Identification of a novel antifungal backbone of naphthalimide thiazoles with synergistic potential for chemical and dynamic treatment

Aim: The high incidence and prevalence of fungal infections call for new antifungal drugs. This work was to develop naphthalimide thiazoles as potential antifungal agents. Results & methodology: These compounds showed significant antifungal potency toward some tested fungi. Especially, naphthalimide thiazole 4h with excellent anti- Candida tropicalis efficacy possessed good hemolysis level, low toxicity and no obvious resistance. Deciphering the mechanism showed that 4h interacted with DNA and disrupted the antioxidant defense system of C. tropicalis. Compound 4h also triggered membrane depolarization, leakage of cytoplasmic contents and LDH inhibition. Simultaneously, 4h rendered metabolic inactivation and eradicated the formed biofilms of C. tropicalis. Conclusion: The multifaceted synergistic effect initiated by naphthalimide thiazoles is a reasonable treatment window for prospective development.

Imaging Acute Stroke: From One-Size-Fit-All to Biomarkers

In acute stroke management, time window has been rigidly used as a guide for decades and the reperfusion treatment is only available in the first few limited hours. Recently, imaging-based selection of patients has successfully expanded the treatment window out to 16 and even 24 h in the DEFUSE 3 and DAWN trials, respectively. Recent guidelines recommend the use of imaging techniques to guide therapeutic decision-making and expanded eligibility in acute ischemic stroke. A tissue window is proposed to replace the time window and serve as the surrogate marker for potentially salvageable tissue. This article reviews the evolution of time window, addresses the advantage of a tissue window in precision medicine for ischemic stroke, and discusses both the established and emerging techniques of neuroimaging and their roles in defining a tissue window. We also emphasize the metabolic imaging and molecular imaging of brain pathophysiology, and highlight its potential in patient selection and treatment response prediction in ischemic stroke.

Polymorphisms in the CYP3A5 gene significantly affect the pharmacokinetics of sirolimus after kidney transplantation

Aim: Sirolimus (SIR) is an immunosuppressant with limitations, including a narrow treatment window, multiple adverse reactions and large differences within and among individuals. Objective: We analyzed the correlation between numerous SNPs and SIR in terms of trough concentration in the early stage after kidney transplantation. Materials & method: A retrospective cohort study involving 69 kidney transplantation recipients was designed. Blood samples were collected to extract total DNAs, and trough SIR concentrations were measured. Logistic regression was used to analyze the association between SNPs and SIR trough concentrations. Result: At 7 days, 1 month and 3 months, the mean SIR trough concentration of patients in the CYP3A5 rs4646453-CC group was significantly higher than that in the CYP3A5 rs4646453-AA and CYP3A5 rs4646453-CA groups (p < 0.001) and CYP3A5 rs15524-AA group was significantly higher than that in the CYP3A5 rs15524-AG and CYP3A5 rs15524-GG groups (p < 0.001). Conclusion: Our study indicated that both CYP3A5 rs4646453 and CYP3A5 rs15524 had a certain influence on SIR trough concentration at 7 days, 1 month and 3 months.

Recalibrated Scales: The Use of Low-dose Isotretinoin in a Case of Epidermolytic Ichthyosis-NPS1 in a Filipino Child

Epidermolytic Ichthyosis (EI) is a rare non-syndromic keratinopathic ichthyosis without definitive treatment. This is a case of EI in a 5-year-old Filipino female who presented with hyperkeratotic scales sparing the palms and soles. Histopathology revealed epidermolytic hyperkeratosis. A trial of treatment with isotretinoin 0.3 mg/kg/day, together with keratolytic agents, urea lotion and lactic acid lotion, resulted in a marked decrease in the thickness of the scales and odor. Interestingly, rebound effects were noted at 0.6 mg/kg/day. Taking into account that EI presents with more skin fragility compared to non-EHK ichthyosis, the authors surmise that there may be a smaller treatment window for patients with EI, which is notably lower than recommended for ichthyosis in general.

Rhinocerebral mucormycosis secondary to severe acute pancreatitis and diabetic ketoacidosis: a case report

Introduction Rhinocerebral mucormycosis is a rare and severe form of opportunistic fungal infection that can develop rapidly and cause significant mortality, particularly among diabetic patients suffering from ketoacidosis. Diagnosing rhinocerebral mucormycosis during the early stages of infection is challenging. Case presentation We describe a case of rhinocerebral mucormycosis secondary to severe acute pancreatitis in a patient suffering from diabetic ketoacidosis. In this case, the condition was not diagnosed during the optimal treatment window. we therefore provide a thorough overview of related clinical findings and histopathological characteristics, and we discuss potential differential diagnoses. Conclusions In summary, we described a case of rhinocerebral mucormycosis secondary to severe acute pancreatitis in a patient suffering from diabetic ketoacidosis, with the optimal treatment window for this condition having been missed. This report suggests that a definitive mucormycosis diagnosis can be made based upon tissue biopsy that reveals the presence of characteristic hyphae. Early diagnosis and treatment are essential in order to improve patient prognosis.

Abstract 56: Incidence of Large Vessel Occlusions in Children Who Present Within Extended Thrombectomy Treatment Window

Introduction: Mechanical thrombectomy (MT) should be considered in children with persistent deficits with large vessel occlusion (LVO), although the recognition and diagnosis of stroke is often delayed. With the recent extension of treatment windows to 24 hours in adult studies, more children may now be MT candidates. The aim of this project was to examine LVO incidence in childhood strokes that present within 24 hours of symptom onset. Methods: Patients with clinical and radiographic confirmed stroke from 1995-2018 were identified via internal database search. Patients with last known normal < 24 hours and imaging within the MT time window (24 hours) were included for analysis. A pediatric neuroradiologist independently reviewed imaging to confirm presence/absence of LVO. Results: Of 165 patients with childhood stroke, 60 (36.3%) had last known normal <24 hours and vessel imaging within the MT timeframe (table). Fourteen patients (8.5%) had an LVO; nine with internal carotid or M1 and five with M2 occlusions. Median time from symptom onset to imaging was 6.47 hours in LVO patients. Most common stroke etiologies with LVO were unilateral focal cerebral arteriopathy of childhood (5) and other (5). One of the LVO patients underwent MT. Conclusions: At our institution, over 1/3 rd of patients presented within 24 hour of symptom onset with vascular imaging, and nearly 1/4 of those children (8.5% overall) had an LVO amenable to potential MT. While not all children with LVO will be MT candidates, this study shows that significant numbers of children present with LVO within the adult MT treatment window.

Predicting neuroimaging eligibility for extended-window endovascular thrombectomy

OBJECTIVEEndovascular thrombectomy (EVT) and tissue plasminogen activator (tPA) are effective ischemic stroke treatments in the initial treatment window. In the extended treatment window, these treatments may offer benefit, but CT and MR perfusion may be necessary to determine patient eligibility. Many hospitals do not have access to advanced imaging tools or EVT capability, and further patient care would require transfer to a facility with these capabilities. To assist transfer decisions, the authors developed risk indices that could identify patients eligible for extended-window EVT or tPA.METHODSThe authors retrospectively identified stroke patients who had concurrent CTA and perfusion and evaluated three potential outcomes that would suggest a benefit from patient transfer. The first outcome was large-vessel occlusion (LVO) and target mismatch (TM) in patients 5–23 hours from last known normal (LKN). The second outcome was TM in patients 5–15 hours from LKN with known LVO. The third outcome was TM in patients 4.5–12 hours from LKN. The authors created multivariable models using backward stepping with an α-error criterion of 0.05 and assessed them using C statistics.RESULTSThe final predictors included the National Institutes of Health Stroke Scale (NIHSS), the Alberta Stroke Program Early CT Score (ASPECTS), and age. The prediction of the first outcome had a C statistic of 0.71 (n = 145), the second outcome had a C statistic of 0.85 (n = 56), and the third outcome had a C statistic of 0.86 (n = 54). With 1 point given for each predictor at different cutoffs, a score of 3 points had probabilities of true positive of 80%, 90%, and 94% for the first, second, and third outcomes, respectively.CONCLUSIONSDespite the limited sample size, compared with perfusion-based examinations, the clinical variables identified in this study accurately predicted which stroke patients would have salvageable penumbra (C statistic 71%–86%) in a range of clinical scenarios and treatment cutoffs. This prediction improved (C statistic 85%–86%) when utilized in patients with confirmed LVO or a less stringent tissue mismatch (TM < 1.2) cutoff. Larger patient registries should be used to validate and improve the predictive ability of these models.

Rhinocerebral Mucormycosis Secondary to Severe Acute Pancreatitis and Diabetic Ketoacidosis: A Case Report

Introduction: Rhinocerebral mucormycosis is a rare and severe form of opportunistic fungal infection that can develop rapidly and cause significant mortality, particularly among diabetic patients suffering from ketoacidosis. Diagnosing rhinocerebral mucormycosis during the early stages of infection is challenging. Case presentation：We describe a case of rhinocerebral mucormycosis secondary to severe acute pancreatitis in a patient suffering from diabetic ketoacidosis. In this case, the condition was not diagnosed during the optimal treatment window. we therefore provide a thorough overview of related clinical findings and histopathological characteristics, and we discuss potential differential diagnoses.Conclusions: In summary, we described a case of rhinocerebral mucormycosis secondary to severe acute pancreatitis in a patient suffering from diabetic ketoacidosis, with the optimal treatment window for this condition having been missed. This report suggests that a definitive mucormycosis diagnosis can be made based upon tissue biopsy that reveals the presence of characteristic hyphae. Early diagnosis and treatment are essential in order to improve patient prognosis.