Citations

AbstractPatient‐derived cancer organoids (PDOs) hold considerable promise for personalizing therapy selection and improving patient outcomes. However, it is challenging to generate PDOs in sufficient numbers to test therapies in standard culture platforms. This challenge is particularly acute for pancreatic ductal adenocarcinoma (PDAC) where most patients are diagnosed at an advanced stage with non‐resectable tumors and where patient tissue is in the form of needle biopsies. Here the development and characterization of microfluidic devices for testing therapies using a limited amount of tissue or PDOs available from PDAC biopsies is described. It is demonstrated that microfluidic PDOs are phenotypically and genotypically similar to the gold‐standard Matrigel organoids with the advantages of 1) spheroid uniformity, 2) minimal cell number requirement, and 3) not relying on Matrigel. The utility of microfluidic PDOs is proven by testing PDO responses to several chemotherapies, including an inhibitor of glycogen synthase kinase (GSKI). In addition, microfluidic organoid cultures are used to test effectiveness of immunotherapy comprised of NK cells in combination with a novel biologic. In summary, our microfluidic device offers considerable benefits for personalizing oncology based on cancer biopsies and may, in the future, be developed into a companion diagnostic for chemotherapy or immunotherapy treatments.

Background and Objectives: Through a comprehensive meta-analysis of the pertinent literature, this study evaluated the utility and efficacy of perioperative infraorbital and/or infratrochlear nerve blocks in reducing postoperative pain and related morbidities in patients undergoing septorhinoplasty. Materials and Methods: We reviewed studies retrieved from the PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases up to August 2023. The analysis included a selection of seven articles that compared a treatment group receiving perioperative infraorbital and/or infratrochlear nerve blocks with a control group that either received a placebo or no treatment. The evaluated outcomes covered parameters such as postoperative pain, the amount and frequency of analgesic medication administration, the incidence of postoperative nausea and vomiting, as well as the manifestation of emergence agitation. Results: The treatment group displayed a significant reduction in postoperative pain (mean difference = −1.7236 [−2.6825; −0.7646], I2 = 98.8%), as well as a significant decrease in both the amount (standardized mean difference = −2.4629 [−3.8042; −1.1216], I2 = 93.0%) and frequency (odds ratio = 0.3584 [0.1383; 0.9287], I2 = 59.7%) of analgesic medication use compared to the control. The incidence of emergence agitation (odds ratio = 0.2040 [0.0907; 0.4590], I2 = 0.0%) was notably lower in the treatment group. The incidence of postoperative nausea and vomiting (odds ratio = 0.5393 [0.1309; 2.2218], I2 = 60.4%) showed a trend towards reduction, although it was not statistically significant. While no adverse effects reaching statistical significance were reported in the analyzed studies, hematoma (proportional rate = 0.2133 [0.0905; 0.4250], I2 = 76.9%) and edema (proportional rate = 0.1935 [0.1048; 0.3296], I2 = 57.2%) after blocks appeared at rates of approximately 20%. Conclusions: Infraorbital and/or infratrochlear nerve blocks for septorhinoplasty effectively reduce postoperative pain and emergence agitation without notable adverse outcomes.

AbstractObjectiveInternal nasal valve dysfunction is a prevalent cause of nasal obstruction. This systematic review, along with a Meta‐analysis, evaluated the efficacy of temperature‐controlled radiofrequency device (RFD) treatment in alleviating nasal obstruction by rectifying nasal valve collapse.Data SourcesA comprehensive review of studies retrieved from PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases (up to December 2022) was conducted.Review MethodsWe included studies that evaluated the quality of life and nasal obstruction scores before and after RFD treatment. In addition, sham‐controlled studies were analyzed.ResultsIn total, 451 patients across 8 studies were included in the analysis. Patients who underwent RFD treatment reported a significantly enhanced quality of life 24 months after treatment compared to pretreatment scores. The rates of clinically improved states and positive responses regarding quality of life after treatment were 82% and 91%, respectively. Moreover, the disease‐specific quality of life, as assessed by the Nasal Obstruction Symptom Evaluation score, significantly improved.ConclusionRFD may help improve nasal obstruction symptoms. Further randomized clinical studies on larger cohorts are essential to substantiate its efficacy in enhancing nasal valve function.

Human pluripotent stem cells (hPSCs) are capable of unlimited proliferation and can undergo differentiation to give rise to cells and tissues of the three primary germ layers. While directing lineage selection of hPSCs has been an active area of research, improving the efficiency of differentiation remains an important objective. In this study, we describe a two-compartment microfluidic device for co-cultivation of adult human hepatocytes and stem cells. Both cell types were cultured in a 3D or spheroid format. Adult hepatocytes remained highly functional in the microfluidic device over the course of 4 weeks and served as a source of instructive paracrine cues to drive hepatic differentiation of stem cells cultured in the neighboring compartment. The differentiation of stem cells was more pronounced in microfluidic co-cultures compared to a standard hepatic differentiation protocol. In addition to improving stem cell differentiation outcomes, the microfluidic co-culture system described here may be used for parsing signals and mechanisms controlling hepatic cell fate.

Background: To evaluate the diagnostic performance of ultrasound risk-stratification systems for the discrimination of benign and malignant thyroid nodules and to determine the optimal cutoff values of individual risk-stratification systems. Methods: PubMed, Embase, SCOPUS, Web of Science, and Cochrane library databases were searched up to August 2022. Sensitivity and specificity data were collected along with the characteristics of each study related to ultrasound risk stratification systems. Results: Sixty-seven studies involving 76,512 thyroid nodules were included in this research. The sensitivity, specificity, diagnostic odds ratios, and area under the curves by K-TIRADS (4), ACR-TIRADS (TR5), ATA (high suspicion), EU-TIRADS (5), and Kwak-TIRADS (4b) for malignancy risk stratification of thyroid nodules were 92.5%, 63.5%, 69.8%, 70.6%, and 95.8%, respectively; 62.8%, 89.6%, 87.2%, 83.9%, and 63.8%, respectively; 20.7111, 16.8442, 15.7398, 12.2986, and 38.0578, respectively; and 0.792, 0.882, 0.859, 0.843, and 0.929, respectively. Conclusion: All ultrasound-based risk-stratification systems had good diagnostic performance. Although this study determined the best cutoff values in individual risk-stratification systems based on statistical assessment, clinicians could adjust or alter cutoff values based on the clinical purpose of the ultrasound and the reciprocal changes in sensitivity and specificity.

(1) Background: To determine the optimal cut-off values of two risk stratification systems to discriminate malignant thyroid nodules and to compare the diagnostic performance; (2) Methods: True and false positive and negative data were collected, and methodological quality was assessed for forty-six studies involving 39,085 patients; (3) Results: The highest area under the receiver operating characteristic (ROC) curve (AUC) of ACR and Kwak TI-RADS were 0.875 and 0.884. Based on the optimal sensitivity and specificity, the highest accuracy values of ROC curves or diagnostic odds ratios (DOR) were taken as the cut-off values for TR4 (moderate suspicious) and 4B. The sensitivity, specificity, DOR, and AUC by ACR (TR4) and Kwak TI-RADS (4B) for malignancy risk stratification of thyroid nodules were 94.3% and 96.4%; 52.2% and 53.7%; 17.5185 and 31.8051; 0.786 and 0.884, respectively. There were no significant differences in diagnostic accuracy in any of the direction comparisons of the two systems; (4) Conclusions: ACR and Kwak TI-RADS had good diagnostic performances (AUCs > 85%). Although we determined the best cut-off values in individual risk stratification systems based on statistical assessment, clinicians can adjust the optimal cut-off value according to the clinical purpose of the ultrasonography because raising or lowering cut-points leads to reciprocal changes in sensitivity and specificity.

Abstract Liver cultures may be used for disease modeling, testing therapies, and predicting drug‐induced injury. The complexity of the liver cultures has evolved from hepatocyte monocultures to co‐cultures with non‐parenchymal cells and finally to precision‐cut liver slices. The latter culture format retains liver's native biomolecular and cellular complexity and therefore holds considerable promise for in vitro testing. However, liver slices remain functional for ≈72 h in vitro and display limited utility for some disease modeling and therapy testing applications that require longer culture times. This paper describes a microfluidic device for longer‐term maintenance of functional organotypic liver cultures. This microfluidic culture system is designed to enable direct injection of liver tissue into a culture chamber through a valve‐enabled side port. Liver tissue is embedded in collagen and remained functional for up to 31 days, highlighted by continued production of albumin and urea. These organotypic cultures also express several enzymes involved in xenobiotic metabolism. Conversely, matched liver tissue embedded in collagen in a 96‐well plate loses its phenotype and function within 3–5 days. The microfluidic organotypic liver cultures described here represent a significant advance in liver cultivation and may be used for future modeling of liver diseases or for individualized liver‐directed therapies.

Background: To assess the safety and effectiveness of transoral robotic thyroidectomy (TORT) in thyroid tumor. Methods: PubMed, Embase, Web of Science, SCOPUS, Cochrane database, and Google Scholar up to June 2022. Studies comparing outcomes and complications between TORT and control groups (robotic bilateral axillo-breast, trans-axillary, postauricular approach, conventional open thyroidectomy (OT), and transoral endoscopic approach) were analyzed. Results: Ten studies of 1420 individuals. The operative time (SMD 1.15, 95%CI [0.48; 1.89]) was significantly longer and the number of retrieved lymph nodes (LNs) (SMD −0.27, 95%CI [−0.39; −0.16]) was fewer in TORT than in the control group. The postoperative cosmetic satisfaction score (SMD 0.60, 95%CI [0.28; 0.92]) was statistically higher in TORT than in the control group. In subgroup analysis, there was no significant difference between robotic surgeries. However, TORT had significantly longer operative times (SMD 2.08, 95%CI [0.95; 3.20]) and fewer retrieved LNs (SMD −0.32, 95%CI [−0.46; −0.17]) than OT. TORT satisfied significantly more patients in cosmetic view. However, it increased hospitalization days and postoperative pain on the operation day and first day compared to OT. Conclusions: TORT is not inferior to other robotic-assisted approaches. Its operation time and hospitalization days are longer and postoperative pain is greater than OT, although its cosmetic satisfaction is high.