Large Cohort Of Patients Research Articles

The feasibility and clinical outcome of endoscopic transorbital transcavernous approaches with or without petrosectomy for petroclival lesions.

Petroclival tumors such as petroclival meningiomas or trigeminal schwannomas extending to the posterior cranial fossa are challenging to treat due to their deep-seated location and proximity to critical neurovascular structures. This study aimed to evaluate the feasibility, safety, and clinical outcomes of endoscopic transorbital surgery for the resection of central skull base tumors involving the petroclival area. The authors conducted a retrospective analysis of 32 patients with petroclival tumors including meningiomas and trigeminal schwannomas who underwent endoscopic transorbital surgery between September 2017 and December 2022. Preoperative clinical and radiological data were collected, and patients were followed up postoperatively for a median period of 34.7 months. Surgical technique, complications, and clinical outcomes were assessed. Endoscopic transorbital surgery provided a minimally invasive and direct corridor to the petroclival region. All 32 patients successfully underwent tumor resection, with gross-total or near-total tumor resection achieved in 28 patients. The mean tumor diameter was 3.5 cm. Based on tumor pathology, the endoscopic transorbital transcavernous trans-Meckel's cave approach (21 cases) or transorbital anterior transpetrosal approach (11 cases) was selected. The most common complication was facial paresthesia in 4 of 21 patients with trigeminal schwannomas and in 1 of 11 patients with petroclival meningiomas. Diplopia due to fourth cranial nerve injury occurred in 3 of 11 patients with petroclival meningiomas. Postoperative clinical improvement in neuralgic pain was observed in 3 of 4 patients. One patient developed a temporary facial palsy (House-Brackmann grade III) and another patient had transient paraparesis after removal of petroclival meningioma. Endoscopic transorbital surgery appears to be a safe and effective technique for the resection of petroclival lesions, offering excellent visualization and access to the tumor while minimizing morbidity. However, further studies with larger patient cohorts and longer follow-up are warranted to validate the long-term efficacy and safety of this approach. This study contributes to the growing body of evidence supporting the utility of endoscopic transorbital techniques in skull base surgery.

Acute Promyelocytic Leukemia: Long-Term Outcomes from the HARMONY Project.

Treatment outcomes for acute promyelocytic leukemia (APL) have improved with the widespread use of targeted therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Our study aimed to validate these data in a large patient cohort, and to redefine prognostic factors. Leveraging the HARMONY Platform, we analyzed 1438 newly-diagnosed APL patients, diagnosed between 1999 to 2022. Patient data derived from the 2 international multicenter GIMEMA-APL0406 and NCRI-AML17 trials, and 4 European registries (HOVON, AMLSG, Swedish AML Registry and SAL). The study cohort included 721 males and 717 females, with a median age of 50.5 years (range 16-94 years). Of 1309 patients starting therapy, 562 received ATRA-ATO, and 747 AIDA-like chemotherapy. Early death (ED) occurred in 85 of 1438 patients (5.9%) at a median of 9 days after APL diagnosis and was independently associated with increasing age and high Sanz risk score (OR:1.06, 95% C.I: 1.04-1.08, and OR:4.65, 95% C.I.:2.55-8.51, respectively).The median follow-up was 5.5 years (IQR=3.2-7.5). ATRA-ATO regimen was associated with the best outcome, reaching 91% 7-year overall survival (vs 81% for AIDA-like, HR:2.14, 95%C.I.:1.51-3.05), 89% event-free survival (vs 71% for AIDA-like, HR:2.72 95%CI: 2.01-3.69) and 3% relapse (vs 13% for AIDA-like, HR:4.19, 95%CI:2.38-7.39, p<0.001 for all outcomes). The survival advantage of ATRA/ATO was independent of patients' age, Sanz-risk score, and treatment scenario. Our study confirms the superiority of ATRA-ATO over ATRA-chemotherapy in APL patients. ED represents an unmet medical need, in particular in older patients and in high-risk APL.

Classification of salivary gland biopsies in Sjögren's syndrome by a convolutional neural network using an auto-machine learning platform.

The histopathological analysis of minor salivary gland biopsies, particularly through the quantification of the Focus Score (FS), is pivotal in the diagnostic workflow for Sjögren's Syndrome (SS). AI-based image recognition using deep learning models has demonstrated potential in enhancing diagnostic accuracy and efficiency in preclinical research. The primary aim of this investigation was to utilize an auto-machine learning (autoML) platform for the automated segmentation and quantification of FS on histopathological slides, aiming to augment diagnostic precision and speed in SS. A cohort comprising 86 patients with sicca syndrome (37 diagnosed with SS based on the 2016 ACR/EULAR Classification Criteria and 49 non-SS) was selected for an in-depth histological examination. A repository of 172 slides (two per patient) was assembled, encompassing 74 slides meeting the classificatory thresholds for SS (FS ≥ 1, indicative of lymphocytic infiltration) and 98 slides showcasing normal salivary gland histology. The autoML platform utilized (Giotto, L2F, Lausanne Switzerland) employed a Convolutional Neural Network (CNN) architecture (ResNet-152) for the training and validation phases, using a dataset of 172 slides. The developed model exhibited a reliability score of 0.88, proficiently distinguishing SS cases, with a sensitivity of 89.47% (95% CI: 66.86% to 98.70%) and a specificity of 88.24% (95% CI: 63.56% to 98.54%). The model found histological slides of suboptimal quality (e.g., those compromised during fixation or staining processes) to be the most challenging for accurate classification. AutoML platforms offer a rapid and flexible approach to developing machine learning models, even with smaller datasets, as demonstrated in this study for SS. These platforms hold significant potential for enhancing diagnostic precision and efficiency in both clinical and research settings. Multicentric studies with larger patient cohorts are essential for thorough evaluation and validation of this innovative diagnostic approach.

Association of the Revised Trauma Score with Mortality and Prehospital LSI Among Trauma and Non-Trauma Patients

ABSTRACT OBJECTIVES The combination of broad conditional applicability and ease of data collection make some general risk scores an attractive tool for clinical decision making under acute care conditions. To date, general risk scores have demonstrated moderate levels of accuracy for key outcomes, but there are no definitive general scores integrated universally into prehospital care. The objective of our study was to demonstrate a relationship between the revised trauma score (RTS) and prehospital lifesaving interventions (LSI) and downstream hospital mortality among a large, diverse, multi-year cohort of critical care transport patients. We hypothesized that the RTS is associated with mortality and prehospital LSI generally across all conditions, including non-trauma. METHODS We conducted a retrospective observational study using a pre-established cohort of sequentially enrolled patients from a regional air medical service between the years 2012 and 2021. Pediatric patients, non-transports, and those transported to hospitals outside the regional health system were excluded from the study. Both trauma and non-trauma patients were included in this study. We performed logistic regressions to evaluate the association between RTS and the outcomes of LSI and hospital mortality, while controlling for age, sex, and medical category. Graphs were constructed to plot RTS against prehospital LSI and survival percentage. RESULTS Our final patient cohort was 62,424 patients. 58.4% of all patients required a prehospital LSI. Non-trauma cases made up 69.7% of the patient population. The Revised Trauma Score was inversely proportional with both prehospital LSI and mortality. The logistic regression model yielded an odds ratio (OR) of 0.55 (95% CI 0.54 - 0.56) for the association between RTS and death. Additionally, when the components of RTS were associated with mortality, they each showed a statistically significant OR. The Revised Trauma Score was also associated with prehospital LSI (OR 0.10; 95% CI 0.03 - 0.33). CONCLUSIONS In a large helicopter EMS cohort of both trauma and non-trauma patients, the RTS was inversely associated with prehospital LSI and hospital mortality. The generalized utility of RTS demonstrated in our study warrants further investigation of this measure as a broader triage tool.

Exploring Extracellular Vesicle Surface Protein Markers Produced by Glioblastoma Tumors: A Characterization Study Using In Vitro 3D Patient-Derived Cultures

Background/Objectives: Glioblastoma (GBM) is an aggressive brain cancer with limited treatment options. Extracellular vesicles (EVs) derived from GBM cells contain important biomarkers, such as microRNAs, proteins, and DNA mutations, which are involved in tumor progression, invasion, and resistance to treatment. Identifying surface markers on these EVs is crucial for their isolation and potential use in noninvasive diagnosis. This study aimed to use tumor-derived explants to investigate the surface markers of EVs and explore their role as diagnostic biomarkers for GBM. Methods: Tumor explants from nine GBM patients without IDH1/IDH2 mutations or 1p-19q co-deletion were cultured to preserve both tumor viability and cytoarchitecture. EVs were collected from the tumor microenvironment using differential centrifugation, filtration, and membrane affinity binding. Their surface protein composition was analyzed through multiplex protein assays. RNA-Seq data from TCGA and GTEx datasets, along with in silico single-cell RNA-seq data, were used to assess EV surface biomarker expression across large GBM patient cohorts. Results: The in vitro model successfully replicated the tumor microenvironment and produced EVs with distinct surface markers. Biomarker analysis in large datasets revealed specific expression patterns unique to GBM patients compared with healthy controls. These markers demonstrated potential as a GBM-specific signature and were correlated with clinical data. Furthermore, in silico single-cell RNA-seq provided detailed insights into biomarker distribution across different cell types within the tumor. Conclusions: This study underscores the efficacy of the tumor-derived explant model and its potential to advance the understanding of GBM biology and EV production. A key innovation is the isolation of EVs from a model that faithfully mimics the tumor’s original cytoarchitecture, offering a deeper understanding of the cells involved in EV release. The identified EV surface markers represent promising targets for enhancing EV isolation and optimizing their use as diagnostic tools. Moreover, further investigation into their molecular cargo may provide crucial insights into tumor characteristics and evolution.

The role of femoral head size in metal-on-metal hip arthroplasty: analysis of a cohort of 3813 patients with long term follow-up.

Metal-on-metal (MoM) large headed arthroplasties were suggested to decrease failure rates by means of reduced volumetric wear and enhanced implant stability. However, they caused high rates of revisions due to adverse reaction to metal debris, osteolysis, pseudotumor growth, and other issues. The study aims to present the long-term outcomes of MoM arthroplasties on a large cohort of patients, evaluatingthe impact of head sizes on survival rate. All data were retrieved from the regional joint register (Registro dell'Implantologia Protesica Ortopedica, RIPO, Italy). We include in the study all patient who underwent cementless MoM total hip arthroplasties (THAs) between 2000 and 2020, dividing them in two subgroups according to head size (<36mm, ≥36mm). Failures were recorded up to December 31, 2020. Patients lost to follow-up were excluded. A total of 3813 THAs met the inclusion/exclusion criteria. The average follow-up period is 12.4years (0-21years). 178/1625 (or 11.0%) small head MoM THAs and 265/2188 large head ones failed by the end of follow up. Large diameter heads reported lower survival rate (p-value < 0.001), with unexpected higher dislocation rate (1.0 vs. 0.4%). Moreover, large head size was found to increases the risk of metallosis (p-value < 0.0001). Gender, patient's age and the use of modular neck were not correlated with higher failure rates. MoM implants implants do not have the same reliability as other couplings, considering the significantly greater failure/complication rates. However, the knowledge of risks linked to head size is fundamental for establishing the right type of follow-up to the patient and recognize any complications early.

Trends in Hip Arthroplasty Cementation: Insights from an Italian Registry of 142,113 Patients

Introduction: The use of cementation in total hip arthroplasty (THA) has evolved over the years, with a notable shift toward cementless and hybrid techniques. The aim of this study is to evaluate data from an Italian registry on the type of fixation used in THA implants and their corresponding survival rates in a large patient cohort with long-term follow-up, and to compare these data with the most recent literature. Methods: From January 2000 to December 2020, a total of 137,256 primary THA procedures were performed, of which 10.4% were fixed with stem cementation. There were 4857 revision implants, of which 11.4% were implanted with stem cementation. Results: The trend showing a significant shift toward cementless fixation methods is particularly pronounced in younger patients, with cementless implants comprising 99.5% of procedures in patients under 40 years of age. As patient age increases, the use of cemented or hybrid fixation methods becomes more common. This trend aligns with existing literature, in which cementation is often preferred for elderly patients due to concerns about bone quality and the potential for better immediate fixation provided by cemented stems. At 10 years, the implant that showed the highest survival rate was the fully cemented implant, with a rate of 94.8%. This study also reports the causes of failure based on the different fixation techniques. Conclusions: The development of standardized guidelines that consider patient-specific factors such as age, bone quality, and comorbidities in the choice of fixation type could help reduce variability in practice and improve overall outcomes in hip arthroplasty.

Psychedelic mushroom-containing chocolate exposures: Case series

IntroductionThe recreational use of psilocybin or psilocin-containing products, a chemical found naturally in certain mushroom species, is on the rise across the United States. Several cases of serious clinical effects related to mushroom-containing products have recently been reported to the Food and Drug Administration (FDA). The emergence of these new products and their health consequences are not yet well understood. This case series aims to characterize exposures to mushroom-containing chocolate products, including patient characteristics, clinical effects, treatment(s), and clinical outcome severity, reported to a poison center network. Material and methodsThis was a retrospective case series conducted in patients exposed to mushroom-containing chocolate products across three poison centers between January 2023 to August 2024. Patients were identified via a database search of ToxSentry®. Patients were included if they were exposed to a mushroom-containing chocolate product. Patients were excluded if they ingested an unrelated product or if there was insufficient information documented within ToxSentry®. The primary endpoint was to describe clinical outcome severity after exposure to mushroom-containing chocolate products. ResultsA query of ToxSentry® identified 164 cases; 36 cases met study criteria. The median age of patients in this case series was 17 years old. For most patients (23, 64 %), the reason for the exposure was intentional, with 20 reporting intentional abuse or misuse of the product. Common clinical effects reported included mental status changes (26, 76 %), paranoia/hallucinations (10, 28 %), dysrhythmias (7, 19 %) and gastrointestinal discomfort (6, 17 %). There was one report of seizure. Most clinical effects lasted between 3 and 24 h after ingestion (29, 81 %). Intravenous fluids (18, 50 %) and benzodiazepines (7, 19 %) were the most common treatments given. No fatalities were reported. DiscussionWhile most patients in this series experienced minor clinical effects, some developed serious effects after ingestion of a mushroom-containing chocolate product. Findings from this study further characterize the limited patient demographics, clinical effects, and outcomes published thus far. Further characterization in a larger cohort of patients could expand on our initial findings and is needed to better identify factors that may influence clinical outcomes.

Unilateral and Bilateral Theta Burst Stimulation for Treatment-Resistant Depression: Follow up on a Naturalistic Observation Study

ObjectivesTheta burst stimulation (TBS) is a novel and faster modality of transcranial magnetic stimulation, which is showing promise as a treatment-resistant depression (TRD) treatment. Though TBS can be applied unilaterally or bilaterally, few studies have compared the effectiveness of both approaches in a naturalistic clinical sample. In this retrospective chart review, we aimed to: (1) replicate previous bilateral sequential TBS effectiveness in a larger cohort of patients at a single centre, (2) present treatment outcome data between unilateral and bilateral TBS approaches, (3) investigate baseline factors associated with our observed outcomes, and (4) examine the sustainability of response, with follow-up data up to 6 months from patients. MethodsWe included 161 patients who received TBS (unilateral: n = 64 (40%), 45.55 ± 14.25 years old, 55% females; bilateral: n = 97 (60%), 47.67 ± 15.11 years old, 58% females). ResultsFirstly, we observed 47% response and 34% remission in the bilateral group, replicating findings from a smaller naturalistic study from our group; patients receiving unilateral TBS displayed 36% response and 26% remission, with no significant differences found between unilateral and bilateral TBS in remission and response rates. Secondly, bilaterally stimulated patients needed fewer treatments than those stimulated unilaterally (27 vs 29 on average respectively, t [159] = 3.31, p = .001), and had significantly lower anxiety symptoms post treatment (GAD-7) relative to patients receiving unilateral stimulation, F (1,148) = 3.95, p =0.049. Thirdly, no baseline factors were found to predict treatment outcomes. Lastly, after six months, 69% of patients who met the response criteria did not require additional treatment or a change in medication. ConclusionsOur findings support the efficacy and tolerability of TBS in TRD and indicate that bilateral TBS may have a superior anxiolytic effect and offer a slightly faster time to response.

Clinical profile of patients with acute traumatic brain injury undergoing cranial surgery in the United States: report from the 18-centre TRACK-TBI cohort study

Contemporary surgical practices for traumatic brain injury (TBI) remain unclear. We describe the clinical profile of an 18-centre US TBI cohort with cranial surgery. The prospective, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (2014-2018; ClinicalTrials.gov #NCT02119182) enrolled subjects who presented to trauma centre and received head computed tomography within 24-h (h) post-TBI. We performed a secondary data analysis in subjects aged ≥17-years with hospitalisation. Clinical characteristics, surgery type/timing, hospital and six-month outcomes were reported. Of 2032 subjects (age: mean=41.4-years, range=17-89-years; male=71% female=29%), 260 underwent cranial surgery, comprising 65% decompressive craniectomy, 23% craniotomy, 12% other surgery. Subjects with surgery (vs. without surgery) presented with worse neurological injury (median Glasgow Coma Scale=6 vs. 15; midline shift ≥5mm: 48% vs. 2%; cisternal effacement: 61% vs. 4%; p<0.0001). Median time-to-craniectomy/craniotomy was 1.8h (interquartile range=1.1-5.0h), and 67% underwent intracranial pressure monitoring. Seventy-three percent of subjects with decompressive craniectomy and 58% of subjects with craniotomy had ≥3 intracranial lesion types. Decompressive craniectomy (vs. craniotomy) was associated with intracranial injury severity (median Rotterdam Score=4 vs. 3, p<0.0001), intensive care length of stay (median=13 vs. 4-days, p=0.0002), and six-month unfavourable outcome (62% vs. 30%; p=0.0001). Earlier time-to-craniectomy was associated with intracranial injury severity. In a large representative cohort of patients hospitalised with TBI, surgical decision-making and time-to-surgery aligned with intracranial injury severity. Multifocal TBIs predominated in patients with cranial surgery. These findings summarise current TBI surgical practice across US trauma centres and provide the foundation for analyses in targeted subpopulations. National Institute of Neurological Disorders and Stroke; US Department of Defense; Neurosurgery Research and Education Foundation.

Riboflavin transporter deficiency, the search for the undiagnosed: a retrospective data mining study

BackgroundRiboflavin transporter deficiency (RTD) is an inborn error of riboflavin transport causing progressive neurological symptoms if left untreated. While infants with symptomatic RTD rapidly deteriorate, presentation later in childhood or in adulthood is more gradual. Symptoms overlap with more common diseases, carrying a risk of misdiagnosis, and given the relatively recent discovery of the genetic basis of RTD in 2010 it is likely that older patients have not been tested. Treatment with oral riboflavin (vitamin B2) halts disease progression and can be lifesaving. We hypothesized that patients may have been left unrecognized at the time of presentation and therefore we performed a datamining study to detect undiagnosed RTD patients in a tertiary referral hospital.MethodsA systematic search in Electronic Health Records (EHR) of all patients visiting the Amsterdam University Medical Centers between January 2004 and July 2021 was performed by a medical data text-mining tool. Pseudonymized patient records, matching pre-defined search terms (hearing loss or auditory neuropathy spectrum disorders combined with key clinical symptoms or riboflavin) were screened and included if no definitive alternative diagnosis for symptoms indicating possible RTD was found. Included patients were offered genetic testing. We documented total number of patients with possible RTD, number of patients that underwent genetic testing for RTD and results of genetic testing.ResultsEHR of 2.288.901 patients were automatically screened. Thirteen patients with possible RTD were identified and offered genetic testing. Seven patients chose not to participate. Genetic testing was performed in 6 patients and was negative. The datamining did detect all previously known RTD patients in the hospital.ConclusionsBy screening a large cohort of patients of all ages in a tertiary referral hospital in a period spanning 17 years, no new RTD patients were found. Although not all suspected patients underwent genetic testing, our findings suggest that the prevalence of RTD is low and the chance of having missed this diagnosis in a tertiary referral hospital is limited.

The Lehigh Valley Health Network narcolepsy cohort: clinical and polysomnographic analysis of 304 cases.

We aimed to characterize clinical features, comorbidities and polysomnographic characteristics of a large cohort of patients with narcolepsy. We undertook a retrospective chart and polysomnographic review of all patients with a diagnosis of narcolepsy type 1 (NT1) or narcolepsy type 2 (NT2) seen within the Lehigh Valley Health Network between 2000 and 2022. We found 304 cases with a diagnosis of narcolepsy (52 NT1, 252 NT2), based on International Classification of Sleep Disorders, third edition criteria. Compared to NT2, patients with NT1 had younger diagnosis age (24.5 versus 27.4 years, p=0.03), shorter diagnostic gap (3.0 versus 4.6 years, p=0.002), more frequent sleep paralysis (55.8% versus 19.4%, p<0.0001) and hypnagogic hallucinations (46.2% versus 25.4%, p=0.003), and higher Epworth Sleepiness Scale (ESS) scores (17.8 versus 16.7, p=0.02). The most common comorbid sleep disorders were breathing disorders (17.4%) and insomnia (15.5%). Migraine was the most common neurological disorder. Depression was more common in NT2 than NT1 [12 (23.1%) versus 94 (37.3%), p=0.05]. On the Multiple Sleep Latency Test, patients with NT1 had more sleep onset REM periods (SOREMPs) than patients with NT2 (≥3 SOREMPs in 59.2% versus 26.9%, p<0.0001). Only in NT2, hypnagogic hallucinations and higher ESS scores were associated with higher numbers of SOREMPs (p=0.0277 and p=0.0179 respectively). This is one of the largest monocentric studies to date of patients with narcolepsy and confirms the frequent comorbidities of narcolepsy. Specific clinical characteristics and comorbidities may help differentiate NT1 from NT2.

Cell-autonomous IL6ST activation suppresses prostate cancer development via STAT3/ARF/p53-driven senescence and confers an immune-active tumor microenvironment

BackgroundProstate cancer ranks as the second most frequently diagnosed cancer in men worldwide. Recent research highlights the crucial roles IL6ST-mediated signaling pathways play in the development and progression of various cancers, particularly through hyperactivated STAT3 signaling. However, the molecular programs mediated by IL6ST/STAT3 in prostate cancer are poorly understood.MethodsTo investigate the role of IL6ST signaling, we constitutively activated IL6ST signaling in the prostate epithelium of a Pten-deficient prostate cancer mouse model in vivo and examined IL6ST expression in large cohorts of prostate cancer patients. We complemented these data with in-depth transcriptomic and multiplex histopathological analyses.ResultsGenetic cell-autonomous activation of the IL6ST receptor in prostate epithelial cells triggers active STAT3 signaling and significantly reduces tumor growth in vivo. Mechanistically, genetic activation of IL6ST signaling mediates senescence via the STAT3/ARF/p53 axis and recruitment of cytotoxic T-cells, ultimately impeding tumor progression. In prostate cancer patients, high IL6ST mRNA expression levels correlate with better recurrence-free survival, increased senescence signals and a transition from an immune-cold to an immune-hot tumor.ConclusionsOur findings demonstrate a context-dependent role of IL6ST/STAT3 in carcinogenesis and a tumor-suppressive function in prostate cancer development by inducing senescence and immune cell attraction. We challenge the prevailing concept of blocking IL6ST/STAT3 signaling as a functional prostate cancer treatment and instead propose cell-autonomous IL6ST activation as a novel therapeutic strategy.

Feasibility, Tolerability, and Preliminary Clinical Response of Fractionated Radiopharmaceutical Therapy with 213Bi-FAPI-46: Pilot Experience in Patients with End-Stage, Progressive Metastatic Tumors.

Radiopharmaceutical therapies (RPTs) based on fibroblast activation protein (FAP) and FAP inhibitors (FAPIs) are a new option for progressive metastatic cancer in patients pretreated multiple times. To date, published in-human data refer to initial experiences with β-emitting 90Y- and 177Lu-based RPT. However, the short tumor retention time of FAPI ligands is considered a major limitation of FAPI RPT. Therefore, fractionated FAPI RPT with 213Bi, an α-emitter with a half-life of 46 min, appears to be a promising FAPI RPT regimen. Here, we report on our initial experiences with regard to the feasibility, tolerability, and response of fractionated 213Bi-FAPI-46 RPT. Methods: Six patients (4 women and 2 men) with progressive metastatic solid tumors (3 colon cancer, 1 anal cancer, 1 breast cancer, and 1 prostate cancer) aged 16-77 y were treated with a mean of 1,609 MBq of 213Bi-FAPI-46, fractionated into 53 single applications (range, 5-12 RPT applications per patient; mean, 8.8 applications) over a period of up to 107 h per patient. Of the 6 patients, 4 patients received adjuvant treatment with pembrolizumab. 18F-FDG (4 patients) and 68Ga-FAPI-46 (5 patients) PET/CT scans were performed before and after RPT. PET images were assessed visually and by calculating total lesion glycolysis and total lesion FAPI. Results: RPT with 213Bi-FAPI-46 was well tolerated without adverse side effects. In terms of visual response assessment, there was 1 partial response (16.7%), 1 patient with stable disease (16.7%), and 4 patients with progressive disease (66.7%). Concordantly, total lesion glycolysis and total lesion FAPI were decreased in the responding patient (not applicable and -24.3%, respectively), slightly decreased in the patient with stable disease (-10.6% and -5.9%, respectively), and increased in the 4 patients with progression (mean, +104.4% and +321.3%, respectively). Conclusion: Fractionated FAPI RPT with the short-half-life α-emitter 213Bi-FAPI-46 is a promising approach that matches the pharmacokinetics of FAPI-46 better than the 177Lu- or 90Y-labeled compounds. In this pilot project, fractionated RPT with 213Bi-FAPI-46 showed good clinical tolerability and even led to regressive or stable disease in the short term in 2 of 6 patients. Further studies with larger patient cohorts are required to evaluate the actual efficacy and long-term effects of this variant of FAPI RPT.

Long-term complications of extracranial pericranial flaps in skull base reconstruction.

Nasoseptal flaps are a frequently used and well characterized means of reconstruction following endoscopic endonasal approach surgery (EEA). However, there are alternative means of reconstruction, including the extracranial pericranial flap (ePCF), that while used infrequently fulfill a specialized need in larger or salvage reconstructions. This review aims to better characterize long-term outcomes using ePCF where there is currently a paucity of objective data on use and outcomes. A traditional pericranial flap involves elevating and rotating the flap through a craniotomy defect to reconstruct defects of the ventral skull base. The ePCF is implemented without performing a craniotomy, and instead tunnels the flap through a bony opening created at the level of the nasion. This review presents outcomes in a large single-center cohort of patients with ePCFs to better characterize the short- and long-term success, risks, and complications of this reconstructive method. Long-term follow-up demonstrates that obstruction of the frontal sinus outflow may occur but rarely requires surgical intervention. ePCF are a reasonable alternative to consider in cases where local tissue would be insufficient, is not available, or has already failed. There is a low risk of flap complications.

A Retrospective Cohort Study of a Newly Proposed Criteria for Sporadic Creutzfeldt–Jakob Disease

Background/Objectives: Sporadic Creutzfeldt–Jakob disease (sCJD) is a fatal neurodegenerative disorder traditionally diagnosed based on the World Health Organization (WHO) criteria in 1998. Recently, Hermann et al. proposed updated diagnostic criteria incorporating advanced biomarkers to enhance early detection of sCJD. This study aimed to evaluate the sensitivity and specificity of Hermann’s criteria compared with those of the WHO criteria in a large cohort of patients suspected of prion disease in Japan. Methods: In this retrospective cohort study, we examined the new criteria using data of 2004 patients with suspected prion disease registered with the Japanese Prion Disease Surveillance (JPDS) between January 2009 and May 2023. Patients with genetic or acquired prion diseases or incomplete data necessary for the diagnostic criteria were excluded, resulting in 786 eligible cases. The sensitivity and specificity of the WHO and Hermann’s criteria were calculated by comparing diagnoses with those made by the JPDS Committee. Results: Of the 786 included cases, Hermann’s criteria helped identify 572 probable cases compared with 448 by the WHO criteria. The sensitivity and specificity of the WHO criteria were 96.4% and 96.6%, respectively. Hermann’s criteria demonstrated a sensitivity of 99.3% and a specificity of 95.2%, indicating higher sensitivity but slightly lower specificity. Fifty-five cases were classified as “definite” by both criteria. Conclusions: The findings suggest that Hermann’s criteria could offer improved sensitivity for detecting sCJD, potentially reducing diagnostic oversight. However, caution is advised in clinical practice to avoid misdiagnosis, particularly in treatable neurological diseases, by ensuring thorough exclusion of other potential conditions.

The peritumoral edema index and related mechanisms influence the prognosis of GBM patients

BackgroundPeritumoral brain edema (PTBE) represents a characteristic phenotype of intracranial gliomas. However, there is a lack of consensus regarding the prognosis and mechanism of PTBE. In this study, clinical imaging data, along with publicly available imaging data, were utilized to assess the prognosis of PTBE in glioblastoma (GBM) patients, and the associated mechanisms were preliminarily analyzed.MethodsWe investigated relevant imaging features, including edema, in GBM patients using ITK-SNAP imaging segmentation software. Risk factors affecting progression-free survival (PFS) and overall survival (OS) were assessed using a Cox proportional hazard regression model. In addition, the impact of PTBE on PFS and OS was analyzed in clinical GBM patients using the Kaplan–Meier survival analysis method, and the results further validated by combining data from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA). Finally, functional enrichment analysis based on TCIA and TCGA datasets identified several pathways potentially involved in the mechanism of edema formation.ResultsThis study included a total of 32 clinical GBM patients and 132 GBM patients from public databases. Univariate and multivariate analyses indicated that age and edema index (EI) are independent risk factors for PFS, but not for OS. Kaplan–Meier curves revealed consistent survival analysis results between IE groups among both clinical patients and TCIA and TCGA patients, suggesting a significant effect of PTBE on PFS but not on OS. Furthermore, functional enrichment analysis predicted the involvement of several pathways related mainly to cellular bioenergetics and vasculogenic processes in the mechanism of PTBE formation. While these novel results warrant confirmation in a larger patient cohort, they support good prognostic value for PTBE assessment in GBM.ConclusionsOur results indicate that a low EI positively impacts disease control in GBM patients, but this does not entirely translate into an improvement in OS. Multiple genes, signaling pathways, and biological processes may contribute to the formation of peritumoral edema in GBM through cytotoxic and vascular mechanisms.

Sex-related differences in demographics, diagnosis and management of patients with chronic coronary syndromes.

The impact of sex-related factors on current clinical management and outcomes of chronic coronary syndromes (CCS) are unclear. All patients belonging to the prospective, nationwide START registry were included. Their baseline characteristics, diagnostic workup, revascularization strategy, pharmacological treatment and 1-year clinical outcomes were compared with respect to sex overall and in age tertiles. A total of 5070 consecutive patients were included. Most patients were males (80.1%). As expected, the prevalence of females increased with age. Distribution of risk factors and history of cardiovascular disease were different depending on sex, as well as diagnostic workup, with lower use of exercise stress testing in women (25.1% vs. 36.7%, P < 0.0001). The use of coronary angiography was similar in the two groups. Women had lower rates of multivessel coronary artery disease (CAD) (33.0% vs. 40.6% P < 0.0001) and higher rates of nonobstructive CAD (18.3% vs. 11.3%, P < 0.0001). Rates of myocardial revascularization were similar, but women were more likely to receive percutaneous coronary intervention than men (84.3% vs. 77.8%, P < 0.0001) and less likely to receive surgical/hybrid revascularization (10.0% vs. 15.1%, P < 0.0001). At 12-month follow-up, no differences were observed for the combined endpoint of all-cause mortality, re-hospitalization for myocardial infarction, heart failure, stroke or myocardial revascularization between males and females; however, a significantly worse perceived quality of life was observed in women. In a large nationwide cohort of patients with CCS, clinical outcomes were not different depending on sex. However, several differences in the diagnostic work-up, treatment strategies and quality of life were found between sexes.

Macular Alterations in a Cohort of Caucasian Patients Affected by Retinitis Pigmentosa

Objectives: Our objective was to investigate the prevalence of macular complications detected by spectral-domain optical coherence tomography (SD-OCT) in a large Caucasian cohort of RP patients, highlight the major alterations in chorioretinal structure, and compare the macular structural changes in eyes affected by retinal dystrophies with those in healthy controls. Methods: This was an observational, retrospective, and cross-sectional study. Three hundred and seven patients with RP were consecutively enrolled and underwent clinical assessment. In particular, SD-OCT images were used to ascertain the morphology of the posterior pole of patients with RP by evaluating the residual ellipsoid zone (EZ), the volume and thickness of the outer nuclear layer (ONLT), and subfoveal choroid thickness (SCT). At the same time, the pathological finding that the patients’ vision was reduced under treatment was analyzed. Results: A total of 436 eyes of 218 patients with RP were studied. Considering all of the eyes studied, 103 had cystoid macular edema (CME) (23.62%), 123 (28.21%) had vitreomacular traction (VMT), and 199 (45.75%) had epiretinal membranes (ERMs). There were also 12 (2.75%) cases of lamellar macular holes (LMHs), of which 3 (1.38% of all patients) cases were bilateral. Only 137 eyes (31.42%) did not have the above-mentioned alterations. SCT was significantly reduced compared to that of the control group (193.03 µm ± 67.90 SD vs. 295 µm ± 69.04 SD), while the foveal central macular thickness (FCMT) was greater (270.91 μm ± 74.04 SD vs. 221 µm ± 37.25 SD). Conclusions: This research highlights the high incidence of macular complications. The results of our study indicate the importance of regular monitoring of RP patients and early intervention to avoid further complications in this group of subjects with severe visual field impairment to avoid further central vision loss.

Oncological and Surgical Outcomes of Oncoplastic Reduction Mammoplasty: A Single-centre Retrospective Study.

Breast-conserving surgery is the preferred treatment for early-stage breast cancer but can often result in unsatisfactory cosmetic outcomes. Oncoplastic surgery aims to improve both oncologic and aesthetic outcomes by combining local excision with plastic surgery techniques. Using breast reduction techniques in breast cancer treatment has been shown to allow for wider margins of excision, leading to enhanced oncological safety and reduced recurrence rates without causing significant asymmetry. This study aimed to analyze the surgical and oncological outcomes of a large cohort of patients undergoing oncoplastic reduction mammoplasty (ORM). A retrospective analysis of postoperative surgical and oncological outcomes of all patients who underwent ORM at a single center between January 2018 and December 2023 was performed. Preoperative patient characteristics, operative and post-operative outcomes were recorded and analyzed. A total of 67 patients that underwent oncologic breast reduction were included in the final analysis - representing a total of 71 ORM, with a mean (SD) age of 53.1 (10.5) years and a mean (SD) BMI of 28.8 (5.9) kg/m2 A superomedial pedicle-based technique was the most frequently used (36.6%), followed by inferior pedicle-based technique (28.1%). A complication rate of 18.3% on the ipsilateral side was observed. Salvage surgery was necessary in five cases (7.0%) due to positive margins - with one patient (1.4%) requiring margin expansion surgery and four (5.6%) a completion mastectomy. This monocentric retrospective study shows that ORM is safe, with a complication rate on par with conventional breast reduction and offers satisfactory oncological outcomes.