Cerebellar Mutism Syndrome and Dentato-Thalamo-Cortical Tract Disruption in Diffusion Tractography Following Surgery for Medulloblastoma.

Background Cerebellar mutism syndrome (CMS), a complication following medulloblastoma surgery, has been linked to dentato-thalamo-cortical tract (DTCT) injury; the association of the degree of DTCT injury with severity of CMS-related symptoms has not been investigated. Purpose To investigate the association between severity of CMS-related symptoms and degree and patterns of DTCT injury with use of diffusion tensor imaging (DTI), and if laterality of injury influences neurologic symptoms. Materials and Methods This retrospective case-control study used prospectively collected clinical and DTI data on patients with medulloblastoma enrolled in a clinical trial (between July 2016 and February 2020) and healthy controls (between April and November 2017), matched with the age range of the participants with medulloblastoma. CMS was divided into types 1 (CMS1) and 2 (CMS2). Multivariable logistic regression was used to investigate the relationship between CMS likelihood and DTCT injury. Results Overall, 82 participants with medulloblastoma (mean age, 11.0 years ± 5.2 [SD]; 53 male) and 35 healthy controls (mean age, 18.0 years ± 3.06; 18 female) were included. In participants with medulloblastoma, DTCT was absent bilaterally (AB), absent on the right side (AR), absent on the left side (AL), or present bilaterally (PB), while it was PB in all healthy controls. Odds of having CMS were associated with higher degree of DTCT damage (AB, odds ratio = 272.7 [95% CI: 269.68, 275.75; P < .001]; AR, odds ratio = 14.40 [95% CI: 2.84, 101.48; P < .001]; and AL, odds ratio = 8.55 [95% CI: 1.15, 74.14; P < .001). Left (coefficient = -0.07, χ2 = 12.4, P < .001) and right (coefficient = -0.15, χ2 = 33.82, P < .001) DTCT volumes were negatively associated with the odds of CMS. More participants with medulloblastoma with AB showed CMS1; unilateral DTCT absence prevailed in CMS2. Lower DTCT volumes correlated with more severe ataxia. Unilateral DTCT injury caused ipsilateral dysmetria; AB caused symmetric dysmetria. PB indicated better neurologic outcome. Conclusion The severity of CMS-associated mutism, ataxia, and dysmetria was associated with DTCT damage severity. DTCT damage patterns differed between CMS1 and CMS2. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Dorigatti Soldatelli and Ertl-Wagner in this issue.

Methods for Silk Property Analyses across Structural Hierarchies and Scales.

Silk from silkworms and spiders is an exceptionally important natural material, inspiring a range of new products and applications due to its high strength, elasticity, and toughness at low density, as well as its unique conductive and optical properties. Transgenic and recombinant technologies offer great promise for the scaled-up production of new silkworm- and spider-silk-inspired fibres. However, despite considerable effort, producing an artificial silk that recaptures the physico-chemical properties of naturally spun silk has thus far proven elusive. The mechanical, biochemical, and other properties of pre-and post-development fibres accordingly should be determined across scales and structural hierarchies whenever feasible. We have herein reviewed and made recommendations on some of those practices for measuring the bulk fibre properties; skin-core structures; and the primary, secondary, and tertiary structures of silk proteins and the properties of dopes and their proteins. We thereupon examine emerging methodologies and make assessments on how they might be utilized to realize the goal of developing high quality bio-inspired fibres.

Unified rhombic lip origins of group 3 and group 4 medulloblastoma.

Medulloblastoma, a malignant childhood cerebellar tumour, segregates molecularly into biologically distinct subgroups, suggesting that a personalized approach to therapy would be beneficial1. Mouse modelling and cross-species genomics have provided increasing evidence of discrete, subgroup-specific developmental origins2. However, the anatomical and cellular complexity of developing human tissues3-particularly within the rhombic lip germinal zone, which produces all glutamatergic neuronal lineages before internalization into the cerebellar nodulus-makes it difficult to validate previous inferences that were derived from studies in mice. Here we use multi-omics to resolve the origins of medulloblastoma subgroups in the developing human cerebellum. Molecular signatures encoded within a human rhombic-lip-derived lineage trajectory aligned with photoreceptor and unipolar brush cell expression profiles that are maintained in group 3 and group 4 medulloblastoma, suggesting a convergent basis. A systematic diagnostic-imaging review of a prospective institutional cohort localized the putative anatomical origins of group 3 and group 4 tumours to the nodulus. Our results connect the molecular and phenotypic features of clinically challenging medulloblastoma subgroups to their unified beginnings in the rhombic lip in the early stages of human development.

Preoperative Management of Medications for Rheumatologic and HIV Diseases: Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement.

Perioperative medical management is challenging because of the rising complexity of patients presenting for surgical procedures. A key part of preoperative optimization is appropriate management of long-term medications, yet guidelines and consensus statements for perioperative medication management are lacking. Available resources use recommendations derived from individual studies and do not include a multidisciplinary focus on formal consensus. The Society for Perioperative Assessment and Quality Improvement identified a lack of authoritative clinical guidance as an opportunity to use its multidisciplinary membership to improve evidence-based perioperative care. The Society for Perioperative Assessment and Quality Improvement seeks to provide guidance on perioperative medication management that synthesizes available literature with expert consensus. The aim of this consensus statement is to provide practical guidance on the preoperative management of immunosuppressive, biologic, antiretroviral, and anti-inflammatory medications. A panel of experts including hospitalists, anesthesiologists, internal medicine physicians, infectious disease specialists, and rheumatologists was appointed to identify the common medications in each of these categories. The authors then used a modified Delphi process to critically review the literature and to generate consensus recommendations.

Coping with systemic lupus erythematosus in patients' words.

OBJECTIVE: Previous research on coping strategies of patients with SLE showed that there are no absolute adaptive or maladaptive strategies and that the range of potential coping strategies is large and heterogeneous. In this paper, we aimed to identify, in a large sample of patients with SLE (N=3222), the most frequent words used by patients to describe their coping strategies, to group them into significant themes and to test their possible association with specific patient characteristics. METHODS: Our analyses were based on the data set of the European survey 'Living with Lupus in 2020' (N=3222). Through the T-LAB software, we analysed the answers that adult participants gave to an open-ended question about how they cope with the disease. We identified the most frequent words, and with hierarchical cluster analysis we grouped them into semantic clusters (ie, themes) that were characterised by specific patterns of words. Finally, we tested the possible association between clusters and illustrative variables (sociodemographics, disease characteristics, quality of life). RESULTS: Five coping strategies were identified, each of them constituting an important percentage of the total word occurrences: positive attitude (22.58%), social support (25.46%), medical treatments (10.77%), healthy habits (20.74%) and avoid stress (20.45%). Each strategy was statistically associated with specific patient characteristics, such as age and organ involvement. CONCLUSIONS: Learning to adapt to a lifetime of having SLE may require replacing old coping strategies with more effective ones. Investigating patients' coping strategies in relation to different patient characteristics represents a useful starting point for developing more targeted and efficacious interventions.

Preoperative Management of Medications for Neurologic Diseases: Society for Perioperative Assessment and Quality Improvement Consensus Statement.

Neurologic diseases are prevalent in patients undergoing invasive procedures; yet, no societal guidelines exist as to best practice in management of perioperative medications prescribed to treat these disorders. The Society for Perioperative Assessment and Quality Improvement tasked experts in internal medicine, anesthesiology, perioperative medicine, and neurology to provide evidence-based recommendations for preoperative management of these medications. The aim of this review is not only to provide consensus recommendations for preoperative management of patients on medications for neurologic disorders, but also to serve as an educational guide to perioperative clinicians. While, in general, medications for neurologic disorders should be continued preoperatively, an individualized approach may be needed in certain situations (eg, holding anticonvulsants on day of surgery if electroencephalographic mapping is planned during epilepsy surgery). Pertinent interactions with commonly used drugs in anesthesia practice, as well as considerations for targeted laboratory testing or perioperative drug substitutions, are addressed as well.

Preoperative Management of Medications for Psychiatric Diseases: Society for Perioperative Assessment and Quality Improvement Consensus Statement.

There is a lack of guidelines for preoperative management of psychiatric medications leading to variation in care and the potential for perioperative complications and surgical procedure cancellations on the day of surgery. The Society for Perioperative Assessment and Quality Improvement identified preoperative psychiatric medication management as an area in which consensus could improve patient care. The aim of this consensus statement is to provide recommendations to clinicians regarding preoperative psychiatric medication management. Several categories of drugs were identified including antidepressants, mood stabilizers, anxiolytics, antipsychotics, and attention deficit hyperactivity disorder medications. Literature searches and review of primary and secondary data sources were performed for each medication/medication class. We used a modified Delphi process to develop consensus recommendations for preoperative management of individual medications in each of these drug categories. While most medications should be continued perioperatively to avoid risk of relapse of the psychiatric condition, adjustments may need to be made on a case-by-case basis for certain drugs.

"If I Get Cured, My Whole Quality of Life Will Change": Patients' Anticipated and Actualized Benefits Following Cure from Chronic Hepatitis C.

BACKGROUND: Patients' motivations for undergoing direct-acting antiviral (DAA) therapy for chronic hepatitis C may include anticipation of treatment benefits not well described in the literature. AIMS: Evaluate patients' anticipated and actualized improvements in several domains of functioning before and after viral cure. METHODS: Pre-post-study utilizing in-depth interviews with 28 patients prior to, and several months after, DAA therapy. Interviews were audio-recorded, transcribed, coded, and analyzed by two qualitative experts. RESULTS: Patients had a median age of 54 years, 43% were male, 57% white, 25% had cirrhosis, and 71% were treated with sofosbuvir/ledipasvir. Pre-treatment, patients hoped for improvements in several domains including psychological, emotional, physical, social, and occupational functioning. After viral cure, increased energy and less fear of transmission were pathways to better quality of life. Psychological and emotional improvements positively affected physical, social, and occupational functioning. Social improvements were due to better mood and motivation, fewer symptoms, and reduced fear of stigma and transmission. Occupational benefits were linked to increased stamina, self-confidence, and less pain, anxiety, and stigma. Reduced fear of stigma had a pervasive impact on all life improvements after cure. Patient characteristics such as the presence of cirrhosis or psychiatric issues influence treatment motivations. Qualitative data correspond with change in pre-post-survey scores. CONCLUSIONS: Tremendous hope is placed on the ability of DAA therapy to bring about substantial improvements in life functioning after viral cure. Highly interconnected effects on quality of life worked synergistically through improved physical and psychological well-being. Stakeholders should appreciate the multi-dimensional benefits that viral eradication bestows upon individuals and society.

The Structure of Liquid and Glassy Carbamazepine.

To enhance the solubility of orally administered pharmaceuticals, liquid capsules or amorphous tablets are often preferred over crystalline drug products. However, little is known regarding the variation in bonding mechanisms between pharmaceutical molecules in their different disordered forms. In this study, liquid and melt-quenched glassy carbamazepine have been studied using high energy X-ray diffraction and modeled using Empirical Potential Structure Refinement. The results show significant structural differences between the liquid and glassy states. The liquid shows a wide range of structures; from isolated molecules, to aromatic ring correlations and NH-O hydrogen bonding. Upon quenching from the liquid to the glass the number of hydrogen bonds per molecule increases by ~50% at the expense of a ~30% decrease in the close contact (non-bonded) carbon-carbon interactions between aromatic rings. During the cooling process, there is an increase in both singly and doubly hydrogen-bonded adjacent molecules. Although hydrogen-bonded dimers found in the crystalline states persist in the glassy state, the absence of a crystalline lattice also allows small, hydrogen-bonded NH-O trimers and tetramers to form. This proposed model for the structure of glassy carbamazepine is consistent with the results from vibrational spectroscopy and nuclear magnetic resonance.

Living with systemic lupus erythematosus in 2020: a European patient survey.

OBJECTIVE: The aim of this study was to analyse the 2020 burden of Systemic Lupus Erythematosus (SLE) in Europe, from the patients' perspective. METHODS: In May 2020, Lupus Europe, the European umbrella patient association for SLE, designed and disseminated a multilingual anonymous online survey to individuals with a self-reported physician's diagnosis of SLE living in Europe. RESULTS: Data from 4375 SLE survey respondents (95.9% women, median age: 45 (IQR: 36-54) years, 70.7% Caucasians) from 35 European countries were analysed. The median age at SLE diagnosis was 30 years (IQR: 22-40) and the median diagnosis delay was 2 years (IQR: 0-6). The most commonly affected organ-systems included the joints (81.8%) and skin (59.4%), with renal involvement in 30%. Another diagnosis was given before that of SLE in 45.0%, including psychological/mental disorders in 9.1% and fibromyalgia in 5.9%. The median number of symptoms reported was 9 (IQR: 6-11) out of 21, with fatigue most common (85.3%) and most bothersome. The median number of SLE-related medications was 5 (IQR: 3-7), including antimalarials (75%), oral glucocorticoids (52.4%), immunosuppressants (39.8%) and biologics (10.9%). Respondents reported significant impact over their studies, career and emotional/sexual life in 50.7%, 57.9% and 38.2%, respectively. Appropriate access to care was highly variable across countries and care component. CONCLUSION: This survey underlines the 2020 burden and strong heterogeneity in the care of SLE across Europe, from the patient's perspective. Altogether, these data may prove crucial to physicians, patients and policy-makers to improve the diagnosis and management of this rare and complex disease.

Automated Frailty Screening At-Scale for Pre-Operative Risk Stratification Using the Electronic Frailty Index.

BACKGROUND: Frailty is associated with numerous post-operative adverse outcomes in older adults. Current pre-operative frailty screening tools require additional data collection or objective assessments, adding expense and limiting large-scale implementation. OBJECTIVE: To evaluate the association of an automated measure of frailty integrated within the Electronic Health Record (EHR) with post-operative outcomes for nonemergency surgeries. DESIGN: Retrospective cohort study. SETTING: Academic Medical Center. PARTICIPANTS: Patients 65 years or older that underwent nonemergency surgery with an inpatient stay 24 hours or more between October 8th, 2017 and June 1st, 2019. EXPOSURES: Frailty as measured by a 54-item electronic frailty index (eFI). OUTCOMES AND MEASUREMENTS: Inpatient length of stay, requirements for post-acute care, 30-day readmission, and 6-month all-cause mortality. RESULTS: Of 4,831 unique patients (2,281 females (47.3%); mean (SD) age, 73.2 (5.9) years), 4,143 (85.7%) had sufficient EHR data to calculate the eFI, with 15.1% categorized as frail (eFI > 0.21) and 50.9% pre-frail (0.10 < eFI ≤ 0.21). For all outcomes, there was a generally a gradation of risk with higher eFI scores. For example, adjusting for age, sex, race/ethnicity, and American Society of Anesthesiologists class, and accounting for variability by service line, patients identified as frail based on the eFI, compared to fit patients, had greater needs for post-acute care (odds ratio (OR) = 1.68; 95% confidence interval (CI) = 1.36-2.08), higher rates of 30-day readmission (hazard ratio (HR) = 2.46; 95%CI = 1.72-3.52) and higher all-cause mortality (HR = 2.86; 95%CI = 1.84-4.44) over 6 months' follow-up. CONCLUSIONS: The eFI, an automated digital marker for frailty integrated within the EHR, can facilitate pre-operative frailty screening at scale.

Launching a Geriatric Surgery Center: Recommendations from the Society for Perioperative Assessment and Quality Improvement.

To prepare for the increasing numbers of older adults undergoing surgery, the American College of Surgeons (ACS) has recently launched the Geriatric Surgery Verification Program with the goal of encouraging the creation of centers of geriatric surgery. Meanwhile, the Society for Perioperative Assessment and Quality Improvement (SPAQI) has published recommendations for the preoperative management of frailty, which state that teams should actively screen for frailty before surgery and that pathways, including geriatric comanagement, shared decision-making, and multimodal prehabilitation, should be embedded in routine care to help improve patient outcomes. Both SPAQI and the ACS advocate for a multidisciplinary approach to improve the value of care for older adults undergoing surgery. However, the best way to implement geriatric services in the surgical setting is yet to be determined. In this statement, we will describe the SPAQI recommendations for launching a geriatric surgery center and the process by which its value should be assessed over time.

Common neurodegenerative disorders in the perioperative setting: Recommendations for screening from the Society for Perioperative Assessment and Quality Improvement (SPAQI).

Aging is associated with normal and abnormal brain and cognitive changes. Due to the expected increase in older adults requiring surgery, perioperative clinicians will be increasingly encountering patients with neurodegenerative disease. To help perioperative clinicians understand signs of abnormal behaviors that may mark an undiagnosed neurodegenerative disorder and alert additional patient monitoring, The Society for Perioperative Assessment and Quality Improvement (SPAQI) worked with experts in dementia, neuropsychology, geriatric medicine, neurology, and anesthesiology to provide a summary of cognitive and behavioral considerations for patients with common neurodegenerative disorders being evaluated at preoperative centers. Patients with neurodegenerative disorders are at high risk for delirium due to known neurochemical disruptions, medication interactions, associated frailty, or vascular risk profiles presenting risk for repeat strokes. We provide basic information on the expected cognitive changes with aging, most common neurodegenerative disorders, a list of behavioral features and considerations to help differentiate neurodegenerative disorders. Finally, we propose screening recommendations intended for a multidisciplinary team in the perioperative setting.

Organisational factors affecting performance in delivering influenza vaccination to staff in NHS Acute Hospital Trusts in England: A qualitative study.

Health care workers are a priority group for seasonal influenza vaccination, which is recommended by the World Health Organisation. There is a wide variation in uptake between and within countries. England has achieved 69.5% of health care workers vaccinated overall in 2017/18 across NHS acute and community health care settings, but it varies between Trusts from 50% to over 92.3%. While attitudinal factors have been well researched, there is limited evidence on organisational factors associated with high uptake. In England, most NHS Trusts are now implementing a similar range of interventions as part of their flu programme, and it remains unclear why performance remains so variable. This qualitative study is the first to explore reasons for this variation and provide recommendations for lower performing Trusts on how to improve. Fifty-seven interviews of managers and vaccinators were conducted in nine hospitals with flu vaccination uptake ranging from just over 55% to above 90%. Our study found that while Trusts deployed a wide range of both demand generating and supply interventions to increase uptake, there were marked differences in the organisational and delivery models utilised. Our study suggests that organisational culture was possibly the most important ingredient when trying to differentiate between high and low performing Trusts. We found that a positive culture aimed at fostering continuous improvement and favouring non-coercion on balance yielded more adherence from staff. Where influenza vaccination was embedded in the organisation wellbeing strategy, rather than executed as a siloed seasonal programme, this tended to foster good performance. Improving performance of influenza vaccination in health care workers will involve not only deploying the right interventions, and following "best practices". It will require the adaptation of flu progamme delivery strategies to the organisation context, and embedding vaccination into the organisational culture, thus supporting the normalisation of yearly vaccination.

Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement on Perioperative Smoking Cessation.

Smokers are at increased risk for surgical complications. Despite the known benefits of smoking cessation, many perioperative health care providers do not routinely provide smoking cessation interventions. The variation in delivery of perioperative smoking cessation interventions may be due to limited high-level evidence for whether smoking cessation interventions used in the general population are effective and feasible in the surgical population, as well as the challenges and barriers to implementation of interventions. Yet smoking is a potentially modifiable risk factor for improving short- and long-term patient outcomes. The purpose of the Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement on Perioperative Smoking Cessation is to present recommendations based on current scientific evidence in surgical patients. These statements address questions regarding the timing and intensity of interventions, roles of perioperative health care providers, and behavioral and pharmacological interventions. Barriers and strategies to overcome challenges surrounding implementation of interventions and future areas of research are identified. These statements are based on the current state of knowledge and its interpretation by a multidisciplinary group of experts at the time of publication.

Using Time-Driven Activity-Based Costing to Demonstrate Value in Perioperative Care: Recommendations and Review from the Society for Perioperative Assessment and Quality Improvement (SPAQI).

A shift in healthcare payment models from volume toward value-based incentives will require deliberate input into systems development from both perioperative clinicians and administrators to ensure appropriate recognition of the value of all services provided-particularly ones that are not reimbursable in current fee-for-service payment models. Time-driven activity-based costing (TDABC) methodology identifies cost drivers and reduces inaccurate costing based on siloed budgets. Inaccurate costing also results from the fact that current costing methods use charges and there has been tremendous cost shifting throughout health care. High cost, high variability processes can be identified for process improvement. As payment models inevitably evolve towards value-based metrics, it will be critical to knowledgably participate in the coordination of these changes. This document provides 8 practical Recommendations from the Society for Perioperative Assessment and Quality Improvement (SPAQI) aimed at outlining the principles of TDABC, creating process maps for patient workflows, understanding payment structures, establishing physician alignment across service lines to create integrated practice units to facilitate development of evidence-based pathways for specific patient risk groups, establishing consistent care delivery, minimizing variability between physicians and departments, utilizing data analytics and information technology tools to track progress and obtain actionable data, and using TDABC to create costing transparency.

Preoperative Sleep Questionnaires Identify Medical Emergency Team Activation in Older Adults.

Patients with obstructive sleep apnea (OSA) have increased postoperative complications that are important for patient safety and healthcare utilization. Questionnaires help identify patients at risk for OSA; however, among older adults who preoperatively self-administered OSA questionnaires, the frequency of postoperative Medical Emergency Team Activation (META), rapid response, code blue, code stroke, is unknown. OBJECTIVES: Identify whether having OSA questionnaires completed by patients is feasible in the preoperative clinic. Determine the frequency of META among older patients at risk for OSA. DESIGN AND INTERVENTION: Cohort of prospective patients independently completed 2 OSA questionnaires in a preoperative clinic, STOP-Bang (SB) and ISNORED (IS). Observers blinded to questionnaire responses recorded incidence of META. SETTING AND PARTICIPANTS: Of the 898 consecutive patients approached in the preoperative assessment clinic and surgical navigation center, 575 (64%) consented and completed the questionnaires in <5 minutes and were included in the analysis. MEASURES: Sleep questionnaire responses and frequency of inpatient postoperative META. RESULTS: With an affirmative response to ≥3 questions on either questionnaire, 65% of patients enrolled were at risk for OSA. Of these, 3.1% sustained an META. In patients at risk for OSA, META occurred in 7.6% (SB+) and 7.2% (IS+) vs 2.5% (SB+) and 1.7% (IS+) for low risk. METAs were disproportionately higher among patients aged ≥65 years (6.3% vs 1.7%; P < .018), American Society of Anesthesiologists (ASA) physical status class ≥3, and IS+. All patients with META positively answered ≥3 of 15 components of the 2 questionnaires. CONCLUSIONS/IMPLICATIONS: Preoperative, self-administration of SB and IS questionnaires is feasible. Overall, 65% of those with affirmative responses to ≥3 questions were at risk for OSA and associated with a disproportionate number of postoperative META in older patients. Additionally, risk of OSA identified by preoperative sleep questionnaires was associated with postoperative META among older adults. Use of clinical tools and OSA questionnaires may improve preoperative identification of META in this population.

Measurement of Projections Between Dentate Nucleus and Contralateral Frontal Cortex in Human Brain Via Diffusion Tensor Tractography.

We propose a probabilistic fiber-tracking scheme to reconstruct the fiber tracts between the dentate nucleus (DN) in the cerebellum and the entire contralateral cerebral frontal cortex in the human brain. We assessed diffusion tensor imaging (DTI) data from 39 healthy controls. The connection fibers between the DN and contralateral frontal cortex of all subjects were successfully reconstructed and studied. We demonstrated that multi-fiber probabilistic models must be used to resolve the challenge of crossing fibers. We also demonstrated that the entire pathway can be reconstructed without using any synaptic regions of interest along the path and that the reconstructed tracts connected the ipsilateral superior cerebellar peduncle, contralateral red nucleus, and ventral lateral and ventral anterior nuclei of thalamus in the path traveling to the contralateral frontal cortex. The fibers in the pathway projected into all areas of the contralateral frontal cortex but were predominantly located in the primary motor and premotor areas. A large portion of fibers terminated in the prefrontal cortex, which included dorsolateral prefrontal areas, anterior prefrontal areas, and the Broca language area. Our findings provide robust, reproducible, and direct DTI-based evidence that the DN through the efferent cerebellar pathway has considerable contribution to high-level executive functions of the human brain.