Citations

Moderate traumatic brain injury (TBI) is a prevalent entity with a wide, dynamic, and heterogeneous injury spectrum. It has its own characteristics. However, it does not receive enough attention, as evidenced by the scarce representation in the literature and the absence of specific guidelines. Its changing epidemiological profile allows us to predict an increase in its incidence in the future, especially in the fragile population. Moderate TBI is not adequately categorized, and the risk of neuroworsening is elevated. The mortality of moderate TBI is not negligible and its functional outcomes are poor. Non-invasive neuromonitoring tools may have a key role in the initial evaluation and categorization of moderate TBI. Moderate TBI has cloudy, dark, and sunny aspects. To analyze these aspects and to propose management strategies constitute the main objective of this narrative review.

Aims Testicular sex cord‐stromal tumours (TSCSTs) are rare neoplasms that arise from (or show differentiation to) elements derived from the sex cords or intertubular stroma. The current classification (World Health Organization, 2022) is based almost entirely on morphology, with many tumour types such as granulosa cell tumours being defined based on their resemblance to ovarian counterparts. Recent studies have uncovered new clinicopathological, molecular and biological nuances within this group of tumours, underscoring differences with ovarian homologues. Methods and results Considering the new data, a group of genitourinary pathology experts (Testicular Sex Cord‐Stromal Tumour [TESST] group) has proposed a revised ‘TESST classification’ that incorporates the best available evidence. This classification is structured and hierarchical, composed of the following tiers: (1) group, (2) category, (3) entity and (4) histological pattern. ‘Group’ refers to the histological compartment a specific tumour belongs to (sex cords, stroma or both), whereas ‘category’ is defined by the phenotype of the tumour, taking non‐neoplastic elements of the ovary and testis as a reference. The third tier, ‘entity’, refers to neoplasms with shared clinicopathological and/or molecular features that justify classifying them as distinct types. Lastly, ‘histological patterns’ are recurrent morphological variations within entities that are not linked to distinct clinicopathological or molecular features. Conclusions We propose a classification that will provide a framework to improve current clinical management and guide future research in the field.

PURPOSE Precision medicine has revolutionized oncology; however, tumor biomarkers are not reflective of the heterogeneous cancer population. We evaluated NRG Oncology prostate cancer (PCa) clinical trials for demographic differences among patients with optional biospecimen collection (BC) consent and biospecimen submission (BSub). METHODS Data from 19 NRG PCa clinical trials closed before 2015 were analyzed. Patients who consented to BC and completed BSub were evaluated by race, ethnicity, median income, area deprivation index (ADI; categorized as highest v lowest three quartiles), age at enrollment, site, and year of enrollment. T/chi-square tests were used for continuous/categorical variables, respectively, followed by logistic regression. RESULTS Of the 15,648 randomized patients eligible for BC, 11,796 (75%) had specimens submitted. In all, 4,598 (82.2%) of 5,597 eligible patients consented for optional BC in nine clinical trials with a separate BC consent process (consent rates by race/ethnicity: 74.1% Black, 72.8% Hispanic/Latino, 83.8% White). A smaller proportion of Black and Hispanic/Latino patients consented to optional BC compared with those who did not (12.1% v 19.5% Black, P < .0001; 3.5% v 5.8% Hispanic, P = .0006). In univariable logistic regression models, high ADI (more socioeconomic disadvantage) was associated with a decreased likelihood for optional BC consent (odds ratio [OR], 0.67 [95% CI, 0.55 to 0.82]; P = .02), but not a decreased likelihood for BSub (OR, 0.74 [95% CI, 0.53 to 1.04]; P = .08). Multivariable models demonstrated that Black/Hispanic/Latino patients were less likely to consent to optional BC, and Black patients were less likely to have BSub ( P < .05 for all). CONCLUSION White/non-Hispanic patients and those with less socioeconomic disadvantage were more likely to consent to optional BC, whereas Black patients were less likely to have BSub. Targeted solutions are needed to improve biorepository representation so that precision medicine approaches better reflect the cancer population.

Abstract Introduction Acute interstitial nephritis is an important differential diagnosis in patients with deteriorating kidney function. Diagnosis currently requires kidney biopsy, an invasive procedure associated with risks. We hypothesized that urinary T cells may serve as a non-invasive biomarker for acute interstitial nephritis. Methods A total of 320 patients undergoing clinically indicated kidney biopsy were enrolled in a discovery cohort at Charité Berlin (n = 80), an internal validation cohort at Charité (n = 100), and an external validation cohort at The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (n = 140). Urinary immune cells were assessed by flow cytometry. Renal T cell infiltration was evaluated by immunofluorescence in kidney biopsy specimens from the discovery and internal validation cohorts, including 16 patients with acute interstitial nephritis and 9 patients without acute interstitial nephritis. Additionally, CXCL9 was measured by ELISA in 102 urine samples from these cohorts. Results Across all cohorts, 27 patients (8.4%) were diagnosed with acute interstitial nephritis. In the discovery cohort, multiple urinary T cell subsets were increased in acute interstitial nephritis, with activated CD4 + effector memory T cells expressing CD38 and HLA-DR showing the strongest diagnostic performance. This marker outperformed urinary monocytes, eosinophils, and CXCL9 and was validated in both independent cohorts. Across all cohorts, the area under the receiver operating characteristic curve was 0.84 and increased to 0.91 after exclusion of 8 patients receiving corticosteroids. A cutoff of 211 activated CD4 + effector memory T cells per 100 mL urine yielded a sensitivity of 78% and a specificity of 81%. Urinary activated CD4 + effector memory T cell counts correlated with renal CD4 + and CD4 + CD38 + T cell infiltration in acute interstitial nephritis. Conclusions Urinary activated CD4 + effector memory T cells expressing CD38 and HLA-DR represent a promising non-invasive biomarker for the diagnosis of acute interstitial nephritis. Lay Summary Acute interstitial nephritis is a frequent cause of acute kidney injury and is usually diagnosed by kidney biopsy, an invasive procedure that carries risks. We investigated whether immune cells in urine could help identify AIN in a less invasive manner. In this multicenter study, urine samples from 320 patients undergoing kidney biopsy in Germany and China were analyzed. We found that a specific population of activated T cells was markedly increased in the urine of patients with AIN compared with patients with other kidney diseases. This urinary marker outperformed other immune cell types and the inflammatory cytokine CXCL9 and was successfully validated in independent cohorts from both Germany and China. Importantly, urinary activated T cell counts correlated with immune cell infiltration within the kidney. These findings suggest that urinary activated T cells may serve as a non-invasive biomarker to support the diagnosis of AIN and facilitate earlier clinical decision-making.

ABSTRACT Management of prostate cancer has improved over the past two decades, driven by innovations in detection of metastatic disease, biomarker characterization, and treatment. This review summarizes the latest progress in managing advanced states of this disease, spanning high risk biochemical recurrence, metastatic hormone sensitive prostate cancer (mHSPC), and metastatic castration resistant prostate cancer (mCRPC). Improved outcomes for patients have been seen with earlier use of androgen receptor pathway inhibitors in the setting of high risk biochemical recurrence and mHSPC. Meanwhile, individuals with mCRPC now represent a more diverse population, differentiated by both their previous treatments and other biological features. Advanced imaging and genomic biomarkers improve patient selection and permit more personalized therapy. Landmark clinical trials and meta-analyses have established and/or refined the role of chemotherapy, poly-ADP ribose polymerase (PARP) inhibitors, and 177 Lu-PSMA-617 in this disease space. Finally, as patients with prostate cancer are living longer, the review focuses on understanding and managing potential adverse events, including cardiac and hematologic toxicity and bone health.

TAF7, a core subunit of the general transcription factor TFIID, regulates transcription and additionally functions as an RNA chaperone that directs nascent nuclear RNAs to cytoplasmic polysomes, thereby influencing protein synthesis. Here, we identify a set of novel cytoplasmic interactors and a previously unappreciated cytoplasmic role for TAF7 in oncogenesis. BioID-mediated proximity labeling identified STAT3 and the CCT and WASH complexes as prominent cytoplasmic interactors of TAF7. These interactions were validated by co-immunoprecipitation and proximity ligation assays. We further showed that cytoplasmic TAF7 levels increased during oncogenesis in proportion to cancer cell pathogenicity. Notably, TAF7 engagement with STAT3, CCT and WASH complexes is markedly enhanced during cellular transformation, consistent with their functions in cancer progression. Together, these findings reveal a cytoplasmic TAF7 interactome and implicate elevated cytoplasmic TAF7 as associated with oncogenesis.

Background: The origin of arthrofibrosis of the knee is multifactorial; however, it is more commonly seen in patients with arthritis, prolonged immobility, or a history of trauma or surgery to the knee. Arthrofibrosis that results in a flexion contracture of the knee is commonly attributable to scarring and shortening of the posterior joint capsule as seen in the setting of operative intervention, such as anterior cruciate ligament reconstruction (ACLR). Indications: Arthroscopic posterior capsular releases of the knee are indicated in patients with recalcitrant arthrofibrosis who have (1) failed nonoperative management and (2) a flexion contracture of ≥10°. Technique Description: This arthroscopic technique utilizes posteromedial and posterolateral portals in addition to the standard anteromedial and anterolateral portals. A transpatellar tendon portal may also be used to create the posterolateral portal. Both a 30° and a 70° arthroscope are used to better visualize the posteromedial and posterolateral inferior and superior releases. In addition to releases of the capsule both inferiorly and posteriorly, the medial and lateral gastrocnemius tendons can be partially released from the femur to allow for a more adequate release. The 70° arthroscope is necessary to access the capsule posterior to the posterior cruciate ligament to ensure complete release. Results: This procedure is typically reserved for patients who have failed conservative management with extension splinting, physical therapy, and the use of corticosteroids. Persistent arthrofibrosis with flexion contracture can occur after ACLR, with an incidence as high as 38% in some series. The specific technique described in this video has documented patient-reported outcomes of achieving full extension in >90% of patients after an arthroscopic posterior capsular release at final follow-up. Discussion/Conclusion: Recalcitrant arthrofibrosis leading to a persisting extension deficit can be devastating for a patient, as it results in increased pain and stiffness, as well as a significant decrease in functionality. Performing a posterior capsular release in addition to the standard manipulation under anesthesia and lysis of adhesions/synovectomy will allow for greater knee range of motion, particularly greater knee extension. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Abstract Unvetted scientific claims about vaccines can spread rapidly and undermine decades of progress in immunization and public trust. A recent non-peer-reviewed analysis, promoted at political hearings, in the documentary “An Inconvenient Study,” and on social media, has been used to suggest that vaccinated children experience higher rates of chronic illness than unvaccinated peers. Despite standard regression models, critical flaws - uncontrolled confounding, exposure misclassification, unequal follow-up, and outcome multiplicity, invalidate causal inference. An independent group of international experts critically appraises this analysis and contrast its claims with the consistent evidence confirming vaccine safety and effectiveness. We also show how poorly designed studies can distort public discourse, amplify misinformation, and fuel vaccine hesitancy. We outline actions to strengthen research integrity, such as transparent data sharing, labeling of non-peer-reviewed content, and evidence-based communication. Safeguarding public health demands that vaccine evidence be methodologically sound, reviewed, and interpreted by qualified experts.

ABSTRACT Context effects are ubiquitous across sensory systems and reflect a general encoding principle for both simple and complex stimuli. One simple context effect, contraction bias, manifests in two-interval perception tasks as a bias of the perceived magnitude of the first stimulus toward the center of the overall magnitude range. The underlying cause of contraction bias is unclear. One explanation is that a listener’s magnitude estimate of the first stimulus is combined with a perceptual anchor, usually the mean stimulus magnitude, biasing it toward the anchor (sensory model). An alternative explanation is that a listener’s response criterion shifts, based on the magnitude of the stimulus pair, relative to the mean magnitude of the stimuli range (decision model). Two pitch-discrimination experiments were performed to test these hypotheses in the auditory domain. The first was a forced-choice discrimination task, where listeners were asked to identify the higher or lower tone in a pair. The second was a same-different task where listeners indicated whether or not the two tones in a pair differed in frequency. Contraction bias was observed in the higher-lower discrimination task, even after extensive perceptual training with feedback. In contrast, no contraction bias was observed in the same-different task. Computational models of the sensory and decision hypotheses were fit to data from both experiments. The sensory model captured the pattern of results the higher-lower experiment but erroneously predicted a contraction bias in the same-different task. The decision model produced similar predictions to the sensory model in the higher-lower task but correctly predicted no contraction bias in the same-different task, and produced lower prediction errors and more stable parameter estimates in both paradigms. Overall, the results suggest that the underlying nature of the contraction bias may reflect decision, rather than sensory, biases based on the context. AUTHOR SUMMARY Every day, people combine experiential knowledge of the world and incoming sensory information to assess their environment. Interestingly, the environment itself can substantially alter how incoming sensory information is processed and perceived. These so-called context effects occur in all sensory modalities. Here, we examine one such context effect, known as “contraction bias”, in a simple pitch-discrimination task. Prior work argued that the contraction bias occurs because observers make biased estimates of stimulus magnitudes due to the influence of recent stimulus history. By combining behavioral data and computational modeling, we offer a different explanation, more consistent with the available data, which posits that the bias can be accounted for by systematic shifts in observers’ response strategies with changes in relative stimulus magnitudes. The results shed light onto how humans compare and process sensory features within their environment.