A real-world observation of patients with glioblastoma treated with a personalized peptide vaccine.

Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. All patients were treated within the scope of an individual healing attempt. Among all vaccinated patients, including 70 treated prior to progression (primary) and 103 treated after progression (recurrent), the median overall survival from first diagnosis is 31.9 months (95% CI: 25.0-36.5). Adverse events are infrequent and are predominantly grade 1 or 2. A vaccine-induced immune response to at least one of the vaccinated peptides is detected in blood samples of 87 of 97 (90%) monitored patients. Vaccine-specific T-cell responses are durable in most patients. Significantly prolonged survival is observed for patients with multiple vaccine-induced T-cell responses (53 months) compared to those with no/low induced responses (27 months; P = 0.03). Altogether, our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment option for GBM patients.

Mechanistic Investigation of Sensitized Europium Luminescence: Excited State Dynamics and Luminescence Lifetime Thermometry.

Fluorescent nanothermometers based on thermal-dependent lifetime have a significant advantage in biological imaging owing to their immunity toward scattering, absorption, and autofluorescence. In this study, we present the first example of a water-soluble europium complex ([L1Eu]-) that exhibits high sensitivity (1.2% K-1 at 298 K) based on a temperature-dependent lifetime in the millisecond time range. This complex and its analogues show considerable potential for organelle imaging. The mechanism behind this thermal-sensitive behavior has been extensively investigated using transient absorption spectroscopy and variable temperature time-resolved luminescence methods. A highly efficient ligand sensitization process and a thermally activated back energy transfer process have been demonstrated. This study bridges the gap in small molecule thermometers with lifetimes longer than 1 ms and provides guidance in ligand design for metal coordination complex thermometers.

Knowledge, attitudes and practices regarding respirable silica exposure and personal protective equipment use among brick kiln workers in Nepal.

OBJECTIVES: Brick kiln workers in Nepal are a neglected population who are exposed to high respirable silica concentrations, and few use interventions to reduce exposure. We aimed to characterise the prevalence of respiratory personal protective equipment (PPE) use, understand knowledge and attitudes towards kiln dust and respiratory PPE and identify factors associated with respiratory PPE use. METHODS: We conducted a cross-sectional study in Bhaktapur, Nepal. We used simple random selection to identify 10 out of 64 total kilns and stratified random sampling of 30 households to enrol workers aged ≥14 years within selected kilns. Field workers surveyed participants using structured questionnaires. Our primary outcome was to characterise the prevalence of current respiratory PPE use and secondary outcomes were summaries of knowledge, attitudes and practice of PPE use. RESULTS: We surveyed 83 workers (mean age 30.8 years, 77.1% male). Of these, 28.9% reported current respiratory PPE use at work, 3.6% heard of silicosis prior to the survey and 24.1% correctly identified the best respiratory PPE (N95, compared with surgical masks and barrier face coverings) for reducing dust exposure. Respiratory PPE users had higher income (mean monthly household income US$206 vs US$145; p=0.04) and education levels (25% vs 5.1% completed more than primary school; p=0.02) compared with non-users. CONCLUSIONS: Respiratory PPE use was low. Workers had poor knowledge of kiln dust health effects and proper respiratory PPE. We highlight important barriers to PPE use, particularly knowledge gaps, which can guide future investigations to reduce the silicosis burden among brick kiln workers.

On the origin of magnetic anisotropy in 4f-free ferromagnets based on the CaCu5structure.

Using first-principles calculations, we investigate the origin of magnetocrystalline anisotropy in a series of 4f-electron-free intermetallics with CaCu5-based structures: YCo5, YCo4B, and Y3Co13B2. The electronic structure of these compounds is characterized by a set of narrow 3dbands near the Fermi level. In YCo5the easy-axis anisotropy originates primarily in the spin-orbit coupling-induced mixing of the electronic states with Codx2-y2anddxycharacter. The analysis ofk-resolved anisotropy shows that positive contributions accumulate from the entire Brillouin zone but are particularly large near thekz=0plane. The analysis of the single-site and two-site terms reveals a large positive single-site contribution to the magnetocrystalline anisotropy from the Co atoms on the honeycomb sublattice, along with two-site contributions from both honeycomb and kagome sublattices.

Bacteriophage-Based Bioanalysis.

Bacteriophages, which are viral predators of bacteria, have evolved to efficiently recognize, bind, infect, and lyse their host, resulting in the release of tens to hundreds of propagated viruses. These abilities have attracted biosensor developers who have developed new methods to detect bacteria. Recently, several comprehensive reviews have covered many of the advances made regarding the performance of phage-based biosensors. Therefore, in this review, we first describe the landscape of phage-based biosensors and then cover advances in other aspects of phage biology and engineering that can be used to make high-impact contributions to biosensor development. Many of these advances are in fields adjacent to analytical chemistry such as synthetic biology, machine learning, and genetic engineering and will allow those looking to develop phage-based biosensors to start taking alternative approaches, such as a bottom-up design and synthesis of custom phages with the singular task of detecting their host.

Late-"de novo" paraesophageal hernia after Roux-en-Y gastric bypass (RYGB)-should it be repaired?

BACKGROUND: This study presents a case series of "de novo" paraesophageal hernia (dnPEH) in post-Roux-en-Y gastric bypass (RYGB) patients and analyzes the predisposing factors, symptoms, and outcomes after repair. This is a lesser known complication after RYGB and when symptomatic, may warrant surgery. METHODS: A retrospective review of data from a single academic institution from 2002 to 2022 was performed identifying patients who developed dnPEH after RYGB and compared them to patients with primary RYGB without post-operative symptomatic dnPEH. Patient characteristics from initial RYGB were analyzed to identify predisposing factors for dnPEH development. Additional information analyzed included time to dnPEH repair, indications for surgery, types of herniation, type of surgical repair, and symptom resolution. RESULTS: There were 6975 RYGB in the study period of which 6619 underwent RYGB alone at index surgery, with 31 of those patients developing late stage PEH requiring repair. Patients with older age (51.8 years with dnPEH vs 45.2 years without, p = 0.001) and increased weight loss at 1 year (33.4% vs 30.5%, p = 0.048) from index RYGB were more likely to develop dnPEH. The incidence of dnPEH was 31/6619 (0.47%). Late dnPEH after RYGB took an average of 74 months (45-102 months IQR) to develop symptoms and undergo repair. The most common symptoms were heartburn/reflux 19/31 (61.3%) and epigastric pain 13/31 (41.9%). Symptom resolution rate after repair was highest with 100% for globus and 89.5% heartburn/reflux. The most common form of dnPEH was pouch herniation in 25/31. Surgical repair most commonly included primary cruroplasty alone in 25/31 with additional mesh in 1 case. Recurrence rate was 2/31 (6.54%). CONCLUSION: Late dnPEH after RYGB is an emerging entity typically occurring years after index RYGB. Symptomatic patients with dnPEH warrant hernia repair and responded well to surgical repair in this case series.

Lateral extra-articular tenodesis does not enhance ACL graft healing, however, does reduce graft tunnel widening.

PURPOSE: The study hypothesized that the addition of lateral extra-articular tenodesis (LEAT) in anterior cruciate ligament reconstruction (ACLR) had a significant effect on ACL graft healing. METHODS: A total of 80 patients were divided into two cohorts matched for gender, age, body mass index, time from surgery to post-operative MRI and graft diameter. Forty patients underwent ACL reconstruction alone, while 40 underwent ACLR in addition to LEAT. Patients underwent a magnetic resonance imaging scan at 12 months post-surgery; tunnel apertures were measured using multiplanar reformation, graft healing was assessed using signal-to-noise quotient (SNQ) in three regions of interest and finally graft maturity and integration were classified using the Howell and Ge scale, respectively. In addition, clinical evaluation and patient-reported outcome measures were collected. RESULTS: The mean femoral tunnel widening at 12 months post-surgery was 39.8 ± 14.0% in the ACLR + LEAT group and 55.2 ± 12.7% in the ACLR alone group (p < 0.05). The mean tibial tunnel widening was 29.3 ± 12.7% in the ACLR + LEAT group and 44.4 ± 12.1% in the ACLR group (p < 0.05). The mean adjusted graft SNQ was 9.0 ± 14.9 in the ACLR + LEAT group and 9.5 ± 11.4 in the ACLR group (n.s.). CONCLUSION: At 1 year post-operatively, we noted significantly less femoral and tibial tunnel widening in the ACLR + LEAT group. LEAT did not result in a statistically significant effect on graft healing. LEVEL OF EVIDENCE: Level III.

Robotic Assessment of Patella Tracking in Total Knee Arthroplasty.

OBJECTIVES: Robotic-tools have been developed to improve planning, accuracy and outcomes in total knee arthroplasty (TKA). The purpose of this study was to describe and illustrate a novel technique for assessing the patellofemoral (PFJ) in TKA using an imageless robotic platform. METHODS: A consecutive series of 30 R-TKA were undertaken by a single-surgeon utilising the described technique. A technique to dynamically assess the PFJ intra-operatively, pre and post implantation was developed. A full set of data from 9 cases was then collected and reviewed for analysis. A series of dynamic PFJ tracks collected intra-operatively pre and post implantation are presented. Furthermore, a full assessment of PFJ over and under-stuffing through a 90° arc of flexion is illustrated. Finally, a pre and post centre of rotation for the PFJ was defined and measured. RESULTS: The described technique was defined over a series of 30 R-TKA using the described robotic platform. Nine cases were analysed to determine what data could be measured using the robotic platform. Intra-operative real-time data allowed a visual assessment of PFJ tracking through a range of motion of 0° to 90° flexion pre and post-implantation. PFJ over and under-stuffing was also assessed intra-operatively through a range of motion of 0° to 90° flexion. Post operative analysis allowed a more detailed study to be performed, including defining a pre and post implantation centre of rotation (COR) for the patella. Defining the COR allowed the definition of a patella plane. Furthermore, patella mediolateral shift in full extension, and end flexion could be measured. CONCLUSION: Intra-operative assessment of the PFJ in TKA is challenging. Robotic tools have been developed to improve measurement, accuracy of delivery and outcomes in TKA. These tools can be adapted in novel ways to assess the PFJ, which may lead to further refinements in TKA techniques.

Meniscal Transplant surgery or Optimised Rehabilitation full randomised trial (MeTeOR2): a study protocol.

INTRODUCTION: Pain and disability after meniscectomy can be a substantial lifelong problem. There are few treatment options, especially for young people. Non-surgical management (rehabilitation) is an option but increasingly surgeons are performing meniscal allograft transplants (MATs) for these individuals. However, this is still an uncommon procedure, and availability and usage of MAT vary widely both in the UK and internationally. It is not known which treatment option is the most effective and cost-effective. METHODS AND ANALYSIS: The Meniscal Transplant surgery or Optimised Rehabilitation trial is an international, multicentre, randomised controlled trial. The aim is to compare the clinical and cost effectiveness of MAT versus an optimised package of individualised, progressive, rehabilitation that we have called personalised knee therapy (PKT).Participants will be recruited from sites across the UK, Australia, Canada and Belgium. The planned 144 participants provide at least 90% power to detect a 10-point difference in the Knee injury and Osteoarthritis Outcome Score (KOOS4) at 24-months post randomisation (primary outcome). A prospectively planned economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data including health utility, occupational status, sports participation, mental well-being, further treatment, and adverse events will be collected at 3, 6, 12, 18, and 24 months. Analysis will be on an intention-to-treat basis and reported in-line with the Consolidated Standards of Reporting Trials statement. ETHICS AND DISSEMINATION: The trial was approved by the London-Bloomsbury Research Ethics Committee on 19 August 2022 (22/LO/0327) and Northern Sydney Local Health District Human Research Ethics Committee, NSW, Australia on the 13 March 2023 (2022/ETH01890).Trial results will be disseminated via peer-reviewed publications, presentations at international conferences, in lay summaries and using social media as appropriate.This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist. TRIAL REGISTRATION NUMBER: ISRCTN87336549.

Characterizing the Relationship between Personality Dimensions and Psychosis-Specific Clinical Characteristics.

Background: Past studies associating personality with psychosis have been limited by small nonclinical samples and a focus on general symptom burden. This study uses a large clinical sample to examine personality's relationship with psychosis-specific features and compare personality dimensions across clinically and neurobiologically defined categories of psychoses. Methods: A total of 1352 participants with schizophrenia, schizoaffective disorder, and bipolar with psychosis, as well as 623 healthy controls (HC), drawn from the Bipolar-Schizophrenia Network for Intermediate Phenotypes (BSNIP-2) study, were included. Three biomarker-derived biotypes were used to separately categorize the probands. Mean personality factors (openness, conscientiousness, extraversion, agreeableness, and neuroticism) were compared between HC and proband subgroups using independent sample t-tests. A robust linear regression was utilized to determine personality differences across biotypes and diagnostic subgroups. Associations between personality factors and cognition were determined through Pearson's correlation. A canonical correlation was run between the personality factors and general functioning, positive symptoms, and negative symptoms to delineate the relationship between personality and clinical outcomes of psychosis. Results: There were significant personality differences between the proband and HC groups across all five personality factors. Overall, the probands had higher neuroticism and lower extraversion, agreeableness, conscientiousness, and openness. Openness showed the greatest difference across the diagnostic subgroups and biotypes, and greatest correlation with cognition. Openness, agreeableness, and extraversion had the strongest associations with symptom severity. Conclusions: Individuals with psychosis have different personality profiles compared to HC. In particular, openness may be relevant in distinguishing psychosis-specific phenotypes and experiences, and associated with biological underpinnings of psychosis, including cognition. Further studies should identify potential causal factors and mediators of this relationship.

Digital twinning of cardiac electrophysiology for congenital heart disease.

In recent years, blending mechanistic knowledge with machine learning has had a major impact in digital healthcare. In this work, we introduce a computational pipeline to build certified digital replicas of cardiac electrophysiology in paediatric patients with congenital heart disease. We construct the patient-specific geometry by means of semi-automatic segmentation and meshing tools. We generate a dataset of electrophysiology simulations covering cell-to-organ level model parameters and using rigorous mathematical models based on differential equations. We previously proposed Branched Latent Neural Maps (BLNMs) as an accurate and efficient means to recapitulate complex physical processes in a neural network. Here, we employ BLNMs to encode the parametrized temporal dynamics of in silico 12-lead electrocardiograms (ECGs). BLNMs act as a geometry-specific surrogate model of cardiac function for fast and robust parameter estimation to match clinical ECGs in paediatric patients. Identifiability and trustworthiness of calibrated model parameters are assessed by sensitivity analysis and uncertainty quantification.

Multiphoton Ionization/Dissociation of Molecular Sulfur S2 in the UV Region.

The multiphoton ionization/dissociation dynamics of molecular sulfur (S2) in the ultraviolet range of 205-300 nm is studied using velocity map ion imaging (VMI). In this one-color experiment, molecular sulfur (S2) is generated in a pulsed discharge and then photodissociated by UV radiation. At the three-photon level, superexcited states are accessed via two different resonant states: the B3Σu- (v' = 8-11) valence states at the one-photon level and a Rydberg state at the two-photon level. Among the decay processes of these superexcited states, dissociation to electronically excited S atoms is dominant as compared to autoionization to ionic states S2+ (X2Πg) at wavelengths λ < 288 nm. The anisotropy parameter extracted from these images reflects the parallel character of these electronic transitions. In contrast, autoionization is found to be particularly efficient at S(1D) and S(1S) detection wavelengths around 288 nm. Information obtained from the kinetic energy distributions of S atoms has revealed the existence of vibrationally excited S2+ (X2Πg (v+ > 11)) that dissociates to ionic products following one-photon absorption. This work also reveals many interesting features of S2 photodynamics compared to those of electronically analogous O2.

Brick kiln pollution and its impact on health: A systematic review and meta-analysis.

Brick kiln emissions adversely affect air pollution and the health of workers and individuals living near the kilns; however, evidence of their impacts remains limited. We conducted a systematic review of brick kiln pollution (emissions, source contributions and personal exposures) and its effects on health. We extracted articles from electronic databases and through manual citation searching. We estimated pooled, sample-size-weighted means and standard deviations for personal exposures by job type; computed mean emission factors and pollutant concentrations by brick kiln design; and meta-analyzed differences in means or proportions for health outcomes between brick kiln workers and controls or for participants living near or far away from kilns. We identified 104 studies; 74 were conducted in South Asia. The most evaluated pollutants were particulate matter (PM; n = 48), sulfur dioxide (SO2; n = 24) and carbon monoxide (CO; n = 22), and the most evaluated health outcomes were respiratory health (n = 34) and musculoskeletal disorders (n = 9). PM and CO emissions were higher among traditional than improved brick kilns. Mean respirable silica exposures were only measured in 4 (4%) studies and were as high as 620 µg/m3, exceeding the NIOSH recommended exposure limit by a factor of over 12. Brick kiln workers had consistently worse lung function, more respiratory symptoms, more musculoskeletal complaints, and more inflammation when compared to unexposed participants across studies; however, most studies had a small sample size and did not fully describe methods used for sampling or data collection. On average, brick kiln workers had worse health outcomes when compared to unexposed controls but study quality supporting the evidence was low. Few studies reported silica concentrations or personal exposures, but the few that did suggest that exposures are high. Further research is needed to better understand the relationship between brick kiln pollution and health among workers, and to evaluate exposure mitigation strategies.

Electronic Real-Time Monitoring Reveals Limited Adherence to Long-Term Opioid Prescriptions in Pain Patients.

Background: Pain management physicians are increasingly focused on limiting prescription opioid abuse, yet existing tools for monitoring adherence have limited accuracy. Medication event monitoring system (MEMS) is an emerging technology for tracking medication usage in real-time but has not been tested in chronic pain patients on long-term opioid regimens. Objective: We conducted a pilot clinical trial to investigate the utility of MEMS for monitoring opioid adherence and compared to traditional methods including self-report diaries, urine drug screen (UDS), and physicians' opinions. Methods: Opioid-maintained chronic pain patients were recruited from a pain management clinic. Participants (n=28) were randomly assigned to either receive MEMS bottles containing their opioid medication for a 90-day period or to continue using standard medication bottles. MEMS bottles were configured to record and timestamp all bottle openings and the number of pills that were removed from the bottle (via measurement of weight change). Results: Participants who received MEMS demonstrated highly heterogenous dosing patterns, with a substantial number of patients rapidly removing excessive amounts of medication and/or "stockpiling" medication. By comparison, physicians rated all participants as either "totally compliant" or "mostly compliant". UDS results did not reveal any illicit drug use, but 25% of participants (n=7) tested negative for their prescribed opioid metabolite. MEMS data did not correlate with physician-rated adherence (P=0.24) and UDS results (P=0.77). MEMS data consistently revealed greater non-adherence than self-report data (P<0.001). Conclusion: These results highlight the limits in our understanding of naturalistic patterns of daily opioid use in chronic pain patients as well as support the use of MEMS for detecting potential misuse as compared to routine adherence monitoring methods. Future research directions include the need to determine how MEMS could be used to improve patient outcomes, minimize harm, and aid in clinical decision-making. Trial Registration: This study was preregistered on ClinicalTrials.gov (NCT03752411).

Reduced amplitude and slowed latency of the acoustic startle response in adolescents and adults with 22q11.2 deletion syndrome.

BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is one of the most robust genetic predictors of psychosis and other psychiatric illnesses. In this study, we examined 22q11DS subjects' acoustic startle responses (ASRs), which putatively index psychosis risk. Latency of the ASR is a presumptive marker of neural processing speed and is prolonged (slower) in schizophrenia. ASR measures correlate with increased psychosis risk, depend on glutamate and dopamine receptor signaling, and could serve as translational biomarkers in interventions for groups at high psychosis risk. METHODS: Startle magnitude, latency, and prepulse inhibition were assessed with a standard acoustic startle paradigm in 31 individuals with 22q11.2DS and 32 healthy comparison (HC) subjects. Surface electrodes placed on participants' orbicularis oculi recorded the electromyographic signal in ASR eyeblinks. Individuals without measurable startle blinks in the initial habituation block were classified as non-startlers. RESULTS: Across the startle session, the ASR magnitude was significantly lower in 22q11DS subjects than HCs because a significantly higher proportion of 22q11DS subjects were non-startlers. Latency of the ASR to pulse-alone stimuli was significantly slower in 22q11DS than HC subjects. Due to the overall lower 22q11DS startle response frequency and magnitudes prepulse inhibition could not be analyzed. CONCLUSIONS: Reduced magnitude and slow latency of 22q11DS subjects' responses suggest reduced central nervous system and neuronal responsiveness. These findings are consistent with significant cognitive impairments observed in 22q11DS subjects. Further research is needed to untangle the connections among basic neurotransmission dysfunction, psychophysiological responsiveness, and cognitive impairment.

What Environments Support Reading Growth Among Current Compared With Former Reading Intervention Recipients? A Multilevel Analysis of Students and Their Schools.

School context can shape relative intervention response in myriad ways due to factors, such as instructional quality, resource allocation, peer effects, and correlations between the school context and characteristics of enrolled students (e.g., higher-poverty students attending higher-poverty schools). In the current study, we used data from 16,000 Grade 3 students in a community-based supplemental reading intervention program to investigate the degree to which school context factors (percentage eligible for free/reduced-price lunch [FRPL], school-level achievement) relate to the differences in triannual reading fluency growth rates between students actively receiving supplemental intervention (active recipients) and those that formerly received intervention (and therefore only received general class instruction at this time; former recipients). Using Bayesian multilevel modeling, our findings indicate that school-level FRPL eligibility played a more prominent factor in growth rate differences between these two groups than school-level reading achievement. However, school-level reading achievement was much more strongly related to reading fluency differences between active and former intervention recipients at the beginning of the school year (when controlling for FRPL). Implications for investigating school-level heterogeneity in intervention response and sustainability are discussed.

Examining emergency department utilization following bariatric surgery.

BACKGROUND: Emergency department (ED) utilization following surgery is poorly understood and places immense strain on the healthcare system, being responsible for up to $38 billion in wasteful spending annually. The aim of this study was to quantify ED utilization following bariatric procedures to identify causes and areas of improvement. MATERIALS AND METHODS: A retrospective review of a prospectively maintained database was conducted for all patients who underwent metabolic bariatric surgery (MBS) between November 2006 and June 2019. The study includes 4703 patients across 8 hospitals in a single health system. Patients who returned to the ED within 30 and 90 days were analyzed for relation to surgery and preventability. RESULTS: Of the 4703 patients that underwent MBS, 907 (19.3%) visited the ED at least once within 90 days and 350 (7.4%) required hospital readmission. The most common bariatric procedure performed was the Roux-en-Y Gastric Bypass (RYGB) (3716/4703) with an average BMI of 43.8. The median length between discharge and ED visit was 19 days. Under 50% of patients called prior to ED presentation and 61% of these ED visits resulted in discharge. CONCLUSION: While hospital readmissions following MBS have been scrutinized in literature, investigation of ED utilization remains scarce. Our study is one of few to investigate postoperative ED utilization up to 90 days following bariatric intervention. A clear opportunity exists to improve discharge education and early post-discharge communication. This would additionally alleviate burden to allow focus on the acutely ill.

Vibrational state-specific nonadiabatic photodissociation dynamics of OCS+ via A2Π1/2 (ν1 0 ν3) states.

The identification and analysis of quantum state-specific effects can significantly deepen our understanding of detailed photodissociation dynamics. Here, we report an experimental investigation on the vibrational state-mediated photodissociation of the OCS+ cation via the A2Π1/2 (ν1 0 ν3) states by using the velocity map ion imaging technique over the photolysis wavelength range of 263-294 nm. It was found that the electronically excited S+ product channel S+(2Du) + CO (X1Σ+) was significantly enhanced when the ν1 and ν3 vibrational modes were excited. Clear deviations in the branching ratios of the electronically excited S+ channel were observed when the vibrational modes ν1 and ν3 were selectively excited. The results reveal that vibrationally excited states play a vital role in influencing the nonadiabatic couplings in the photodissociation process.

Enlarged pituitary gland volume: a possible state rather than trait marker of psychotic disorders.

BACKGROUND: Enlarged pituitary gland volume could be a marker of psychotic disorders. However, previous studies report conflicting results. To better understand the role of the pituitary gland in psychosis, we examined a large transdiagnostic sample of individuals with psychotic disorders. METHODS: The study included 751 participants (174 with schizophrenia, 114 with schizoaffective disorder, 167 with psychotic bipolar disorder, and 296 healthy controls) across six sites in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium. Structural magnetic resonance images were obtained, and pituitary gland volumes were measured using the MAGeT brain algorithm. Linear mixed models examined between-group differences with controls and among patient subgroups based on diagnosis, as well as how pituitary volumes were associated with symptom severity, cognitive function, antipsychotic dose, and illness duration. RESULTS: Mean pituitary gland volume did not significantly differ between patients and controls. No significant effect of diagnosis was observed. Larger pituitary gland volume was associated with greater symptom severity (F = 13.61, p = 0.0002), lower cognitive function (F = 4.76, p = 0.03), and higher antipsychotic dose (F = 5.20, p = 0.02). Illness duration was not significantly associated with pituitary gland volume. When all variables were considered, only symptom severity significantly predicted pituitary gland volume (F = 7.54, p = 0.006). CONCLUSIONS: Although pituitary volumes were not increased in psychotic disorders, larger size may be a marker associated with more severe symptoms in the progression of psychosis. This finding helps clarify previous inconsistent reports and highlights the need for further research into pituitary gland-related factors in individuals with psychosis.