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INTRODUCTION: Burnout is a common issue that impacts students across professional programs, where symptoms such as loneliness and isolation lead to a decrease in student and faculty success. The primary tactic utilized to combat burnout in pharmacists has been an emphasis on wellbeing strategies. COMMENTARY: Psychological safety is an important cultural dynamic that allows individuals to feel included, supported, and heard. This is particularly important as developing a professional setting of inclusivity and safety is associated with reducing the impact of psychosocial stressors on an individual outside of their professional setting. However, psychological safety has not yet been explored as a means to combat burnout in pharmacy education. IMPLICATIONS: Making space for inclusion, learning, contribution, and challenge in pharmacy education curriculums is necessary to create psychologically safe learning environments, which thereby increases feelings of belonging and community among students and faculty and subsequently reduces feelings of isolation and burnout. A commitment from administrators, faculty, and preceptors is necessary to encourage egalitarian dialogue and imagine a more dynamic, collegial relationship among students and faculty. Ultimately, this commitment communicates to students that they are valued as human beings, respected as individuals, and empowered as future healthcare providers well before they are asked to rise to the role of pharmacist.
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BACKGROUND: A blood-stage Plasmodium falciparum malaria vaccine would provide a second line of defence to complement partially effective or waning immunity conferred by the approved pre-erythrocytic vaccines. RH5.1 is a soluble protein vaccine candidate for blood-stage P falciparum, formulated with Matrix-M adjuvant to assess safety and immunogenicity in a malaria-endemic adult and paediatric population for the first time. METHODS: We did a non-randomised, phase 1b, single-centre, dose-escalation, age de-escalation, first-in-human trial of RH5.1/Matrix-M in Bagamoyo, Tanzania. We recruited healthy adults (aged 18-45 years) and children (aged 5-17 months) to receive the RH5.1/Matrix-M vaccine candidate in the following three-dose regimens: 10 µg RH5.1 at 0, 1, and 2 months (Adults 10M), and the higher dose of 50 µg RH5.1 at 0 and 1 month and 10 µg RH5.1 at 6 months (delayed-fractional third dose regimen; Adults DFx). Children received either 10 µg RH5.1 at 0, 1, and 2 months (Children 10M) or 10 µg RH5.1 at 0, 1, and 6 months (delayed third dose regimen; Children 10D), and were recruited in parallel, followed by children who received the dose-escalation regimen (Children DFx) and children with higher malaria pre-exposure who also received the dose-escalation regimen (High Children DFx). All RH5.1 doses were formulated with 50 µg Matrix-M adjuvant. Primary outcomes for vaccine safety were solicited and unsolicited adverse events after each vaccination, along with any serious adverse events during the study period. The secondary outcome measures for immunogenicity were the concentration and avidity of anti-RH5.1 serum IgG antibodies and their percentage growth inhibition activity (GIA) in vitro, as well as cellular immunogenicity to RH5.1. All participants receiving at least one dose of vaccine were included in the primary analyses. This trial is registered at ClinicalTrials.gov, NCT04318002, and is now complete. FINDINGS: Between Jan 25, 2021, and April 15, 2021, we recruited 12 adults (six [50%] in the Adults 10M group and six [50%] in the Adults DFx group) and 48 children (12 each in the Children 10M, Children 10D, Children DFx, and High Children DFx groups). 57 (95%) of 60 participants completed the vaccination series and 55 (92%) completed 22 months of follow-up following the third vaccination. Vaccinations were well-tolerated across both age groups. There were five serious adverse events involving four child participants during the trial, none of which were deemed related to vaccination. RH5-specific T cell and serum IgG antibody responses were induced by vaccination and purified total IgG showed in vitro GIA against P falciparum. We found similar functional quality (ie, GIA per µg RH5-specific IgG) across all age groups and dosing regimens at 14 days after the final vaccination; the concentration of RH5.1-specific polyclonal IgG required to give 50% GIA was 14·3 µg/mL (95% CI 13·4-15·2). 11 children were vaccinated with the delayed third dose regimen and showed the highest median anti-RH5 serum IgG concentration 14 days following the third vaccination (723 µg/mL [IQR 511-1000]), resulting in all 11 who received the full series showing greater than 60% GIA following dilution of total IgG to 2·5 mg/mL (median 88% [IQR 81-94]). INTERPRETATION: The RH5.1/Matrix-M vaccine candidate shows an acceptable safety and reactogenicity profile in both adults and 5-17-month-old children residing in a malaria-endemic area, with all children in the delayed third dose regimen reaching a level of GIA previously associated with protective outcome against blood-stage P falciparum challenge in non-human primates. These data support onward efficacy assessment of this vaccine candidate against clinical malaria in young African children. FUNDING: The European and Developing Countries Clinical Trials Partnership; the UK Medical Research Council; the UK Department for International Development; the National Institute for Health and Care Research Oxford Biomedical Research Centre; the Division of Intramural Research, National Institute of Allergy and Infectious Diseases; the US Agency for International Development; and the Wellcome Trust.
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Leukocytoclastic vasculitis (LCV) is a small-vessel vasculitis characterized by inflammation and damage to the walls of small blood vessels. It typically presents with palpable purpura and can be associated with various systemic conditions. Although its etiology is diverse, LCV has been associated with systemic diseases, infections, medications, and autoimmune disorders. Here, we present a case of LCV in a patient with decompensated heart failure. A 58-year-old man presented with progressively deteriorating swelling in both his lower limbs and scrotum, a persistent dry cough associated with minor ulcerative lesions on his shins, and a patchy rash with pustules and flat reddish spots. He was hospitalized three days prior due to atrial fibrillation and rapid ventricular rate, for which he was commenced on amiodarone. This rash persisted for three days, yet he denied experiencing any discomfort or itchiness along with it. Based on his clinical picture, laboratory evaluations, and imaging findings, he was diagnosed with LCV induced by amiodarone.
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Using scoping review methods, we systematically searched multiple online databases for publications in the first year of the pandemic that proposed pragmatic population or health system-level solutions to health inequities. We found 77 publications with proposed solutions to pandemic-related health inequities. Most were commentaries, letters, or editorials from the USA, offering untested solutions, and no robust evidence on effectiveness. Some of the proposed solutions could unintentionally exacerbate health inequities. We call on health policymakers to co-create, co-design, and co-produce equity-focussed, evidence-based interventions with communities, focussing on those most at risk to protect the population as a whole. Epidemiologists collaborating with people from other relevant disciplines may provide methodological expertise for these processes. As epidemiologists, we must interrogate our own methods to avoid propagating any unscientific biases we may hold. Epidemiology must be used to address, and never exacerbate, health inequities-in the pandemic and beyond.
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COVID-19 , Health Equity , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Health Inequities , Health PolicyABSTRACT
Background The Liver Imaging Reporting and Data System version 2018 (LI-RADS) treatment response algorithm (TRA) is a high-specificity, lower-sensitivity grading system to diagnose hepatocellular carcinoma (HCC) and recurrence after local-regional therapy. However, the emphasis on specificity can result in disease understaging, potentially leading to poorer posttransplant outcomes. Purpose To determine the negative predictive value (NPV) of pretransplant CT and MRI assessment for viable HCC on a per-patient basis using the LI-RADS TRA, considering explant pathology as the reference standard. Materials and Methods Patient records from 218 consecutive adult patients from a single institution with HCC who underwent liver transplant from January 2011 to November 2017 were retrospectively reviewed. Two readers blinded to the original report reviewed immediate (within 90 days) pretransplant imaging and characterized observations according to the LI-RADS TRA. Based on this, patients with LR-4, LR-5, or LR-TR (treatment response) viable tumors were designated as viable tumor; patients with solely LR-3 or LR-TR equivocal tumors were designated as equivocal; and patients with only LR-TR nonviable lesions were designated as no viable disease. Patients were designated as within or outside the Milan criteria. These per-patient designations were compared with the presence of viable disease at explant pathology. Fisher exact test was used to compare the differences between CT and MRI. Weighted κ values were used to calculate interreader reliability. Results Final study sample consisted of 206 patients (median age, 61 years [IQR, 57-65 years]; 157 male patients and 49 female patients). Per-patient LI-RADS TRA assessment of pretransplant imaging had an NPV of 32% (95% CI: 27, 38) and 26% (95% CI: 20, 33) (readers 1 and 2, respectively) for predicting viable disease. Seventy-five percent (reader 1) and 77% (reader 2) of patients deemed equivocal had residual tumors at explant pathology. Weighted interreader reliability was substantial (κ = 0.62). Conclusion Patient-based stratification of viable, equivocal, and nonviable disease at pretransplant CT or MRI, based on LI-RADS TRA, demonstrated low negative predictive value in excluding HCC at explant pathology. © RSNA, 2023 See also the editorial by Tamir and Tau in this issue.
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Carcinoma, Hepatocellular , Liver Neoplasms , Adult , Humans , Male , Female , Middle Aged , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/therapy , Liver Neoplasms/pathology , Predictive Value of Tests , Retrospective Studies , Reproducibility of Results , Magnetic Resonance Imaging/methods , Algorithms , Tomography, X-Ray Computed/methods , Sensitivity and Specificity , Contrast MediaABSTRACT
Modern diabetic treatment has gone beyond glycemic control, with the choice of different medications to attain therapeutic targets also affected by the risk of long-term outcomes and safety profiles. The effect of diabetes on increased morbidity and mortality and its relationship to cardiovascular outcomes and coronary artery diseases have driven recent diabetes studies toward medications that improve cardiovascular outcomes and reduce all-cause mortality. This is attained by holistically treating cardiovascular complications in type 2 diabetic patients beyond glycemic control. Moreover, both diabetes and pre-diabetes are considered risk factors for both microvascular and macrovascular cardiac events. Despite the fact that initial research acknowledged fluid retention as a safety issue in pioglitazone use, clinical trial data have not presented conclusive proof of a positive or negative impact on cardiac function. This comprehensive literature review aims to evaluate the effect of pioglitazone on all-cause mortality, hospitalizations for heart failure, and major adverse cardiovascular outcomes, including the individual outcomes of non-fatal stroke, non-fatal myocardial infarction, and cardiovascular mortality.
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Hyperthyroidism is an endocrine disorder characterized by excess thyroid hormone production. Its classic symptoms include weight loss, palpitations, tremors, and anxiety. We present a case of a 33-year-old female who initially presented with anxiety-like symptoms, leading to a misdiagnosis of generalized anxiety disorder. Upon further evaluation, the patient was diagnosed with hyperthyroidism, highlighting the importance of evaluating endocrine causes in patients presenting with anxiety-like symptoms. This case report underscores the significance of a comprehensive medical evaluation in patients with anxiety to avoid misdiagnoses and ensure appropriate management.
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Vancomycin is a widely used tricyclic glycopeptide antibiotic for treating various Gram-positive infections, including Clostridium difficile colitis. Although considered generally safe, it has been associated with several side effects. In this case report, we highlight a rare adverse effect in which a patient experienced chronic photophobia following treatment with oral vancomycin. This sheds light upon a potential relationship between oral vancomycin therapy and photophobia, emphasizing the need for increased awareness in clinical practice and urging further investigation into this association.
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Cleft lip is a common craniofacial anomaly and aesthetic obstacle. Different procedures, techniques, and steps are required for repair. These procedures may result in secondary abnormalities or volume deficiencies that can be managed by different methods such as autologous fat grafting. We aim through this study to identify the technique of autologous fat graft in cleft lip deformity and the patient characteristics for selecting this particular technique. This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The study systematically reviewed MEDLINE, Cochrane, and EMBASE databases without time-limitation. A total of 14 articles published in the period between 2004 and 2022 were included, then patients in each study who did not meet the inclusion criteria were excluded. A total of 519 patients who underwent autologous adipose tissue augmentation of cleft lip deformity were included and analyed. Autologous fat graft is found to be safe, effective in improving lip appearance as well as contour, and associated with high satisfaction rate among cleft lip patients. A selected patients with vermilion deficiency, whistle deformity, or overall lip volume deficiency is found to have a higher satisfaction rate. The most frequently reported complications were excess fullness, nodule formation, graft resorption, and nostril deformity.
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Systemic lupus erythematosus (SLE) is an autoimmune condition characterized by multi-organ involvement. The clinical presentation often varies from mild to moderate to severe. The cardiovascular system may also be affected, often portending a poor prognosis for patients. Although the relationship between SLE and cardiovascular disorders has been extensively explored through case reports and literature reviews, few systematic reviews explicitly focusing on this association have been conducted. In light of this, this systematic review aims to analyze the extent of the association between SLE and cardiovascular diseases (CVDs), by exploring the risk of developing CVDs, including myocardial infarction (MI), atherosclerosis, myocarditis, pericarditis and arrhythmias, in SLE patients vs. non-SLE patients. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to perform the systematic review. A detailed search was done covering the period from March 2003 to March 2023 using three databases: PubMed, Google Scholar, and Cochrane. The PubMed search identified 597 articles, while Google Scholar and Cochrane searches yielded 559 and three articles, respectively. Of the 1159 articles retrieved, we chose eight for final consideration, after excluding papers that did not discuss the role of SLE in CVDs, papers published earlier than 2003, and papers with incomplete data. The eight studies chosen included two narrative reviews, two systematic reviews, and four observational studies. In this systematic review, SLE was proven to have a strong relationship with diverse CVDs, including rare ones scarcely discussed in the literature, such as vasculitis and aortic dissection. All eight of the final papers indicated a connection between SLE and CVDs, based on the systematic analysis of these articles, which revealed that most recent research supports a higher risk of peripheral arterial occlusive disease (PAOD), MI, pericarditis, myocarditis, and other cardiovascular disorders in individuals with SLE. These associations may have certain gray areas, as patient characteristics and comorbidities often affect the extent of illness and long-term prognosis. Larger-scale studies are required to probe this relationship further and research the etiopathogenesis involved in order to improve patient outcomes. The effects of SLE on the heart are, however, unequivocal.
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BACKGROUND: While social media continues to dominate, social media platforms have become powerful health communication tools for older users. However, fulfilling their social media needs can be both detrimental and beneficial to their quality of life (QoL). This study assessed social media needs as they relate to QoL among older adults in Malaysia. METHODS: We conducted a cross-sectional study and adopted convenience sampling to recruit participants. The participants were required to self-report their sociodemographic profile, social media use and needs, and QoL. Social media use and needs were assessed using the Social Networking Sites Uses and Needs (SNSUN) scale, and QoL was assessed using the WHOQOL-BREF questionnaire. Multiple linear regression was performed to identify the predictors of QoL. RESULTS: The findings revealed that the fulfilment of social integrative needs was the strongest predictor of higher QoL in all domains. However, those using social media for their affective needs demonstrated lower psychological health quality. CONCLUSIONS: Fulfilling social integrative needs is the key to improving the QoL among older adults. The continuous development of age-friendly applications is essential to keep up with constantly changing social media trends and bridge the gap of social media inequalities. More importantly, it would enable older adults to utilize social media to its fullest potential and enjoy a higher QoL through accessible health communication tools.
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BACKGROUND AND OBJECTIVE: Postoperative pain is frequently reported following scleral buckle (SB) surgery. This study assessed the efficacy of perioperative dexamethasone on postoperative pain and opioid use following SB. MATERIALS AND METHODS: Forty-five patients with rhegmatogenous retinal detachments undergoing SB or SB and pars plana vitrectomy were randomly assigned to either standard care of postoperative oral acetaminophen and oxycodone/acetaminophen as needed or standard care plus 8 mg single-dose peri-operative intravenous dexamethasone. A questionnaire was administered on postoperative days 0, 1, and 7 to determine visual analog scale 0 to 10 pain score and number of opioid tablets consumed. RESULTS: Mean visual analog scale score and opioid use were significantly lower in the dexamethasone group on postoperative day 0 compared with control (2.76 ± 1.96 vs 5.64 ± 3.40, P = 0.002; 0.41 ± 0.92 vs 1.34 ± 1.43, P = 0.016). The dexamethasone group also demonstrated significantly lower total opioid use (0.97 ± 1.88 vs 3.69 ± 5.32, P = 0.047). No significant differences in pain score or opioid use were observed on days 1 or 7 (P = 0.078; P = 0.311; P = 0.326; P = 0.334). CONCLUSION: Single-dose intravenous dexamethasone following SB can significantly reduce postoperative pain and opioid use. [Ophthalmic Surg Lasers Imaging Retina 2023;54:238-242.].
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Analgesia , Retinal Detachment , Humans , Acetaminophen/therapeutic use , Analgesics, Opioid/therapeutic use , Visual Acuity , Scleral Buckling/methods , Retinal Detachment/surgery , Retinal Detachment/drug therapy , Pain, Postoperative/drug therapy , Pain, Postoperative/prevention & control , Pain, Postoperative/surgery , Vitrectomy/methods , Dexamethasone , Treatment OutcomeABSTRACT
The integration of antennas in composite structures is gaining popularity with advances in wireless communications and the ever-increasing demands for efficient smart structures. Efforts are ongoing to ensure that antenna-embedded composite structures are robust and resilient to inevitable impacts, loading and other external factors that threaten the structural integrity of these structures. Undoubtedly, the in situ inspection of such structures to identify anomalies and predict failures is required. In this paper, the microwave non-destructive testing (NDT) of antenna-embedded composite structures is introduced for the first time. The objective is accomplished using a planar resonator probe operating in the UHF frequency range (~525 MHz). High-resolution images of a C-band patch antenna fabricated on an aramid paper-based honeycomb substrate and covered with a glass fiber reinforced polymer (GFRP) sheet are presented. The imaging prowess of microwave NDT and its distinct advantages in inspecting such structures are highlighted. The qualitative as well as the quantitative evaluation of the images produced by the planar resonator probe and a conventional K-band rectangular aperture probe are included. Overall, the potential utility of microwave NDT for the inspection of smart structures is demonstrated.
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This research investigates the synthesis and characterization of hydrogel and cryogel microspheres that are doped with green synthesised silver nanoparticles (CS-AgNPs). Also, the study assesses the antibacterial activity of hydrogel and cryogel microspheres by comparing them with commercial antibiotics. The porous structure of CS and the adequate dispersion of AgNPs were confirmed by SEM and EDX techniques, respectively. The disk diffusion method and the optical density measurement (OD600) confirm the outstanding antimicrobial activity of CS-AgNPs hydrogel and cryogel microspheres in comparison to antibiotics for both Gram-positive and Gram-negative bacteria. The CS-AgNPs microspheres demonstrate promising antimicrobial and biocompatible agents for medical field applications.
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Anti-Infective Agents , Chitosan , Metal Nanoparticles , Anti-Bacterial Agents/chemistry , Cryogels , Chitosan/chemistry , Silver/chemistry , Gram-Negative Bacteria , Metal Nanoparticles/chemistry , Microspheres , Gram-Positive Bacteria , Anti-Infective Agents/pharmacologyABSTRACT
Vitamin D is a vital nutrient that plays a significant part in several physiological processes within the human body, including calcium metabolism, bone health, immune function, and cell growth and differentiation. It is obtained mainly through exposure to sunlight but can be acquired from certain foods and supplements as well. Vitamin D deficiency (VDD) could be the risk factor for cardiovascular diseases (CVDs), such as heart disease and stroke. In blood vitamin D low levels have been linked with an enhanced risk of developing CVDs. However, it is unclear whether vitamin D levels are the leading cause or consequence of these conditions. While some studies highlight that taking vitamin D supplements could decrease the risk of CVD; however, more research is required to better understand the association between vitamin D and cardiovascular health. In this review, we aimed to summarize the currently available evidence supporting the association between vitamin D and CVDs and anesthesia considerations.
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Background: Due to the global surge in COVID-19 cases, numerous countries have enforced lockdowns of varying stringency. Social isolation and stay-at-home orders have detrimental effects on one's lifestyle and dietary habits. This study aimed to assess the dietary patterns, food preferences, shopping behavior and weight gain during the lockdown among students in a private university in Malaysia. Design and Methods: We conducted a cross-sectional study among 426 students using convenience sampling method one-month after initiating the Conditional Movement Control Order (November 15-30, 2020), using a validated self-administered web-based survey. Chi-square test with post-hoc and planned comparison procedures were performed. Results: Of the 426 participants, more than half were females (55.9%). Over half of the surveyed students reported increased eating (51.2%), snacking (55.2%) and online food ordering (71.1%) during the lockdown. Meat products and sweet drinks (both >90%) were the most consumed food among individuals with higher BMI. 45.5% of the participants reported weight gain (mean 3.36, SD 1.61kg) one month after the lockdown. Female, youth (aged 19-24), working remotely, increased eating, snacking, cooking, and online food ordering were positively associated with weight gain. Conclusions: Findings suggested that unintended consequences of lockdown have negative impacts on dietary habits and food preferences among university students. Advocacy and public health measures for nutritional support amidst the pandemic are crucial, especially for at-risk groups such as overweight and obese individuals.
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Importance: Coronary artery calcium scores (CACS) are used to help assess patients' cardiovascular status and risk. However, their best use in risk assessment beyond traditional cardiovascular factors in primary prevention is uncertain. Objective: To find, assess, and synthesize all cohort studies that assessed the incremental gain from the addition of a CACS to a standard cardiovascular disease (CVD) risk calculator (or CVD risk factors for a standard calculator), that is, comparing CVD risk score plus CACS with CVD risk score alone. Evidence Review: Eligible studies needed to be cohort studies in primary prevention populations that used 1 of the CVD risk calculators recommended by national guidelines (Framingham Risk Score, QRISK, pooled cohort equation, NZ PREDICT, NORRISK, or SCORE) and assessed and reported incremental discrimination with CACS for estimating the risk of a future cardiovascular event. Findings: From 2772 records screened, 6 eligible cohort studies were identified (with 1043 CVD events in 17â¯961 unique participants) from the US (n = 3), the Netherlands (n = 1), Germany (n = 1), and South Korea (n = 1). Studies varied in size from 470 to 5185 participants (range of mean [SD] ages, 50 [10] to 75.1 [7.3] years; 38.4%-59.4% were women). The C statistic for the CVD risk models without CACS ranged from 0.693 (95% CI, 0.661-0.726) to 0.80. The pooled gain in C statistic from adding CACS was 0.036 (95% CI, 0.020-0.052). Among participants classified as being at low risk by the risk score and reclassified as at intermediate or high risk by CACS, 85.5% (65 of 76) to 96.4% (349 of 362) did not have a CVD event during follow-up (range, 5.1-10.0 years). Among participants classified as being at high risk by the risk score and reclassified as being at low risk by CACS, 91.4% (202 of 221) to 99.2% (502 of 506) did not have a CVD event during follow-up. Conclusions and Relevance: This systematic review and meta-analysis found that the CACS appears to add some further discrimination to the traditional CVD risk assessment equations used in these studies, which appears to be relatively consistent across studies. However, the modest gain may often be outweighed by costs, rates of incidental findings, and radiation risks. Although the CACS may have a role for refining risk assessment in selected patients, which patients would benefit remains unclear. At present, no evidence suggests that adding CACS to traditional risk scores provides clinical benefit.
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Cardiovascular Diseases , Coronary Artery Disease , Vascular Calcification , Calcium , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Coronary Artery Disease/diagnosis , Coronary Artery Disease/epidemiology , Female , Heart Disease Risk Factors , Humans , Male , Middle Aged , Predictive Value of Tests , Risk Assessment , Risk Factors , Vascular Calcification/diagnostic imagingABSTRACT
BACKGROUND AND PURPOSE: Astroblastoma is a rare type of glial tumor, histologically classified into two types with different prognoses: high and low grade. We aimed to investigate the CT and MRI findings of astroblastomas by collecting studies with analyzable neuroimaging data and extracting the imaging features useful for tumor grading. METHODS: We searched for reports of pathologically proven astroblastomas with analyzable neuroimaging data using PubMed, Scopus, and Embase. Sixty-five studies with 71 patients with astroblastomas met the criteria for a systematic review. We added eight patients from our hospital, resulting in a final study cohort of 79 patients. The proportion of high-grade tumors was compared in groups based on the morphology (typical and atypical) using Fisher's exact test. RESULTS: High- and low-grade tumors were 35/71 (49.3%) and 36/71 (50.7%), respectively. There was a significant difference in the proportion of high-grade tumors based on the tumor morphology (typical morphology: high-grade = 33/58 [56.9%] vs. atypical morphology, 2/13 [15.4%], p = .012). The reviews of neuroimaging findings were performed using the images included in each article. The articles had missing data due to the heterogeneity of the collected studies. CONCLUSIONS: Detailed neuroimaging features were clarified, including tumor location, margin status, morphology, CT attenuation, MRI signal intensity, and contrast enhancement pattern. The classification of tumor morphology may help predict the tumor's histological grade, contributing to clinical care and future oncologic research.
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Brain Neoplasms , Glioma , Neoplasms, Neuroepithelial , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Humans , Magnetic Resonance Imaging , Neoplasms, Neuroepithelial/diagnostic imaging , Neoplasms, Neuroepithelial/pathology , NeuroimagingABSTRACT
Primary or acquired therapy resistance is a major obstacle to the effective treatment of cancer. Resistance to apoptosis has long been thought to contribute to therapy resistance. We show here that recombinant TRAIL and CDK9 inhibition cooperate in killing cells derived from a broad range of cancers, importantly without inducing detectable adverse events. Remarkably, the combination of TRAIL with CDK9 inhibition was also highly effective on cancers resistant to both, standard-of-care chemotherapy and various targeted therapeutic approaches. Dynamic BH3 profiling revealed that, mechanistically, combining TRAIL with CDK9 inhibition induced a drastic increase in the mitochondrial priming of cancer cells. Intriguingly, this increase occurred irrespective of whether the cancer cells were sensitive or resistant to chemo- or targeted therapy. We conclude that this pro-apoptotic combination therapy has the potential to serve as a highly effective new treatment option for a variety of different cancers. Notably, this includes cancers that are resistant to currently available treatment modalities.
Subject(s)
Antineoplastic Agents , Neoplasms , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis , Cell Line, Tumor , Mitochondria , Neoplasms/drug therapy , TNF-Related Apoptosis-Inducing Ligand/pharmacologyABSTRACT
BACKGROUND: Treating congenital blepharoptosis is often mandatory to clear the visual access and avoid amblyopia; however, when the levator function is poor, achieving a satisfactory long-term outcome is challenging. This study aimed to compare the outcomes of maximal levator resection (MLR) with those of frontalis suspension (FS) using Gore-Tex ®, in the treatment of congenital blepharoptosis with poor levator function. PATIENTS AND METHODS: The study included 102 eyelids of 66 patients of mean age 4.3 ± 1.6 standard deviation (SD) years, randomly divided into two groups (51 eyes each). Group A: FS using Gore-Tex ®, Group B: MLR. Postoperative outcomes were evaluated at 1, 6 and 12 months. Patients' ophthalmic examination including margin-reflex distance (MRD1) before and after surgery and postoperative complications were recorded. RESULTS: At the end of the follow-up, the mean MRD1 increased from 0.3 ± 0.7 SD mm in Group A, 0.4 ± 0.8 SD mm in Group B preoperatively, to 2.7 ± 0.5 SD mm and 2.9 ± 0.7 SD mm, respectively (P < 0.001 in both groups). Results of Group B were significantly higher than Group A (P = 0.047). Success was achieved in 77 eyelids (75.4%), distributed as follows: 36 eyelids (70.6%) in Group A, and 41 eyelids (80.1%) in Group B. The total recurrence rate was 6.9% (seven eyes), while other complications were recorded in 23 eyes (22.5%). CONCLUSION: MLR, compared to FS with Gore-Tex® sling, can be a more efficient surgical option to correct congenital blepharoptosis with poor levator excursion. Prominent postoperative lagophthalmos warrants close ocular surface observation in early follow-up weeks.