Outcomes and Cost-Analysis of Open Versus Endovascular Abdominal Aortic Aneurysm Repair in a Developing Country: A 15-year Experience at a Tertiary Medical Center.

BACKGROUND: Endovascular aortic aneurysm repair (EVAR) has become the most common procedure for treating abdominal aortic aneurysms based on multiple studies conducted in the western world. The implication of such findings in developing countries is not well demonstrated. The objective of this study was to compare medical outcomes and costs of EVAR and open surgical repair (OSR) in a developing country. METHODS: This is a retrospective study of all patients undergoing elective abdominal aortic aneurysm repair between 2005 and 2020 at a tertiary medical center in a developing country. Medical records were used to retrieve demographics, comorbidities, and perioperative complications. Medical records were also used to provide data on the need of reintervention, date of last follow-up, and mortality. RESULTS: The study included a total of 164 patients. Median follow-up time was 41 months. The mean age was 69.9 +/- 7.84 years and 90.24% (n = 148) of patients were males. Regarding long-term mortality outcomes, no significant difference was detected between both groups; OSR patients had a survival rate of 91.38% and 74.86% at 5 and 10 years, compared to 77.29% and 56.52% in the EVAR group (P value = 0.10). Both groups had comparable long-term reintervention rates (P value = 0.334). The OSR group was charged significantly less than the EVAR group ($27,666.35 vs. $44,528.04, P value = 0.008). CONCLUSIONS: OSR and EVAR have comparable survival and reintervention outcomes. Unlike what was reported in developed countries, patients undergoing OSR in countries with low hospital stay costs incur lower treatment costs.

The association of hearing loss with frailty among community-dwelling older adults: findings from the National Health and Aging Trends Study.

BACKGROUND: The identification of modifiable risk factors is crucial for the prevention and/or reversal of frailty, which is associated with significant morbidity and mortality. Hearing loss affects two-thirds of older adults in the United States (U.S.) and is associated with physical and cognitive decline which may increase frailty risk. We investigated the association of hearing loss and hearing aid use with frailty and pre-frailty in a nationally representative sample of older adults in the U.S. METHODS: Cross-sectional analysis of the National Health and Aging Trends Study (2021 round). The better-hearing ear pure-tone average (BPTA) at speech-frequencies (0.5-4 kHz) was modeled continuously (per 10 dB) and categorically (no ≤ 25 dB, mild 26-40 dB, moderate or greater > 40 dB hearing loss). Hearing aid use was self-reported. The physical frailty phenotype (frail, pre-frail, robust) was determined based on Fried criteria: unintentional weight loss, exhaustion, low physical activity, weakness, slow walking speed. We used multinomial multivariable regression adjusted for sociodemographic and health characteristics (odds ratios [95% Confidence Intervals]). RESULTS: Among 2,361 participants (mean age = 81 years, 56% female, 19% Black), 860 (36%) had mild and 864 (37%) had moderate or greater hearing loss. Worse hearing was associated with greater odds of being frail versus robust (OR = 1.20 [1.05-1.38] per 10 dB difference). Categorically, moderate or greater hearing loss was associated with greater odds of being frail (OR = 1.84 [1.01-3.08]) and pre-frail (OR = 1.46 [1.01-2.10]) versus robust. Among 1,724 participants with hearing loss, compared to hearing aid users (N = 522), nonusers had greater odds of being frail (OR = 2.54 [1.54-4.18]) and pre-frail (OR = 1.51 [1.05-2.17]) versus robust, and frail versus pre-frail (OR = 1.68 [1.04-2.72]). CONCLUSIONS: In a nationally representative sample of older adults in the U.S., using gold-standard hearing measures and a validated frailty phenotype, hearing loss and lack of hearing aid use was cross-sectionally associated with frailty and pre-frailty. Future longitudinal studies are needed to establish if hearing loss is a risk factor for frailty, which may have significant clinical importance.

Hypoalbuminemia is Associated with Mortality in Patients Undergoing Lower Extremity Amputation.

BACKGROUND: Poor nutritional status is common among patients undergoing lower extremity amputation (LEA). In this study, the association between preoperative hypoalbuminemia, a marker for malnutrition, and postoperative mortality in patients undergoing LEA was explored. METHODS: Data on patients undergoing LEA between 2005 and 2017 were retrospectively analyzed from the prospectively collected American College of Surgeons National Surgical Quality Improvement Program database. Patients were divided into clinically relevant categories based on their serum albumin level (<2.5, 2.5-3.39, ≥3.4 g/dl) and were further stratified according to amputation level. Operative death was compared across groups and multivariable logistic regression was performed to estimate risk-adjusted odds ratio (AOR). RESULTS: In 35,383 patients, the rate of 30-day postoperative mortality was 7.6% (n = 2693). Mortality rate was highest in patients with very low albumin levels (11%) as compared to low (6.8%) and normal levels (3.9%). On multivariable analysis, lower albumin levels emerged as a risk-adjusted independent predictor of mortality. After risk-adjustment, patients with very low albumin levels (AOR [95% CI]: 2.25 [1.969-2.56], P < 0.001) and low albumin levels (AOR [95% CI]: 1.42 [1.239-1.616], P < 0.001) had higher odds of mortality when compared to patients with normal albumin levels. On sensitivity analysis, a similar trend was seen in patients undergoing above knee amputation but not in patients undergoing minor amputations. CONCLUSIONS: In patients undergoing major LEA, hypoalbuminemia is associated with an increased risk of postoperative mortality in a dose response manner, specifically in above knee amputations. Monitoring and optimizing patients' nutritional status before surgery, when possible, may be warranted and should be further explored.

Association of Single and Dual Sensory Impairment with Falls among Medicare Beneficiaries.

Objective: The purpose of this study was to determine if dual sensory impairment (DSI) is associated with falls and fear of falling among older adults. Methods: Using data from the 2019 Medicare Current Beneficiary Survey (MCBS), we studied the cross-sectional association of self-reported hearing/vision impairment with self-reported history/number of falls over the past year, fear of falling (scale 1-6), and a fall requiring medical help using weighted multivariable regressions adjusted for demographic and clinical covariates. Results: Among 11,089 Medicare beneficiaries (mean age = 74, 55% female, 9% Black), DSI is associated with increased prevalence (prevalence ratio = 1.45 [1.28-1.65]) and incidence (incidence ratio = 2.21 [1.79-2.75]) rate of falls, and greater odds of a higher fear of falling score (odds ratio = 1.38 [1.08-1.77]). Discussion: DSI is associated with falls among older adults. Consideration of DSI as a marker to initiate fall prevention programs and inclusion of sensory interventions in these programs may be valuable.

Hearing Loss and Physical Activity Among Older Adults in the United States.

BACKGROUND: Hearing loss is associated with adverse health outcomes among older adults. Lower physical activity levels may partly explain these observations, yet the association between hearing loss, hearing aid use, and physical activity among older adults is understudied. METHODS: Cross-sectional analysis of National Health and Aging Trends Study (2021) participants. The better-hearing ear pure-tone average (BPTA) at speech frequencies (0.5-4 kHz) was modeled continuously (10-dB increments) and categorically (no: ≤25 dB, mild: 26-40 dB, moderate or greater: >40 dB hearing loss). Activity measures were wrist accelerometry-derived (Actigraph) total activity counts, daily active minutes, activity fragmentation (using active-to-sedentary transition probability), and self-reported participation in vigorous activities and walking for exercise in the last month. We used multivariable regression adjusted for sociodemographic and health covariates. RESULTS: Among 504 participants excluding hearing aid users (mean age = 79 years, 57% female, 9% Black), 338 (67%) had hearing loss. Worse hearing (continuously and categorically) was associated with fewer counts and active minutes, more fragmented activity, and greater odds of not reporting recent vigorous activities. Among 472 participants with hearing loss including hearing aid users, nonusers (n = 338) had more fragmented activity and greater odds of not reporting walking for exercise compared to users. CONCLUSIONS: Older adults with hearing loss are less physically active. This may mediate the association between hearing loss and other adverse outcomes. Recognition of this potential association is essential for providers to better support older adults in maintaining an active lifestyle. Future research is warranted to understand the impact of hearing interventions.

Population prevalence of dual sensory loss in community-dwelling US adults 71 years and older: Evidence from the National Health and Aging Trends Study.

BACKGROUND: Existing estimates for the prevalence of dual sensory loss (vision and hearing) among older adults are either based on self-reported measures or aggregated for older age groups. Current and detailed estimates based on objective measures are needed for public health, clinical, and policy decision-making. METHODS: We estimated the prevalence of dual sensory loss (DSL) using National Health Aging Trends Study (NHATS) Round 11 data (2021). We restricted to community-dwelling adults aged ≥71 years with complete sensory testing data (N = 2579). Hearing loss was defined by a 4-frequency (0.5, 1, 2 and 4 kHz) pure tone average for the better-hearing ear (>25 decibel hearing level). Vision loss was defined by the presence of distance, near (logarithm of the minimum angle of resolution >0.30), or contrast sensitivity loss (log contrast sensitivity <1.55). Participants were categorized into three groups: no sensory loss, single sensory loss (vision or hearing loss), and DSL (hearing and vision). Sensory loss prevalence was estimated by age group and sociodemographic characteristics. RESULTS: In weighted analyses, among older Medicare beneficiaries (53% female, 7% Black, 6% Hispanic), 28% had no sensory loss and 22% had DSL. Prevalence of DSL increased with age. Most adults aged ≥90 years experienced DSL (59%), as opposed to single (39%) or no sensory loss (2%). DSL prevalence was greater among older adults with low education attainment (34%) and household income (43%). A higher proportion of older adults with a college education (17%), or from wealthier households (16%), had no sensory loss. CONCLUSIONS: One in 5 community-dwelling Medicare beneficiaries aged ≥71 years have DSL, increasing to 3 in 5 for those aged ≥90 years. Prevalence is higher among older adults with low education attainment and from low-income households, characteristics associated with low treatment. Policies increasing access and affordability of vision and hearing care could benefit millions of older Americans experiencing sensory loss.

Hearing Loss, Hearing Aids, and Satisfaction With Health Care in the National Health Interview Survey.

OBJECTIVE: Hearing loss may negatively impact satisfaction with health care via patient-provider communication barriers and may be amenable to hearing care treatment. STUDY DESIGN: Cross-sectional. SETTING: National Health Interview Survey, a nationally representative survey of noninstitutionalized US residents, 2013 to 2018 pooled cycles. METHODS: Participants described satisfaction with health care in the past year, categorized as optimal (very satisfied) versus suboptimal (satisfied, dissatisfied, very dissatisfied) satisfaction. Self-report hearing without hearing aids (excellent, good, a little trouble, moderate trouble, a lot of trouble) and hearing aid use (yes, no) were collected. Weighted Poisson regression models adjusted for sociodemographic and health covariates were used to estimate prevalence rate ratios (PRRs) of satisfaction with care by hearing loss and hearing aid use. RESULTS: Among 137,216 participants (mean age 50.9 years, 56% female, 12% black), representing 77.2 million Americans in the weighted model, 19% reported trouble hearing. Those with good (PRR = 1.20, 95% confidence interval [CI]: 1.18-1.23), a little trouble (PRR = 1.27, 95% CI, 1.23-1.31), moderate trouble (PRR = 1.29, 95% CI, 1.24-1.35), and a lot of trouble hearing (PRR = 1.26, 95% CI, 1.18-1.33) had a higher prevalence rate of suboptimal satisfaction with care relative to those with excellent hearing. Among all participants with trouble hearing, hearing aid users had a 17% decrease in the prevalence rate of suboptimal satisfaction with care (PRR = 0.83, 95% CI, 0.78-0.88) compared to nonusers. CONCLUSION: Hearing loss decreases patient satisfaction with health care, which is tied to Medicare hospital reimbursement models. Hearing aid use may improve patient-provider communication and patient satisfaction, although prospective studies are warranted to truly establish their protective effect.

Hearing Loss, Hearing Aids, and Functional Status.

Importance: Hearing loss may contribute to poor functional status via cognitive impairment and social isolation. Hearing aids may play a protective role by attenuating these downstream outcomes. However, population-based evidence is lacking. Objective: To examine the association of hearing loss and hearing aids with functional status. Design, Setting, and Participants: This cross-sectional (2016-2017) and longitudinal (2016-2022) analysis of data from the Atherosclerosis Risk in Communities cohort study included older, community-dwelling adults with complete data. Data were analyzed from June to December 2023. Exposures: The better-hearing ear's pure tone average (BPTA) at speech frequencies (0.5-4 kHz) was modeled categorically (no [BPTA ≤25 dB], mild [26-40 dB], and moderate or greater hearing loss [>40 dB]). Hearing aid use was self-reported. Main Outcomes and Measures: Difficulties in activities of daily living (ADLs; eg, dressing and eating), instrumental activities of daily living (IADLS; eg, household chores and meal preparation), and heavier tasks (eg, walking a quarter of a mile) were self-reported at visit 6. The ability to perform usual activities, walk a half mile, walk up and down stairs, and do heavy housework without help were collected in follow-up surveys. Linear and logistic regression models were used that were adjusted for sociodemographic and health covariates. Results: Among 3142 participants (mean [SD] age, 79.3 [4.6] years; 1828 women [58.2%]), 1013 (32.2%) had no hearing loss, 1220 (38.8%) had mild hearing loss, and 909 (29.0%) had moderate or greater hearing loss. Moderate or greater hearing loss was cross-sectionally associated with difficulty in 1 or more ADLs (odds ratio [OR], 1.27; 95% CI, 1.02-1.58), IADLs (OR, 1.34; 95% CI, 1.05-1.71), and heavier tasks (OR, 1.29; 95% CI, 1.04-1.62) compared with no hearing loss. Over time (mean [SD] follow-up, 1.9 [1.8] years), moderate or greater hearing loss was associated with a faster decline in the number of activities participants were able to do (ß = -0.07 per year; 95% CI, -0.09 to -0.06) and greater odds of reporting inability to do 1 or more of the 4 activities (OR, 1.14; 95% CI, 1.05-1.24). Hearing aid users and nonusers did not differ. Conclusions and Relevance: The results of this study suggest that moderate or greater hearing loss was associated with functional difficulties and may contribute to a faster decline in function longitudinally independent of sociodemographic and health covariates. Hearing aids did not change the association among those with hearing loss.

Readability of Patient Education Materials in Head and Neck Cancer: A Systematic Review.

Importance: Patient education materials (PEMs) can promote patient engagement, satisfaction, and treatment adherence. The American Medical Association recommends that PEMs be developed for a sixth-grade or lower reading level. Health literacy (HL) refers to an individual's ability to seek, understand, and use health information to make appropriate decisions regarding their health. Patients with suboptimal HL may not be able to understand or act on health information and are at risk for adverse health outcomes. Objective: To assess the readability of PEMs on head and neck cancer (HNC) and to evaluate HL among patients with HNC. Evidence Review: A systematic review of the literature was performed by searching Cochrane, PubMed, and Scopus for peer-reviewed studies published from 1995 to 2024 using the keywords head and neck cancer, readability, health literacy, and related synonyms. Full-text studies in English that evaluated readability and/or HL measures were included. Readability assessments included the Flesch-Kincaid Grade Level (FKGL grade, 0-20, with higher grades indicating greater reading difficulty) and Flesch Reading Ease (FRE score, 1-100, with higher scores indicating easier readability), among others. Reviews, conference materials, opinion letters, and guidelines were excluded. Study quality was assessed using the Appraisal Tool for Cross-Sectional Studies. Findings: Of the 3235 studies identified, 17 studies assessing the readability of 1124 HNC PEMs produced by professional societies, hospitals, and others were included. The mean FKGL grade ranged from 8.8 to 14.8; none of the studies reported a mean FKGL of grade 6 or lower. Eight studies assessed HL and found inadequate HL prevalence ranging from 11.9% to 47.0%. Conclusions and Relevance: These findings indicate that more than one-third of patients with HNC demonstrate inadequate HL, yet none of the PEMs assessed were developed for a sixth grade or lower reading level, as recommended by the American Medical Association. This incongruence highlights the need to address the readability of HNC PEMs to improve patient understanding of the disease and to mitigate potential barriers to shared decision-making for patients with HNC. It is crucial to acknowledge the responsibility of health care professionals to produce and promote more effective PEMs to dismantle the potentially preventable literacy barriers.

Potential Role for Diet in Mediating the Association of Olfactory Dysfunction and Cognitive Decline: A Nationally Representative Study.

In the context of a growing body of evidence associating olfactory dysfunction (OD) with cognitive decline, this cross-sectional study used data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) sample in order to explore the role of dietary intake in this association. Leveraging a nationally representative sample of U.S. adults aged 60 years and older, this study analyzed dietary patterns using exploratory factor analysis. OD was categorized based on the NHANES Pocket Smell Test, and cognitive function was measured with a battery of tests. Survey-weighted multivariable regressions and causal mediation analysis were used to examine the relationship between dietary patterns, OD, and cognitive function. Results indicated that a poor adherence to a diet rich in monounsaturated fats (MUFAs) and polyunsaturated fats (PUFAs) was independently associated with both cognitive and olfactory dysfunctions, after adjusting for sociodemographic and health factors. Moreover, the relationship between OD and cognitive decline was found to be partly mediated by adherence to such a diet. This study proposes a potential link between diet, olfactory function, and cognitive decline, highlighting the role of nutritional interventions in mitigating cognitive decline, particularly in individuals with olfactory impairment.

Outcome of Endoscopic Repair of Nasal Septal Perforation.

INTRODUCTION: The anterior ethmoidal artery (AEA) flap has been demonstrated to be a reliable option for endoscopic repair of symptomatic nasal septal perforations. The purpose of this study is to study the outcome of this technique. METHODS: A retrospective case series of all consecutive patients who underwent repair of nasal septal perforation utilizing the AEA flap among 2 institutions from August 2020 to July of 2022 was conducted. Demographics and comorbidities were collected preoperatively and postoperatively. The main outcome of this study was to identify the risk factors for surgical failure. RESULTS: Forty-one patients were included. Mean perforation size was 2.2 cm (range 0.5-4.5 cm). Mean age was 42.5 years (range 14-65 years), 53.6% were female, 39% were active smokers, mean body-mass-index (BMI) was 31.9 (range 19.1-45.5), 20% with history of CRS and 31.7% had diabetes mellitus (DM). Etiologies of the perforation included idiopathic (n = 12), iatrogenic (n = 13), intranasal drug use (n = 7), trauma (n = 6), and secondary to tumor resection (n = 3). Overall success rate for complete closure was 73.2%. Active smoking, history of intranasal drug use, and DM were significantly associated with surgical failure (72.7%vs 26.7%, P = .007; 36.4%vs 10%, P = .047; and 63.6%vs 20%, P = .008 respectively). CONCLUSION: The endoscopic AEA flap is a reliable technique for closure of nasal septal perforation. It may not work when the etiology is intranasal drug use. Close attention to diabetes and smoking status is also needed.

Socioeconomic Disparities in the Pursuit of Care at a High-Volume Institution for Surgical Resection of Vestibular Schwannomas.

OBJECTIVE: Increased institutional surgical resection case volume for vestibular schwannomas (VSs) has been associated with improved patient outcomes, including reduced risk of prolonged hospital stay and readmission. Socioeconomic disparities in the pursuit of care at these high-volume institutions remain unknown. STUDY DESIGN: Retrospective cohort epidemiological study. SETTING: National Cancer Database, a hospital-based registry of over 1,500 facilities in the United States. PATIENTS: Adult VS patients (age, >18 years) treated surgically. INTERVENTIONS: High- versus low-volume facilities, defined using a facility case volume threshold of 25 cases per year. A risk-adjusted restricted cubic spline model was previously used to identify this risk threshold beyond which the incremental benefit of increasing case volume began to plateau. MAIN OUTCOME MEASURES: Sociodemographic factors, including race, ethnicity, income, insurance status, and rurality. Multivariable analyses were adjusted for patient and tumor characteristics, including age, sex, Charlson-Deyo score, and tumor size. RESULTS: A totoal of 10,048 patients were identified (median [interquartile range] age = 51 [41-60] years, 54% female, 87% Caucasian). Patients with Spanish/Hispanic ethnicity (OR = 0.71, 95% confidence interval [CI] = 0.52-0.96), income below median (OR = 0.63, 95% CI = 0.55-0.73]), and Medicare, Medicaid, or other government insurance versus private insurance (OR = 0.63, 95% CI = 0.53-0.74) had reduced odds of treatment at a high-volume facility. Further sensitivity analyses in which facility volume was operationalized continuously reinforced direction and significance of these associations. CONCLUSIONS: Socioeconomic disparities exist in the propensity for VS patients to be treated at a high-volume facility. Further work is needed to understand the nature of these associations and whether interventions can be designed to mitigate them.

Hearing Loss and Frailty among Older Adults: The Atherosclerosis Risk in Communities Study.

OBJECTIVES: Hearing loss may contribute to frailty through cognitive and physical decline, but population-based evidence using validated measures remains scarce. We investigated the association of hearing loss with phenotypic frailty and its individual components and explored the potential protective role of hearing aid use. DESIGN: Cross-sectional study of community-dwelling older adults at visit 6 (2016-2017) of the Atherosclerosis Risk in Communities (ARIC) study, a cohort study of older adults from 4 U.S. communities (Washington County, MD; Forsyth County, NC; Jackson, MS; and Minneapolis, MN). SETTING AND PARTICIPANTS: Population-based study of 3179 participants (mean age = 79.2 years, 58.9% female). METHODS: Pure-tone audiometry at 0.5-4 kHz was used to assess unaided hearing, and the better-hearing ear's pure-tone average was categorized as follows: no [≤25 dB hearing level (HL)], mild (26-40 dB HL), and moderate or greater (>40 dB HL) hearing loss. Hearing aid use was self-reported. The Fried/physical frailty phenotype was used to categorize frailty status (robust, pre-frail, or frail). Multivariable multinomial and logistic regression models were used to study the association of hearing loss/hearing aid use with frailty status and individual frailty components, respectively. RESULTS: In our sample, 40% had mild and 27% had moderate or greater hearing loss (12% and 55% reported hearing aid use, respectively). Moderate or greater hearing loss was associated with greater odds of being pre-frail [odds ratio (OR), 1.25; 95% CI, 1.01-1.57] and frail (OR, 1.62; 95% CI, 1.06-2.47) vs robust, and greater odds of having slow gait, low physical activity, and exhaustion, compared with no hearing loss. Among those with hearing loss (>25 dB HL), compared with hearing aid users, nonusers had greater odds of being frail vs robust, and having unintentional weight loss, slow gait, and low physical activity. CONCLUSIONS AND IMPLICATIONS: Hearing loss is associated with pre-frailty and frailty. Longitudinal studies are warranted to establish if hearing aid use may prevent or delay frailty onset.

Emerging genetic biomarkers in lung adenocarcinoma.

Comprehensive genomic profiling is a next-generation sequencing approach used to detect several known and emerging genomic alterations. Many genomic variants detected by comprehensive genomic profiling have become recognized as significant cancer biomarkers, leading to the development of major clinical trials. Lung adenocarcinoma has become one of the most targeted cancers for genomic profiling with a series of actionable mutations such as EGFR, KRAS, HER2, BRAF, FGFR, MET, ALK, and many others. The importance of these mutations lies in establishing targeted therapies that significantly change the outcome in lung adenocarcinoma besides the prognostic value of some mutations. This review sheds light on the development of the comprehensive genomic profiling field, mainly lung adenocarcinoma, and discusses the role of a group of mutations in this disease.

Prognostic indicators of survival in patients with small-cell lung cancer at a tertiary care center in Lebanon.

OBJECTIVE: Small-cell lung cancer is a very aggressive tumor associated with high invasiveness and ease of metastasis and therefore poor prognosis. In the literature, several demographical, clinical as well as pathological factors including age, stage, gender and smoking were cited as independent prognosticators of survival. MATERIAL AND METHODS: This is a retrospective cohort study that includes 222 patients diagnosed with small-cell lung cancer between 2010 and 2019. Clinical and demographic data were extracted from their medical records. The Kaplan-Meier and logistic regression models of statistical analysis were used to evaluate the association of these variables with survival. RESULTS: Forty-five percent of patients were found to be alive at the time of data collection. The median survival of patients with small-cell lung cancer was found to be 14 months. On univariate analysis, increasing age as well as stage (extensive disease) were found to be significantly associated with decreased survival at 3 years. On the contrary, both gender and smoking status at diagnosis were not shown to significantly influence survival. On multivariate analysis, both age as well as stage remained significantly associated with survival. CONCLUSION: Limited data exist in the literature regarding the prognostic indicators of survival in small-cell lung cancer, especially from the Middle East area. In our study, both age and stage at the time of diagnosis were found to significantly influence survival. Further studies are needed to assess the association of other factors with survival.

Stem Cells: In Sickness and in Health.

Stem cells are undifferentiated cells with the ability to proliferate and convert to different types of differentiated cells that make up the various tissues and organs in the body. They exist both in embryos as pluripotent stem cells that can differentiate into the three germ layers and as multipotent or unipotent stem cells in adult tissues to aid in repair and homeostasis. Perturbations in these cells' normal functions can give rise to a wide variety of diseases. In this review, we discuss the origin of different stem cell types, their properties and characteristics, their role in tissue homeostasis, current research, and their potential applications in various life-threatening diseases. We focus on neural stem cells, their role in neurogenesis and how they can be exploited to treat diseases of the brain including neurodegenerative diseases and cancer. Next, we explore current research in Induced Pluripotent Stem Cells (iPSC) techniques and their clinical applications in regenerative and personalized medicine. Lastly, we tackle a special type of stem cells called Cancer Stem Cells (CSCs) and how they can be responsible for therapy resistance and tumor recurrence and explore ways to target them.

The potential use of tideglusib as an adjuvant radio-therapeutic treatment for glioblastoma multiforme cancer stem-like cells.

BACKGROUND: Glioblastoma multiforme (GBM), a stage IV astrocytoma, is the most common brain malignancy among adults. Conventional treatments of surgical resection followed by radio and/or chemotherapy fail to completely eradicate the tumor. Resistance to the currently available therapies is mainly attributed to a subpopulation of cancer stem cells (CSCs) present within the tumor bulk that self-renew leading to tumor relapse with time. Therefore, identification of characteristic markers specific to these cells is crucial for the development of targeted therapies. Glycogen synthase kinase 3 (GSK-3), a serine-threonine kinase, is deregulated in a wide range of diseases, including cancer. In GBM, GSK-3ß is overexpressed and its suppression in vitro has been shown to induce apoptosis of cancer cells. METHODS: In our study, we assessed the effect of GSK-3ß inhibition with Tideglusib (TDG), an irreversible non-ATP competitive inhibitor, using two human GBM cell lines, U-251 MG and U-118 MG. In addition, we combined TDG with radiotherapy to assess whether this inhibition enhances the effect of standard treatment. RESULTS: Our results showed that TDG significantly reduced cell proliferation, cell viability, and migration of both GBM cell lines in a dose- and time-dependent manner in vitro. Treatment with TDG alone and in combination with radiation significantly decreased the colony formation of U-251 MG cells and the sphere formation of both cell lines, by targeting and reducing their glioblastoma cancer stem-like cells (GSCs) population. Finally, cells treated with TDG showed an increased level of unrepaired radio-induced DNA damage and, thus, became sensitized toward radiation. CONCLUSIONS: In conclusion, TDG has proven its effectiveness in targeting the cancerous properties of GBM in vitro and may, hence, serve as a potential adjuvant radio-therapeutic agent to better target this deadly tumor.

Tideglusib attenuates growth of neuroblastoma cancer stem/progenitor cells in vitro and in vivo by specifically targeting GSK-3ß.

BACKGROUND: Neuroblastoma (NB) is the most frequently diagnosed extracranial solid tumor among the pediatric population. It is an embryonic tumor with high relapse rates pertaining to the presence of dormant slowly dividing cancer stem cells (CSC) within the tumor bulk that are responsible for therapy resistance. Therefore, there is a dire need to develop new therapeutic approaches that specifically target NB CSCs. Glycogen synthase kinase (GSK)-3ß is a serine/threonine kinase that represents a common signaling node at the intersection of many pathways implicated in NB CSCs. GSK-3ß sustains the survival and maintenance of CSCs and renders them insensitive to chemotherapeutic agents and radiation. METHODS: In our study, we aimed at evaluating the potential anti-tumor effect of Tideglusib (TDG), an irreversible GSK-3ß inhibitor drug, on three human NB cell lines, SK-N-SH, SH-SY5Y, and IMR-32. RESULTS: Our results showed that TDG significantly reduced cell proliferation, viability, and migration of the NB cells, in a dose- and time-dependent manner, and also significantly hindered the neurospheres formation eradicating the self-renewal ability of highly resistant CSCs. Besides, TDG potently reduced CD133 cancer stem cell marker expression in both SH-SY5Y cells and G1 spheres. Lastly, TDG inhibited NB tumor growth and progression in vivo. CONCLUSION: Collectively, we concluded that TDG could serve as an effective treatment capable of targeting the NB CSCs and hence overcoming therapy resistance. Yet, future studies are warranted to further investigate its potential role in NB and decipher the subcellular and molecular mechanisms underlying this role.

A Bibliometric Analysis of COVID-19 Research Activity: A Call for Increased Output.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has impacted many countries across all inhabited continents, and is now considered a global pandemic, due to its high rate of infectivity. Research related to this disease is pivotal for assessing pathogenic characteristics and formulating therapeutic strategies. The aim of this paper is to explore the activity and trends of COVID-19 research since its outbreak in December 2019. METHODS: We explored the PubMed database and the World Health Organization (WHO) database for publications pertaining to COVID-19 since December 2019 up until March 18, 2020. Only relevant observational and interventional studies were included in our study. Data on COVID-19 incidence were extracted from the WHO situation reports. Research output was assessed with respect to gross domestic product (GDP) and population of each country. RESULTS: Only 564 publications met our inclusion criteria. These articles came from 39 different countries, constituting 24% of all affected countries. China produced the greatest number of publications with 377 publications (67%). With respect to continental research activity, Asian countries had the highest research activity with 434 original publications (77%). In terms of publications per million persons (PPMPs), Singapore had the highest number of publications with 1.069 PPMPs. In terms of publications per billion-dollar GDP, Mauritius ranked first with 0.075. CONCLUSION: COVID-19 is a major disease that has impacted international public health on a global level. Observational studies and therapeutic trials pertaining to COVID-19 are essential for assessing pathogenic characteristics and developing novel treatment options.

Cancer Stem Cells in Neuroblastoma: Expanding the Therapeutic Frontier.

Neuroblastoma (NB) is the most common extracranial solid tumor often diagnosed in childhood. Despite intense efforts to develop a successful treatment, current available therapies are still challenged by high rates of resistance, recurrence and progression, most notably in advanced cases and highly malignant tumors. Emerging evidence proposes that this might be due to a subpopulation of cancer stem cells (CSCs) or tumor-initiating cells (TICs) found in the bulk of the tumor. Therefore, the development of more targeted therapy is highly dependent on the identification of the molecular signatures and genetic aberrations characteristic to this subpopulation of cells. This review aims at providing an overview of the key molecular players involved in NB CSCs and focuses on the experimental evidence from NB cell lines, patient-derived xenografts and primary tumors. It also provides some novel approaches of targeting multiple drivers governing the stemness of CSCs to achieve better anti-tumor effects than the currently used therapeutic agents.