Finger and forehead photoplethysmography-derived pulse-pressure variation and the benefits of baseline correction.

To non-invasively predict fluid responsiveness, respiration-induced pulse amplitude variation (PAV) in the photoplethysmographic (PPG) signal has been proposed as an alternative to pulse pressure variation (PPV) in the arterial blood pressure (ABP) signal. However, it is still unclear how the performance of the PPG-derived PAV is site-dependent during surgery. The aim of this study is to compare finger- and forehead-PPG derived PAV in their ability to approach the value and trend of ABP-derived PPV. Furthermore, this study investigates four potential confounding factors, (1) baseline variation, (2) PPV, (3) ratio of respiration and heart rate, and (4) perfusion index, which might affect the agreement between PPV and PAV. In this work, ABP, finger PPG, and forehead PPG were continuously recorded in 29 patients undergoing major surgery in the operating room. A total of 91.2 h data were used for analysis, from which PAV and PPV were calculated and compared. We analyzed the impact of the four factors using a multiple linear regression (MLR) analysis. The results show that compared with the ABP-derived PPV, finger-derived PAV had an agreement of 3.2 ± 5.1%, whereas forehead-PAV had an agreement of 12.0 ± 9.1%. From the MLR analysis, we found that baseline variation was a factor significantly affecting the agreement between PPV and PAV. After correcting for respiration-induced baseline variation, the agreements for finger- and forehead-derived PAV were improved to reach an agreement of - 1.2 ± 3.8% and 3.3 ± 4.8%, respectively. To conclude, finger-derived PAV showed better agreement with ABP-derived PPV compared to forehead-derived PAV. Baseline variation was a factor that significantly affected the agreement between PPV and PAV. By correcting for the baseline variation, improved agreements were obtained for both the finger and forehead, and the difference between these two agreements was diminished. The tracking abilities for both finger- and forehead-derived PAV still warrant improvement for wide use in clinical practice. Overall, our results show that baseline-corrected finger- and forehead-derived PAV may provide a non-invasive alternative for PPV.

Evaluating Cellularity Estimation Methods: Comparing AI Counting with Pathologists' Visual Estimates.

The development of next-generation sequencing (NGS) has enabled the discovery of cancer-specific driver gene alternations, making precision medicine possible. However, accurate genetic testing requires a sufficient amount of tumor cells in the specimen. The evaluation of tumor content ratio (TCR) from hematoxylin and eosin (H&E)-stained images has been found to vary between pathologists, making it an important challenge to obtain an accurate TCR. In this study, three pathologists exhaustively labeled all cells in 41 regions from 41 lung cancer cases as either tumor, non-tumor or indistinguishable, thus establishing a "gold standard" TCR. We then compared the accuracy of the TCR estimated by 13 pathologists based on visual assessment and the TCR calculated by an AI model that we have developed. It is a compact and fast model that follows a fully convolutional neural network architecture and produces cell detection maps which can be efficiently post-processed to obtain tumor and non-tumor cell counts from which TCR is calculated. Its raw cell detection accuracy is 92% while its classification accuracy is 84%. The results show that the error between the gold standard TCR and the AI calculation was significantly smaller than that between the gold standard TCR and the pathologist's visual assessment (p<0.05). Additionally, the robustness of AI models across institutions is a key issue and we demonstrate that the variation in AI was smaller than that in the average of pathologists when evaluated by institution. These findings suggest that the accuracy of tumor cellularity assessments in clinical workflows is significantly improved by the introduction of robust AI models, leading to more efficient genetic testing and ultimately to better patient outcomes.

Design and evaluation of in vivo bioavailability in beagle dogs of bilayer tablet consisting of immediate release nanosuspension and sustained release layers of rebamipide.

The purpose of this study was to develop a once-daily, bilayer matrix tablet with immediate (IR) and sustained release (SR) layers of poorly water-soluble and absorption site dependent rebamipide (RBM) to substitute three times a day IR tablet. Owing to the pH-dependent poor water solubility of RBM in low pH condition, salt-caged nanosuspensions (NSPs) consisting of RBM and poloxamer 407 (POX 407) or poloxamer 188 (POX 188) were prepared using an acid-base neutralization method to increase the dissolution rate, which was subsequently applied to the immediate-release (IR) layer. Polyethylene oxide (PEO) with different molecular weights (PEO 100,000 and PEO 5,000,000) and hydroxypropyl methylcellulose 4000 (HPMC 4000) were then investigated as SR agents to incorporate into the SR layer with pure RBM via wet granulation method. The dissolution profile of the optimized bilayer tablet having 50% IR and 50% SR layer of 300 mg RBM showed that the IR layer could rapidly disintegrate in pH 1.2 buffer solution within 2 h, reaching 50% of drug release from the tablet, followed by an extended drug release from the SR layer in pH 6.8 buffer over 24 h. An in vivo pharmacokinetic study was carried out in beagle dogs to compare the optimal formulation (300 mg RBM bilayer tablet) and the commercial tablet (Mucosta® 100 mg) as a reference. Unexpectedly, despite enhanced dissolution rate in a controlled manner, a designed bilayer tablet had no dose- and dosage form dependent in vivo bioavailability in beagle dogs as compared with IR 100 mg RBM reference tablet. It was evident that solubility in low pH condition, gastric residence time and absorption site of RBM should be carefully considered for designing specific SR or gastroretentive dosage form to improve therapeutic outcomes.