Citations

Ovarian cancer (OC) has the highest mortality rate among gynecologic malignant tumors and is clinically difficult to cure. Traditional Chinese medicine (TCM) has shown unique advantages in the treatment of OC. However, there is currently a lack of normative guidance documents for the treatment of OC with integrated traditional Chinese and western medicine. The guidelines are the first comprehensive approach to diagnosing and treating OC by integrating TCM with western medicine. Adhering to evidence-based principles, the guidelines draw on the most recent advancements in OC treatment from both domestic and international researches. The guidelines formulate a variety of therapeutic methods, including oral Chinese herbal medicine, acupuncture, and external treatments, providing a treatment strategy for the combined use of TCM and western medicine in OC. Furthermore, the guidelines establish a diagnostic and treatment pathway for the holistic management of OC with TCM throughout the disease’s progression. The guidelines were officially published in the China Association of Chinese Medicine in January 2023, which provided a scientific basis for the formulation of clinical diagnosis and treatment strategies and promoted integration with international academic standards. This paper interpreted the features of the guidelines and the 7 PICO issues (Population, Intervention, Comparison, Outcome) in the whole TCM management of OC, aiming to help TCM and western medicine practitioners better understand and apply the guidelines, and provide better medical services for patients with OC.

Gastric cancer is a significant global health concern, with CDH1-associated gastric cancer representing a small but important subset of cases. Historically, individuals with CDH1 pathogenic germline variants were advised to undergo prophylactic total gastrectomy due to the high reported risk of gastric cancer and the limited sensitivity of upper endoscopy in detecting signet ring cell carcinoma (SRCC). However, emerging data suggest that the cumulative lifetime risk of advanced gastric cancer among CDH1 germline pathogenic variant carriers is lower than previously thought, and early-stage SRCC detected on endoscopy does not necessarily indicate imminent—or even eventual—progression to advanced cancer. The near-universal presence of T1a SRCC in gastrectomy specimens from asymptomatic CDH1 pathogenic variant carriers calls into question the reflexive recommendation for gastrectomy, including upon detection of SRCC during surveillance. Furthermore, the morbidity and quality-of-life impact associated with total gastrectomy require careful consideration. Active endoscopic surveillance has shown promise as an alternative management strategy for gastrectomy in patients lacking indicators of >T1a SRCC, though current data are limited by short follow-up periods and selection bias. This review synthesizes recent findings on the natural history of CDH1-associated gastric cancer and evaluates the risks and benefits of gastrectomy versus active endoscopic surveillance, with the goal of helping clinicians provide personalized and evidence-based recommendations for patients with CDH1 pathogenic variants.

Abstract Hereditary tumor predisposition syndromes pose a challenge for early detection and timely treatment of tumors. In von Hippel–Lindau disease, desirable personalized surveillance programs are lacking due to insufficient data on genotype-specific risk profiles of individual mutations. To describe neoplastic risk profiles for carriers of pathogenic and likely pathogenic VHL germline mutations, our observational study recruited 1,350 participants from 40 centers worldwide. 432 different VHL germline mutations were observed, with p.Asn78Ser, p.Arg161Ter, p.Arg161Gln, p.Arg167Gln, p.Arg167Trp and p.Tyr98His being the six most frequent, occurring in a total of 493 carriers (36.5%) and in ≥30 patients each. Age-related penetrance risks for retinal hemangioblastoma, central nervous system hemangioblastoma, renal cell carcinoma, pancreatic neuroendocrine tumors and pheochromocytoma/paraganglioma in carriers of the most frequent VHL mutations were assessed. In addition, the number of organs affected, the frequency of surgery and the outcome are reported. Pairwise comparisons of the age-dependent tumor penetrance of these six mutations showed that 47 out of 90 pairs were significantly different. The most significant associations were found in p.Tyr98His (n = 19), followed by p.Arg161Ter (n = 10). All pairwise comparisons of mutations affecting different codons showed at least one significant (P < 0.05) difference, except for p.Asn78Ser vs p.Arg161Ter. Thus, tumor risk varied by VHL mutation type and location, but did not differ between the truncating mutation p.Arg161Ter and the missense mutation p.Asn78Ser. Our study demonstrates the importance of mutation-specific phenotype prediction. With appropriate validation, the data have important implications for risk assessment and decision making in tumor prevention for carriers of the respective VHL mutations.

Artificial intelligence (AI) has emerged as a promising adjunct in the diagnosis and management of infective endocarditis (IE), a disease characterized by diagnostic complexity and significant morbidity. Machine learning (ML) models such as SABIER and SYSUPMIE have demonstrated strong predictive accuracy for early IE diagnosis, embolic risk stratification, and postoperative mortality, surpassing traditional clinical scoring systems. In imaging, AI-enhanced echocardiography and advanced modalities like FDG-PET/CT offer improved sensitivity, specificity, and reduced inter-observer variability, potentially transforming clinical decision making. Additionally, AI-powered microbiological techniques, including MALDI-TOF mass spectrometry combined with ML and neural network-based metagenomic classifiers, show promise in rapidly identifying pathogens and predicting antimicrobial resistance. Despite encouraging early results, widespread adoption faces barriers, including data limitations, interpretability issues, ethical concerns, and the need for robust validation. Future directions include leveraging generative AI as clinical consultative tools, provided their capabilities and limitations are carefully managed. Ultimately, collaborative efforts addressing these challenges could transform IE care, enhancing diagnostic accuracy, clinical outcomes, and patient safety.

Abstract Microbial communities, such as biofilms, consist of bacteria that exhibit cell-to-cell heterogeneity in their physiological properties, including enzyme activity and gene expression. This single-cell heterogeneity influences the community’s overall metabolic activity and contributes to stress tolerance, such as antimicrobial resistance. To study the impact of single-cell heterogeneity on population-level behaviors, methods have been developed to isolate and characterize bacteria at the single-cell level. One such method includes water-in-oil drop-based microfluidics. However, a limitation of this approach is that the droplet contents cannot be exchanged during experiments, making it difficult to investigate how cells respond to changing environmental conditions. To address this limitation, we developed a drop-based microfluidic technique called Bioflex, which creates permeable hydrogel-shell microcapsules that act as growth chambers for individual bacterial cells. The microcapsules are formed by crosslinking a shell made from a PEG-based hydrogel (4-arm PEG-maleimide) around a dextran core. After cross-linking, the dextran core diffuses out of the capsules and is replaced with buffer or growth medium. By adjusting fluid flow rates during the process, we can control the size and shell thickness of the microcapsules, allowing the production of different capsule architectures. The Bioflex capsules are biocompatible, supporting the encapsulation and growth of Pseudomonas aeruginosa by allowing nutrient transport across the capsule shell. Moreover, the capsules remained permeable to antimicrobial treatments introduced during P. aeruginosa incubation. For example, P. aeruginosa cells in Bioflex capsules responded to externally delivered ciprofloxacin treatments, with their responses varying depending on the timing of the antibiotic introduction. In summary, Bioflex capsules provide a novel, high-throughput platform for isolating single-cells and testing how single-cell derived communities react to time-dependent stresses, such as antibiotic treatments. Graphical Abstract Bacterial cultivation using permeable microscale Bioflex capsules. (A) P. aeruginosa PAO1 expressing eGFP cultured in a Bioflex capsule starting from a single cell. (B) Bioflex capsules are permeable to nutrient and waste transport. (C) The capsules allow for exchange of media to study the responses of single cells or small populations of cells within the drops using time-lapse imaging.

Abstract Purpose Data regarding the incidence, onset, and management of complex outpatient antimicrobial therapy–induced neutropenia (COIN) are limited, and pharmacist involvement in COIN management has not been reported. This report describes the incidence, onset, and management of COIN at a large academic medical center. Methods This multisite retrospective cohort study examined adult patients undergoing serum laboratory monitoring for antimicrobials over a 4-year period. Patients receiving chemotherapy or immunosuppressants were excluded. Data collected included the antimicrobial regimen, complete blood count, duration of antimicrobial therapy until outcome occurrence, infectious syndrome, type of intervention, outcome, and pharmacist involvement. Logistic regression was used to assess risk factors for COIN incidence. The primary outcome was the incidence of COIN by antimicrobial drug. Results From 4,261 treatment episodes, 161 cases of COIN were identified (3.8% COIN incidence). The most common antimicrobials associated with COIN were intravenous piperacillin/tazobactam, cefepime, and meropenem. The majority of COIN events were attributed to a combination of at least 2 antimicrobials. Piperacillin/tazobactam was significantly associated with higher odds of developing COIN (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.04-3.34; P = 0.038), whereas ertapenem was associated with significantly lower odds of COIN (OR, 0.43; 95% CI, 0.24-0.77; P = 0.005). The median time to neutropenia diagnosis was 22 days (interquartile range, 14-29 days) from the time of inpatient antimicrobial start. Intervention for COIN occurred in 66.5% of cases, with neutrophil count recovering in 96.9% of these patients. Clinical pharmacists initiated 74.8% of interventions. Conclusion COIN can be effectively identified and managed by a multidisciplinary team reviewing routine laboratory monitoring, enabling most patients to safely complete antimicrobial treatment.