Citations

Abstract The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve the reliability of response assessment in glioma trials. Over time some limitations of these criteria were identified, and uncertainty emerged regarding integrating features of the modified RANO (mRANO) or the immunotherapy RANO (iRANO) criteria. Informed by data from a cohort of glioblastoma patients and other evaluations of RANO criteria that allowed evaluation of features of the different criteria, we propose updates to the RANO criteria (RANO 2.0). Based on the 2021 WHO classification of gliomas, we recommend a standard set of criteria for both high and low-grade gliomas, to be used for all trials regardless of the treatment modalities being evaluated. In the newly diagnosed setting, the post-radiotherapy MRI, rather than the post-surgical MRI, will be used as the baseline for future comparison. Since the incidence of pseudoprogression is high in the 12 weeks following radiotherapy, continuation of treatment and confirmation of progression during this period with a repeat MRI, or histopathologic evidence of unequivocal recurrent tumor, is required to define tumor progression. However, confirmation scans are not mandatory after this period nor for recurrent tumors. For treatments with a high likelihood of pseudoprogression, mandatory confirmation of progression with a repeat MRI is an option. The primary measurement remains the maximum cross-sectional area of tumor (2-dimensional) but volumetric measurements are an option. For IDH-wildtype glioblastoma, the non-enhancing disease will no longer be evaluated. In IDH-mutated tumors with a significant non-enhancing component, clinical trials may require evaluating both the enhancing and non-enhancing tumor components for response assessment.

Background: The normal limits of nerve conduction studies are commonly determined by testing healthy subjects. However, in comprehensive real-life nerve conduction electrodiagnostic (EDX) evaluations, multiple nerves are tested, including normal nerves, for purposes of comparison with abnormal ones. Objective: This study aims to evaluate the average values of normal nerve conduction studies in a large population and examined the influence of age and sex. Methods: EDX parameters were extracted from an electronic database of studies performed from May 2016 to February 2022. Established normal values were used to determine the classification of a nerve study as normal. Results: We identified 10,648 EDX reports with 5077 normally interpreted nerve conduction studies (47.6%) of which 57% ( n = 2890) were for females. The median age of studies with no abnormalities was 45.1 years (range < 1 to 92) overall and 42.5 years (range: 0.16 –89.5 years) for males and 47.5 years (range:<1 –91.7) for females. Correlations between age and amplitude, latency, and velocity ( p < 0.001) were observed in most nerves. Amplitude correlated negatively with age in adults in all nerves with a mean of –0.44 (range: –0.24 to –0.62). However, in the pediatric population (age < 18 years), amplitude as well as velocity increased significantly with age. In the adult cohort, sex differences were noted, where females had higher mean sensory nerve action potentials in ulnar, median, and radial evaluations ( p < 0.001). In older patients (aged > 70 years) with normally interpreted EDX studies (845 records of 528 patients), sural responses were present in 97%. Conclusions: This real-life study confirms that advanced aging is associated with decreased nerve conduction amplitudes, increased latency, and the slowing of conduction velocity. The findings also indicate higher sensory amplitudes and conduction velocities in females. Sural nerve responses were identified in most adults over age 70.

Context.— Unlike B-cell acute lymphoblastic leukemia/lymphoma (ALL/LBL), there have been few therapeutic advances in T-cell ALL (T-ALL)/LBL, an aggressive ALL/LBL subtype. Objective.— To perform a focused tissue array study to elucidate tumor markers of therapeutic potential in T-ALL/LBL. Design.— Using immunohistochemistry, we evaluated expression of leukemic antigens of interest, specifically CC-chemokine receptor 4 (CCR4), among others, on available remnant diagnostic material, including tumor tissue slides obtained from formalin-fixed, paraffin-embedded preserved tissues. Results.— Our analysis identified, for the first time, expression of CCR4 in T-ALL/LBL in 11 of 27 cases (40.7%) and confirmed common expression of BCL2, CD38, and CD47, as reported previously. We also identified the expression of CD123 in 4 of 26 cases (15.4%), whereas BCL6 and PDL1 were expressed in a small number of T-ALL/LBL cases. The potential novel target CCR4 was significantly more common in the Pre/Pro-T immunophenotypic subtype, 6 of 9 (66.7%, P = .01). No additional differences in clinical and epidemiologic variables were noted among positive or negative CCR4 cases. Conclusions.— These findings support preclinical and clinical testing of therapies targeting CCR4, CD47, BCL2, CD38, and CD123 in T-ALL/LBL, and may help guide the development of targeted clinical trials in T-ALL/LBL, a rare disease in urgent need of novel therapies.

Abstract Meningiomas are the most common primary intracranial tumor. They are slow growing and often incidentally found tumors that arise from the arachnoid villi. As they grow, they have a greater likelihood of becoming symptomatic with seizures being one of the most clinically significant symptoms. Seizures are more likely to present as a symptom of larger meningiomas and meningiomas that compress cortical areas particularly those in non-skull base locations. These seizures are often managed medically, utilizing the same anti-seizure medications that are used to treat other causes of epilepsy. We discuss common anti-seizure medications used including valproate, phenobarbital, carbamazepine, phenytoin, lacosamide, lamotrigine, levetiracetam and topiramate and their common adverse effects. The goal of pharmacotherapy for seizure control is to maximize seizure control while minimizing the adverse effects of the medication. The decision to provide medical management is dependent on individual seizure history and plans for surgical treatment. Patients who did not require seizure prophylaxis before surgery are commonly prescribed seizure prophylaxis postoperatively. Symptomatic meningiomas not controlled by medical management alone are commonly evaluated for surgical resection. The efficacy of surgical resection in providing seizure freedom is dependent on several features of the tumor including tumor size, the extent of the peritumoral edema, the number of tumors, sinus infiltration and the degree of resection.

Background: Obstructive sleep apnea (OSA) increases the risk of stroke and cardiovascular diseases. However, its impact on geriatric patients with a prior history of stroke/transient ischemic attack (TIA) has not been adequately studied. Methods: We utilized the 2019 National Inpatient Sample in the US to identify geriatric patients with OSA (G-OSA) who had a prior history of stroke/TIA. We then compared subsequent stroke (SS) rates among sex and race subgroups. We also compared the demographics and comorbidities of SS+ and SS− groups and utilized logistic regression models to assess outcomes. Results: Out of 133,545 G-OSA patients admitted with a prior history of stroke/TIA, 4.9% (6520) had SS. Males had a higher prevalence of SS, while Asian-Pacific Islanders and Native Americans had the highest prevalence of SS, followed by Whites, Blacks, and Hispanics. The SS+ group had higher all-cause in-hospital mortality rates, with Hispanics showing the highest rate compared to Whites and Blacks (10.6% vs. 4.9% vs. 4.4%, p < 0.001), respectively. Adjusted analysis for covariates showed that complicated and uncomplicated hypertension (aOR 2.17 [95% CI 1.78–2.64]; 3.18 [95% CI 2.58–3.92]), diabetes with chronic complications (aOR 1.28 [95% CI 1.08–1.51]), hyperlipidemia (aOR 1.24 [95% CI 1.08–1.43]), and thyroid disorders (aOR 1.69 [95% CI 1.14–2.49]) were independent predictors of SS. The SS+ group had fewer routine discharges and higher healthcare costs. Conclusions: Our study shows that about 5% of G-OSA patients with a prior history of stroke/TIA are at risk of hospitalization due to SS, which is associated with higher mortality and healthcare utilization. Complicated and uncomplicated hypertension, diabetes with chronic complications, hyperlipidemia, thyroid disorders, and admission to rural hospitals predict subsequent stroke.

(1) Background: COVID-19 caused the worst international public health crisis, accompanied by major global economic downturns and mass-scale job losses, which impacted the psychosocial wellbeing of the worldwide population, including Saudi Arabia. Evidence of the high-risk groups impacted by the pandemic has been non-existent in Saudi Arabia. Therefore, this study examined factors associated with psychosocial distress, fear of COVID-19 and coping strategies among the general population in Saudi Arabia. (2) Methods: A cross-sectional study was conducted in healthcare and community settings in the Saudi Arabia using an anonymous online questionnaire. The Kessler Psychological Distress Scale (K-10), Fear of COVID-19 Scale (FCV-19S) and Brief Resilient Coping Scale (BRCS) were used to assess psychological distress, fear and coping strategies, respectively. Multivariate logistic regressions were used, and an Adjusted Odds Ratio (AOR) with 95% Confidence Intervals (CIs) was reported. (3) Results: Among 803 participants, 70% (n = 556) were females, and the median age was 27 years; 35% (n = 278) were frontline or essential service workers; and 24% (n = 195) reported comorbid conditions including mental health illness. Of the respondents, 175 (21.8%) and 207 (25.8%) reported high and very high psychological distress, respectively. Factors associated with moderate to high levels of psychological distress were: youth, females, non-Saudi nationals, those experiencing a change in employment or a negative financial impact, having comorbidities, and current smoking. A high level of fear was reported by 89 participants (11.1%), and this was associated with being ex-smokers (3.72, 1.14–12.14, 0.029) and changes in employment (3.42, 1.91–6.11, 0.000). A high resilience was reported by 115 participants (14.3%), and 333 participants (41.5%) had medium resilience. Financial impact and contact with known/suspected cases (1.63, 1.12–2.38, 0.011) were associated with low, medium, to high resilient coping. (4) Conclusions: People in Saudi Arabia were at a higher risk of psychosocial distress along with medium-high resilience during the COVID-19 pandemic, warranting urgent attention from healthcare providers and policymakers to provide specific mental health support strategies for their current wellbeing and to avoid a post-pandemic mental health crisis.

Abstract INTRODUCTION The ketogenic diet (KD) is an intriguing therapeutic candidate for Alzheimer's disease (AD) given its protective effects against metabolic dysregulation and seizures. Gut microbiota are essential for KD‐mediated neuroprotection against seizures as well as modulation of bile acids, which play a major role in cholesterol metabolism. These relationships motivated our analysis of gut microbiota and metabolites related to cognitive status following a controlled KD intervention compared with a low‐fat‐diet intervention. METHODS Prediabetic adults, either with mild cognitive impairment (MCI) or cognitively normal (CN), were placed on either a low‐fat American Heart Association diet or high‐fat modified Mediterranean KD (MMKD) for 6 weeks; then, after a 6‐week washout period, they crossed over to the alternate diet. We collected stool samples for shotgun metagenomics and untargeted metabolomics at five time points to investigate individuals’ microbiome and metabolome throughout the dietary interventions. RESULTS Participants with MCI on the MMKD had lower levels of GABA‐producing microbes Alistipes sp. CAG:514 and GABA, and higher levels of GABA‐regulating microbes Akkermansia muciniphila . MCI individuals with curcumin in their diet had lower levels of bile salt hydrolase‐containing microbes and an altered bile acid pool, suggesting reduced gut motility. DISCUSSION Our results suggest that the MMKD may benefit adults with MCI through modulation of GABA levels and gut‐transit time.

Abstract Background: Hypertension is a widely prevalent condition associated with significant morbidity and premature mortality, primarily because it is a risk factor for CVDs. The aim of this study was to estimate the trend of the burden of hypertension in Saudi Arabia in the last three decades. Methods: We conducted a systematic analysis of secondary data obtained from the Global Burden of Disease Study (GBD). We estimated sex-stratified, age-standardised and age-specific rates (per 100,000) of prevalence, deaths, and disability-adjusted years (DALYs) associated with hypertension in adults aged 20-94 years in Saudi Arabia between 1990 and 2019. Results: In Saudi Arabia, the age-standardised prevalence of hypertension increased from 87.7 cases per 100,000 in 1990 to 94.9 per 100,000 in 2019. More women than men had hypertension throughout the past three decades. The death and DALYs rate, however, decreased during this time. In 1990, 9.2 deaths per 100,000 in women and 3.0 deaths per 100,000 in men were due to hypertension; the respective rates declined to 6.5 and 2.8 in 2019. While the rates of DALYs in women declined steadily from 211.7 to 151.8 per 100,000 DALYs between 1990 and 2019, the rate in males did not decline considerably. The burden of hypertension–prevalence, deaths, and DALYs–were greater in older people. Conclusion: The prevalence of hypertension has increased in Saudi Arabia during the last 30 years; however, death rates and DALY related to hypertension has decreased during this time. Age- and sex-specific strategies are needed to decrease the prevalence of hypertension in Saudi Arabia.