Efficacy of an Artificial Intelligence App (Aysa) in Dermatological Diagnosis: Cross-Sectional Analysis.

BACKGROUND: Dermatology is an ideal specialty for artificial intelligence (AI)-driven image recognition to improve diagnostic accuracy and patient care. Lack of dermatologists in many parts of the world and the high frequency of cutaneous disorders and malignancies highlight the increasing need for AI-aided diagnosis. Although AI-based applications for the identification of dermatological conditions are widely available, research assessing their reliability and accuracy is lacking. OBJECTIVE: The aim of this study was to analyze the efficacy of the Aysa AI app as a preliminary diagnostic tool for various dermatological conditions in a semiurban town in India. METHODS: This observational cross-sectional study included patients over the age of 2 years who visited the dermatology clinic. Images of lesions from individuals with various skin disorders were uploaded to the app after obtaining informed consent. The app was used to make a patient profile, identify lesion morphology, plot the location on a human model, and answer questions regarding duration and symptoms. The app presented eight differential diagnoses, which were compared with the clinical diagnosis. The model's performance was evaluated using sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and F1-score. Comparison of categorical variables was performed with the χ2 test and statistical significance was considered at P<.05. RESULTS: A total of 700 patients were part of the study. A wide variety of skin conditions were grouped into 12 categories. The AI model had a mean top-1 sensitivity of 71% (95% CI 61.5%-74.3%), top-3 sensitivity of 86.1% (95% CI 83.4%-88.6%), and all-8 sensitivity of 95.1% (95% CI 93.3%-96.6%). The top-1 sensitivities for diagnosis of skin infestations, disorders of keratinization, other inflammatory conditions, and bacterial infections were 85.7%, 85.7%, 82.7%, and 81.8%, respectively. In the case of photodermatoses and malignant tumors, the top-1 sensitivities were 33.3% and 10%, respectively. Each category had a strong correlation between the clinical diagnosis and the probable diagnoses (P<.001). CONCLUSIONS: The Aysa app showed promising results in identifying most dermatoses.

The efficacy of physeal bar resection with guided growth in the treatment of physeal arrest with angular limb deformity.

Premature physeal arrest can cause progressive deformities and functional disabilities of the lower limbs. This study addressed the outcomes after physeal bar resection with or without guided growth (temporary hemiepiphysiodesis) for the treatment of angular limb deformities. We retrospectively analyzed 27 patients (mean 9 years; range, 3-12 years) who underwent physeal bar resection of the distal femur (15 patients), proximal tibia (3 patients), and distal tibia (9 patients) between 2002 and 2020. Fifteen patients underwent physeal bar resection only (Group A), and the other twelve underwent simultaneous guided growth (Group B). The correction angle (angle change between the preoperative and last follow-up values) was compared and analyzed. The overall mean correction angle was 2.9° (range, - 9 to 18.3°). A total of 12 (45%) patients had a > 5° angular deformity improvement (mean, 9.6°; range, 5-18.3°), 9 (33%) had a < 5° angular change; and 6 (22%) had a > 5° worsening of the angular deformity (mean, 6.7°; range, 5.2-9°). The correction angle in Group B (mean 7.6° ± 6.2) was significantly higher than that in Group A (mean - 0.77° ± 6.3) (P = 0.01). We found six (40%) and zero patients with a > 5° angular deformity increase in Groups A and B, respectively (P < 0.047). The group that underwent physeal bar resection with guided growth showed significantly higher correction angles than the group that underwent physeal bar resection alone. Additionally, none of the patients in the guided growth group experienced an increased angular deformity. Therefore, combining guided growth with physeal bar resection may lead to better outcomes in the treatment of growth arrest with angular deformities.

Volumetric microscopy of cerebral arteries with a miniaturized optical coherence tomography imaging probe.

Endovascular interventions are increasingly becoming the preferred approach for treating strokes and cerebral artery diseases. These procedures rely on sophisticated angiographical imaging guidance, which encounters challenges because of limited contrast and spatial resolution. Achieving a more precise visualization of the underlying arterial pathology and neurovascular implants is crucial for accurate procedural decision-making. In a human study involving 32 patients, we introduced the clinical application of a miniaturized endovascular neuro optical coherence tomography (nOCT) imaging probe. This technology was designed to navigate the tortuous paths of the cerebrovascular circulation and to offer high-resolution imaging in situ. The nOCT probe is compatible with standard neurovascular microcatheters, integrating with the procedural workflow used in clinical routine. Equipped with a miniaturized optical fiber and a distal lens, the probe illuminates the tissue and collects the backscattered, near-infrared light. While rotating the fiber and the lens at high speed, the probe is rapidly retracted, creating a spiral-shaped light pattern to comprehensively capture the arterial wall and implanted devices. Using nOCT, we demonstrated volumetric microscopy of cerebral arteries in patients undergoing endovascular procedures. We imaged the anterior and posterior circulation of the brain, including distal segments of the internal carotid and middle-cerebral arteries, as well as the vertebral, basilar, and posterior cerebral arteries. We captured a broad spectrum of neurovascular pathologies, such as brain aneurysms, ischemic stroke, arterial stenoses, dissections, and intracranial atherosclerotic disease. nOCT offered artifact-free, high-resolution visualizations of intracranial artery pathology and neurovascular devices.

Association of Human Leukocyte Antigen (HLA) class II (DRB1 and DQB1) alleles and haplotypes with Rheumatoid Arthritis in Sudanese patients.

The aim of this study was to determine the Human Leukocyte Antigen (HLA) class II (DRB1 and DQB1) alleles and haplotype frequency in Rheumatoid Arthritis (RA) in the Sudanese population. The frequency of HLA-DRB1 and -DQB1 alleles and DRB1-DQB1 haplotypes were determined in 122 RA patients and 100 controls. HLA alleles were genotyped by the polymerase chain reaction-sequence specific primers (PCR-SSP) method. In RA patients, HLA-DRB1*04 and *10 alleles were high in frequency (9.6% vs 14.2%, P = 0.038 and P = 0.042, respectively), and dependently on anti-citrullinated protein antibodies (ACPAs) seropositivity (P = 0.044 and P = 0.027, respectively). In contrast, the frequency of the HLA-DRB1*07 allele was significantly low in patients than in controls (11.7% vs 5.0%, P = 0.010). Moreover, the HLA-DQB1*03 allele was strongly associated with RA risk (42.2%, P = 2.2x10-8), whereas, HLA-DQB1*02 and *06 showed protective effects against RA (23.1% and 42.2%, P = 0.024 and P = 2.2x10-6, respectively). Five different HLA haplotypes, DRB1*03-DQB1*03 (P = 0.00003), DRB1*04-DQB1*03 (P = 0.00014), DRB1*08-DQB1*03 (P = 0.027), DRB1*13-DQB1*02 (P = 0.004), and DRB1*13-DQB1*03 (P = 3.79x10-8) were significantly associated with RA risk, while 3 protective haplotypes, DRB1*03-DQB1*02 (Pc = 0.008), DRB1*07-DQB1*02 (Pc = 0.004), and DRB1*13-DQB1*06 (Pc = 0.02) were identified. This is the first study determining the association between HLA class II alleles and haplotypes and RA risk in our population.

In-hospital Outcomes and the Impact of Transfer Status in Nonelective vs Elective Transcatheter Aortic Valve Replacement.

Background: Nonelective transcatheter aortic valve replacement (TAVR) requires additional research to be fully understood. Methods: Using the National Inpatient Sample database (2016-2019), we conducted a retrospective cohort study comparing nonelective vs elective TAVR. The primary outcome of interest was the in-hospital mortality rate among patients undergoing nonelective TAVR, compared to that among patients undergoing elective TAVR. We matched patients in a greedy nearest-neighbor 1:1 model and multivariable logistic regression, which was adjusted for demographics, hospital factors, and comorbidities, and was used to compare mortality in our matched cohort. Results: Each cohort had 4389 patients in each cohort. When adjusted for age, race, sex, and comorbidities, nonelective TAVR patients had 1.99 times higher odds of suffering in-hospital mortality compared to elective admissions (adjusted odds ratio 1.99, 95% confidence interval: 1.42-2.81; P < 0.001). When separated by transfer status, nonelective patients admitted as regular hospital admissions or transferred from other acute-care centres also had higher odds of suffering in-hospital mortality compared to elective admissions. Conclusions: Our findings illustrate that nonelective TAVR patients are a vulnerable population that require additional medical support in the acute-care setting. As the demand for TAVR increases, further discussions regarding access to healthcare in underserved regions, the national physician shortage, and the future of the TAVR industry are imperative.

Contexte: Le remplacement valvulaire aortique par cathéter (RVAC) d'urgence nécessite plus de recherche pour être bien compris. Méthodologie: À partir de la base de données National Inpatient Sample (2016-2019), nous avons réalisé une étude rétrospective de cohortes comparant le RVAC non urgent et le RVAC d'urgence. Celle-ci avait pour principal critère d'évaluation la comparaison du taux de mortalité à l'hôpital chez les patients soumis à un RVAC d'urgence à celui noté chez ceux qui subissent un RVAC non urgent. Nous avons apparié les patients selon le modèle du plus proche voisin, avec un rapport 1:1, et utilisé une régression logistique multivariée, ajustée en fonction des caractéristiques démographiques, des facteurs hospitaliers et des affections concomitantes, pour comparer le taux de mortalité dans les cohortes appariées. Résultats: Chaque cohorte comportait 4 389 patients. Après correction pour tenir compte de l'âge, de l'origine ethnique, du sexe et des affections concomitantes, nous avons constaté que le risque des patients ayant subi un RVAC d'urgence de mourir à l'hôpital était 1,99 fois plus élevé que celui des patients chez qui un RVAC non urgent a été effectué (rapport des risques ajustés : 1,99; intervalle de confiance à 95 % : 1,42 à 2,81; p < 0,001). De plus, les patients chez qui l'intervention a été pratiquée d'urgence courraient également un risque plus élevé de décéder à l'hôpital que ceux soumis à un RVAC non urgent, qu'ils aient été admis directement à l'hôpital ou transférés d'autres centres de soins de courte durée. Conclusions: Nos conclusions montrent que les patients ayant subi un RVAC d'urgence forment une population vulnérable qui requiert un soutien médical supplémentaire dans un milieu de soins de courte durée. Comme la demande pour des RVAC augmente, d'autres discussions sur l'accès aux soins de santé dans les régions mal desservies, la pénurie nationale de médecins et l'avenir de l'industrie du RVAC s'imposent.

Evaluation of Cisplatin-Induced Acute Renal Failure Amelioration Using Fondaparinux and Alteplase.

Acute renal failure (ARF) is a deleterious condition with increased mortality or healthcare costs or dialysis-dependent end-stage renal disease. The study aims to compare prophylaxis with fondaparinux (Fund) vs. treatment with alteplase (Alt) in ameliorating cisplatin (Cis)-induced ARF. Sixty male mice were equally divided randomly into six groups of control, Cis, Alt, and Cis + Alt groups receiving normal saline for 10 days. All four groups except for the control received Cis (30 mg/kg, i.p.) on day 7, and 6 h later, both the Alt groups received Alt (0.9 mg/kg, i.v.). The animal groups Fund and Fund + Cis received Fund (5 mg/kg, i.p.) for 10 days, and the Fund + Cis group on day 7 received Cis. All the animal groups were euthanized 72 h after the Cis dose. The Fund + Cis group showed significantly increased expression levels of platelet count, retinoid X receptor alpha (RXR-α) and phosphorylated Akt (p-Akt) in addition to decreased levels of urea, blood urea nitrogen (BUN), uric acid, white blood cells (WBCs), red blood cells (RBCs), relative kidney body weight, kidney injury score, glucose, prothrombin (PT), A Disintegrin And Metalloproteinases-10 (ADAM10), extracellular matrix deposition, protease-activated receptor 2 (PAR-2), and fibrinogen expression when compared to the Cis-only group. Meanwhile, the Cis + Alt group showed increased caspase-3 expression in addition to decreased levels of urea, BUN, uric acid, WBCs, RBCs, glucose, platelet count and PT expression with a marked decrease in PAR-2 protein expression compared to the Cis group. The creatinine levels for both the Fund + Cis and Cis + Alt groups were found to be comparable to those of the Cis-only group. The results demonstrate that the coagulation system's activation through the stimulation of PAR-2 and fibrinogen due to Cis-induced ADAM10 protein expression mediated the apoptotic pathway, as indicated by caspase-3 expression through the p-Akt pathway. This is normally accompanied by the loss of RXR-α distal and proximal tubules as lipid droplets. When the animals were pre-treated with the anticoagulant, Fund, the previous deleterious effect was halted while the fibrinolytic agent, Alt, most of the time failed to treat Cis-induced toxicity.

Nonfatal Injuries Sustained in Mass Shootings in the US, 2012-2019: Injury Diagnosis Matrix, Incident Context, and Public Health Considerations.

INTRODUCTION: The epidemic of gun violence in the United States (US) is exacerbated by frequent mass shootings. In 2021, there were 698 mass shootings in the US, resulting in 705 deaths and 2,830 injuries. This is a companion paper to a publication in JAMA Network Open, in which the nonfatal outcomes of victims of mass shootings have been only partially described. METHODS: We gathered clinical and logistic information from 31 hospitals in the US about 403 survivors of 13 mass shootings, each event involving greater than 10 injuries, from 2012-19. Local champions in emergency medicine and trauma surgery provided clinical data from electronic health records within 24 hours of a mass shooting. We organized descriptive statistics of individual-level diagnoses recorded in medical records using International Classification of Diseases codes, according to the Barell Injury Diagnosis Matrix (BIDM), a standardized tool that classifies 12 types of injuries within 36 body regions. RESULTS: Of the 403 patients who were evaluated at a hospital, 364 sustained physical injuries-252 by gunshot wound (GSW) and 112 by non-ballistic trauma-and 39 were uninjured. Fifty patients had 75 psychiatric diagnoses. Nearly 10% of victims came to the hospital for symptoms triggered by, but not directly related to, the shooting, or for exacerbations of underlying conditions. There were 362 gunshot wounds recorded in the Barell Matrix (1.44 per patient). The Emergency Severity Index (ESI) distribution was skewed toward higher acuity than typical for an emergency department (ED), with 15.1% ESI 1 and 17.6% ESI 2 patients. Semi-automatic firearms were used in 100% of these civilian public mass shootings, with 50 total weapons for 13 shootings (Route 91 Harvest Festival, Las Vegas. 24). Assailant motivations were reported to be associated with hate crimes in 23.1%. CONCLUSION: Survivors of mass shootings have substantial morbidity and characteristic injury distribution, but 37% of victims had no GSW. Law enforcement, emergency medical systems, and hospital and ED disaster planners can use this information for injury mitigation and public policy planning. The BIDM is useful to organize data regarding gun violence injuries. We call for additional research funding to prevent and mitigate interpersonal firearm injuries, and for the National Violent Death Reporting System to expand tracking of injuries, their sequelae, complications, and societal costs.

Assessment of thrombectomy procedure difficulty by neurointerventionalists based on vessel geometry parameters from carotid artery 3D reconstructions.

BACKGROUND: Diagnosing and treating acute ischemic stroke patients within a narrow timeframe is challenging. Time needed to access the occluded vessel and initiate thrombectomy is dictated by the availability of information regarding vascular anatomy and trajectory. Absence of such information potentially impacts device selection, procedure success, and stroke outcomes. While the cervical vessels allow neurointerventionalists to navigate devices to the occlusion site, procedures are often encumbered due to tortuous pathways. The purpose of this retrospective study was to determine how neurointerventionalists consider the physical nature of carotid segments when evaluating a procedure's difficulty. METHODS: Seven neurointerventionalists reviewed 3D reconstructions of CT angiograms of left and right carotid arteries from 49 subjects and rated the perceived procedural difficulty on a three-point scale (easy, medium, difficult) to reach the targeted M1. Twenty-two vessel metrics were quantified by dividing the carotids into 5 segments and measuring the radius of curvature, tortuosity, vessel radius, and vessel length of each segment. RESULTS: The tortuosity and length of the arch-cervical and cervical regions significantly impacted difficulty ratings. Additionally, two-way interaction between the radius of curvature and tortuosity on the arch-cervical region was significant (p < 0.0001) wherein, for example, at a given arch-cervical tortuosity, an increased radius of curvature reduced the perceived case difficulty. CONCLUSIONS: Examining the vessel metrics and providing detailed vascular data tailored to patient characteristics may result in better procedure preparation, facilitate faster vessel access time, and improve thrombectomy outcomes. Additionally, documenting these correlations can enhance device design to ensure they suitably function under various vessel conditions.

A Comparative Study of Acute Alcoholic Hepatitis vs. Non-Alcoholic Hepatitis Patients from a Cohort with Chronic Alcohol Dependence.

The rate of alcoholic hepatitis (AH) has risen in recent years. AH can cause as much as 40-50% mortality in severe cases. Successful abstinence has been the only therapy associated with long-term survival in patients with AH. Thus, it is crucial to be able to identify at-risk individuals in order to implement preventative measures. From the patient database, adult patients (age 18 and above) with AH were identified using the ICD-10 classification from November 2017 to October 2019. Liver biopsies are not routinely performed at our institution. Therefore, patients were diagnosed with AH based on clinical parameters and were divided into "probable" and "possible" AH. Logistic regression analysis was performed to determine risk factors associated with AH. A sub-analysis was performed to determine variables associated with mortality in AH patients. Among the 192 patients with alcohol dependence, there were 100 patients with AH and 92 patients without AH. The mean age was 49.3 years in the AH cohort, compared to 54.5 years in the non-AH cohort. Binge drinking (OR 2.698; 95% CI 1.079, 6.745; p = 0.03), heavy drinking (OR 3.169; 95% CI 1.348, 7.452; p = 0.01), and the presence of cirrhosis (OR 3.392; 95% CI 1.306, 8.811; p = 0.01) were identified as characteristics more commonly found in the AH cohort. Further, a higher inpatient mortality was seen in those with a probable AH diagnosis (OR 6.79; 95% CI 1.38, 44.9; p = 0.03) and hypertension (OR 6.51; 95% CI 9.49, 35.7; p = 0.02). A higher incidence of mortality was also noted among the non-Caucasian race (OR 2.72; 95% CI 4.92; 22.3; p = 0.29). A higher mortality rate despite a lower incidence of alcohol use among non-Caucasian patients may indicate healthcare disparities.

Kratom-induced acute liver injury: A case study and the importance of herbal supplement regulation.

Alternative medicine supplements have become the second most common cause of drug-induced liver injury (DILI) in the US. Kratom is a herbal supplement that is popular for its psychotropic and opioid-like activity. It has become increasingly available in western countries, which often have no specific regulations on its use. However, reports of adverse events linked to kratom use have been increasing; it has been implicated in acute liver injury (mostly cholestatic), acute liver failure, organ dysfunction, toxicity, coma, seizures, and death. Herein, we aim to increase healthcare provider and public awareness of the risks posed by kratom and ultimately support increased regulation of its use.

A Rare Case of Methotrexate-Induced Gastric Ulcer.

Methotrexate is commonly used to treat autoimmune conditions and malignancy. Peptic ulcer disease is a sparsely documented side effect of methotrexate. A 70-year-old female patient with rheumatoid arthritis on methotrexate presented with generalized fatigue and was found to be anemic. Endoscopy revealed gastric ulcers, the etiology of which was attributed to methotrexate use after careful exclusion of other possible causes. Cessation of methotrexate has been reported in the literature as vital to the healing of ulcers. Proton pump inhibitors or histamine 2 receptor (H2R) blockers may also be used as treatment; however, methotrexate should be discontinued before initiation of proton pump inhibitors, which can hinder the metabolism of methotrexate and can, in turn, lead to a worsening of the peptic ulcer disease.

Development of an in-vitro model based on patient vessel geometry for simulated use testing in neurointerventional surgery.

BACKGROUND: Neurointerventionalists use in-vitro vascular models to train for worst-case scenarios and test new devices in a simulated use environment to predict clinical performance. According to the Food and Drug Administration (FDA), any neurovascular navigation device should be able to successfully navigate two 360-degree turns and two 180-degree turns at the distal portion of the anatomical model. Here, we present a device benchmarking vascular model that complies with FDA recommendations. METHODS: Our vascular model was assembled from quantitative characterization of 49 patients who underwent CT angiography either for acute ischemic stroke caused by large vessel occlusion or for aneurysm treatment. Following complete characterization of these data, the vascular segments were 3D reconstructed from CT angiograms of 6 selected patients that presented with challenging anatomy. The curvature and total rotational angle were calculated for each segment and the anatomical parts that complied with FDA recommendations were fused together into a single in-vitro model. RESULTS: The model was constructed containing two common carotid branches arising from a type two aortic arch and the dimensions of the overall model exceeded the recommendations of the FDA. Two experienced neurointerventionalists tested the model for navigation difficulty using several devices on an in-vitro perfusion system and concluded that the model provided a realistic, challenging scenario. CONCLUSIONS: This model provides a first prototype designed according to FDA recommendations of cumulative angle while also integrating an aggregation of actual patient-specific anatomy. The availability of this clinically relevant benchmark model presents a potential standardized approach for neurovascular device testing.

Nasogastric Tube-Induced Catastrophic Airway Compromise Due to a Large Blood Clot.

Nasogastric and orogastric tube (NGT/OGT) insertion is a routine in-hospital procedure used in patients who need enteral feeding, medication administration, and gastric decompression in a patient unable to tolerate per oral administration. NGT insertion has a relatively low complication rate when performed adequately; however, previous studies demonstrate that associated complications range from delicate, simple nose bleeds to more severe conditions such as nasal mucosal bleeding, which can be easily aspirated in a patient with encephalopathy or other conditions associated with the inability to protect the airway. Here we present a case of traumatic NGT insertion causing nasal bleeding, leading to respiratory distress secondary to aspiration of blood clot obscuring the airway.

Artificial Intelligence in Breast X-Ray Imaging.

This topical review is focused on the clinical breast x-ray imaging applications of the rapidly evolving field of artificial intelligence (AI). The range of AI applications is broad. AI can be used for breast cancer risk estimation that could allow for tailoring the screening interval and the protocol that are woman-specific and for triaging the screening exams. It also can serve as a tool to aid in the detection and diagnosis for improved sensitivity and specificity and as a tool to reduce radiologists' reading time. AI can also serve as a potential second 'reader' during screening interpretation. During the last decade, numerous studies have shown the potential of AI-assisted interpretation of mammography and to a lesser extent digital breast tomosynthesis; however, most of these studies are retrospective in nature. There is a need for prospective clinical studies to evaluate these technologies to better understand their real-world efficacy. Further, there are ethical, medicolegal, and liability concerns that need to be considered prior to the routine use of AI in the breast imaging clinic.

In Vivo and In Silico Analgesic Activity of Ficus populifolia Extract Containing 2-O-ß-D-(3',4',6'-Tri-acetyl)-glucopyranosyl-3-methyl Pentanoic Acid.

Natural product-based structural templates have immensely shaped small molecule drug discovery, and new biogenic natural products have randomly provided the leads and molecular targets in anti-analgesic activity spheres. Pain relief achieved through opiates and non-steroidal anti-inflammatory drugs (NSAIDs) has been under constant scrutiny owing to their tolerance, dependency, and other organs toxicities and tissue damage, including harm to the gastrointestinal tract (GIT) and renal tissues. A new, 3',4',6'-triacetylated-glucoside, 2-O-ß-D-(3',4',6'-tri-acetyl)-glucopyranosyl-3-methyl pentanoic acid was obtained from Ficus populifolia, and characterized through a detailed NMR spectroscopic analysis, i.e., 1H-NMR, 13C-DEPT-135, and the 2D nuclear magnetic resonance (NMR) correlations. The product was in silico investigated for its analgesic prowess, COX-2 binding feasibility and scores, drug likeliness, ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties, possible biosystem's toxicity using the Discovery Studio®, and other molecular studies computational software programs. The glycosidic product showed strong potential as an analgesic agent. However, an in vivo evaluation, though at strong levels of pain-relieving action, was estimated on the compound's extract owing to the quantity and yield issues of the glycosidic product. Nonetheless, the F. populifolia extract showed the analgesic potency in eight-week-old male mice on day seven of the administration of the extract's dose in acetic acid-induced writhing and hot-plate methods. Acetic acid-induced abdominal writhing for all the treated groups decreased significantly (p < 0.0001), as compared to the control group (n = 6) by 62.9%, 67.9%, and 70.9% of a dose of 100 mg/kg (n = 6), 200 mg/kg (n = 6), and 400 mg/kg (n = 6), respectively. Similarly, using the analgesia meter, the reaction time to pain sensation increased significantly (p < 0.0001), as compared to the control (n = 6). The findings indicated peripheral and central-nervous-system-mediated analgesic action of the product obtained from the corresponding extract.

Glb1 knockout mouse model shares natural history with type II GM1 gangliosidosis patients.

GM1 gangliosidosis is a rare lysosomal storage disorder affecting multiple organ systems, primarily the central nervous system, and is caused by functional deficiency of ß-galactosidase (GLB1). Using CRISPR/Cas9 genome editing, we generated a mouse model to evaluate characteristics of the disease in comparison to GM1 gangliosidosis patients. Our Glb1-/- mice contain small deletions in exons 2 and 6, producing a null allele. Longevity is approximately 50 weeks and studies demonstrated that female Glb1-/- mice die six weeks earlier than male Glb1-/- mice. Gait analyses showed progressive abnormalities including abnormal foot placement, decreased stride length and increased stance width, comparable with what is observed in type II GM1 gangliosidosis patients. Furthermore, Glb1-/- mice show loss of motor skills by 20 weeks assessed by adhesive dot, hanging wire, and inverted grid tests, and deterioration of motor coordination by 32 weeks of age when evaluated by rotarod testing. Brain MRI showed progressive cerebellar atrophy in Glb1-/- mice as seen in some patients. In addition, Glb1-/- mice also show significantly increased levels of a novel pentasaccharide biomarker in urine and plasma which we also observed in GM1 gangliosidosis patients. Glb1-/- mice also exhibit accumulation of glycosphingolipids in the brain with increases in GM1 and GA1 beginning by 8 weeks. Surprisingly, despite being a null variant, this Glb1-/- mouse most closely models the less severe type II disease and will guide the development of new therapies for patients with the disorder.

A randomized controlled study to compare analgesic efficacy of sublingual buprenorphine and intravenous tramadol in patients undergoing mastectomy.

Sublingual (SL) buprenorphine is approved for managing acute postoperative pain, characterized by easy administration, good pain relief and good patient compliance. We hypothesized that SL buprenorphine would be a better perioperative analgesic compared to intravenous (IV) opioids like tramadol in patients undergoing mastectomy surgery for breast cancer. After institutional ethics committee approval, we randomized 60 patients with breast cancer into 2 groups. In buprenorphine group, patients received 200 µg of SL buprenorphine thrice daily and in tramadol group patients received 100 mg of IV tramadol thrice daily. The analgesic efficacy of SL buprenorphine was comparable to that of IV tramadol. Visual Analogue Scale scores had no significant difference between the two groups at various time frames (0, 1, 3, 6, 12, 18 and 24 hours) at rest and movement except at 0 and 3 hours during movement when the score was lower in the tramadol group than the buprenorphine group. Four patients in the buprenorphine group received rescue analgesic (IV morphine 3 mg). Analgesic efficacy of SL buprenorphine appears comparable to IV tramadol for managing postoperative pain after mastectomy. SL buprenorphine can be administered sublingually, which is an advantage.

High-frequency optical coherence tomography predictors of aneurysm occlusion following flow diverter treatment in a preclinical model.

BACKGROUND: High-frequency optical coherence tomography (HF-OCT) is an intravascular imaging method that allows for volumetric imaging of flow diverters in vivo. OBJECTIVE: To examine the hypothesis that a threshold for both volume and area of communicating malapposition can be predictive of early aneurysm occlusion. METHODS: Fifty-two rabbits underwent elastase aneurysm formation, followed by treatment with a flow diverter. At the time of implant, HF-OCT was acquired to study the rate and degree of communicating malapposition. Treated aneurysms were allowed to heal for either 90 or 180 days and euthanized following catheter angiography. Healing was dichotomized into aneurysm remnant or neck remnant/complete occlusion. Communicating malapposition was measured by HF-OCT using a semi-automatic algorithm able to detect any points where the flow diverter was more than 50 µm from the vessel wall. This was then summed across image slices to either a volume or area. Finally, a subsampled population was used to train a statistical classifier for the larger dataset. RESULTS: No difference in occlusion rate was found between device type or follow-up time (p=0.28 and p=0.67, respectively). Both volume and area of malapposition were significantly lower in aneurysms with a good outcome (p<0.001, both). From the statistical model, a volume of less than 0.56 mm3 or a normalized area less than 0.69 as quantified by HF-OCT was predictive of occlusion (p<0.001, each). CONCLUSIONS: HF-OCT allows for measurements of both volume and area of malapposition and, from these measurements, an accurate prediction for early aneurysm occlusion can be made.

Efficacy and Safety of Fecal Microbiota Transplantation in Treatment of Clostridioides difficile Infection among Pediatric Patients: A Systematic Review and Meta-Analysis.

Background and Aims: Cases of Clostridioides difficile infection have been rising among the pediatric and adolescent population. Fecal microbiota transplantation (FMT) has emerged as an alternative therapy for recurrent C. difficile infection. We aim to perform the first systematic review and meta-analysis investigating the safety and efficacy of fecal microbiota transplantation for C. difficile infection in children and adolescents. Methods: A literature search was performed using variations of the keywords "pediatrics", "C. difficile infection", and "fecal microbiota transplantation" in PubMed, EMBASE, CINAHL, Cochrane, and Google Scholar from inception to 30 June 2022. The resulting 575 articles were independently screened by three authors. Fourteen studies that satisfied the eligibility criteria were included in the meta-analysis. Results: The pooled success rate of FMT in the overall cohort was 86% (95% confidence interval: 77−95%; p < 0.001; I2 = 70%). There were 38 serious adverse events in 36 patients with a pooled rate of 2.0% (95% confidence interval: 0.0−3.0%; p = 0.1; I2 = 0.0%) and 47 adverse events in 45 patients with a pooled rate of 15% (95% confidence interval: 5.0−25.0%; p = 0.02; I2 = 54.0%). There was no death associated with FMT. Conclusions: FMT was concluded to be an effective and safe therapy in pediatric and adolescent patients with C. difficile infection. Underlying comorbidities may impede the efficacy. A rigorous screening process of the donors is recommended prior to embarking on FMT. There is no universal and cost-effective way to monitor the long-term outcomes of FMT. While promising, metagenomic sequencing may not be available in settings with limited resources. Robust data from randomized clinical trials is warranted.

Topical Eucalyptol Ointment Accelerates Wound Healing and Exerts Antioxidant and Anti-Inflammatory Effects in Rats' Skin Burn Model.

Eucalyptol is a major volatile constituent among well-known wound healing medicinal plants. The current study evaluated eucalyptol wound healing activity in the rat's third-degree skin-burn model. The parameters, i.e., skin-healing, oxidative/antioxidant markers, pro-/anti-inflammatory markers, were evaluated after 1- and 2-weeks of treatment regimens with 5% eucalyptol ointment. Eucalyptol-loaded ointment base of 5% w/w strength was formulated using fusion method and physically evaluated for consistency, stability, and homogeneity. A 25-rats were divided randomly into intact, negative control (untreated), silver sulfadiazine (SS, positive control), 1-week, and 2-weeks treated eucalyptol groups. Using an aluminum cylinder (120℃, 10 second duration), 3rd-degree skin burns were created on the rat's dorsum. Skin biopsies were collected at the end of the experiment for biochemical and histological investigations. Compared to the negative group; time-dependent wound size reduction and decreased edema were observed in eucalyptol-treated animals. Histopathological examinations demonstrated epidermis integrity, decreased neutrophil, and increased capillaries number in the 2-weeks and SS groups, compared to the negative and 1-week treated eucalyptol groups. Compared to the untreated animals, the 1- and 2-weeks eucalyptol treated groups' demonstrated significantly increased antioxidant superoxide dismutase (SOD, p=0.002 and p=0.003, respectively) and reduced lipid peroxide (LP, p=0.005 and p=0.0006, respectively). However, a significant increment of catalase (CAT, p=0.0009) was found only in the 2-weeks of eucalyptol group at a level of 2.42 ± 0.39 ng/g compared to 1.14 ± 0.04 ng/g in the untreated animals. Also, significant reductions in the cytokines, IL-1b, IL-6, and TNF-α (p < 0.05); and increase in the pro-angiogenic marker, IL-10, were detected in the 2-weeks (p=0.001) and SS (p=0.002) treated animals compared to the negative and 1-week eucalyptol treated groups. The study concluded that eucalyptol induced significant duration-based wound healing properties attributed to its antioxidant and anti-inflammatory effects.