; p<0.001) among intervention group patients from baseline to T3 vs, control group. Subgroup analysis also suggested improvements across all clinical situations. Conclusion: Patients with breast cancer suffer from psychological problems including anxiety and depression during and after therapy. Personalized, supportive care with the app PINK! Coach turned out as a promising opportunity to significantly improve psychological distress in a convenient, accessible, and low-threshold manner for breast cancer patients independent of their stage of disease (EBC/MBC), therapy phase (aftercare or therapy) or therapy itself (chemotherapy/other therapy options). The app is routinely available in Germany as a DiGA. Clinical Trial Registration: DRKS Trial Registry (DRKS00028699).

Junior and senior students possess differential preferences towards multimodal digital anatomy resources.

Digital technologies are changing how anatomy is taught tremendously. However, little is known about the effective integration of multimodal digital resources when concurrently provided in an anatomy course. To address this question, an array of digital anatomy resources including Augmented Reality (AR) and Virtual Reality (VR) anatomy resources were concurrently trialed by a total of 326 undergraduate and postgraduate students across three undergraduate (systemic anatomy, neuroanatomy, and regional anatomy) and one postgraduate anatomy (applied musculoskeletal anatomy) curricula in 2022. A five-point Likert scale learning and teaching survey was conducted to evaluate students' experiences, preferences, and perceptions. Most undergraduate (81% systemic anatomy, 76% neuroanatomy, and 87% regional anatomy) and postgraduate (97%) participants across the four cohorts felt confident in studying anatomy using digital resources and the majority (>80% undergraduate and >90% postgraduate) found the multimodal digital anatomy resources interactive and stimulating. The response showed that undergraduate (77% systemic anatomy, 81% neuroanatomy, and 97% regional anatomy) and postgraduate students (92%) consistently enjoyed their experience of using multimodal digital anatomy resources and thought that these resources enhanced their interest in studying anatomy. However, there are significant differences in ratings of specific digital resources among the junior (first-year undergraduates) and senior (third-year undergraduates and postgraduates) students. The virtual dissection table was uniformly preferred by the four cohorts of students across the board. Interestingly, however, VR anatomy and radiographic-based digital anatomy resources received diverse ratings. VR anatomy was valued most by junior undergraduate students (84%) who studied systemic anatomy compared to their senior counterparts (73%) who studied regional anatomy, whereas radiographic-based digital anatomy resources were more valued by the postgraduate students (93%) compared to undergraduates (65% systemic anatomy, 73% neuroanatomy, and 48% regional anatomy). This study identifies that while students uniformly appreciate the value of multimodal digital anatomy teaching, there is a clear difference in their perceptions towards individual resources, likely in a course-specific manner. We conclude that the selection and adoption of digital anatomy tools must be tailored as part of course design and that digital anatomy tools should be used in combination to provide an effective learning experience for students.

Textbook outcome after esophagectomy: A retrospective study from a high-volume center.

BACKGROUND: Textbook outcome is a composite quality measurement in esophageal cancer surgery. This study aimed to estimate the rate of textbook outcome esophagectomies at a high-volume center and investigate associations between textbook outcome and overall and recurrence-free survival. METHODS: A retrospective single-center study was conducted at Copenhagen University Hospital, Rigshospitalet, Denmark, analyzing esophagectomies performed from November 1, 2016, to December 31, 2021. Patients with primary carcinoma of the gastroesophageal junction who underwent elective and curative esophagectomy were included. The rate of textbook outcome esophagectomies was calculated, and the impact of textbook outcome on overall and recurrence-free survival was analyzed using Kaplan-Meier and Cox regression. RESULTS: A total of 433 patients were included in the study. Textbook outcome was achieved in 195 patients (45%). Achieving textbook outcome was independently associated with improved overall survival (HR 0.67; P = .011) and with a median overall survival of 57 months and 32 months for patients with or without textbook outcome, respectively. A trend for improved recurrence-free survival was observed for patients with textbook outcome (HR 0.74; P = .064). CONCLUSION: The present study found a consensus-based textbook outcome rate of 45%. Textbook outcome was found to be directly associated with improved overall survival. These results emphasize the association between improved short-term outcomes and long-term survival.

Unilateral renal fungus ball caused by Candida glabrata.

A 46-year-old diabetic woman with unilateral renal fungus ball was successfully treated with antifungal therapy, endoscopic extraction and ureteral stent placement. The patient was initially treated for a right staghorn calculus, thereafter developed urinary symptoms. Imaging revealed distal left ureter filling defects and a previous stent at the ureteropelvic junction. Urine culture confirmed Candida glabrata sensitive to Micafungin. Bilateral ureteroscopy facilitated the extraction of a left renal pelvis fungus ball. This case underscores the challenges in diagnosing fungal UTIs in patients with predisposing factors, and highlights a combined medical and surgical approach for effective treatment of renal fungus balls.

Splenic Surprise: Investigating a Case of Splenic Infarct as an Isolated COVID-19 Manifestation.

Coronavirus disease 2019 (COVID-19) infection has been associated with a multitude of complications, one established complication being thromboembolism, a result of the proinflammatory state induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This prothrombotic state is a cumulation of many inflammatory pathways at work. Here, we present an interesting case of a 43-year-old female who did not present with the typical COVID-19 clinical picture. Instead, she presented with periumbilical pain, nausea, and vomiting. Upon further investigation, she was found to have a splenic infarct on a computed tomography (CT) scan. An extensive workup was performed to explore possible etiologies; however, it was concluded that her splenic infarct was secondary to her COVID-19 infection. With this case, we aim to add to the literature regarding the manifestations of the prothrombotic state of SARS-CoV-2.

Cranial Conundrum: An Unusual Case of an Epidermoid Cyst in the Prepontine Cistern.

We present a fascinating case of a patient who suffered from persistent headaches for three months due to an epidermoid cyst located in the prepontine cistern. Epidermoid cysts are a very uncommon type of intracranial tumor, known for their slow growth and gradual onset of neurological symptoms. In this particular case, our patient, a 35-year-old, experienced a headache that was accompanied by dizziness, photophobia, and pain when moving their eyes. Further imaging revealed a cystic lesion in the prepontine cistern, which had a mass effect on the pons. After confirming the lesion was likely an epidermoid cyst through an MRI, the patient underwent surgery to have it removed. We hope to highlight the rarity of this type of tumor and its unique features when viewed through imaging.

Randomized controlled trial of nasogastric tube use after esophagectomy: study protocol for the kinetic trial.

Esophagectomy is a complex and complication laden procedure. Despite centralization, variations in perioparative strategies reflect a paucity of evidence regarding optimal routines. The use of nasogastric (NG) tubes post esophagectomy is typically associated with significant discomfort for the patients. We hypothesize that immediate postoperative removal of the NG tube is non-inferior to current routines. All Nordic Upper Gastrointestinal Cancer centers were invited to participate in this open-label pragmatic randomized controlled trial (RCT). Inclusion criteria include resection for locally advanced esophageal cancer with gastric tube reconstruction. A pretrial survey was undertaken and was the foundation for a consensus process resulting in the Kinetic trial, an RCT allocating patients to either no use of a NG tube (intervention) or 5 days of postoperative NG tube use (control) with anastomotic leakage as primary endpoint. Secondary endpoints include pulmonary complications, overall complications, length of stay, health related quality of life. A sample size of 450 patients is planned (Kinetic trial: https://www.isrctn.com/ISRCTN39935085). Thirteen Nordic centers with a combined catchment area of 17 million inhabitants have entered the trial and ethical approval was granted in Sweden, Norway, Finland, and Denmark. All centers routinely use NG tube and all but one center use total or hybrid minimally invasive-surgical approach. Inclusion began in January 2022 and the first annual safety board assessment has deemed the trial safe and recommended continuation. We have launched the first adequately powered multi-center pragmatic controlled randomized clinical trial regarding NG tube use after esophagectomy with gastric conduit reconstruction.

Budget Impact of the Oncotype DX Breast Recurrence Score® Test in Patients with Early Primary Hormone-Receptor-Positive, HER2-Negative, Node-Positive Breast Cancer in Germany.

Background: Gene expression tests can inform decisions on whether to recommend or omit chemotherapy for patients with early HR+, HER2- breast cancer. The benefit of these tests is well established and fully reimbursed by sickness funds for lymph node-negative (pN0) patients in Germany. A budget impact model was built to evaluate the effect of using the Oncotype DX Breast Recurrence Score® test also for node-positive (pN1: 1-3 positive lymph nodes) patients. Methods: The prospective randomized clinical trial, RxPONDER, defined conditions (Recurrence Score result 0-25 for postmenopausal patients with 1-3 positive lymph nodes) under which omitting chemotherapy does not significantly impact invasive disease-free survival with results currently reported for 5-year follow-up. The present budget impact model calculates average total cost per node-positive patient versus no testing from a sickness funds perspective, taking into account not only the budgetary impact of avoiding chemotherapy and associated side effects, but also the costs of treating those patients who develop distant metastasis. The stability of the results was investigated by probabilistic multivariate sensitivity analysis. Results: After deducting testing cost, applying the Oncotype DX Breast Recurrence Score test yielded an average savings per node-positive patient of EUR 4,272. Without the test costs, the greatest savings resulted from reductions in direct treatment costs and costs arising from the treatment of chemotherapy-related side effects, which together averaged EUR 6,677. The targeted use of chemotherapy after testing also resulted in slightly lower costs for treatment of distant metastasis, if it did occur. The multivariate sensitivity analysis also almost exclusively resulted in cost savings. Conclusion: Analogous to the pN0 situation, this budget impact model demonstrates that the Oncotype DX Breast Recurrence Score test can also reduce healthcare costs in Germany in treatment of node-positive (pN1: 1-3 positive lymph nodes) patients by minimizing both unnecessary chemotherapy and undertreatment. Additional benefits to patients would include reduced morbidity and improved quality of life for those patients who can safely avoid chemotherapy or undertreatment.

Iodine density mapping for the diagnosis of acute bowel ischemia using fast kV-switching dual-energy CT.

PURPOSE: To evaluate the diagnostic capabilities of a supplementary color ramped iodine density map compared to virtual monoenergetic images (VMIs) at 74 keV in the diagnosis of acute bowel ischemia (ABI). METHODS: Data for this study were prospectively gathered and retrospectively evaluated. Patients referred to the Department of Diagnostic Radiology between October 2020 and August 2022 on the suspicion of ABI and underwent surgery < 12 h following fast kV-switching venous phase abdominal dual-energy CT (DECT) were consecutively included. Images were evaluated by two board-certified radiologists and two radiology residents. First round included only 74 keV VMIs resembling conventional 120 kVp images, and the second round included a supplementary iodine density map. Readers were asked to register presence of ABI as well as their confidence in their diagnosis based on a 5-point Likert scale. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each observer with the surgical findings as the gold-standard. McNemar's and Wilcoxon signed-rank test were used to compare registrations and diagnostic confidence across assessment rounds. RESULTS: A total of 29 patients resulting in 31 DECT scans were included. Fourteen cases of ischemic/necrotic bowel were reported following surgery. Sensitivity and NPV were decreased with the use of supplementary iodine map images compared to 120 kVp-like images without supplementary iodine map images for three of four observers (round 1 range: 71.4-92.9% and 78.0-94.8%; round 2 range: 57.1-78.6% and 70.1-83.3%, respectively), while specificity and PPV were increased for three of four observers (round 1 range: 64.7-94.1% and 67.4-93.1%; round 2 range: 88.2-94.1% and 73.8-91.1%, respectively). However, no significant difference in ABI diagnosis or diagnostic confidence was found (p-value range: 0.07-1.00 and 0.23-0.58, respectively). CONCLUSION: No significant difference for the diagnosis of ABI was found using supplementary iodine mapping. Our study may suggest a trend of increased specificity and decreased sensitivity, hence, the use of supplementary iodine mapping should be carefully considered.

Who gets staged surgery in severe pediatric and adolescent spine deformity?

BACKGROUND: There is significant debate regarding the indications of staged surgery for severe adolescent spinal deformity, and the factors associated with the decision to perform staged compared to same-day surgery have not been previously investigated. Thus, the purpose of this study was to determine which factors were most strongly associated with this decision. METHODS: A prospective multicenter registry of adolescent patients with severe spinal deformity was reviewed. Two cohorts were identified: those who underwent a planned staged surgical procedure for deformity correction and those who underwent a same-day procedure. Patients who underwent an unplanned staged procedure secondary to complications during the initial procedure were excluded. Comparisons were made between these cohorts with respect to preoperative patient and radiographic variables to determine which factors were associated with the decision to perform a staged procedure. Surgical data was also compared to evaluate for differences in the intraoperative management of staged versus same-day patients. RESULTS: Two hundred and twenty-nine patients with severe spinal deformities were identified. Forty patients (17%) underwent a planned staged procedure and 189 patients (80%) underwent a same-day procedure. On univariate analysis of preoperative variables, patients who underwent staged surgery had a significantly younger age at surgery, greater major curve magnitude, greater major curve AVT to CSVL, lesser thoracic spine height, greater radiographic trunk shift, and a greater proportion of patients undergoing revision surgery (as opposed to primary correction) compared to those who underwent a planned single-stage procedure. Multivariate logistic regression of pre-operative variables showed that age < 16 years, maximum cobb angle ≥ 120 degrees, major curve AVT to CSVL of ≥ 3.5 cm, and revision surgery were independently associated with the decision to perform a staged procedure. Intraoperatively, patients in the staged cohort more frequently underwent combined anterior and posterior procedures, grade 4 or higher Schwab osteotomies, and had a greater number of levels fused. CONCLUSION: There is substantial variability with respect to the decision to perform surgery for severe adolescent spine deformities in a staged versus same-day fashion. This large analysis of prospectively collected data is the first to describe the factors most strongly associated with the decision to perform a staged procedure and may help guide the surgical decision-making for these patients.

Automatic measurement of departing times in smartphone alerting systems: A pilot study.

Aim: Smartphone alerting systems (SAS) alert volunteers in close vicinity of suspected out-of-hospital cardiac arrest. Some systems use sophisticated algorithms to select those who will probably arrive first. Precise estimation of departing times and travel times may help to further improve algorithms. We developed a global positioning system (GPS) based method for automatic measurements of departing times. The aim of this pilot study was to evaluate feasibility and precision of the method. Methods: Region of Lifesavers alerting app (iOS/ Android, version 3.0, FirstAED ApS, Denmark) was used in this study. 27 experiments were performed with 9 students, who were instructed to stay in their flats during the study days. A geofence was set for each alarm in the alerting system with a radius of 10 m (8 cases), 15 m (10 cases), and 20 m (9 cases) around the GPS position at which the alarm was accepted in the app. The system logged responders as being departed when the smartphone position was registered outside the geofence. The students were instructed to manually start a stopwatch at the time of the alert and to stop the stopwatch once they had entered the street in front of their flat. Results: The median difference between automatically and manually retrieved times were -16 seconds [interquartile range IQR 50 seconds] (geofence 10 m), 30 seconds [IQR 25 seconds] (15 m), and 20 seconds [IQR 13 seconds] (20 m), respectively. The 20 m geofence was associated with the smallest interquartile range. Conclusion: Departing times of volunteer responders in SAS can be retrieved automatically using GPS and a geofence.