Identification of hair shaft progenitors that create a niche for hair pigmentation.

Hair differentiates from follicle stem cells through progenitor cells in the matrix. In contrast to stem cells in the bulge, the identities of the progenitors and the mechanisms by which they regulate hair shaft components are poorly understood. Hair is also pigmented by melanocytes in the follicle. However, the niche that regulates follicular melanocytes is not well characterized. Here, we report the identification of hair shaft progenitors in the matrix that are differentiated from follicular epithelial cells expressing transcription factor KROX20. Depletion of Krox20 lineage cells results in arrest of hair growth, confirming the critical role of KROX20+ cells as antecedents of structural cells found in hair. Expression of stem cell factor (SCF) by these cells is necessary for the maintenance of differentiated melanocytes and for hair pigmentation. Our findings reveal the identities of hair matrix progenitors that regulate hair growth and pigmentation, partly by creating an SCF-dependent niche for follicular melanocytes.

Resident Salary Compared to Living Wages at United States Training Institutions.

OBJECTIVE: To compare living wages and salaries at US residency programs. SUMMARY BACKGROUND DATA: It is unknown how resident salary compares to living wages across the United States (US). METHODS: Cross-sectional analysis of publicly available resident salary affordability from training centers with post-graduate-year (PGY)-1 through PGY-7 resident compensation for 2022-2023 was compared with the Massachusetts Institute of Technology (MIT) Living-Wage Calculator. Resident salary to living wage ratios were calculated using PGY-4 salary for each family composition. Univariate and multivariable analysis of PGY-4 salary affordability was performed, accounting for proportion of expected living wages to taxes, transportation, housing, healthcare, childcare, and food, as well as unionization and state income-tax. RESULTS: 118 residency programs, representing over 60% of US trainees, were included, 20 (17%) of which were unionized. Single-parent families were unable to earn a living wage until PGY-7. Residents with 1 child in 2-adult (single-income) and 2-adult (dual-income) families earn below living wages until PGY-5 and PGY-3, respectively. Residents with more than 1 child never earn a living wage. Multivariable regression analysis using PGY-4 salary: living wage ratios in single-child, 2-parent homes showed food expense and unionization status were consistent predictors of affordability. Unionization was associated with lower affordability pre-stipend, almost equivalent affordability post-stipend, and lower affordability post-stipend and union dues. CONCLUSIONS: Resident salaries often preclude residents with children from earning a living wage. Unionization is not associated with increased resident affordability in this cross-sectional analysis. All annual reimbursement data should be centrally compiled, and additional stipends should be considered for residents with children.

Long-Chain Lipids Facilitate Insertion of Large Nanoparticles into Membranes of Small Unilamellar Vesicles.

Insertion of hydrophobic nanoparticles into phospholipid bilayers is limited to small particles that can incorporate into a hydrophobic membrane core between two lipid leaflets. Incorporation of nanoparticles above this size limit requires the development of challenging surface engineering methodologies. In principle, increasing the long-chain lipid component in the lipid mixture should facilitate incorporation of larger nanoparticles. Here, we explore the effect of incorporating very long phospholipids (C24:1) into small unilamellar vesicles on the membrane insertion efficiency of hydrophobic nanoparticles that are 5-11 nm in diameter. To this end, we improve an existing vesicle preparation protocol and utilized cryogenic electron microscopy imaging to examine the mode of interaction and evaluate the insertion efficiency of membrane-inserted nanoparticles. We also perform classical coarse-grained molecular dynamics simulations to identify changes in lipid membrane structural properties that may increase insertion efficiency. Our results indicate that long-chain lipids increase the insertion efficiency by preferentially accumulating near membrane-inserted nanoparticles to reduce the thermodynamically unfavorable disruption of the membrane.

Heparin-induced Thrombocytopenia (HIT) in the DOAC Era.

OBJECTIVES: Heparin-induced thrombocytopenia (HIT) is an uncommon complication of heparin therapy with significant risk for severe morbidity and mortality. We investigated the role and outcome of direct oral anticoagulants (DOACs) for the management of HIT. METHODS: After IRB approval, a retrospective review was performed identifying all patients with positive HIT serotonin-release assays between 2020 and 2022 at two hospitals. Demographic and clinical variables were collected: initial anticoagulant, dosing and indication, interval before onset of HIT, thrombotic complications, platelet nadir and recovery, direct thrombin inhibitor (DTI) and DOAC usage, and clinical outcomes. RESULTS: 15 patients were included in the study. 8 underwent a vascular procedure, 3 had cardiac surgery, 1 patient had both and was included in both groups, and 5 patients had either non-cardiac, non-vascular surgery or no surgery. 14 patients received unfractionated heparin (93% with therapeutic dosing) and 1 received prophylactic enoxaparin prior to diagnosis of HIT. The average time to diagnosis of HIT was 10.77 days after initial anticoagulation. In-hospital mortality was 27%, related to Covid-19 infection (3/4) and intracranial hemorrhage (1/4). 40% developed thrombosis (67% venous, 33% arterial) after the diagnosis of HIT. 8/11 survivors were discharged on a DOAC. With DOAC therapy, platelet counts rebounded to an average of 265K (+/- 104.6K) within an average of 2.3 days and 364K (+/- 273.9K) within 30 days after initiation of a DOAC. No recurrent thrombosis occurred after DOAC administration and only one patient had persistent thrombocytopenia within 30 days. CONCLUSIONS: Mortality and thrombosis (arterial and venous) are common complications in patients diagnosed with HIT. In patients who survive to discharge, DOACs are the most common discharge antithrombotic agent, with low rates of recurrent thrombosis and thrombocytopenia.

Importance of Various E-Cigarette Device and E-Liquid Characteristics by Smoking Status among Young Adults Who Vape.

BACKGROUND: E-cigarette product characteristics are known to influence appeal among young adults. Understanding which characteristics appeal to individuals with (vs. without) a history of combusted tobacco use is essential for developing effective tobacco control policies. METHODS: Anonymous, self-report data were collected from young adults (18-30 years) who had used e-cigarettes in the past 30 days (n = 295) online via Prolific from September-October 2019. Using a visual analogue scale (range: 0-100), participants rated the importance of ten e-cigarette device and nine e-liquid characteristics. Adjusted linear regression models were used to evaluate the association of combusted tobacco use status (never, former, current) with mean rating scores for each of the nineteen characteristics. RESULTS: The most important e-cigarette device characteristics were price (Mean = 81.1; [SD = 17.9]), size (Mean = 75.5 [SD = 20.9]), and hit strength (Mean = 73.8 [SD = 20.4]) while the most important e-liquid characteristics were flavor (M = 85.1 [SD = 16.3]), price (M = 80.9 [SD = 18.4]), and nicotine level (M = 77.8 [18.9]). Differences by combusted tobacco use status were observed for device brand, temperature/voltage, customizability, color, and popularity, with the highest ratings generally observed among those concurrently using combustible tobacco products. For e-liquids, differences by use status were observed for flavor, price, and bottle type. Notably, those concurrently using combusted products rated flavor as less important than those with no history of combustible tobacco use (B=-5.01[95%CI=-9.97, -0.05]). CONCLUSIONS: The self-rated importance of e-cigarette device and e-liquid attributes varies by combustible tobacco use status among young adults which may be used to inform regulatory decisions regarding e-cigarette product characteristics.

Compliance-Adjusted Estimates of Aspirin Effects Among Older Persons in the ASPREE Randomized Trial.

The Aspirin in Reducing Events in the Elderly (ASPREE) Trial recruited 19,114 participants across Australia and the United States during 2010-2014. Participants were randomized to receive either 100 mg of aspirin daily or matching placebo, with disability-free survival as the primary outcome. During a median 4.7 years of follow-up, 37% of participants in the aspirin group permanently ceased taking their study medication and 10% commenced open-label aspirin use. In the placebo group, 35% and 11% ceased using study medication and commenced open-label aspirin use, respectively. In order to estimate compliance-adjusted effects of aspirin, we applied rank-preserving structural failure time models. The results for disability-free survival and most secondary endpoints were similar in intention-to-treat and compliance-adjusted analyses. For major hemorrhage, cancer mortality, and all-cause mortality, compliance-adjusted effects of aspirin indicated greater risks than were seen in intention-to-treat analyses. These findings were robust in a range of sensitivity analyses. In accordance with the original trial analyses, compliance-adjusted results showed an absence of benefit with aspirin for primary prevention in older people, along with an elevated risk of clinically significant bleeding.

J-Difference editing (MEGA) of lactate in the human brain at 3T.

PURPOSE: The need to detect and quantify brain lactate accurately by MRS has stimulated the development of editing sequences based on J coupling effects. In J-difference editing of lactate, threonine can be co-edited and it contaminates lactate estimates due to the spectral proximity of the coupling partners of their methyl protons. We therefore implemented narrow-band editing 180° pulses (E180) in MEGA-PRESS acquisitions to resolve separately the 1.3-ppm resonances of lactate and threonine. METHODS: Two 45.3-ms rectangular E180 pulses, which had negligible effects 0.15-ppm away from the carrier frequency, were implemented in a MEGA-PRESS sequence with TE 139 ms. Three acquisitions were designed to selectively edit lactate and threonine, in which the E180 pulses were tuned to 4.1 ppm, 4.25 ppm, and a frequency far off resonance. Editing performance was validated with numerical analyses and acquisitions from phantoms. The narrow-band E180 MEGA and another MEGA-PRESS sequence with broad-band E180 pulses were evaluated in six healthy subjects. RESULTS: The 45.3-ms E180 MEGA offered a difference-edited lactate signal with lower intensity and reduced contamination from threonine compared to the broad-band E180 MEGA. The 45.3 ms E180 pulse had MEGA editing effects over a frequency range larger than seen in the singlet-resonance inversion profile. Lactate and threonine in healthy brain were both estimated to be 0.4 ± 0.1 mM, with reference to N-acetylaspartate at 12 mM. CONCLUSION: Narrow-band E180 MEGA editing minimizes threonine contamination of lactate spectra and may improve the ability to detect modest changes in lactate levels.

Hybrid approach to pulmonary vein stenting after Fontan palliation.

Pulmonary vein stenosis is poorly tolerated in patients who have undergone Fontan palliation and typically requires surgical or transcatheter intervention. Percutaneous transcatheter approaches to intervention can be technically difficult due to challenging anatomy. A hybrid per-atrial transcatheter approach for stenting pulmonary veins provides a direct approach to the pulmonary veins and has the potential to improve safety and efficacy of this complex intervention. We describe our experience with hybrid per-atrial pulmonary vein stenting in three patients with pulmonary vein stenosis following Fontan palliation.

Interactions of Bacterial Quorum Sensing Signals with Model Lipid Membranes: Influence of Membrane Composition on Membrane Remodeling.

We report the influence of membrane composition on the multiscale remodeling of multicomponent lipid bilayers initiated by contact with the amphiphilic bacterial quorum sensing signal N-(3-oxo)-dodecanoyl-l-homoserine lactone (3-oxo-C12-AHL) and its anionic headgroup hydrolysis product, 3-oxo-C12-HS. We used fluorescence microscopy and quartz crystal microbalance with dissipation (QCM-D) to characterize membrane reformation that occurs when these amphiphiles are placed in contact with supported lipid bilayers (SLBs) composed of (i) 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) containing varying amounts of cholesterol or (ii) mixtures of DOPC and either 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE, a conical zwitterionic lipid) or 1,2-dioleoyl-sn-glycero-3-phospho-l-serine (DOPS, a model anionic lipid). In general, we observe these mixed-lipid membranes to undergo remodeling events, including the formation and subsequent collapse of long tubules and the formation of hemispherical caps, upon introduction to biologically relevant concentrations of 3-oxo-C12-AHL and 3-oxo-C12-HS in ways that differ substantially from those observed in single-component DOPC membranes. These differences in bilayer reformation and their associated dynamics can be understood in terms of the influence of membrane composition on the time scales of molecular flip-flop, lipid packing defects, and lipid phase segregation in these materials. The lipid components investigated here are representative of classes of lipids that comprise both naturally occurring cell membranes and many useful synthetic soft materials. These studies thus represent a first step toward understanding the ways in which membrane composition can impact interactions with this important class of bacterial signaling molecules.

Effects of 'Ice' flavoured e-cigarettes with synthetic cooling agent WS-23 or menthol on user-reported appeal and sensory attributes.

BACKGROUND: This clinical experiment tested the effects of exposure to e-cigarettes with WS-23 or menthol cooling additives on user appeal and sensory attributes, and, secondarily, whether WS-23 effects generalised across base characterising flavour, nicotine concentration, or nicotine/tobacco product use status. METHODS: In this within-participant double-blind experiment, adult tobacco/nicotine users administered standardised puffs of 18 different e-cigarette solutions in randomised sequences using a pod-style device. Each of three base characterising e-cigarette flavour solutions ('bold tobacco', 'mango,' 'wintergreen') in both 2% and 4% concentrations of nicotine benzoate salt were manipulated by adding either: (1) Menthol (0.5%), (2) WS-23 (0.75%) or (3) No cooling agent. After each administration, participants rated 3 appeal and 5 sensory attributes (0-100 scales). RESULTS: Participants (n=84; M(SD)=38.6 (13.6) years old) were either exclusive e-cigarette (25.0%), cigarette (36.9%) or dual (38.1%) users. WS-23 versus no coolant products produced higher liking, willingness to use again, smoothness, and coolness and lower disliking, bitterness, and harshness ratings (|B|difference range: 4.8 to 20.1; ps<0.005). Menthol (vs no coolant) increased willingness to use again and reduced harshness and coolness (ps<0.05). Flavours with WS-23 (vs menthol) were rated as smoother, cooler and less harsh (ps<0.05). Coolant effects did not differ by base flavour, nicotine concentration, or tobacco use status. CONCLUSIONS: Adding synthetic coolant WS-23 to e-cigarettes appears to make the vaping user experience more appealing, regardless of characterising base flavour. Regulatory agencies should be aware that the manufacturing process of adding synthetic coolants may increase the attractiveness of various e-cigarette products.Cite Now.

Testing mechanisms of DNA sliding by architectural DNA-binding proteins: dynamics of single wild-type and mutant protein molecules in vitro and in vivo.

Architectural DNA-binding proteins (ADBPs) are abundant constituents of eukaryotic or bacterial chromosomes that bind DNA promiscuously and function in diverse DNA reactions. They generate large conformational changes in DNA upon binding yet can slide along DNA when searching for functional binding sites. Here we investigate the mechanism by which ADBPs diffuse on DNA by single-molecule analyses of mutant proteins rationally chosen to distinguish between rotation-coupled diffusion and DNA surface sliding after transient unbinding from the groove(s). The properties of yeast Nhp6A mutant proteins, combined with molecular dynamics simulations, suggest Nhp6A switches between two binding modes: a static state, in which the HMGB domain is bound within the minor groove with the DNA highly bent, and a mobile state, where the protein is traveling along the DNA surface by means of its flexible N-terminal basic arm. The behaviors of Fis mutants, a bacterial nucleoid-associated helix-turn-helix dimer, are best explained by mobile proteins unbinding from the major groove and diffusing along the DNA surface. Nhp6A, Fis, and bacterial HU are all near exclusively associated with the chromosome, as packaged within the bacterial nucleoid, and can be modeled by three diffusion modes where HU exhibits the fastest and Fis the slowest diffusion.

Update on Transcatheter Device Closure of Congenital Septal Defects.

PURPOSE OF REVIEW: The goal of this paper is to review currently available devices for closure of atrial septal defects (ASDs) and ventricular septal defects (VSDs). RECENT FINDINGS: Favorable results from the ASSURED trial resulted in FDA approval for the most recently developed device for transcatheter ASD closure in the United States. Further studies are required to assist in the development or approval of safe devices for transcatheter perimembranous VSD closure in pediatric patients. Device closure is the less invasive and preferred management option for many ASDs, with multiple studies demonstrating lower complication rates, shorter hospital stays, and lower mortality than surgical repair. Complex ASDs that make device closure more difficult include large defects, rim deficiencies, fenestrated defects, multiple defects, and the presence of pulmonary arterial hypertension. Device closure has also become an accepted alternative to surgery for some types of ventricular septal defects VSDs, though challenges and limitations remain. Future innovations including novel devices and techniques are needed to further expand on the types of defects that can be safely closed via transcatheter approach.

Embedding rapid reviews in health policy and systems decision-making: Impacts and lessons learned from four low- and middle-income countries.

BACKGROUND: Demand for rapid evidence-based syntheses to inform health policy and systems decision-making has increased worldwide, including in low- and middle-income countries (LMICs). To promote use of rapid syntheses in LMICs, the WHO's Alliance for Health Policy and Systems Research (AHPSR) created the Embedding Rapid Reviews in Health Systems Decision-Making (ERA) Initiative. Following a call for proposals, four LMICs were selected (Georgia, India, Malaysia and Zimbabwe) and supported for 1 year to embed rapid response platforms within a public institution with a health policy or systems decision-making mandate. METHODS: While the selected platforms had experience in health policy and systems research and evidence syntheses, platforms were less confident conducting rapid evidence syntheses. A technical assistance centre (TAC) was created from the outset to develop and lead a capacity-strengthening program for rapid syntheses, tailored to the platforms based on their original proposals and needs as assessed in a baseline questionnaire. The program included training in rapid synthesis methods, as well as generating synthesis demand, engaging knowledge users and ensuring knowledge uptake. Modalities included live training webinars, in-country workshops and support through phone, email and an online platform. LMICs provided regular updates on policy-makers' requests and the rapid products provided, as well as barriers, facilitators and impacts. Post-initiative, platforms were surveyed. RESULTS: Platforms provided rapid syntheses across a range of AHPSR themes, and successfully engaged national- and state-level policy-makers. Examples of substantial policy impact were observed, including for COVID-19. Although the post-initiative survey response rate was low, three quarters of those responding felt confident in their ability to conduct a rapid evidence synthesis. Lessons learned coalesced around three themes - the importance of context-specific expertise in conducting reviews, facilitating cross-platform learning, and planning for platform sustainability. CONCLUSIONS: The ERA initiative successfully established rapid response platforms in four LMICs. The short timeframe limited the number of rapid products produced, but there were examples of substantial impact and growing demand. We emphasize that LMICs can and should be involved not only in identifying and articulating needs but as co-designers in their own capacity-strengthening programs. More time is required to assess whether these platforms will be sustained for the long-term.

Clinical and descriptive characteristics associated with high-grade meningioma in a large clinical series.

PURPOSE: We studied 571 patients with intracranial meningioma for clinical characteristics and tumor location associated with high grade meningioma (WHO II/III). MATERIALS AND METHODS: Patients were participants in a multicentre epidemiologic study of risk factors for primary brain tumors including meningioma recruited from September 2005 to November 2019. We included patients 18 or older with a recent diagnosis of a primary intracranial meningioma of any subtype (ICD9/10: 9530-0, 9531-0, 9532-0, 9537-0, 9533-0, 9534-0, 9530-0, 9538-1, 9538-3) who were enrolled at neuro-oncology and neuro-surgery clinics in the southeastern U.S. RESULTS: The median patient age was 58 years (IQR: 48-68) and the majority of patients were female (n = 415; 72.7%) and Caucasian (n = 516; 90.4%). Most patients were symptomatic (n = 460; 80.6%) and their tumours more commonly occurred in a non-skull base location (n = 298; 52.2%). A total of 86 patients (15.0%) had a WHO grade II/III meningioma. Compared to patients with WHO grade I tumours, patients with WHO II/III meningiomas were over 3-times more likely to be male (odds ratio (OR): 3.25; 95% confidence interval (CI): 1.98, 5.35) adjusting for age, race, symptomatic presentation, and skull-based location. Moreover, a WHO grade II/III meningioma was substantially less likely to be observed in asymptomatic patients (OR: 0.15, 95% CI: 0.04, 0.42), and in patients with a skull-based tumour (OR: 0.40, 95% CI: 0.24, 0.66), adjusting for other factors. Male gender, symptomatic tumour, and a non-skull base location were independently associated with WHO grade II/III meningioma. CONCLUSION: These findings may shed additional light on the underlying pathogenesis of meningioma.

Medium-Chain Lipid Conjugation Facilitates Cell-Permeability and Bioactivity.

The majority of bioactive molecules act on membrane proteins or intracellular targets and therefore needs to partition into or cross biological membranes. Natural products often exhibit lipid modifications to facilitate critical molecule-membrane interactions, and in many cases their bioactivity is markedly reduced upon removal of a lipid group. However, despite its importance in nature, lipid-conjugation of small molecules is not commonly used in chemical biology and medicinal chemistry, and the effect of such conjugation has not been systematically studied. To understand the composition of lipids found in natural products, we carried out a chemoinformatic characterization of the "natural product lipidome". According to this analysis, lipidated natural products predominantly contain saturated medium-chain lipids (MCLs), which are significantly shorter than the long-chain lipids (LCLs) found in membranes and lipidated proteins. To study the usefulness of such modifications in probe design, we systematically explored the effect of lipid conjugation on five different small molecule chemotypes and find that permeability, cellular retention, subcellular localization, and bioactivity can be significantly modulated depending on the type of lipid tail used. We demonstrate that MCL conjugation can render molecules cell-permeable and modulate their bioactivity. With all explored chemotypes, MCL-conjugates consistently exhibited superior uptake or bioactivity compared to LCL-conjugates and either comparable or superior uptake or bioactivity to short-chain lipid (SCL)-conjugates. Together, our findings suggest that conjugation of small molecules with MCLs could be a powerful strategy for the design of probes and drugs.

Ordering Transitions of Liquid Crystals Triggered by Metal Oxide-catalyzed Reactions of Sulfur Oxide Species.

Liquid crystals (LCs), when supported on reactive surfaces, undergo changes in ordering that can propagate over distances of micrometers, thus providing a general and facile mechanism to amplify atomic-scale transformations on surfaces into the optical scale. While reactions on organic and metal substrates have been coupled to LC-ordering transitions, metal oxide substrates, which offer unique catalytic activities for reactions involving atmospherically important chemical species such as oxidized sulfur species, have not been explored. Here, we investigate this opportunity by designing LCs that contain 4'-cyanobiphenyl-4-carboxylic acid (CBCA) and respond to surface reactions triggered by parts-per-billion concentrations of SO2 gas on anatase (101) substrates. We used electronic structure calculations to predict that the carboxylic acid group of CBCA binds strongly to anatase (101) in a perpendicular orientation, a prediction that we validated in experiments in which CBCA (0.005 mol %) was doped into an LC (4'-n-pentyl-4-biphenylcarbonitrile). Both experiment and computational modeling further demonstrated that SO3-like species, produced by a surface-catalyzed reaction of SO2 with H2O on anatase (101), displace CBCA from the anatase surface, resulting in an orientational transition of the LC. Experiments also reveal the LC response to be highly selective to SO2 over other atmospheric chemical species (including H2O, NH3, H2S, and NO2), in agreement with our computational predictions for anatase (101) surfaces. Overall, we establish that the catalytic activities of metal oxide surfaces offer the basis of a new class of substrates that trigger LCs to undergo ordering transitions in response to chemical species of relevance to atmospheric chemistry.

An international, open-label, randomised trial comparing a two-step approach versus the standard three-step approach of the WHO analgesic ladder in patients with cancer.

BACKGROUND: Worldwide, cancer pain management follows the World Health Organization (WHO) three-step analgesic ladder. Using weak opioids (e.g. codeine) at step 2 is debatable with low-dose strong opioids being potentially better, particularly in low- and middle-income countries where weak opioids are expensive. We wanted to assess the efficiency, safety and cost of omitting step 2 of the WHO ladder. PATIENTS AND METHODS: We carried out an international, open-label, randomised (1 : 1) parallel group trial. Eligible patients had cancer, pain ≥4/10 on a 0-10 numerical rating scale, required at least step 1 (paracetamol) of the WHO ladder and were randomised to the control arm (weak opioid, step 2 of the WHO ladder) or the experimental arm (strong opioid, step 3). Primary outcome was time to stable pain control (3 consecutive days with pain ≤3). Secondary outcomes included distress, opioid-related side-effects and costs. The primary outcome analysis was by intention to treat and the follow-up was for 20 days. RESULTS: One hundred and fifty-three patients were randomised (76 control, 77 experimental). There was no statistically significant difference in time to stable pain control between the arms, P = 0.667 (log-rank test). The adjusted hazard ratio for the control arm was 1.03 (95% confidence interval 0.72-1.49). In the control arm, 38 patients (53%) needed to change to a strong opioid due to ineffective analgesia. The median time to change was day 6 (interquartile range 4-11). Compared to the control arm, patients in the experimental arm had less nausea (P = 0.009) and costs were less. CONCLUSION: This trial provides some evidence that the two-step approach is an alternative option for cancer pain management.

Outcomes following surgical resection of cystic intracranial meningiomas.

INTRODUCTION: Cystic meningiomas are rare, accounting for 2-7% of all intracranial meningiomas. Little is known regarding whether these meningiomas behave differently compared to solid meningiomas. We sought to study this relatively uncommon imaging appearance of meningioma and to evaluate its clinical significance. METHODS: A single-institution retrospective cohort study of surgically-treated meningioma patients between 2000 and 2019 was conducted. Cystic meningioma was defined as a tumor with an intratumoral or peritumoral cyst present on preoperative imaging. Demographics, preoperative imaging, histopathology characteristics, operative data, and surgical outcomes were reviewed. Imaging variables, histopathology and outcomes were reported for cystic meningiomas and compared with non-cystic meningiomas. Univariate/multivariable analyses were conducted. RESULTS: Of 737 total meningiomas treated surgically, 38 (5.2%) were cystic. Gross total resection (GTR) was achieved in 84.2% of cystic meningioma patients. Eighty-two percent of cystic meningiomas were WHO grade I (n = 31), 15.7% were grade II and 2.6% were grade III. Most cystic meningiomas had low Ki-67/MIB-1 proliferation index (n = 24, 63.2%). A total of 18.4% (n = 7) patients with cystic meningioma had recurrence compared to 12.2% (n = 80) of patients with non-cystic meningioma (p = 0.228). No significant difference in median time to recurrence was observed between cystic and non-cystic meningiomas (25.4, Q1:13.9, Q3:46.9 months vs. 13.4, Q1:8.6, Q3:35.5 months, p = 0.080). CONCLUSIONS: A small portion of intracranial meningiomas have cystic characteristics on imaging. Cystic meningiomas are frequently WHO grade I, have low proliferation index, and had similar outcomes compared to non-cystic meningioma. Cysts in meningioma may not be a surrogate to determine aggressive meningioma behavior.

Matched case-control analysis of outcomes following surgical resection of incidental meningioma.

PURPOSE: The management of incidentally discovered meningioma remains controversial. We sought to compare outcomes following surgical resection of incidental meningioma to a matched cohort of symptomatic meningiomas. METHODS: A retrospective single-center case-control study was conducted for patients undergoing resection of incidental meningioma from 2000 to 2019. A 1:1 case-control matching for incidental and symptomatic meningioma was performed using the following variables: age at initial visit, gender, tumor location/size, and presence of peritumoral edema. Primary outcomes included (1) WHO grading/histopathological subtype/MIB-1 index, (2) extent of resection (gross total resection or subtotal resection), and (3) recurrence. Outcomes were compared between groups using descriptive/bivariate analyses. RESULTS: A total of 91 incidental meningiomas were analyzed. Trauma was the most common reason (n = 19, 21%) to obtain imaging, and tumor size the leading reason to operate (n = 37, 41%). Median time-to-surgery from initial clinical encounter was 5-months (Q1:3, Q3:16.5). More incidental meningioma patients (n = 47, 52%) were privately insured compared to their matched symptomatic cohort (n = 30, 33%) (P = 0.006). Patients with incidental meningioma had significantly higher mean Karnofsky Performance Scale at time-of-surgery (93.2, SD:11.1 vs. 81.4, SD:12.7) (P < 0.001). There were no significant differences in primary/secondary outcomes between the groups. Incidental meningioma was not associated with recurrence on Cox proportional hazards analysis (HR: 0.795, 95%CI: 0.3-2.1, P = 0.637). CONCLUSION: Matched case-control analysis demonstrated no significant differences in clinical, histopathological, and functional outcomes following resection of incidental and symptomatic meningioma. While non-operative management with close follow-up and serial imaging is preferred for incidental meningiomas, those undergoing resection when indicated can anticipate similar safety and efficacy as symptomatic meningiomas.

Alcohol use trajectories among U.S. adults during the first 42 weeks of the COVID-19 pandemic.

BACKGROUND: This study characterized the prevalence, drinking patterns, and sociodemographic characteristics of U.S. adult subpopulations with distinct drinking trajectories during the COVID-19 pandemic's first 42 weeks. METHODS: Adult respondents (n = 8130) in a nationally representative prospective longitudinal study completed 21 biweekly web surveys (March 2020 to January 2021). Past-week alcohol drinking frequency (drinking days [range: 0 to 7]) and intensity (binge drinking on usual past-week drinking day [yes/no]) were assessed at each timepoint. Growth mixture models identified multiple subpopulations with homogenous drinking trajectories based on mean drinking days or binge drinking proportional probabilities across time. RESULTS: Four drinking frequency trajectories were identified: Minimal/stable (72.8% [95% CI = 71.8 to 73.8]) with <1 mean past-week drinking days throughout; Moderate/late decreasing (6.7% [95% CI = 6.2 to 7.3) with 3.13 mean March drinking days and reductions during summer, reaching 2.12 days by January 2021; Moderate/early increasing (12.9% [95% CI = 12.2 to 13.6) with 2.13 mean March drinking days that increased in April and then plateaued, ending with 3.20 mean days in January 2021; and Near daily/early increasing (7.6% [95% CI = 7.0 to 8.2]) with 5.58 mean March drinking days that continued increasing without returning to baseline. Four drinking intensity trajectories were identified: Minimal/stable (85.8% [95% CI = 85.0% to 86.5%]) with <0.01 binge drinking probabilities throughout; Low-to-moderate/fluctuating (7.4% [95% CI = 6.8% to 8%]) with varying binge probabilities across timepoints (range:0.12 to 0.26); Moderate/mid increasing (4.2% [95% CI = 3.7% to 4.6%]) with 0.39 April binge drinking probability rising to 0.65 during August-September without returning to baseline; High/early increasing trajectory (2.7% [95% CI = 2.3% to 3%]) with 0.84 binge drinking probability rising to 0.96 by June without returning to baseline. Males, Whites, middle-aged/older adults, college degree recipients, those consistently working, and those above the poverty limit were overrepresented in various increasing (vs. minimal/stable) frequency trajectories. Males, Whites, nonmarried, those without college degree, 18 to 39-year-olds, and middle aged were overrepresented in increasing (vs. minimal/stable) intensity trajectories. CONCLUSIONS: Several distinct U.S. adult sociodemographic subpopulations appear to have acquired new drinking patterns during the pandemic's first 42 weeks. Frequent alcohol use assessment in the COVID-19 era could improve personalized medicine and population health efforts to reduce drinking.