Search

Functional constipation (FC) is a common condition in childhood in the United Kingdom and worldwide. Various radiological approaches have been established for diagnostic purposes. The radiopaque marker study (ROMS) is universally accepted and used to assess colonic transit time (CTT) in children with FC. Despite being widely used, there is a lack of standardization with various technical protocols, reproducibility of different populations, the purpose for using investigation, variance in the number of markers used, the amount of study days and calculations, the need to empty the colon before performing the test, and whether to perform on medication or off, or the use of specific diets. As part of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) motility working group (MWG), we decided to explore further into the evidence, in order to provide guidance regarding the use of ROMS in dealing with FC in the pediatric population. [ABSTRACT FROM AUTHOR]

Importance: Office-based phototherapy is cost-effective for psoriasis but difficult to access. Home-based phototherapy is patient preferred but has limited clinical data, particularly in patients with darker skin., Objective: To compare the effectiveness of home- vs office-based narrowband UV-B phototherapy for psoriasis., Design, Setting, and Participants: The Light Treatment Effectiveness study was an investigator-initiated, pragmatic, open-label, parallel-group, multicenter, noninferiority randomized clinical trial embedded in routine care at 42 academic and private clinical dermatology practices in the US. Enrollment occurred from March 1, 2019, to December 4, 2023, with follow-up through June 2024. Participants were 12 years and older with plaque or guttate psoriasis who were candidates for home- and office-based phototherapy., Interventions: Participants were randomized to receive a home narrowband UV-B machine with guided mode dosimetry or routine care with office-based narrowband UV-B for 12 weeks, followed by an additional 12-week observation period., Main Outcomes and Measures: The coprimary effectiveness outcomes were Physician Global Assessment (PGA) dichotomized as clear/almost clear skin (score of ≤1) at the end of the intervention period and Dermatology Life Quality Index (DLQI) score of 5 or lower (no to small effect on quality of life) at week 12., Results: Of 783 patients enrolled (mean [SD] age, 48.0 [15.5] years; 376 [48.0%] female), 393 received home-based phototherapy and 390 received office-based phototherapy, with 350 (44.7%) having skin phototype (SPT) I/II, 350 (44.7%) having SPT III/IV, and 83 (10.6%) having SPT V/VI. A total of 93 patients (11.9%) were receiving systemic treatment. At baseline, mean (SD) PGA was 2.7 (0.8) and DLQI was 12.2 (7.2). At week 12, 129 patients (32.8%) receiving home-based phototherapy and 100 patients (25.6%) receiving office-based phototherapy achieved clear/almost clear skin, and 206 (52.4%) and 131 (33.6%) achieved DLQI of 5 or lower, respectively. Home-based phototherapy was noninferior to office-based phototherapy for PGA and DLQI in the overall population and across all SPTs. Home-based phototherapy, compared to office-based phototherapy, was associated with better treatment adherence (202 patients [51.4%] vs 62 patients [15.9%]; P < .001), lower burden of indirect costs to patients, and more episodes of persistent erythema (466 of 7957 treatments [5.9%] vs 46 of 3934 treatments [1.2%]; P < .001). Both treatments were well tolerated with no discontinuations due to adverse events., Conclusions and Relevance: In this randomized clinical trial, home-based phototherapy was as effective as office-based phototherapy for plaque or guttate psoriasis in everyday clinical practice and had less burden to patients., Trial Registration: ClinicalTrials.gov Identifier: NCT03726489.

Background: The accurate diagnosis of bacterial infections remains a critical challenge in clinical practice. Traditional imaging modalities like computed tomography (CT) and magnetic resonance imaging (MRI) often fail to distinguish bacterial infections from sterile inflammation. Nuclear medicine, such as technetium-99m ( 99m Tc) radiopharmaceuticals, offers a promising alternative due to its ideal characteristics. Methods: This study explores the development of [2 + 1] mixed-ligand 99m Tc-labeled ciprofloxacin dithiocarbamate (Cip-DTC) complexes combined with various phosphine ligands, including triphenylphosphine (PPh 3 ), tris(4-methoxyphenyl)phosphine (TMPP), methyl(diphenyl)phosphine (MePPh 2 ), dimethylphenylphosphine (DMPP), and 1,3,5-triaza-7-phosphaadamantane (ADAP). The characterization of 99m Tc-complexes was conducted using rhenium analogs as structural models to ensure similar coordination. Results: Stability studies demonstrated the high integrity (97-98%) of the complexes under various conditions, including cysteine and histidine challenges. Lipophilicity studies indicated that complexes with higher logD 7.4 values (1.6-2.7) exhibited enhanced tissue penetration and prolonged circulation. Biodistribution studies in Swiss Albino mice with induced infections and aseptic inflammation revealed distinct patterns. Specifically, the complex fac -[ 99m Tc(CO) 3 (Cip-DTC)(PPh 3 )] ( 2' ) showed high infected/normal muscle ratios (4.62 at 120 min), while the complex fac -[ 99m Tc(CO) 3 (Cip-DTC)(TMPP)] ( 3' ) demonstrated delayed but effective targeting (infected/normal muscle ratio of 3.32 at 120 min). Conclusions: These findings highlight the potential of 99m Tc-labeled complexes as effective radiopharmaceuticals for the differential diagnosis of bacterial infections, advancing nuclear medicine diagnostics. Future studies will focus on optimizing molecular weight, lipophilicity, and stability to further enhance the diagnostic specificity and clinical utility of these radiopharmaceuticals.

Corticotropin-releasing factor (CRF) is a key neuropeptide hormone that is secreted from the hypothalamus. It is the master hormone of the HPA axis, which orchestrates the physiological and behavioral responses to stress. Many disorders, including anxiety, depression, addiction relapse, and others, are related to over-activation of this system. Thus, new molecules that may interfere with CRF receptor binding may be of value to treat neuropsychiatric stress-related disorders. Also, CRF 1 R antagonists have recently emerged as potential treatment options for congenital adrenal hyperplasia. Previously, several series of CRF 1 receptor antagonists were developed by our group. In continuation of our efforts in this direction, herein we report the synthesis and biological evaluation of a new series of CRF 1 R antagonists. Representative compounds were evaluated for their binding affinities compared to antalarmin. Four compounds ( 2 , 5 , 20 , and 21 ) showed log IC 50 values of -8.22, -7.95, -8.04, and -7.88, respectively, compared to -7.78 for antalarmin. This result indicates that these four compounds are superior to antalarmin by 2.5, 1.4, 1.7, and 1.25 times, respectively. It is worth mentioning that compound 2 , in terms of IC 50 , is among the best CRF 1 R antagonists ever developed in the last 40 years. The in silico physicochemical properties of the lead compounds showed good drug-like properties. Thus, further research in this direction may lead to better and safer CRF receptor antagonists that may have clinical applications, particularly for stress-related disorders and the treatment of congenital adrenal hyperplasia.

Background/aims: Excessive use of antibiotics has led to development of antibiotic resistance and other antibiotic-associated complications. Dermatologists prescribe more antibiotics per clinician than any other major specialty, with much of this use for acne. Alternative acne treatments are available but are used much less often than antibiotics, at least partially because dermatologists feel that they are less effective. Spironolactone, a hormonal therapy with antiandrogen effects that can address the hormonal pathogenesis of acne, may represent a therapeutic alternative to oral antibiotics for women with acne. However, the comparative effects of spironolactone and oral antibiotics in the treatment of acne have not been definitively studied. The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation (SD-ACNE) trial aims to answer whether spironolactone, in addition to standard topical therapy, is noninferior to doxycycline (an oral antibiotic) for women with acne. Several interesting challenges arose in the development of this study, including determining acceptability of the comparative regimens to participating dermatologists, identifying data to support a noninferiority margin, and establishing a process for unblinding participants after they completed the study while maintaining the blind for study investigators., Methods: We present the scientific and clinical rationale for the decisions made in the design of the trial, including input from key stakeholders through a Delphi consensus process., Results: The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation trial (NCT04582383) is being conducted at a range of community and academic sites in the United States. To maximize external validity and inform clinical practice, the study is designed with broad eligibility criteria and no prohibition of use of topical medications. Participants in the trial will be randomized to receive either spironolactone 100 mg/day or doxycycline hyclate 100 mg/day for 16 weeks. The primary outcome is the absolute decrease in inflammatory lesion count, and we have established a noninferiority margin of four inflammatory lesions. Secondary outcomes include the percentage of participants achieving Investigator Global Assessment success, change in quality of life, and microbiome changes and diversity., Conclusions: The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation trial will have substantial implications for the treatment of acne and antibiotic stewardship. In addition, this study will provide important information on the effect of these systemic agents on the development of changes to the microbiome and antibiotic resistance in a healthy population of patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.S.B. has received consulting fees from Dexcel Pharma for work unrelated to this study.

Backgound: The number of endovascular abdominal aortic aneurysm repairs (EVARs) has surpassed the number of open surgical repair of AAAs worldwide with a great variety of endografts being available. The aim of this study is to conduct a systematic review of the literature and meta-analysis of studies reporting patients with infrarenal abdominal aortic aneurysm (AAA) subjected to EVAR with the Anaconda endograft., Methods: We performed a systematic review of multiple electronic databases for studies including patients with infrarenal AAA who were subjected to elective EVAR with Anaconda endograft exclusively. We conducted a proportional meta-analysis cumulating the results of the included studies. The endpoints were first month overall mortality, first and second-year survival after EVAR, AAA-related deaths, incidence of endoleaks, endograft migration, endograft occlusion, open conversion, and primary and secondary technical success. The mean value for each separate studied factor was calculated, and the respective percentage or incidence was extracted so that it can be compared to endograft outcome studies in the literature. We assessed the methodologic quality of studies by using the Briggs Institute critical appraisal tool., Results: Seven observational studies were found including 954 patients (males 91.9%, mean age 73.38 ± 6.97 years). The mean transverse diameter of AAAs was 56.83 ± 9.97 mm. The mean proximal aortic neck diameter and length were 23.06 ± 3.33 mm and 24.14 ± 12.16 mm, respectively. Increased aortic neck calcification and aortic neck thrombus were present in 12.5% of patients. The 30-day overall mortality post-EVAR was 1.3%, 1 and 2-year survival rates were 95.9% and 91.4%, respectively. The mean follow-up period in the studies was 46.59 ± 15.5 months. AAA-related mortality was 1.3%. Primary technical success was 97.9% and secondary success was 99.3%. Open conversion was required in 3.4% of all patients (0.6% during the primary operation [Prim. Op]). The most common endoleak was type II, reported in 17.4% of all patients. Early type Ia endoleak was reported in 1.5% of patients and late type Ia in 1.7%. Overall, 2 endoleaks type III and 1 type IV were reported. Endograft migration occurred in 1.7% of patients. Main body and/or one/both iliac legs thrombotic occlusion was found totally in 7.6% of patients (5 main body occlusions and 64 iliac leg occlusions)., Conclusions: The use of Anaconda endograft in electively treated patients with infrarenal AAAs presented good results with high technical success and low postoperative and mid-term complications, except for an increased incidence of stent-graft thrombosis, which seems to be the "Achilles heel" of the device., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Βlunt trauma is a common injury in children; however, blunt abdominal aortic trauma is extremely rare and is accompanied by high rates of morbidity and mortality. We report our initial experience with the endovascular management of an abdominal aortic rupture in a 12-year-old boy after he was involved in a motor vehicle accident. The patient was a backseat-restrained passenger. Upon admission, he had a Glasgow Coma Scale of 15, was hemodynamically stable, and complained of abdominal pain. The computed tomography revealed a rupture in the abdominal aorta along with a distally extending pseudoaneurysm, free fluid in the peritoneal cavity, and a large retroperitoneal hematoma. The rest associated injuries were a Grade III splenic injury, a retroclival epidural hematoma in the first cervical vertebra level, a right clavicle fracture, a bilateral minor pneumothorax, along with bilateral pulmonary lacerations and contusions in the thoracic vertebrae. Given the extent of the intraabdominal injuries and the risk for open laparotomy, the decision to proceed with endovascular stenting instead of open surgical repair was made. The patient tolerated the procedure well and an angiography confirmed the result. The postoperative period was uneventful and the associated injuries were treated conservatively without complications. Although blunt abdominal aortic trauma is extremely rare in children, endovascular management seems to be a new and feasible therapeutic approach., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Florou et al.)

Hepatic artery aneurysms (HAAs) are an uncommon vascular disease, which account for 20% of visceral artery aneurysms. The majority are usually asymptomatic and discovered accidentally during imaging control, but occasionally, they can present as acute abdominal pain, haemobilia, obstructive jaundice, or gastrointestinal bleeding due to aneurysm sac expansion or rupture with catastrophic consequences. We present the case of a 51-year-old male patient with a giant common HAA of 11.1 cm who was managed endovascularly. A combined endovascular approach was decided due to the anatomy of the aneurysm. Endovascular embolization with coils in the distal part of the aneurysm and deployment of a stent graft proximally to exclude inflow were used. At six months, the aneurysm size was regressed at 5 cm; however, seven months after the operation, the patient presented with pylorus perforation due to coil migration which was managed by coil removal, peripheral gastrectomy, and Roux-en-Y gastric bypass. We provide a narrative literature review regarding the endovascular repair of giant HAAs. The PubMed, Scopus, and Google Scholar databases were searched for articles up to January 2024. Thirty-eight studies (case reports, case series) were retrieved. The conclusion is that giant HAAs are a rare and severe condition in which their treatment can be challenging with unexpected adverse events. The literature review suggests that the endovascular approach whenever feasible is a safe and effective treatment option with low morbidity and mortality., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tigkiropoulos et al.)

The number of endovascular aortic repairs (EVARs) has surpassed the number of open surgical repairs of abdominal aortic aneurysms (AAAs) worldwide. The available commercial endoprostheses are composed of materials that are stiffer than the native aortic wall. As a consequence, the implantation of stent-graft endoprostheses during EVAR increases aortic rigidity and thus aortic stiffness, resulting in a decrease in abdominal aorta compliance. EVAR has been found to have a possibly harmful effect not only on heart functions but also on other vascular beds, including kidney function, due to the decrease in aortic compliance that it causes. Aortic stiffness is measured by various hemodynamic indices like the pulse wave velocity (PWV), the central aortic pressure (CAP), and the augmentation index (AIx). In the literature, there are increasing numbers of studies investigating the properties of endografts, which are strongly related to increases in aortic stiffness. However, there is a lack of data on whether there is a correlation between the length of various endografts implanted during EVAR and the increase in the PWV, CAP, and AIx postoperatively compared to the preoperative values. The aim of this prospective, observational, monocentric, single-arm study is to investigate the correlation between endograft length and the postoperative increase in the PWV, CAP, and AIx in patients subjected to EVAR. Additionally, this study intends to identify other endograft properties related to increases in the PWV, CAP, and AIx. Other endpoints to be studied are the existence of immediate postoperative myocardial and kidney injury after EVAR. The prediction of cardiovascular events caused by endograft-related increased aortic stiffness could contribute to the improvement of various endograft properties so that the impact of endografts on the native aortic wall can be minimized.

In critically ill newborns, exposure to hypercapnia (HC) is common and often accepted in neonatal intensive care units to prevent severe lung injury. However, as a "safe" range of arterial partial pressure of carbon dioxide levels in neonates has not been established, the potential impact of HC on the neurodevelopmental outcomes in these newborns remains a matter of concern. Here, in a newborn Yorkshire piglet model of either sex, we show that acute exposure to HC induced persistent cortical neuronal injury, associated cognitive and learning deficits, and long-term suppression of cortical electroencephalogram frequencies. HC induced a transient energy failure in cortical neurons, a persistent dysregulation of calcium-dependent proapoptotic signaling in the cerebral cortex, and activation of the apoptotic cascade, leading to nuclear deoxyribonucleic acid fragmentation. While neither 1 h of HC nor the rapid normalization of HC was associated with changes in cortical bioenergetics, rapid resuscitation resulted in a delayed onset of synaptosomal membrane lipid peroxidation, suggesting a dissociation between energy failure and the occurrence of synaptosomal lipid peroxidation. Even short durations of HC triggered biochemical responses at the subcellular level of the cortical neurons resulting in altered cortical activity and impaired neurobehavior. The deleterious effects of HC on the developing brain should be carefully considered as crucial elements of clinical decisions in the neonatal intensive care unit., (Copyright © 2024 Fritz et al.)

Background : Prospective single and multicenter studies have shown improved outcomes of patients who underwent carotid artery stenting with the novel CGuard dual-layer mesh stent at 1 year. Objectives : The aim of this study is to conduct a systematic review and meta-analysis of all published studies to assess 1-year efficacy and outcomes of CGuard in patients with carotid stenting. Methods: A systematic search was performed. All studies enrolling at least 20 patients were included in our analysis. The primary endpoints were death (all-cause, cardiovascular and ipsilateral stroke-related death) and stroke rate at 1 year. The secondary endpoint was in-stent restenosis at 1 year. Results : The final analysis included 1709 patients. The one-year all-cause mortality rate was 2.97% (39/1699, 95% CI: 1.26-6.86%, I 2 = 67%, t 2 = 0.3442, p < 0.01), cardiovascular-related death was 0.92% (10/1616, 95% CI: 0.35-2.39%, I 2 = 34%, t 2 = 0.2302, p = 0.18), and ipsilateral stroke-related death was 0.3% (1/1649, 95% CI: 0.1-0.87%, I 2 = 0%, t 2 = 0, p = 0.69). The one-year ipsilateral stroke rate was 1.21% (16/1649, 95% CI: 0.58-2.5%, I 2 = 28%, t 2 = 0.1433, p = 0.23), transient ischemic attacks (TIAs) rate was 1.78% (19/1149, 95% CI: 1.11-2.84%, I 2 = 0%, t 2 = 0, p = 0.69), and total composite 1-year stroke/TIA rate was 2.97% (32/1149, 95% CI: 1.84-4.77%, I 2 = 0%, t 2 = 0, p = 0.41). The in-stent restenosis rate at 1 year was 1.06% (13/1653, 95% CI: 0.48-2.34%, I 2 = 28%, t 2 = 0.2308, p = 0.22). Conclusions : This meta-analysis shows that CAS with CGuard is safe with minimal neurological adverse events and in-stent restenosis rate at 1 year.

Introduction: One of the primary motivations for studying the human brain is to comprehend how external sensory input is processed and ultimately perceived by the brain. A good understanding of these processes can promote the identification of biomarkers for the diagnosis of various neurological disorders; it can also provide ways of evaluating therapeutic techniques. In this work, we seek the minimal requirements for identifying key stages of activity in the brain elicited by median nerve stimulation., Methods: We have used a priori knowledge and applied a simple, linear, spatial filter on the electroencephalography and magnetoencephalography signals to identify the early responses in the thalamus and cortex evoked by short electrical stimulation of the median nerve at the wrist. The spatial filter is defined first from the average EEG and MEG signals and then refined using consistency selection rules across ST. The refined spatial filter is then applied to extract the timecourses of each ST in each targeted generator. These ST timecourses are studied through clustering to quantify the ST variability. The nature of ST connectivity between thalamic and cortical generators is then studied within each identified cluster using linear and non-linear algorithms with time delays to extract linked and directional activities. A novel combination of linear and non-linear methods provides in addition discrimination of influences as excitatory or inhibitory., Results: Our method identifies two key aspects of the evoked response. Firstly, the early onset of activity in the thalamus and the somatosensory cortex, known as the P14 and P20 in EEG and the second M20 for MEG. Secondly, good estimates are obtained for the early timecourse of activity from these two areas. The results confirm the existence of variability in ST brain activations and reveal distinct and novel patterns of connectivity in different clusters., Discussion: It has been demonstrated that we can extract new insights into stimulus processing without the use of computationally costly source reconstruction techniques which require assumptions and detailed modeling of the brain. Our methodology, thanks to its simplicity and minimal computational requirements, has the potential for real-time applications such as in neurofeedback systems and brain-computer interfaces., Competing Interests: CK, GO, and AI are employed by AAI Scientific Cultural Services Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Karittevlis, Papadopoulos, Lima, Orphanides, Tiwari, Antonakakis, Papadopoulou Lesta and Ioannides.)

Recent magnetic resonance imaging (MRI) studies showed that colonic volumes in children are different between health and functional constipation. The length of the colon has however been rarely measured and principally using unphysiological colon preparations or cadaver studies. The main objective of this study was to measure the length of the undisturbed colon in children with functional constipation (FC) and healthy controls. Here, the colon of 19 healthy controls (10-18 years old) and 16 children with FC (7-18 years old) was imaged using MRI. Different regions of the colon (ascending, transverse, descending, and sigmoid-rectum) were first segmented manually on the MRI images. Three-dimensional skeletonization image analysis methods were then used to reduce the regions of interest to a central, measurable line. Total colon length (corrected for body surface area) in healthy controls was 56±2 cm/m2 (mean±SEM). Total colon length was significantly longer in children with FC 69±3 cm/m2 compared to controls (p = 0.0037). The colon regions showing the largest differences between groups were the ascending colon (p = 0.0479) and the sigmoid-rectum (p = 0.0003). In a linear regression model, there was a positive significant correlation between total colon length and age (R = 0.45, p = 0.0064), height (R = 0.49, p = 0.0031), weight (R = 0.46, p = 0.0059) and colon volume (R = 0.4543, p = 0.0061). Our findings showed significant differences in colon lengths between healthy controls and children with constipation. A new objective diagnostic imaging endpoint such as colon length may help to improve knowledge of colon morphology and function and, in turn, understanding of colon functional pathology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sharif et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)