An injectable subunit vaccine containing Elongation Factor Tu and Heat Shock Protein 70 partially protects American bison from Mycoplasma bovis infection.

Mycoplasma bovis (M. bovis) is the etiologic agent of high mortality epizootics of chronic respiratory disease in American bison (Bison bison). Despite the severity of the disease, no efficacious commercial vaccines have been licensed for the prevention of M. bovis infection in bison. Elongation factor thermal unstable (EFTu) and Heat Shock Protein 70 (Hsp70, DnaK) are highly conserved, constitutively expressed proteins that have previously been shown to provide protection against M. bovis infection in cattle. To assess the suitability of EFTu and Hsp70 as vaccine antigens in bison, the immune response to and protection conferred by an injectable, adjuvanted subunit vaccine comprised of recombinantly expressed EFTu and Hsp70 was evaluated. Vaccinates developed robust antibody and cellular immune responses against both EFTu and Hsp70 antigens. To assess vaccine efficacy, unvaccinated control and vaccinated bison were experimentally challenged with bovine herpes virus-1 (BHV-1) 4 days prior to intranasal infection with M. bovis. Vaccinated bison displayed reductions in joint infection, lung bacterial loads, and lung lesions compared to unvaccinated controls. Together, these results showed that this subunit vaccine reduced clinical disease and bacterial dissemination from the lungs in M. bovis challenged bison and support the further development of protein subunit vaccines against M. bovis for use in bison.

Incidence of brain metastasis according to patient race and primary cancer origin: a systematic review.

PURPOSE: A systematic review was conducted to investigate differences in incidence and primary origin of synchronous brain metastasis (sBM) in varying racial groups with different primary cancers. METHODS: Adhering to PRISMA 2020 guidelines a search was conducted using PubMed and Ovid databases for publications from January 2000 to January 2023, with search terms including combinations of "brain metastasis," "race," "ethnicity," and "incidence." Three independent reviewers screened for inclusion criteria encompassing studies clearly reporting primary cancer sites, patient demographics including race, and synchronous BM (sBM) incidence. RESULTS: Of 806 articles, 10 studies comprised of mainly adult patients from the United States met final inclusion for data analysis. Higher sBM incidence proportions were observed in American Indian/Alaska native patients for primary breast (p < 0.001), colorectal (p = 0.015), and esophageal cancers (p = 0.024) as well as in Asian or Pacific islanders for primary stomach (p < 0.001), thyroid (p = 0.006), and lung/bronchus cancers (p < 0.001) yet higher proportions in White patients for malignant melanoma (p < 0.001). Compared to White patients, Black patients had higher sBM incidence likelihood in breast cancer (OR = 1.27, p = 0.01) but lower likelihood in renal (OR = 0.46, p < 0.001) and esophageal cancers (OR = 0.31, p = 0.005). American Indian/Alaska native patients had a higher sBM likelihood (OR = 3.78, p = 0.004) relative to White patients in esophageal cancer. CONCLUSIONS: These findings reveal several comparative racial differences in sBM incidence arising from different primary cancer origins, underscoring a need for further research to explain these variations. Identifying the factors contributing to these disparities holds the potential to promote greater equity in oncological care according to cancer type.

International Consensus Statements on Intraoperative Testing for Cochlear Implantation Surgery.

OBJECTIVES: A wide variety of intraoperative tests are available in cochlear implantation. However, no consensus exists on which tests constitute the minimum necessary battery. We assembled an international panel of clinical experts to develop, refine, and vote upon a set of core consensus statements. DESIGN: A literature review was used to identify intraoperative tests currently used in the field and draft a set of provisional statements. For statement evaluation and refinement, we used a modified Delphi consensus panel structure. Multiple interactive rounds of voting, evaluation, and feedback were conducted to achieve convergence. RESULTS: Twenty-nine provisional statements were included in the original draft. In the first voting round, consensus was reached on 15 statements. Of the 14 statements that did not reach consensus, 12 were revised based on feedback provided by the expert practitioners, and 2 were eliminated. In the second voting round, 10 of the 12 revised statements reached a consensus. The two statements which did not achieve consensus were further revised and subjected to a third voting round. However, both statements failed to achieve consensus in the third round. In addition, during the final revision, one more statement was decided to be deleted due to overlap with another modified statement. CONCLUSIONS: A final core set of 24 consensus statements was generated, covering wide areas of intraoperative testing during CI surgery. These statements may provide utility as evidence-based guidelines to improve quality and achieve uniformity of surgical practice.

Vestibular Schwannoma International Study of Active Surveillance Versus Stereotactic Radiosurgery: The VISAS Study.

PURPOSE: The present study assesses the safety and efficacy of stereotactic radiosurgery (SRS) versus observation for Koos grade 1 and 2 vestibular schwannoma (VS), benign tumors affecting hearing and neurological function. METHODS AND MATERIALS: This multicenter study analyzed data from Koos grade 1 and 2 VS patients managed with SRS (SRS group) or observation (observation group). Propensity score matching balanced patient demographics, tumor volume, and audiometry. Outcomes measured were tumor control, serviceable hearing preservation, and neurological outcomes. RESULTS: In 125 matched patients in each group with a 36-month median follow-up (P = .49), SRS yielded superior 5- and 10-year tumor control rates (99% CI, 97.1%-100%, and 91.9% CI, 79.4%-100%) versus observation (45.8% CI, 36.8%-57.2%, and 22% CI, 13.2%-36.7%; P < .001). Serviceable hearing preservation rates at 5 and 9 years were comparable (SRS 60.4% CI, 49.9%-73%, vs observation 51.4% CI, 41.3%-63.9%, and SRS 27% CI, 14.5%-50.5%, vs observation 30% CI, 17.2%-52.2%; P = .53). SRS were associated with lower odds of tinnitus (OR = 0.39, P = .01), vestibular dysfunction (OR = 0.11, P = .004), and any cranial nerve palsy (OR = 0.36, P = .003), with no change in cranial nerves 5 or 7 (P > .05). Composite endpoints of tumor progression and/or any of the previous outcomes showed significant lower odds associated with SRS compared with observation alone (P < .001). CONCLUSIONS: SRS management in matched cohorts of Koos grade 1 and 2 VS patients demonstrated superior tumor control, comparable hearing preservation rates, and significantly lower odds of experiencing neurological deficits. These findings delineate the safety and efficacy of SRS in the management of this patient population.

Neuromodulation of Eating Disorders: A Review of Underlying Neural Network Activity and Neuromodulatory Treatments.

Eating disorders are a group of psychiatric conditions that involve pathological relationships between patients and food. The most prolific of these disorders are anorexia nervosa, bulimia nervosa, and binge eating disorder. The current standard of care involves psychotherapy, pharmacotherapy, and the management of comorbid conditions, with nutritional rehabilitation reserved for severe cases of anorexia nervosa. Unfortunately, many patients often fail to respond, leaving a concerning treatment gap between the current and requisite treatments for eating disorders. To better understand the neurobiology underlying these eating disorders, investigations have been undertaken to characterize the activity of various neural networks, primarily those activated during tasks of executive inhibition, reward processing, and self-reference. Various neuromodulatory techniques have been proposed to stimulate these networks with the goal of improving patients' BMI and mental health. The aim of this review is to compile a comprehensive summarization of the current literature regarding the underlying neural connectivity of anorexia nervosa, bulimia nervosa, and binge eating disorder as well as the numerous neuromodulatory modalities that have been investigated. Importantly, we aimed to summarize the most significant clinical trials to date as well as to provide an updated assessment of the role of deep brain stimulation, summarizing numerous recently published clinical studies that have greatly contributed to the literature. In this review, we found therapeutic evidence for transcranial magnetic stimulation and transcranial direct current stimulation in treating individuals suffering from anorexia nervosa, bulimia nervosa, and binge eating disorder. We also found significant evidence for the role of deep brain stimulation, particularly as an escalatory therapy option for the those who failed standard therapy. Finally, we hope to provide promising directions for future clinical investigations.

Comparative Clinical Effectiveness and Cost-Effectiveness of the Cochlear Osia System and Baha Attract System in Patients with Conductive or Mixed Hearing Loss or Single-Sided Deafness.

The aim of this study was to evaluate the comparative clinical effectiveness and cost-utility of the active transcutaneous Osia® System versus the passive transcutaneous Baha® Attract System for patients with conductive or mixed hearing loss or single-sided deafness in an Australian healthcare setting. In the absence of direct comparative evidence, an indirect treatment comparison (ITC) of the clinical effectiveness and utility gains was needed. The ITC was informed by three studies identified through a systematic literature review. A Markov model was developed to evaluate the cost-utility of the Osia System. The literature review identified three studies suitable to inform an ITC: Mylanus et al. 2020 and Briggs et al. 2022 (Osia System) and den Besten et al. 2019 (Baha Attract System). The Osia System was found to be clinically superior to the Baha Attract System, across objective audiological outcomes resulting in a clinically meaningful utility benefit of 0.03 measured by the Health Utility Index with at least equivalent safety. In conclusion, the Osia System is more effective than the Baha Attract System, providing better hearing and health-related quality of life outcomes. In an Australian healthcare setting, the Osia System is cost-effective as demonstrated in a cost-utility analysis versus the Baha Attract System.

Transcriptomic profiles of Mannheimia haemolytica planktonic and biofilm associated cells.

Mannheimia haemolytica is the principal agent contributing to bovine respiratory disease and can form biofilms with increased resistance to antibiotic treatment and host immune defenses. To investigate the molecular mechanisms underlying M. haemolytica biofilm formation, transcriptomic analyses were performed with mRNAs sequenced from planktonic and biofilm cultures of pathogenic serotypes 1 (St 1; strain D153) and St 6 (strain D174), and St 2 (strain D35). The three M. haemolytica serotypes were cultured in two different media, Roswell Park Memorial Institute (RPMI) 1640 and brain heart infusion (BHI) to form the biofilms. Transcriptomic analyses revealed that the functions of the differentially expressed genes (DEGs) in biofilm associated cells were not significantly affected by the two media. A total of 476 to 662 DEGs were identified between biofilm associated cells and planktonic cells cultured under BHI medium. Functional analysis of the DEGs indicated that those genes were significantly enriched in translation and many biosynthetic processes. There were 234 DEGs identified in St 1 and 6, but not in St 2. The functions of the DEGs included structural constituents of ribosomes, transmembrane proton transportation, proton channels, and proton-transporting ATP synthase. Potentially, some of the DEGs identified in this study provide insight into the design of new M. haemolytica vaccine candidates.

Long-term antipsychotic use, orthostatic hypotension and falls in older adults with Alzheimer's disease.

PURPOSE: Antipsychotic use in Alzheimer disease (AD) is associated with adverse events and mortality. Whilst postulated to cause/exacerbate orthostatic hypotension (OH), the exact relationship between antipsychotic use and OH has never been explored in AD-a group who are particularly vulnerable to neuro-cardiovascular instability and adverse effects of medication on orthostatic blood pressure (BP) behaviour. METHODS: We analysed longitudinal data from an 18-month trial of Nilvadipine in mild-moderate AD. We assessed the effect of long-term antipsychotic use (for the entire 18-month study duration) on orthostatic BP phenotypes measured on eight occasions, in addition to the relationship between antipsychotic use, BP phenotypes and incident falls. RESULTS: Of 509 older adults with AD (aged 72.9 ± 8.3 years, 61.9% female), 10.6% (n = 54) were prescribed a long-term antipsychotic. Over 18 months, long-term antipsychotic use was associated with a greater likelihood of experiencing sit-to-stand OH (ssOH) (OR: 1.21; 1.05-1.38, p = 0.009) which persisted on covariate adjustment. Following adjustment for important clinical confounders, both antipsychotic use (IRR: 1.80, 1.11-2.92, p = 0.018) and ssOH (IRR: 1.44, 1.00-2.06, p = 0.048) were associated with a greater risk of falls/syncope over 18 months in older adults with mild-moderate AD. CONCLUSION: Even in mild-to-moderate AD, long-term antipsychotic use was associated with ssOH. Both antipsychotic use and ssOH were associated with a greater risk of incident falls/syncope over 18 months. Further attention to optimal prescribing interventions in this cohort is warranted and may involve screening older adults with AD prescribed antipsychotics for both orthostatic symptoms and falls.

Trans-mastoid plugging of superior semicircular canal dehiscence: long-term follow-up.

OBJECTIVE: To evaluate the long-term outcomes of trans-mastoid plugging of superior semicircular canal dehiscence (SSCD), focusing on complicated cases. METHODS: In this cohort study, we included all patients who underwent trans-mastoid plugging of SSCD between 2009 and 2019. We evaluated the symptoms (autophony, sound-/pressure-induced vertigo, disequilibrium, aural fullness and pulsatile tinnitus) before and 1 year after surgery in the medical records. We systematically assessed the current symptoms 6.2 ± 3 years postoperative (range 2.2-12.3 years) using questionnaires sent by post and validated by telephone interviews. We also documented any complications and the need for further procedures. We compared pure tone and speech audiometry before and 1 year after surgery. Finally, the degree of mastoid pneumatisation and mastoid tegmen anatomy were reviewed on preoperative CT scans. RESULTS: We included 24 ears in 23 patients. No complications were recorded, and none required a second procedure for SSCD. Following surgery, oscillopsia and Tullio phenomena resolved in all patients. Hyperacusis, autophony, and aural fullness were also settled in all patients except one. Balance impairment persisted to some degree in 35% of patients. No deterioration over the years was reported regarding the above symptoms. On average, bone conduction pure tone average pre- and 1 year postoperative were 13.7 ± 17 and 20.5 ± 18 dB, respectively (P = 0.002). Air bone gaps were reduced from 12.7 ± 8 to 5.9 ± 6 (P = 0.001). Two patients had a significant sclerotic mastoid, three had a prominent low-lying mastoid tegmen, and two had both. Anatomy had no effect on outcome. CONCLUSION: Trans-mastoid plugging of SSCD is a reliable and effective technique which achieves long-lasting symptom control, even in cases with sclerotic mastoid or low-lying mastoid tegmen.

Clinical Implications of Pituitary Adenomas Exhibiting Dual Transcription Factor Staining: A Case Series of 27 Patients.

OBJECTIVE: According to the 2017 World Health Organization classification of neuro-endocrine tumors, pituitary adenomas (PAs) are classified according to immunoexpression of the pituitary-specific transcription factors (TFs). A small subset of PAs exhibit multiple TF staining on immunohistochemistry and we present a series of 27 pathologically-confirmed cases of dual TF staining PAs (dsTF-PAs), and report clinically relevant implications. METHODS: A retrospective chart review of a multi-institutional database of patients with PAs surgically resected between 2008-2021 was performed. PAs expressing immunopositivity 2+ TFs. Patient demographics, neuro-imaging characteristics, histopathologic findings, and clinical data were collected. RESULTS: Twenty-seven patients had pathologically verified dsTF-PAs, of whom 17 were female (63%), with ages ranging from 20-84 years. Twenty-three (85.2%) patients harbored functional PAs, with acromegaly being the most common functional subtype (86.4%). The most common combination of TFs within a single tumor was PIT-1/SF-1 (85.2%). Six PAs exhibited Knosp cavernous sinus invasion grades of 3 or 4 and the Ki-67 labeling index was ≥3% in 6 patients (24.0%) and all stained for PIT-1/SF-1. Hormonal remission was achieved in 78% of functional dsTF-PAs. No PAs showed evidence of recurrence or progression over the mean follow-up period of 28.5 months. CONCLUSIONS: PAs exhibiting dsTF-PAs represent a small but clinically relevant diagnostic subset of PAs according to the 2021 World Health Organization criteria, as a majority are GH-producing. Precise classification using TF staining plays a key role in understanding the biology of these tumors. Favorable outcomes can be achieved in this subset of PAs with evolving TF classification.

Clinical performance, safety, and patient-reported outcomes of an active osseointegrated bone-conduction hearing implant system at 24-month follow-up.

PURPOSE: To investigate 2-year post-operative hearing performance, safety, and patient-reported outcomes of hearing-impaired adults treated with the Osia® 2 System, an active osseointegrated bone-conduction hearing implant that uses piezoelectric technology. METHODS: A prospective, multicenter, open-label, single-arm, within-subject clinical study conducted at three tertiary referral clinical centers located in Melbourne, Sydney and Hong Kong. Twenty adult recipients of the Osia 2 System were enrolled and followed up between 12 and 24 months post-implantation: 17 with mixed or conductive hearing loss and 3 with single-sided sensorineural deafness. Safety data, audiological thresholds, speech recognition thresholds in noise, and patient-reported outcomes were collected and evaluated. In addition, pre-and 6-month post-implantation data were collected retrospectively for this recipient cohort enrolled into the earlier study (ClinicalTrials.gov NCT04041700). RESULTS: Between 6- and 24-month follow-up, there was no statistically significant change in free-field hearing thresholds or speech reception thresholds in noise (p = > 0.05), indicating that aided improvements were maintained up to 24 months of follow-up. Furthermore, improvements in health-related quality of life and daily hearing ability, as well as clinical and subjective measures of hearing benefit remained stable over the 24-month period. No serious adverse events were reported during extended follow-up. CONCLUSIONS: These study results provide further evidence to support the longer term clinical safety, hearing performance, and patient-related benefits of the Osia 2 System in patients with either a conductive hearing loss, mixed hearing loss, or single-sided sensorineural deafness. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04754477. First posted: February 15, 2021.

Impact of Multiple Sclerosis Subtypes on Pain Management in Patients With Trigeminal Neuralgia After Stereotactic Radiosurgery: An International Multicenter Analysis.

BACKGROUND AND OBJECTIVES: Trigeminal neuralgia affects approximately 2% of patients with multiple sclerosis (MS) and often shows higher rates of pain recurrence after treatment. Previous studies on the effectiveness of stereotactic radiosurgery (SRS) for trigeminal neuralgia did not consider the different MS subtypes, including remitting relapsing (RRMS), primary progressive (PPMS), and secondary progressive (SPMS). Our objective was to investigate how MS subtypes are related to pain control (PC) rates after SRS. METHODS: We conducted a retrospective multicenter analysis of prospectively collected databases. Pain status was assessed using the Barrow National Institute Pain Intensity Scales. Time to recurrence was estimated through the Kaplan-Meier method and compared groups using log-rank tests. Logistic regression was used to calculate the odds ratio (OR). RESULTS: Two hundred and fifty-eight patients, 135 (52.4%) RRMS, 30 (11.6%) PPMS, and 93 (36%) SPMS, were included from 14 institutions. In total, 84.6% of patients achieved initial pain relief, with a median time of 1 month; 78.7% had some degree of pain recurrence with a median time of 10.2 months for RRMS, 8 months for PPMS, 8.1 months for SPMS ( P = .424). Achieving Barrow National Institute-I after SRS was a predictor for longer periods without recurrence ( P = .028). Analyzing PC at the last available follow-up and comparing with RRMS, PPMS was less likely to have PC (OR = 0.389; 95% CI 0.153-0.986; P = .047) and SPMS was more likely (OR = 2.0; 95% CI 0.967-4.136; P = .062). A subgroup of 149 patients did not have other procedures apart from SRS. The median times to recurrence in this group were 11.1, 9.8, and 19.6 months for RRMS, PPMS, and SPMS, respectively (log-rank, P = .045). CONCLUSION: This study is the first to investigate the relationship between MS subtypes and PC after SRS, and our results provide preliminary evidence that subtypes may influence pain outcomes, with PPMS posing the greatest challenge to pain management.

A parcellation-based connectomic model of hemispatial neglect.

BACKGROUND AND PURPOSE: Hemispatial neglect is characterized by a reduced awareness to stimuli on the contralateral side. Current literature suggesting that damage to the right parietal lobe and attention networks may cause hemispatial neglect is conflicting and can be improved by investigating a connectomic model of the "neglect system" and the anatomical specificity of regions involved in it. METHODS: A meta-analysis of voxel-based morphometry magnetic resonance imaging (MRI) studies of hemispatial neglect was used to identify regions associated with neglect. We applied parcellation schemes to these regions and performed diffusion spectrum imaging (DSI) tractography to determine their connectivity. By overlaying neglect areas and maps of the attention networks, we studied the relationship between them. RESULTS: The meta-analysis generated a list of 13 right hemisphere parcellations. These 13 neglect-related parcellations were predominantly linked by the superior longitudinal fasciculus (SLF) throughout a fronto-parietal-temporal network. We found that the dorsal and ventral attention networks showed partial overlap with the neglect system and included various other higher-order networks. CONCLUSIONS: We provide an anatomically specific connectomic model of the neurobehavioral substrates underlying hemispatial neglect. Our model suggests a fronto-parietal-temporal network linked via the SLF supports the functions impaired in neglect and implicates various higher-order networks which are not limited to the attention networks.

Countermovement Jump Force-Time Curve Analyses: Reliability and Comparability Across Force Plate Systems.

ABSTRACT: Merrigan, JJ, Strang, A, Eckerle, J, Mackowski, N, Hierholzer, K, Ray, NT, Smith, R, Hagen, JA, and Briggs, RA. Countermovement jump force-time curve analyses: reliability and comparability across force plate systems. J Strength Cond Res 38(1): 30-37, 2024-Considering the growing prevalence of commercial force plates providing automated force-time analyses, understanding levels of agreement across force plate systems is warranted. Countermovement jump (CMJ) metrics across Vald ForceDecks (FD), Hawkin Dynamics (HD), and Sparta Science (SS) force plate systems were compared. Twenty-two subjects completed CMJ testing (∼128 comparisons) on each force plate system separately with rest between jumps. Baseline testing occurred 3 times and demonstrated poor test-retest reliability for modified reactive strength index (mRSI) and rate of force development (RFD). ForceDecks and HD comparisons yielded acceptable agreement for concentric/propulsive relative force and net impulse, jump height, eccentric/braking RFD, and mRSI, but systematic and proportionate bias existed for RFD. Sparta Science jump height and reactive strength index (RSI) demonstrated systematic overestimations compared with HD and FD, but jump height had acceptable agreement according to concordance correlation coefficients (CCC = 0.92-0.95). Agreement between SS load (eccentric RFD) and HD braking RFD was acceptable (CCC = 0.91), whereas agreement between SS load and FD deceleration RFD was considered acceptable (CCC = 0.81-0.87) but demonstrated systematic and proportionate bias. ForceDecks (CCC = 0.89) and HD (CCC = 0.85) average relative concentric/propulsive force yielded acceptable agreement with SS explode (average relative concentric force), but SS explode demonstrated systematically lower values than FD and HD. Sparta Science drive (concentric impulse) yielded acceptable agreement with HD relative propulsive impulse (CCC = 0.85), but not FD concentric impulse. Human performance practitioners need to be aware of inconsistencies among testing procedures and analyses across force plate systems, such as differences in metric definitions and units of measurement, before making comparisons across systems.

Enhanced phagocytosis and complement-mediated killing of Mannheimia haemolytica serotype 1 following in-frame CMP-sialic acid synthetase (neuA) gene deletion.

IMPORTANCE: The Gram-negative coccobacillus Mannheimia haemolytica is a natural inhabitant of the upper respiratory tract in ruminants and the most common bacterial agent involved in bovine respiratory disease complex development. Key virulence factors harbored by M. haemolytica are leukotoxin, lipopolysaccharide, capsule, adhesins, and neuraminidase which are involved in evading innate and adaptive immune responses. In this study, we have shown that CMP-sialic acid synthetase (neuA) is necessary for the incorporation of sialic acid onto the membrane, and inactivation of neuA results in increased phagocytosis and complement-mediated killing of M. haemolytica, thus demonstrating that sialylation contributes to the virulence of M. haemolytica.

Comparison of preoperative versus postoperative treatment dosimetry plans of single-fraction stereotactic radiosurgery for surgically resected brain metastases.

OBJECTIVE: Stereotactic radiosurgery (SRS) for operative brain metastasis (BrM) is usually administered 1 to 6 weeks after resection. Preoperative versus postoperative timing of SRS delivery related to surgery remains a critical question, as a pattern of failure is the development of leptomeningeal disease (LMD) in as many as 35% of patients who undergo postoperative SRS or the occurrence of radiation necrosis. As they await level I clinical data from ongoing trials, the authors aimed to bridge the gap by comparing postoperative with simulated preoperative single-fraction SRS dosimetry plans for patients with surgically resected BrM. METHODS: The authors queried their institutional database to retrospectively identify patients who underwent postoperative Gamma Knife SRS (GKSRS) after resection of BrM between January 2014 and January 2021. Exclusion criteria were prior radiation delivered to the lesion, age < 18 years, and prior diagnosis of LMD. Once identified, a simulated preoperative SRS plan was designed to treat the unresected BrM and compared with the standard postoperative treatment delivered to the resection cavity per Radiation Therapy Oncology Group (RTOG) 90-05 guidelines. Numerous comparisons between preoperative and postoperative GKSRS treatment parameters were then made using paired statistical analyses. RESULTS: The authors' cohort included 45 patients with a median age of 59 years who were treated with GKSRS after resection of a BrM. Primary cancer origins included colorectal cancer (27%), non-small cell lung cancer (22%), breast cancer (11%), melanoma (11%), and others (29%). The mean tumor and cavity volumes were 15.06 cm3 and 12.61 cm3, respectively. In a paired comparison, there was no significant difference in the planned treatment volumes between the two groups. When the authors compared the volume of surrounding brain that received 12 Gy or more (V12Gy), an important predictor of radiation necrosis, 64% of patient plans in the postoperative SRS group (29/45, p = 0.008) recorded greater V12 volumes. Preoperative plans were more conformal (p < 0.001) and exhibited sharper dose drop-off at the lesion margins (p = 0.0018) when compared with postoperative plans. CONCLUSIONS: Comparison of simulated preoperative and delivered postoperative SRS plans administered to the BrM or resection cavity suggested that preoperative SRS allows for more highly conformal lesional coverage and sharper dose drop-off compared with postoperative plans. Furthermore, V12Gy was lower in the presurgical GKSRS plans, which may account for the decreased incidence of radiation necrosis seen in prior retrospective studies.

The use of the World Guidelines for Falls Prevention and Management's risk stratification algorithm in predicting falls in The Irish Longitudinal Study on Ageing (TILDA).

BACKGROUND: the aim of this study was to retrospectively operationalise the World Guidelines for Falls Prevention and Management (WGFPM) falls risk stratification algorithm using data from The Irish Longitudinal Study on Ageing (TILDA). We described how easy the algorithm was to operationalise in TILDA and determined its utility in predicting falls in this population. METHODS: participants aged ≥50 years were stratified as 'low risk', 'intermediate' or 'high risk' as per WGFPM stratification based on their Wave 1 TILDA assessments. Groups were compared for number of falls, number of people who experienced one or more falls and number of people who experienced an injury when falling between Wave 1 and Wave 2 (approximately 2 years). RESULTS: 5,882 participants were included in the study; 4,521, 42 and 1,309 were classified as low, intermediate and high risk, respectively, and 10 participants could not be categorised due to missing data. At Wave 2, 17.4%, 43.8% and 40.5% of low-, intermediate- and high-risk groups reported having fallen, and 7.1%, 18.8% and 18.7%, respectively, reported having sustained an injury from falling. CONCLUSION: the implementation of the WGFPM risk assessment algorithm was feasible in TILDA and successfully differentiated those at greater risk of falling. The high number of participants classified in the low-risk group and lack of differences between the intermediate and high-risk groups may be related to the non-clinical nature of the TILDA sample, and further study in other samples is warranted.

An electronic medical record reminder is independently associated with improved opportunistic influenza vaccination rates for older inpatients.

BACKGROUND: Influenza vaccination will have added importance this winter given the possibility of further waves of the COVID-19 pandemic. This study examines the impact of an electronic medical record (EMR) reminder on influenza vaccine uptake among eligible hospital inpatients. METHODS: We included a convenience sample of 750 adults (median age 77 years) who are eligible for influenza vaccination (⩾65 years and/or length of stay >30 days). A live electronic dashboard identified patients eligible for vaccination, prompting reminders sent to the clinical teams via the EMR. RESULTS: The EMR reminder was associated with almost a 50% higher likelihood of vaccination after adjusting for other covariates (odds ratio 1.48 (95% confidence interval 1.00-2.20); p = 0.048). DISCUSSION: Reminders sent to the clinical team via the EMR appear to be an effective means of increasing vaccine uptake and should be considered as part of this year's drive to vaccinate eligible patients in hospital.

You Dropped the Bomb on Me: A Case Series of Carbon Tetrachloride Toxicity.

Carbon tetrachloride (CCl4) is a halogenated hydrocarbon that is a colorless, clear liquid with a sweetish, ether-like, nonirritant odor. It was previously used in dry cleaning agents, refrigerants, and fire extinguishers. CCl4 toxicity is rarely observed. Two patients with acute hepatitis following exposure to a CCl4-containing antique fire extinguisher are presented. A son (patient 1) and father (patient 2) were admitted to the hospital with acute, unexplained elevated transaminases. After extensive questioning, they reported recent exposure to a large amount of CCl4 when an antique firebomb shattered in their home. Both patients cleaned the debris without personal protective equipment and slept in the contaminated area. The patients presented to the emergency department (ED) at varying times between 24 and 72 hours after CCl4 exposure. Both patients received intravenous N-acetylcysteine (NAC); patient 1 also received oral cimetidine. Both recovered uneventfully without sequelae. Extensive workup for other causes of elevated transaminases was unremarkable. Serum analyses for CCl4 were also unremarkable due to the delay between exposure and hospital presentation. CCl4 is a potent hepatotoxin. CCl4 metabolism via cytochrome CYP2E1 produces its toxic metabolite, the trichloromethyl radical. This radical covalently binds to hepatocyte macromolecules and causes lipid peroxidation and oxidative damage with ensuing centrilobular necrosis. Treatment is not well established, but NAC is likely beneficial via glutathione repletion and antioxidant effects. Cimetidine blocks cytochrome P450 and, thus, metabolite formation. Cimetidine may also promote the stimulation of regenerative processes acting on DNA synthesis. CCl4 toxicity is rare and infrequently reported in current literature but should be maintained in the differential of acute hepatitis. Two patients presenting nearly identically - at two different ages but from the same household - offered a clue to this enigmatic diagnosis.