Citations

PURPOSE Limited treatment options exist for patients with locally advanced or metastatic biliary tract cancers (BTCs). Recently, several clinical trials provided preliminary evidence for human epidermal growth factor receptor 2 (HER2) as a new target for patients with HER2-expressing BTC. We conducted a systematic review and pooled analysis of the safety and efficacy of anti-HER2 agents in patients with advanced BTCs. METHODS A comprehensive search of PubMed/MEDLINE and EMBASE was performed to identify phase I, II, or III clinical trials published between January 2019 and March 2024 that evaluated anti-HER2 therapy in locally advanced or metastatic BTC. Participant data included in the analysis were from trials evaluating the efficacy and safety of various anti-HER2 agents. The primary end points included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). The secondary end points included incidence of treatment-related adverse events (TRAEs), rate of treatment discontinuation, and death. RESULTS The analysis included 368 patients from eight publications diagnosed with advanced BTC. Patients were treated with several anti-HER2 agents including zanidatamab, pertuzumab plus trastuzumab, tucatinib plus trastuzumab, trastuzumab deruxtecan, trastuzumab plus chemotherapy, trastuzumab-pkrb plus chemotherapy, and neratinib. The pooled ORR and DCR were 34% (95% CI, 24 to 44) and 64% (95% CI, 51 to 77), respectively. The pooled weighted PFS and median overall survival were 4.8 and 9.4 months, respectively. The pooled duration of response for the reporting trials was 5.0 months. In the study cohort, 82.6% of patients experienced any adverse event and 32.1% experienced a grade 3-4 adverse event. Only 5.7% of the patients discontinued treatment secondary to TRAEs. CONCLUSION In patients with HER2-expressing BTCs, anti-HER2 therapies are viable options, particularly in the second-line setting.

Abstract Reprogramming of aged donor tissue cells into induced pluripotent stem cells (A-iPSC) preserved the epigenetic memory of aged-donor tissue, defined as genomic instability and poor tissue differentiation in our previous study. The unbalanced expression of RNA exosome subunits affects the RNA degradation complex function and is associated with geriatric diseases including premature aging and cancer progression. We hypothesized that the age-dependent progressive subtle dysregulation of EXOSC2 (exosome component 2) causes the aging traits (abnormal cell cycle and poor tissue differentiation). We used embryonic stem cells as a tool to study EXOSC2 function as the aging trait epigenetic memory determined in A-iPSC because these aging traits could not be studied in senesced aged cells or immortalized cancer cells. We found that the regulatory subunit of PP2A phosphatase, PPP2R5E, is a key target of EXOSC2 and this regulation is preserved in stem cells and cancer.

Key Points Pooled discrimination metrics were acceptable (area under the receiver operating characteristic curve >0.70) for all AKI risk classification categories in both internal and external validation. Better performance was observed in most recently published studies and those with a low or unclear risk of bias. Significant heterogeneity in patient populations, definitions, clinical predictors, and methods limit implementation in real-world clinical scenarios. Background Artificial intelligence through machine learning models seems to provide accurate and precise AKI risk classification in some clinical settings, but their performance and implementation in real-world settings has not been established. Methods PubMed, Excerpta Medica (EMBASE) database, Web of Science, and Scopus were searched until August 2023. Articles reporting on externally validated models for prediction of AKI onset, AKI severity, and post-AKI complications in hospitalized adult and pediatric patients were searched using text words related to AKI, artificial intelligence, and machine learning. Two independent reviewers screened article titles, abstracts, and full texts. Areas under the receiver operating characteristic curves (AUCs) were used to compare model discrimination and pooled using a random-effects model. Results Of the 4816 articles initially identified and screened, 95 were included, representing 3.8 million admissions. The Kidney Disease Improving Global Outcomes (KDIGO)-AKI criteria were most frequently used to define AKI (72%). We identified 302 models, with the most common being logistic regression (37%), neural networks (10%), random forest (9%), and eXtreme gradient boosting (9%). The most frequently reported predictors of hospitalized incident AKI were age, sex, diabetes, serum creatinine, and hemoglobin. The pooled AUCs for AKI onset were 0.82 (95% confidence interval, 0.80 to 0.84) and 0.78 (95% confidence interval, 0.76 to 0.80) for internal and external validation, respectively. Pooled AUCs across multiple clinical settings, AKI severities, and post-AKI complications ranged from 0.78 to 0.87 for internal validation and 0.73 to 0.84 for external validation. Although data were limited, results in the pediatric population aligned with those observed in adults. Between-study heterogeneity was high for all outcomes (I 2 >90%), and most studies presented high risk of bias (86%) according to the Prediction Model Risk of Bias Assessment Tool. Conclusions Most externally validated models performed well in predicting AKI onset, AKI severity, and post-AKI complications in hospitalized adult and pediatric populations. However, heterogeneity in clinical settings, study populations, and predictors limits their generalizability and implementation at the bedside.

Background Spinal subdural empyema rarely involves the spinal cord and may result in devastating neurological deficits. These lesions typically require prompt diagnosis, surgical evacuation, and antibiotic therapy. Here, we present the clinical course, imaging, and narrated operative video of a thoracic spinal subdural empyema initially diagnosed as an intramedullary neoplasm. Case Description A 73-year-old female presented with a 6-month history of worsening thoracic myelopathy; over the last few weeks, she rapidly developed paraplegia. She was initially diagnosed with an enlarging thoracic intramedullary mass. A spinal biopsy was performed for the presumptive diagnosis of primary intramedullary central nervous system lymphoma. However, at surgery, the thoracic lesion proved to be a chronic subdural empyema (i.e., surrounded by arachnoid granulations and soft-purulent tissue). Interestingly, the operative specimen failed to grow any specific organism. Conclusion Spinal subdural empyema should be one of the differential diagnoses considered for patients presenting with intradural spinal cord lesions.

Background: Static ice storage (SIS) has long been accepted as the conventional lung preservation method, assuming to maintain 4 °C temperature. Although never directly confirmed by temperature measurements, this assumption has been widely accepted. We aimed to measure lung and preservation temperature with SIS in porcine experiments and clinical observations. Methods: Porcine lungs were preserved with SIS for 8 h (group I, n = 3) and 3 h followed by 10 °C storage (group II, n = 3). Tissue (tissueT°), first bag preservation solution (psT°) and second bag saline (salineT°) temperature were monitored. In clinical lungs (n = 4), psT° was monitored during SIS. Surface (surfaceT°) and core (coreT°) temperature were assessed before and after SIS (n = 62). Results: After 4 h in porcine lung group I, average tissueT° was 0.66 °C, psT° was 0.12 °C and salineT° was −0.02 °C. After 3 h in group II, average tissueT° was 1.90 °C, psT° was 0.57 °C and salineT° was 2.33 °C. In clinical observations, psT° was below 4 °C after 9–13 min and 0 °C after 78–267 min. After SIS, median surfaceT° was 1.25 °C (min-max; −3.2–9.2 °C) and coreT° was 1.45 °C (−0.4–4.8 °C). Conclusions: SIS leads to rapid temperature drops below 4 °C, approaching 0 °C within 2–4 h. The post-SIS lung temperature shows considerable variability and does not consistently remain at the commonly assumed 4 °C, posing potential freezing injury to donor lungs.

Précis: 240-degree and 360-degree goniotomy (GT) demonstrated similar efficacy in intraocular pressure (IOP) reduction, both outperforming 120-degree GT in patients with juvenile open angle glaucoma (JOAG) at postoperative 6-month follow-up. Objective: To compare the surgical efficacy and safety of 120-degree, 240-degree, and 360-degree GT for patients with JOAG. Patients and Methods: This multicenter retrospective study included 102 eyes of 102 patients with JOAG, who underwent GT with a follow-up of at least 6 months. Patients were categorized into 3 groups: (1) 120-degree GT, (2) 240-degree GT, and (3) 360-degree GT. IOP, glaucoma medications, and complications were recorded at baseline and the final visit. Complete success and qualified success were defined as a postoperative IOP ≤21 mm Hg without and with medications, respectively. Results: Mean age of the participants was 24.4 ± 7.9 years. After a mean follow-up of 8.1 ± 2.7 months, complete success rates were similar between the 240-degree GT (45.2%) and the 360-degree GT (63.2%; P = 0.135), and both were superior to 120-degree GT (18.2%; P < 0.05). Qualified success rates among patients in the 120-degree, 240-degree, and 360-degree GT groups were 93.9%, 96.8%, and 100%, respectively, and showed no statistically significant difference (P = 0.292). 360-degree GT required fewer medications than 240-degree GT and 120-degree GT (P < 0.05), with no significant difference in medications between 120-degree GT and 240-degree GT (P > 0.05). Hyphema was the most common postoperative complication, with a significantly higher incidence in the 360-degree GT (68.4%) compared with the 240-degree GT (41.9%) and 120-degree GT (33.3%; P < 0.05). Conclusions: 240-degree and 360-degree GT showed similar efficacy in IOP reduction and were superior to 120-degree GT. More extensive GT may provide better outcomes in JOAG.

Abstract Solid tumors develop within a complex environment called the tumor microenvironment (TME), which is sculpted by the presence of other cells, such as cancer‐associated fibroblasts (CAFs) and immune cells like macrophages (Mφs). Despite the presence of immune cells, tumor cells orchestrate a tumor‐supportive environment through intricate interaction with the components of the TME. However, the specific mechanism by which this intercellular dialogue is regulated is not fully understood. To that end, the development of an organotypic 3D breast TME‐on‐a‐chip (TMEC) model, integrated with single‐cell RNA sequencing analysis, is reported to mechanistically evaluate the progression of triple‐negative breast cancer (TNBC) cells in the presence of patient‐derived CAFs and Mφs. Extensive functional assays, including invasion and morphometric characterization, reveal the synergistic influence of CAFs and Mφs on tumor cells. Furthermore, gene expression and pathway enrichment analyses identify the involvement of the KYNU gene, suggesting a potential immune evasion mechanism through the kynurenine pathway. Lastly, the pharmacological targeting of the identified pathway is investigated.