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Objective: This study characterized caregivers' beliefs related to early intervention services for children with sickle cell disease (SCD) to gain an indepth understanding of caregivers' experiences and desires for early intervention services., Methods: Both qualitative and quantitative data were collected from caregivers of children aged 0-4 years with SCD across two sites in the United States. Caregivers completed the Knowledge of Infant Development Inventory, a custom survey about their experiences with early intervention, and a qualitative interview., Results: A total of 127 caregivers were approached, 47 participated in surveys, and 20 completed interviews. Caregivers expressed varying levels of confidence and understanding of developmental milestones across sites. Interviews highlighted three main themes: fear of SCD-related complications, variable buy-in to early intervention, and the importance of provider-caregiver relationships. While some caregivers appreciated early intervention, others questioned its necessity. Caregivers communicated interest in connecting with other families facing similar challenges, emphasizing the need for increased awareness of available resources., Conclusions: Fear about their child's well-being was expressed by many caregivers, emphasizing the need for a supportive healthcare team that can help families connect with preventive interventions. While about a quarter of children had been referred to rehabilitation services, caregivers were unaware of the elevated risk for developmental delay, which diminished caregiver interest in participating in programs like early intervention. This study underscores the importance of addressing knowledge gaps and overcoming barriers to enhance care for families affected by SCD., (© 2024 Wiley Periodicals LLC.)

Liquid biopsy with sequencing of circulating tumor DNA (ctDNA) is a minimally invasive method for sampling body fluids and offers a promising alternative to tissue biopsies that involve greater risks, costs, and time. ctDNA not only identifies actionable targets by revealing unique molecular signatures in cancer, but also may assess treatment response, treatment resistance and progression, and recurrence. Imaging correlates of these applications are already being identified and utilized for various solid tumors. Radiologists have new challenges in interpreting oncologic imaging. Given their integral role in cancer surveillance, they must become familiar with the importance of ctDNA in detecting recurrence and minimal residual disease, measuring treatment response, predicting survival and metastatic patterns, and identifying new molecular therapeutic targets. In this review, we provide an overview of ctDNA testing, and a snapshot of current clinical guidelines from the National Comprehensive Cancer Network and the European Society of Molecular Oncology on the use of ctDNA in lung, breast, colorectal, pancreatic, and hepatobiliary cancers. For each cancer type, we also highlight current research applications of ctDNA that are relevant to the field of diagnostic radiology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

This statement from the Pediatric Academic Societies Maternal Child Health: First 1,000 Days Special Interest Group provides an overview of the rationale, evidence, and key action steps needed to engage Community Health Workers (CHWs) into team-based well-child care (WCC) for families in low-income communities. CHWs have been defined as public health workers who have a trusted and valued connection to a community. Integrating CHWs into early childhood WCC can allow for greater cultural relevancy for families, reduce the burden on clinicians to provide the wide range of WCC services, many of which do not require the expertise of a high-level clinician, and improve preventive care services to families during the vulnerable but critical period of early childhood. There are evidence-based approaches to integrating CHWs into early childhood WCC, as well as payment models that can support them. Implementation and spread of these models will require collaboration and engagement across health systems, clinics, payors, and CHWs; flexibility for local adaptation of these models to meet the needs of clinics, practices, CHWs, and communities; publicly available training resources for CHW education; and research findings to guide effective implementation that incorporates parent and caregiver engagement as well as sustainable payment models., (© 2024. The Author(s).)

As glia mature, they undergo glial tiling to abut one another without invading each other's boundaries. Upon the loss of the secreted neurotrophin Spätzle3 (Spz3), Drosophila cortex glia transform morphologically and lose their intricate interactions with neurons and surrounding glial subtypes. Here, we reveal that all neighboring glial cell types (astrocytes, ensheathing glia, and subperineurial glia) react by extending processes into the previous cortex glial territory to compensate for lost cortex glial function and reduce the buildup of neuronal debris. However, the loss of Spz3 alone is not sufficient for glia to cross their natural borders, as blocking CNS growth via nutrient-restriction blocks the aberrant infiltration induced by the loss of Spz3. Surprisingly, even when these neighboring glia divert their cellular resources beyond their typical borders to take on new compensatory roles, they are able to multitask to continue to preserve their own normal functions to maintain CNS homeostasis., Competing Interests: Declaration of Interests The authors declare no competing interests.

Purpose: Determine the level of agreement of three activity monitors compared with the gold standard (video review) on the activity level of patients with stroke., Methods: A prospective, observational, agreement study was performed on 47 individuals with sub-acute stroke in an inpatient rehabilitation facility. Data was collected during one physical therapy session. Individuals wore three device types; Actigraph (AG), Activpal (AP), and stepwatch activity monitor (SAM). Variables assessed were step counts for each limb (hemiparetic and non-hemiparetic) and percent time standing and other., Analysis: Results from the activity monitors were compared to the video review and assessed for agreement using the intraclass correlation coefficient (ICC) and accuracy of mean difference from video observation., Results: The step counts with the SAM on the non-hemiparetic limb had the highest ICC for step counts (ICC = 0.98, p  < 0.001) and were overestimated with 21% accuracy. The SAM on the hemiparetic limb had 9.7% accuracy (ICC = 0.92, p  < 0.001). For percent standing time all devices overestimated with poor reliability. For percent other activity time, the AP had the best accuracy and underestimated for both the hemiparetic limb (9.9% accuracy; ICC = 0.90, p  < 0.001) and non-hemiparetic limb (8.3% accuracy; ICC = 0.84, p  < 0.001)., Conclusions: The use of multiple devices may be warranted to capture an accurate understanding of activity levels in this population of individuals with sub-acute stroke. There are concerns with all monitors and clinicians and researchers should be aware of what measures they are wanting to understand about their population.

The lateral transorbital approach is a minimally invasive approach that was first described for accessing the cavernous sinus.1 Although other minimally invasive approaches have been broadly applied to aneurysm surgery,2 the use of transorbital keyholes for this is still quite rare.3,4 We present a 72-year-old man with an incidentally discovered 5-mm middle cerebral artery aneurysm. Despite a low rupture risk,5 the patient himself opted for treatment, and because of the complex shape of the aneurysm, he chose surgical clipping as the treatment of choice. Two unique aspects of the patient's anatomy brought forth transorbital approach for consideration. He had a wide fissure, which opened to the orbital wall, and a giant frontal sinus made its avoidance difficult with any anterolateral transcranial approach. The lateral transorbital approach was started with a transpalpebral incision.4,6,7 Both wings of the sphenoid bone were drilled until the frontal and temporal dura was exposed. Opening this through the orbit gained direct access to the large Sylvian fissure. Two specific challenges were specific to this opening: the aneurysm dome pointed straight at the surgeon, and the M1 segment, needed for proximal control, was directly behind the aneurysm. Despite these, the aneurysm was successfully eliminated through the transorbital approach with no residual or normal branch compromise. Given the specific anatomical provisions, the lateral transorbital approach was an effective and safety alternative to the pterional approach for middle cerebral artery aneurysms. No Institutional Review Board approval was sought or necessary as the patient provided consent for the procedure, publication of his image, and this submission., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

One of the key concepts behind minimally invasive keyhole cranial surgery is that as the operative corridor deepens, it also widens. The corridor should therefore be designed parallel to the long-axis of the tumor to optimize visualization.1 These ideas were applied in a duo-keyhole operation for a falcine meningioma. The patient is a 79-year-old woman diagnosed with a large falcine meningioma compressing both frontal lobes. Her tumor was oriented with the long-axis, perpendicular to the superior sagittal sinus, and has bulbous extensions on both sides of the falx. Incisions on the falx, anterior and posterior to the tumor, in addition to a cut between it and the undersurface of the superior sagittal sinus, would render it practically devascularized and "free-floating.2" One keyhole was insufficient, but one anterior and another posterior to the tumor would make the falcine cuts feasible. The operation was performed with the above scheme and the posterior keyhole to the left and anterior one to the right of midline to facilitate surface vascular detachment on both sides. The patient recovered well and was discharged home after 4 days. This procedure highlights that flexible application of the principles of minimally invasive keyhole. Neurosurgery can tailor-make an operation to precisely fit the unique features of a patient and the tumor. The procedure was performed under the ethical guidelines of our hospital. No Institutional Review Board consent was required or sought because the patient gave specific consent to the procedure and publication of her image., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Reducing waiting times is a priority in public health systems. Efforts of healthcare providers to shorten waiting times could be negated if they simultaneously induce substantial increases in demand. However, separating out the effects of changes in supply and demand on waiting times requires an exogenous change in one element. We examine the impact of a pilot programme in some English hospitals to shorten waiting times for urgent diagnosis of suspected cancer on family doctors' referrals. We examine referrals from 6,666 family doctor partnerships to 145 hospitals between 1st April 2012 and 31st March 2019. Five hospitals piloted shorter waiting times initiatives in 2017. Using continuous difference-in-differences regression, we exploit the pilot as a 'supply shifter' to estimate the effect of waiting times on referral volumes for two suspected cancer types: bowel and lung. The proportion of referred patients breaching two-week waiting times targets for suspected bowel cancer fell by 3.9 percentage points in pilot hospitals in response to the policy, from a baseline of 4.8%. Family doctors exposed to the pilot increased their referrals (demand) by 10.8%. However, the pilot was not successful for lung cancer, with some evidence that waiting times increased, and a corresponding reduction in referrals of -10.5%. Family doctor referrals for suspected cancer are responsive at the margin to waiting times. Healthcare providers may struggle to achieve long-term reductions in waiting times if supply-side improvements are offset by increases in demand., (© 2023. The Author(s).)

Introduction: Reducing waiting times is a major policy objective in publicly-funded healthcare systems. However, reductions in waiting times can produce a demand response, which may offset increases in capacity. Early detection and diagnosis of cancer is a policy focus in many OECD countries, but prolonged waiting periods for specialist confirmation of diagnosis could impede this goal. We examine whether urgent GP referrals for suspected cancer patients are responsive to local hospital waiting times., Method: We used annual counts of referrals from all 6,667 general practices to all 185 hospital Trusts in England between April 2012 and March 2018. Using a practice-level measure of local hospital waiting times based on breaches of the two-week maximum waiting time target, we examined the relationship between waiting times and urgent GP referrals for suspected cancer. To identify whether the relationship is driven by differences between practices or changes over time, we estimated three regression models: pooled linear regression, a between-practice estimator, and a within-practice estimator., Results: Ten percent higher rates of patients breaching the two-week wait target in local hospitals were associated with higher volumes of referrals in the pooled linear model (4.4%; CI 2.4% to 6.4%) and the between-practice estimator (12.0%; CI 5.5% to 18.5%). The relationship was not statistically significant using the within-practice estimator (1.0%; CI -0.4% to 2.5%)., Conclusion: The positive association between local hospital waiting times and GP demand for specialist diagnosis was caused by practices with higher levels of referrals facing longer local waiting times. Temporal changes in waiting times faced by individual practices were not related to changes in their referral volumes. GP referrals for diagnostic cancer services were not found to respond to waiting times in the short-term. In this setting, it may therefore be possible to reduce waiting times by increasing supply without consequently increasing demand., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hayes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Payments for some diagnostic scans undertaken in outpatient settings were unbundled from Diagnosis Related Group based payments in England in April 2013 to address under-provision. Unbundled scans attracted additional payments of between £45 and £748 directly following the reform. We examined the effect on utilization of these scans for patients with suspected cancer. We also explored whether any detected effects represented real increases in use of scans or better coding of activity. We applied difference-in-differences regression to patient-level data from Hospital Episodes Statistics for 180 NHS hospital Trusts in England, between April 2010 and March 2018. We also explored heterogeneity in recorded use of scans before and after the unbundling at hospital Trust-level. Use of scans increased by 0.137 scans per patient following unbundling, a 134% relative increase. This increased annual national provider payments by £79.2 million. Over 15% of scans recorded after the unbundling were at providers that previously recorded no scans, suggesting some of the observed increase in activity reflected previous under-coding. Hospitals recorded substantial increases in diagnostic imaging for suspected cancer in response to payment unbundling. Results suggest that the reform also encouraged improvements in recording, so the real increase in testing is likely lower than detected., (© 2024 The Authors. Health Economics published by John Wiley & Sons Ltd.)

Parafalcine and parasagittal (PFPS) are common locations for meningiomas. Surgical resection for these tumors, the first-line treatment, poses challenges due to their proximity to critical structures. This systematic review investigates the use of stereotactic radiosurgery (SRS) as a treatment for PFPS meningiomas, aiming to elucidate its safety and efficacy. The review adhered to PRISMA guidelines. Searches were conducted on MEDLINE, Embase, and Cochrane. Inclusion criteria involved studies on SRS for PFPS meningiomas, reporting procedure outcomes and complications. Tumors were presumed or confirmed to be WHO grade 1. Data was systematically extracted. Meta-analysis was performed where applicable. The review included data from eight studies, 821 patients with 878 lesions. Tumor control was achieved in greater than 80% of cases. Adverse radiation effects were reported in 7.3% of them. Recurrence and further surgical approach were observed in 17.1% and 9.2% of cases, respectively. Symptom improvement was noted in 33.2% of patients. Edema occurred in approximately 25.1% of patients. A subgroup of 283 patients had upfront SRS, achieving tumor control in approximately 97% of such cases. SRS is a safe and effective treatment for PFPS meningiomas, both as an adjuvant therapy and as an upfront treatment for often smaller tumors. Post-SRS edema can typically be managed medically and usually does not require further surgical intervention. Further studies should provide more specific data on PFPS meningiomas. The use of single and hypofractionated SRS for larger volume PFPS meningiomas should be more explored to better define the risks and benefits., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Preliminary studies show that patients with large vessel occlusion (LVO) acute ischemic strokes have worse outcomes with concurrent COVID-19 infection. We investigated the outcomes for patients with LVO strokes undergoing mechanical thrombectomy (MT) with concurrent COVID-19 infection., Methods: The National Inpatient Database (NIS) was used for our analysis. Patients in the year 2020 with an ICD-10 diagnosis code for acute ischemic stroke and procedural code for MT were included with and without COVID-19. Odds ratios (OR) were calculated using a logistic regression model with age, sex, stroke location, Elixhauser comorbidity score, and other patient variables deemed clinically relevant as covariates., Results: Patients in the COVID-19 group were younger (64.3±14.4 vs 69.4±14.5 years, P<0.001), had a higher rate of inpatient mortality (22.4% vs 10.1%, P<0.001), and a longer length of stay (10 vs 6 days, P<0.001). Patients with COVID-19 had higher odds of death (OR 2.78, 95% CI 2.11 to 3.65) and lower odds of a routine discharge (OR 0.65, 95% CI 0.48 to 0.89). There was no difference in the odds of subsequent stroke and cerebral hemorrhage, but patients with COVID-19 had statistically significantly higher odds of respiratory failure, pulmonary embolism, deep vein thrombosis, myocardial infarction, acute kidney injury, and sepsis., Conclusions: Patients with LVOs undergoing MT within the 2020 NIS database had worse outcomes when co-diagnosed with COVID-19, likely due to non-neurological manifestations of COVID-19., Competing Interests: Competing interests: The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. RMS has consulting and teaching agreements with Penumbra, Abbott, Medtronic, InNeuroCo, and Cerenovus., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Left ventricular (LV) assist devices (LVADs) can prolong survival and improve quality of life in end-stage heart failure., Aims: Review outcomes of the Western Australian LVAD programme., Methods: Retrospective database and medical record review., Results: One hundred forty-seven LVADs have been implanted in 23 years, of which 95 were newer-generation devices (HeartWare HVAD [HW], HeartMate II and HeartMate 3). Presented data refer to these devices only. Most patients (94%) were classed as bridge-to-transplant or -candidacy/decision, with the remainder classed as 'destination therapy' (DT). Mean LV ejection fraction was 20%, and 36% had severe right ventricular dysfunction. Sixty-two percent of patients had a nonischaemic cardiomyopathy. Following LVAD implant, the median length of stay in intensive care was 2 days, and in the hospital overall was 23 days. Ninety-six percent of patients survived to hospital discharge, and, following discharge, 98% of days with LVAD were spent as an outpatient. The median number of hospital readmissions was 1.5 per patient per year. LVAD-associated infection requiring admission or intravenous antibiotics at any time after implant occurred in 36%, significant gastrointestinal bleeding in 19% and stroke in 11%. The percentage of patients alive with LVAD still in situ at 1, 2 and 5 years was 94%, 88% and 62% respectively, which exceeds current international registry outcomes. All DT patients survived at least 4 years, spending 97% of days with LVAD as an outpatient. The two longest-surviving HW DT patients worldwide (11.3 and 10.5 years) are among this cohort., Conclusions: Excellent outcomes can be achieved with LVADs in appropriately selected patients., (© 2023 Royal Australasian College of Physicians.)

Per- and polyfluoroalkyl substances (PFAS) are used in various industrial products; however, they pose serious health risks. In this study, soil, soil gas, and groundwater samples were collected at a PFAS manufacturing facility in New Jersey, USA, to determine the presence and distribution of PFASs from the soil surface to groundwater and at various distances from the presumed source. Fluorotelomer alcohols (FTOHs) were detected in soil (< 0.26-36.15 ng/g) and soil gas (160-12,000 E µg/m 3 ), while perfluorinated carboxylic acids (PFCAs) were found in soil (4.3-810 ng/g), soil gas (<0.10-180 µg/m 3 ), and groundwater (37-49 µg/L). FTOH and PFCA concentrations decreased as the distance from the presumed source increased, suggesting that PFCAs are likely to migrate in groundwater, whereas FTOHs primarily move in the vapor phase. The presence of PFAS in the groundwater, soil, and soil gas samples indicate its potential for vapor intrusion; thus, some PFAS may contribute to indoor air inhalation exposure. To the best of our knowledge, this is the first report on the quantification of volatile PFAS in soil gas at a PFAS manufacturing facility., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

In this chapter, we explore the role of mixed reality (MxR), a synergy of virtual reality (VR) and augmented reality (AR), in neurosurgery. MxR marks a significant advancement in surgical planning and execution, enhancing precision, safety, and outcomes. We trace the evolution of neurosurgical techniques, positioning MxR as the latest innovation in a series of technological advancements aimed at improving surgical accuracy and patient safety.The chapter details VR's role in providing immersive preoperative environments for detailed surgical rehearsal, utilizing 3D reconstructions of patient-specific neuroanatomy. AR complements this by overlaying critical digital information onto the surgeon's real-time view, thus reducing cognitive load and enhancing focus during critical surgical phases.We specifically highlight MxR's application in brain tumor and skull base surgery, demonstrating its capacity to facilitate meticulous planning and navigation through complex anatomical structures. The chapter includes case studies illustrating MxR's effectiveness in cerebrovascular surgeries, such as arteriovenous malformations (AVM) and aneurysm treatments, and discusses its potential in neurosurgical training and custom implant design.Concluding with a discussion of the challenges in MxR adoption and future perspectives, the chapter underscores MxR's potential to revolutionize neurosurgical interventions, making them safer, more efficient, and tailored to individual patient needs., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Transvenous access is a necessary tool for numerous cerebrovascular pathologies.Transvenous access in the arm offers several benefits compared with transfemoral access, including patient comfort, the avoidance of transfemoral access complications, and the ability to close both radial arterial access and distal arm venous access with a single transradial compression band.1In this video we describe the indications, technical nuances, benefits, and limitations of transvenous access in the arm.neurintsurg;jnis-2023-020996v1/V1F1V1Video 1- Combined venous and arterial access in the arm for treatment of a complex dural arteriovenous fistulaWe present the case of a young patient who presented with pulsatile tinnitus and was found to have a Cognard type IIa dural arteriovenous fistula near the left transverse sigmoid junction.The patient was treated with transvenous embolization via the distal right basilic vein, and a single radial compression band served to close both the arterial and venous access sites., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Cerebral air embolism (CAE) is a rare, yet potentially devastating condition characterized by entrance of air into cerebral vasculature, that is nearly always iatrogenic. While many findings of CAE are subclinical and incidental at computed tomography (CT), there remain cases of catastrophic and fatal embolisms. Increasing physician awareness of prevention, presentation, and treatment for CAE is crucial for reducing morbidity and mortality. In this case series, we highlight this preventable entity by comparing three cases of CAE that showcase a diverse array of presentations, radiologic findings, and clinical outcomes. We will also explore predisposing factors, prognostic predictors, diagnostic considerations, and available treatments., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Saroglitazar magnesium, a dual peroxisome proliferator-activated receptor agonist, is under evaluation for treating various liver conditions. While the pharmacokinetics (PK) of saroglitazar have been extensively studied in diverse preclinical models and healthy subjects, a comprehensive assessment of its PK behavior under conditions of hepatic impairment is lacking. In this Phase 1, open-label, parallel-group study, the PK of a single dose of 4-mg saroglitazar magnesium was investigated in subjects having varying degrees of hepatic impairment with and without portal hypertension compared with appropriately matched individuals having normal hepatic function. Treatment-emergent adverse events for safety were also evaluated. Thirty-two subjects were enrolled in the hepatic-impaired groups and 23 subjects in the normal hepatic function group. Mild and moderate hepatic impairment did not significantly affect the PK of saroglitazar, compared with normal hepatic function. Although severe hepatic impairment did not alter maximum observed plasma concentration and half-life; saroglitazar exposure (area under the plasma concentration-time curve from time 0 to infinity) increased 3-fold, while the clearance was 61% lower compared to the subjects with normal hepatic function. This may require close monitoring or dose adjustments in individuals with severe hepatic impairment. A single oral dose of saroglitazar magnesium 4 mg was found to be safe and well tolerated in subjects with varying degrees of hepatic function., (© 2023, The American College of Clinical Pharmacology.)

Deficiency in the adipose-derived hormone leptin or leptin receptor signaling causes class 3 obesity in individuals with genetic loss-of-function mutations in leptin or its receptor LEPR and metabolic and liver disease in individuals with hypoleptinemia secondary to lipoatrophy such as in individuals with generalized lipodystrophy. Therapies that restore leptin-LEPR signaling may resolve these metabolic sequelae. We developed a fully human monoclonal antibody (mAb), REGN4461 (mibavademab), that activates the human LEPR in the absence or presence of leptin. In obese leptin knockout mice, REGN4461 normalized body weight, food intake, blood glucose, and insulin sensitivity. In a mouse model of generalized lipodystrophy, REGN4461 alleviated hyperphagia, hyperglycemia, insulin resistance, dyslipidemia, and hepatic steatosis. In a phase 1, randomized, double-blind, placebo-controlled two-part study, REGN4461 was well tolerated with an acceptable safety profile. Treatment of individuals with overweight or obesity with REGN4461 decreased body weight over 12 weeks in those with low circulating leptin concentrations (<8 ng/ml) but had no effect on body weight in individuals with higher baseline leptin. Furthermore, compassionate-use treatment of a single patient with atypical partial lipodystrophy and a history of undetectable leptin concentrations associated with neutralizing antibodies to metreleptin was associated with noteable improvements in circulating triglycerides and hepatic steatosis. Collectively, these translational data unveil an agonist LEPR mAb that may provide clinical benefit in disorders associated with relatively low leptin concentrations.

Bariatric surgery, including sleeve gastrectomy (SG), improves systolic and diastolic function, which is independent of weight loss in rodent models. The cause of weight loss-independent improvements in cardiac function are unknown but may originate from the gastrointestinal tract. In this study, we investigated whether a circulating blood factor is a mechanism for acute cardioprotection after SG by testing the utility of rodent SG plasma to reduce metabolic stress in vitro. For the initial experiment, obese male Zucker rats underwent SG, ad lib sham, or pair-fed sham surgeries (n = six SG, n = eight SH, n = eight PF). For all other studies, a second group of Zucker rats underwent SG or ad lib sham surgeries (n = eight SH, n = six SG). Six weeks following surgery, plasma was collected from each group, both in the fasting and post-prandial (pp) state. This plasma was then pooled per surgical group and nutrient state and tested in multiple in vitro cell culture and extra-cellular assays to determine the effect of SG on myotubular metabolic stress compared to the sham surgeries. Post-prandial SG plasma (ppSG), but not fasting SG, pp, or fasting sham plasma, reduced the metabolic stress of the H9c2 cells as measured by lactate dehydrogenase (LDH) release ( p < 0.01). Unlike SG, weight reduction through pair-feeding did not prevent H9c2 metabolic stress. The PpSG plasma had the slowest rate of extracellular hydrogen peroxide consumption and peroxidatic activity compared to the pp sham, fasting SG, and fasting sham groups. Redox testing of plasma with aminiobenzoic acid hydrazide and edaravone suggested a pattern supporting myeloperoxidase (MPO), or other peroxidases, as the primary component responsible for reduced metabolic stress with ppSG plasma. The PpSG plasma contained 35% less circulating MPO protein as compared to the pp sham and fasting SG plasma. The plasma from an MPO global knockout rat also prevented metabolic stress of the H9c2 cells, compared to the significant increase in LDH release from the plasma of the WT controls ( p < 0.01). The MPO global knockout plasma also had a rate of extracellular hydrogen peroxide consumption and peroxidatic activity comparable to the ppSG plasma. These studies suggest that one of the weight loss-independent mechanisms by which SG improves myocellular function could be a reduced pro-oxidative environment due to lower circulating levels of MPO. It appears that the gastrointestinal tract is of critical importance to these findings, as the MPO levels were only lowered after enteral, nutrient stimulation in the SG rats. If this surgical effect is confirmed in humans, SG may be a unique surgical treatment for multiple diseases with a pathogenesis of inflammation and oxidative damage, including obesity-associated heart failure with preserved ejection fraction.

Robotic assistance in stereoelectroencephalography (SEEG) holds promising potential for enhancing accuracy, efficiency, and safety during electrode placement and surgical procedures. This systematic review and meta-analysis, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and International Prospective Register of Systematic Reviews (PROSPERO) registration, delves into the latest advancements and implications of robotic systems in SEEG, while meticulously evaluating outcomes and safety measures. Among 855 patients suffering from medication-refractory epilepsy who underwent SEEG in 29 studies, averaging 24.6 years in age, the most prevalent robots employed were robotic surgical assistant (ROSA) (450 patients), Neuromate (207), Sinovation (140), and ISys1 (58). A total of 8,184 electrodes were successfully implanted, with an average operative time of 157.2 minutes per procedure and 15.1 minutes per electrode, resulting in an overall mean operative time of 157.7 minutes across all studies. Notably, the mean target point error (TPE) stood at 2.13 mm, the mean entry point error (EPE) at 1.48 mm, and postoperative complications occurred in 7.69% of robotically assisted (RA) SEEG cases (60), with 85% of these complications being asymptomatic. This comprehensive analysis underscores the safety and efficacy of RA-SEEG in patients with medication-refractory epilepsy, characterized by low complication rates, reduced operative time, and precise electrode placement, supporting its widespread adoption in clinical practice, with no discernible differences noted among the various robotic systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Vasconcellos et al.)

Introduction: Elevated interleukin-6 (IL-6) plasma levels have been associated with abdominal aortic aneurysm (AAA), but whether this cytokine plays a causative role in the degenerative remodeling or represents an effect from the inflammatory cascades initiated by infiltrating leukocytes remained unclear. This project aims to demonstrate that within the aortic wall, signaling from IL-6 through the STAT3 transcription factor is necessary for infiltration of proteolytically-active macrophages and development of small AAA., Methods: Following measurement of baseline infrarenal aortic diameter (AoD, digital microscopy), C57Bl/6 and IL-6 knockout (IL-6KO) mice underwent AAA induction by application of peri-adventitial CaCl 2 (0.5 M) +/- implantation of an osmotic mini-pump delivering IL-6 (4.36 µg/kg/day over 21 days). At the terminal procedure, AoDs were measured by digital microscopy and aortas harvested for immunoblot (pSTAT3/STAT3), matrix metalloproteinase (MMP) quantification, or flow cytometric analysis of macrophage content. Plasma was collected for cytokine analysis., Results: IL-6 infusion significantly increased the plasma IL-6 levels in C57Bl/6 and IL-6KO animals. The C57Bl/6 + CaCl 2 group developed AAA (AoD >50% above baseline) but IL-6KO + CaCl 2 did not. In the IL-6KO + IL-6+CaCl2 group, AAA developed to match that of C57Bl/6 + CaCl 2 mice. STAT3 activity was significantly increased in animals with advanced stages of dilation (>40% from baseline), compared to those with ectasia (≤25%). Although cytokine profiles did not support T-cells or neutrophils as being active contributors in this stage of aortic remodeling, changes in the profile of elaborated MMPs suggested macrophage activity with a trend toward alternatively activated pathways. Flow cytometry confirmed significantly increased macrophage abundance specifically in animals with upregulated STAT3 activity and advanced aortic dilation., Conclusion: In this murine model of AAA, progressive dilation to development of true AAA was only accomplished when IL-6 signaling upregulated STAT3 activity to effect accumulation of proteolytically-active macrophages. This pathway warrants further investigation to identify potential therapeutic avenues to abrogate growth of small AAA.

Background Content: Diffuse gliomas of the spine (DGS)-consisting of intradural intramedullary glioblastoma, astrocytoma, and oligodendroglioma-are exceedingly rare tumors that account for about 2% of primary spinal cord tumors. Much is unknown about their optimal treatment regimen due to a relative lack of clinical outcome data., Purpose: To provide an updated analysis on treatment and outcomes in DGS., Study Design/setting: Observational cohort study using The National Cancer Database (NCDB), a multicenter prospectively collected oncology outcomes database. A systematic literature review was also performed to compare the resulting data to previous series., Patient Sample: Patients with histologically confirmed DGS from 2004 to 2018., Outcome Measures: Long-term overall survival and short-term 30/90-day postsurgical mortality, 30-day readmission, and prolonged hospital length of stay., Methods: Impact of extent of resection and adjuvant therapy on overall survival was evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression. Univariate and multivariate logistic regression was used to analyze covariables and their prognostic impact on short-term surgical outcomes., Results: Of the 747 cases that met inclusion criteria, there were 439 astrocytomas, 14 oligodendrogliomas, and 208 glioblastomas. Sixty percent (n=442) of patients received radiation, and 45% (n=324) received chemotherapy. Tumor histology significantly impacted survival; glioblastoma had the poorest survival (median survival time [MS]: 12.3 months), followed by astrocytoma (MS: 70.8 months) and oligodendroglioma (MS: 71.6 months) (p<.001). Gross total resection (GTR) independently conferred a survival benefit in patients with glioblastoma (hazard ratio [HR]: 0.194, p<0.001) and other WHO grade four tumors (HR: 0.223, p=.003). Adjuvant chemotherapy also improved survival in patients with glioblastoma (HR: 0.244, p=.007) and WHO grade four tumors (HR: 0.252, p<.001). Systematic literature review identified 14 prior studies with a combined DGS mortality rate of 1.3%, which is lower than the 4% real-world outcomes calculated from the NCDB. This difference may be explained by selection biases in previously published literature in which only centers with favorable outcomes publish their results., Conclusions: There remains a paucity of data regarding treatment paradigms and outcomes for DGS. Our analysis, the largest to date, demonstrates that GTR and adjuvant therapy independently improve survival for certain high-grade subgroups of DGS. This best-available data informs optimal management for such patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Fragile X syndrome is a neurodevelopmental disorder caused by the absence of the mRNA-binding protein fragile X messenger ribonucleoprotein (FMRP). Because FMRP is a highly pleiotropic protein controlling the expression of hundreds of genes, viral vector-mediated gene replacement therapy is viewed as a potential viable treatment to correct the fundamental underlying molecular pathology inherent in the disorder. Here, we studied the safety profile and therapeutic effects of a clinically relevant dose of a self-complementary adeno-associated viral (AAV) vector containing a major human brain isoform of FMRP after intrathecal injection into wild-type and fragile X-KO mice. Analysis of the cellular transduction in the brain indicated primarily neuronal transduction with relatively sparse glial expression, similar to endogenous FMRP expression in untreated wild-type mice. AAV vector-treated KO mice showed recovery from epileptic seizures, normalization of fear conditioning, reversal of slow-wave deficits as measured via electroencephalographic recordings, and restoration of abnormal circadian motor activity and sleep. Further assessment of vector efficacy by tracking and analyzing individual responses demonstrated correlations between the level and distribution of brain transduction and drug response. These preclinical findings further demonstrate the validity of AAV vector-mediated gene therapy for treating the most common genetic cause of cognitive impairment and autism in children.

Although postoperative physical therapy (PT) has long been considered essential to successful total knee arthroplasty (TKA) recovery, recent literature has suggested that unsupervised home exercise regimens may offer similar benefits to formal supervised sessions. We aimed to compare objectively measured physical function and subjective patient-reported outcomes (PROs) between primary TKA patients who received formal supervised physical therapy sessions and those who received unsupervised home exercise regimens after discharge. Six electronic databases were queried to identify randomized controlled trials comparing supervised physical therapy to unsupervised home exercise regimens in primary TKA patients after discharge. Outcomes of interest included change from baseline in objective measures (knee flexion range of motion (ROM), lower extremity strength, and aerobic capacity) and PROs (physical function and quality of life scores). These outcomes were subdivided into short-term (<6 months from surgery; closest data point to three months is used if multiple measurements were made in this time period) and long-term (≥6 months from surgery; closest data point to 12 months is used if multiple measurements were made in this time period) assessments. A total of 1,884 cases performed in 11 studies were included in this review. There were no significant differences between cohorts with regard to short-term knee flexion ROM (p = 0.7), lower extremity strength (p = 0.6), or patient-reported quality of life (p = 0.5), as well as long-term knee flexion ROM (p = 0.7), patient-reported quality of life (p = 0.2), or patient-reported physical outcome scores (p = 0.3). A small difference in short-term patient-reported physical outcomes was observed in favor of the supervised cohort (standardized mean difference (SMD): 0.3 (95% confidence interval (CI): 0.01, 0.6); I 2  = 82%; p = 0.04). Formal supervised physical therapy regimens do not confer clinically significant benefits over unsupervised home exercise regimens following primary TKA. The routine use of supervised physical therapy after discharge may not be warranted. Further study is needed to determine the subset of patients that may benefit from supervised care., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Chaudhry et al.)

Objective: To evaluate the posterior tilt angle (PTA) in predicting treatment failure after internal fixation of nondisplaced femoral neck fractures as graded by the Garden classification, which is based solely on anterior-posterior radiographic evaluation., Data Sources: A search was conducted of all published literature in the following databases from inception to December 20, 2021: PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov ., Study Selection: We included English-language randomized controlled trials, prospective and retrospective cohort studies that reported malunion/nonunion, avascular necrosis, fixation failure, or reoperations in patients with nondisplaced femoral neck fractures treated with internal fixation who were evaluated for PTA using either lateral radiograph or computed tomography., Data Extraction: All abstract, screening, and quality appraisal was conducted independently by 2 authors. Data from included studies were extracted manually and summarized. The Methodological Index for Non-Randomized Studies criteria was used for quality appraisal., Data Synthesis: Odds ratios with 95% confidence intervals were calculated for treatment failure, defined as nonunion/malunion, avascular necrosis, fixation failure, or reoperation, in cases involving preoperative PTA ≥20-degrees and <20-degrees. Statistical significance was set at P < 0.05., Results: Nondisplaced femoral neck fractures with PTA >20-degrees had a 24% rate of treatment failure compared with 12% for those <20-degrees [odds ratios, 3.21 (95% confidence intervals, 1.95-5.28); P < 0.001]., Conclusion: PTA is a predictor of treatment failure in nondisplaced femoral neck fractures treated with internal fixation. Nondisplaced femoral neck fractures with a PTA >20-degrees may warrant alternative treatment modalities., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Polycystic kidney disease (PKD) is an inherited disorder that results in large kidneys, numerous fluid-filled cysts, and ultimately end-stage kidney disease. PKD is either autosomal dominant caused by mutations in PKD1 or PKD2 genes or autosomal recessive caused by mutations in the PKHD1 or DZIP1L genes. While the genetic basis of PKD is known, the downstream molecular mechanisms and signaling pathways that lead to deregulation of proliferation, apoptosis, and differentiation are not completely understood. The Notch pathway plays critical roles during kidney development including directing differentiation of various progenitor cells, and aberrant Notch signaling results in gross alternations in cell fate. In the present study, we generated and studied transgenic mice that have overexpression of an intracellular fragment of mouse Notch1 ('NotchIC') in renin-expressing cells. Mice with overexpression of NotchIC in renin-expressing cells developed numerous fluid-filled cysts, enlarged kidneys, anemia, renal insufficiency, and early death. Cysts developed in both glomeruli and proximal tubules, had increased proliferation marks, and had increased levels of Myc. The present work implicates the Notch signaling pathway as a central player in PKD pathogenesis and suggests that the Notch-Myc axis may be an important target for therapeutic intervention., (© 2023 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Research Question: What is the relationship between oocyte donor characteristics and their pain perception, their expectation and experience of pain, and the interaction between pain and overall satisfaction with the donation process?, Design: Institutional Review Board approved, retrospective survey of commercial, US oocyte donors was emailed to recent donors recruited through Donor Egg Bank USA before 2020., Results: Of the 503 opened emails, 246 individuals responded (48.9%). Most donors ranked their pain between minimal and moderate at all time points analysed. Altruistically motivated donors and parous donors were less likely to experience unexpected levels of pain. A high proportion (93.9%) of donors reported being informed of the risk of pain. Those who recalled being informed of the risk of pain were less likely to report higher levels of pain than expected. Although 94.2% of donors reported having an average to positive experience overall, 92.3% (12 out of 13 donors) in the group reporting a negative overall experience said they felt more pain than expected., Conclusions: Donors were well informed about the risk of pain. Altruistically motivated donors and parous donors were less likely to experience unexpected levels of pain. Report of unexpected levels of pain was highly related to low donor satisfaction., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Although it is widely accepted that patients do better when evidence-based health care practices are used, there is less acknowledgment of the positive outcomes associated with evidence-based policy making. To address the need for high-quality evidence to inform mental health policies, Psychiatric Services has recently launched a new article format: the Policy Review. This review type defines a specific policy-relevant issue affecting behavioral health systems, describes current knowledge and limitations, and discusses policy implications. Reviews can focus on mental health policies or examine how other health or social policies affect people with mental illness or substance use disorders. This brief overview of the need for a policy review article type describes differences between evidence-based policy making and practices and looks at research approaches focused on evidence-based policy making, as well as legislative and other efforts to support it. Broad guidelines for potential submissions are also provided.

Historically, postoperative exercise and physical therapy (PT) have been viewed as crucial to a successful outcome following primary total hip arthroplasty (THA). This systematic review and meta-analysis aimed to assess differences in both short- and long-term objective and self-reported measures between primary THA patients with formal supervised physical therapy versus unsupervised home exercises after discharge. A search was conducted of six electronic databases from inception to December 14, 2020, for randomized controlled trials (RCTs) comparing changes from baseline in lower extremity strength (LES), aerobic capacity, and self-reported physical function and quality of life (QoL) between supervised and unsupervised physical therapy/exercise regimens following primary THA. Outcomes were separated into short-term (<6 months from surgery, closest to 3 months) and long-term (≥6 months from surgery, closest to 12 months) measures. Meta-analyses were performed when possible and reported in standardized mean differences (SMDs) with 95% confidence intervals (CI). Seven studies (N=398) were included for review. No significant differences were observed with regard to lower extremity strength (p=0.85), aerobic capacity (p=0.98), or short-term quality of life scores (p=0.18). Although patients in supervised physical therapy demonstrated improved short-term self-reported outcomes compared to those performing unsupervised exercises, this was represented by a small effect size (SMD 0.23 [95% CI, 0.02-0.44]; p=0.04). No differences were observed between groups regarding long-term lower extremity strength (p=0.24), physical outcome scores (p=0.37), or quality of life (p=0.14). The routine use of supervised physical therapy may not provide any clinically significant benefit over unsupervised exercises following primary THA. These results suggest that providers should reconsider the routine use of supervised physical therapy after discharge., Competing Interests: Zachary Wells - stock in Johnson & Johnson. Harpal Khanuja - paid consultant for Smith & Nephew, institutional support from Smith & Nephew, editorial/governing board of Journal of Arthroplasty, committee appointments for AAOS and AAHKS. Carl Deirmengian - paid consultant for Zimmer Biomet, stock options in Biostar Ventures and Trice Inc, research support from Zimmer Biomet, (Copyright © 2022, Chaudhry et al.)

Context: Current Endocrine Society guidelines recommend that transgender women taking spironolactone have their potassium levels checked every 3 months for the first year after initiating therapy and annually thereafter to monitor for hyperkalemia., Objective: The goal of this study was to assess the need for such frequent potassium monitoring and to investigate whether age plays a role in potassium abnormalities in transgender, gender diverse, and nonbinary (TGDNB) individuals taking spironolactone., Methods: Using EPIC-Clarity, a retrospective study of healthy, adult individuals with gender-identity disorder listed in their problem list and taking spironolactone was performed. We analyzed the incidence of hyperkalemia in this population. Data from June 2006 through November 2021 were obtained. Exclusion criteria included hypertension, renal failure, diabetes mellitus, heart failure, and medications that affect the renin-angiotensin-aldosterone system., Results: 318 healthy TGDNB individuals met our inclusion criteria. We identified 8/318 (2.5%) individuals with hyperkalemia on spironolactone. There was a significant difference in incidence of hyperkalemia events in those >45 years old and those ≤45 years old (8.9% vs 1.5%, P = .016)., Conclusion: Our data suggest the incidence of hyperkalemia in our TGDNB population is low, particularly in those ≤45 years old; however, this risk increases with age. These findings suggest practice guidelines may need to be adjusted to minimize unnecessary testing in the population ≤45 years old who are not plagued by comorbidities that affect potassium handling., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Training and retaining a competent public health workforce are challenging. Residency programs for new and transitioning professionals are effective in other fields but rare in governmental public health. The New to Public Health Residency Program is a residency program for professionals entering public health practice. On the basis of the Foundational Public Health Services model, the program was designed using adult learning principles and best practices from nurse residency programs. Content created by public health experts is delivered over 12 months through online course sessions that include interactive learning activities. Additional program components include monthly synchronous online discussions and support from a mentor. Residents apply their learning through implementation of an evidence-based practice project at their workplace. The program is accredited for continuing professional development contact hours. Agencies with limited resources to support new public health employees may find the New to Public Health Residency Program a vital training resource., Competing Interests: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To achieve effectiveness and reduce inequality in everyday cardiac rehabilitation, this study aims to compare individual patient characteristics along with completion rates to traditional and evolving modes of delivery in cardiac rehabilitation., Method: Patients were included from the UK National Audit of Cardiac Rehabilitation (NACR) database. All patients with coronary heart disease (≥18 years) between the 1st of January 2014 to 31st of December 2019 that started core rehabilitation with a recorded mode of cardiac rehabilitation delivery were eligible. Modes of delivery were divided into: centre-based, home-based, and hybrid. Logistic regression models were used to investigate association between modes of delivery and completion adjusting for patient demographics., Result: In total 182,722 patients had mode of delivery recorded: 72.8% centre-based, 8.3% home-based and 18.9% hybrid. The home-based mode in comparison to hybrid and centre-based had significantly higher rates of females, single, white, and unemployed patients (p < 0.001). There was a higher proportion of cardiovascular risk factors in home-based than the other modes (p < 0.001). There was a reduced likelihood of completing home-based cardiac rehabilitation compared to centre-based with an odds ratio of 0.66, (95% CI: 0.48 to 0.91) but no significant difference between hybrid and centre-based modes (odds ratio, 1.18; 95% CI 0.92 to 1.51)., Conclusions: From large real-world data, home-based modes of delivery appear to have significantly lower levels of completion than centre-based modes. Cardiac rehabilitation programs offering home-based and hybrid delivery modes need to be structured to ensure adequacy of completion., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The gastrointestinal hormone glucagon-like peptide-1 (GLP-1) is increased after sleeve gastrectomy (SG). Rat and clinical studies support, while mouse studies refute, a role for GLP-1R signaling after SG. Therefore, we developed a global GLP-1R knockout (KO) rat to test the hypothesis that a functional GLP-1R is critical to induce weight loss and metabolic disease improvement after SG., Methodology: A 4 bp deletion was created in exon 2 of the GLP-1R gene on a Lewis strain background to create a global GLP-1R KO rat. KO and Lewis rats were placed on a high-fat or low-fat diet and phenotyped followed by SG or Sham surgery and assessed for the effect of GLP-1R KO on surgical and metabolic efficacy., Results: Loss of the GLP-1R created an obesity-prone rodent without changes in energy expenditure. Both male and female KO rats had significantly greater insulin concentrations after an oral glucose gavage, augmented by a high-fat diet, compared to Lewis rats despite similar glucose concentrations. GLP-1R KO caused hepatomegaly and increased triglyceride deposition compared to Lewis rats. We found no difference between SG GLP-1R KO and Lewis groups when considering efficacy on body weight, glucose tolerance, and a robustly preserved improvement in fatty liver disease., Conclusions: Loss of the GLP-1R in rats resulted in increased adiposity, insulin resistance, and severe steatosis. A functional GLP-1R is not critical to the metabolic efficacy of SG in Lewis rats, similar to mouse studies, but importantly including steatosis, supporting a GLP-1R-independent mechanism for the improvement in fatty liver disease after SG., (© 2022. The Society for Surgery of the Alimentary Tract.)

Background: Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes., Study Design and Methods: Dual-center, retrospective cohort study conducted over 6 months (March-August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 h were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of - 3 to - 5 or Riker Sedation-Agitation Scale of 1-3. To examine impact of early sedation depth on hospital mortality (primary outcome), we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days., Results: 391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation (p < 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65-7.17; p < 0.01). These results were stable in the subgroup of patients with COVID-19., Conclusions: The management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach., (© 2022. The Author(s).)

Question: In patients with previously diagnosed glioblastoma who are suspected of experiencing progression, does repeat cytoreductive surgery improve progression free survival or overall survival compared to alternative interventions?, Target Population: These recommendations apply to adults with previously diagnosed glioblastoma who are suspected of experiencing progression of the neoplastic process and are amenable to surgical resection., Recommendation: Level II: Repeat cytoreductive surgery is recommended in progressive glioblastoma patients to improve overall survival., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The Institute of Medicine best practice recommendation to review guidelines every 5 years is followed by the Congress of Neurological Surgeons Guidelines Committee. The aim of this work was to provide an updated literature review and evidence-based recommendations on the topic of diagnosis and treatment of patients with progressive glioblastoma (pGBM)., Objective: To review the literature published since the last guidelines on pGBM dated 2014, with literature search ending in June 2012., Methods: PubMed, Embase, and Cochrane were searched for the period July 1, 2012, to March 31, 2019, using search terms and search strategies to identify pertinent abstracts. These were then screened using published exclusion/inclusion criteria to identify full-text review articles. Evidence tables were constructed using data derived from full-text reviews and recommendations made from the evidence derived., Results: From the total 8786 abstracts identified by the search, 237 full-text articles met inclusion/exclusion criteria and were included in this update. Two new level II recommendations derived from this work. For the diagnosis of patients with GBM, the use of diffusion-weighted images is recommended to be included in the magnetic resonance images with and without contrast used for surveillance to detect pGBM. For the treatment of patients with pGBM, repeat cytoreductive surgery is recommended to improve overall survival. An additional 21 level III recommendations were provided., Conclusion: Recent published literature provides new recommendations for the diagnosis and treatment of pGBM. The Central Nervous System Guidelines Committee will continue to pursue timely updates to further improve the care of patients with diagnosis.https://www.cns.org/guidelines/browse-guidelines-detail/guidelines-management-of-progressive-glioblastoma., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background: Access to affordable and effective menstrual hygiene products (MHP) is critical to the menstrual health of adolescent girls and young women (AGYW). In this mixed-methods analysis, we use data from a programme delivering comprehensive sexual and reproductive health (SRH) services to describe access to MHP and how COVID-19-related closures affected access to MHP; we use qualitative data to understand AGYW's experience accessing products during the study., Methods: Between September 2019-January 2021, we used data routinely collected from ten Yathu Yathu hubs offering community-based, peer-led SRH services to adolescents and young people aged 15-24. Hubs offered free MHP (primarily disposable pads) as a service. To incentivise service access, a "loyalty" card system was embedded within Yathu Yathu, allowing individuals to gain points for services accessed and redeem rewards using these points. Branded pads, tampons and reusable pads were among available rewards. We describe access to service pads and to reward MHP, and use logistic regression to investigate factors associated with accessing pads and reward products before (Sept 2019-March 2020) and after (July 2020-Jan 2021) COVID-19-related closures. Focus group discussions explored accessibility of offering MHP through hubs., Results: Between September 2019-January 2021, 6374 AGYW made 34,116 hub visits to access an SRH service and/or redeem a reward. At 30% of these visits, AGYW accessed any MHP. Before COVID19-closures, an average of 17% of monthly visits were for freely-available disposable pads compared to 34% after hubs reopened (p < 0.001). Results were similar for reward visits. Overall, 63% of 6374 AGYW collected pads as a service at least once. Prior to COVID19-closures, AGYW aged 18-24 were more likely to access service pads than adolescents (15-17-years). After reopening, access was lower among older AGYW. Prior to hub closures, uptake of reward MHP was higher among AGYW with some secondary education but not after reopening. Discussions revealed that, for adolescents aged 15-19, COVID-19-related hub closures required reverting to using ineffective materials to manage menstruation., Conclusion: Availability of MHP through Yathu Yathu provided a large number of AGYW with access to these products. Hubs seemed particularly important for adolescent girls. Community-based, peer-led hubs should be considered as spaces to provide AGYW access to affordable and effective MHP., (© 2022. The Author(s).)

Understanding how urbanization alters functional interactions among pollinators and plants is critically important given increasing anthropogenic land use and declines in pollinator populations. Pollinators often exhibit short-term specialization and visit plants of the same species during one foraging trip. This facilitates plant receipt of conspecific pollen-pollen on a pollinator that is the same species as the plant on which the pollinator was foraging. Conspecific pollen receipt facilitates plant reproductive success and is thus important to plant and pollinator persistence. We investigated how urbanization affects short-term specialization of insect pollinators by examining pollen loads on insects' bodies and identifying the number and species of pollen grains on insects caught in urban habitat fragments and natural areas. We assessed possible drivers of differences between urban and natural areas, including frequency dependence in foraging, species richness and diversity of the plant and pollinator communities, floral abundance, and the presence of invasive plant species. Pollinators were more specialized in urban fragments than in natural areas, despite no differences in the species richness of plant communities across site types. These differences were likely driven by higher specialization of common pollinators, which were more abundant in urban sites. In addition, pollinators preferred to forage on invasive plants at urban sites and native plants at natural sites. Our findings reveal indirect effects of urbanization on pollinator fidelity to individual plant species and have implications for the maintenance of plant species diversity in small habitat fragments. Higher preference of pollinators for invasive plants at urban sites suggests that native species may receive fewer visits by pollinators. Therefore, native plant species diversity may decline in urban sites without continued augmentation of urban flora or removal of invasive species., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Competing Interests: Competing interests: none declared