An intact kidney filter is vital to retention of essential proteins in the blood and removal of waste from the body. Damage to the filtration barrier results in albumin loss in the urine, a hallmark of cardiovascular disease and kidney failure. Here we found that the ion channel TRPC5 mediates filtration barrier injury. Using Trpc5-KO mice, a small-molecule inhibitor of TRPC5, Ca 2+ imaging in isolated kidney glomeruli, and live imagining of podocyte actin dynamics, we determined that loss of TRPC5 or its inhibition abrogates podocyte cytoskeletal remodeling. Inhibition or loss of TRPC5 prevented activation of the small GTP-binding protein Rac1 and stabilized synaptopodin. Importantly, genetic deletion or pharmacologic inhibition of TRPC5 protected mice from albuminuria. These data reveal that the Ca 2+ -permeable channel TRPC5 is an important determinant of albuminuria and identify TRPC5 inhibition as a therapeutic strategy for the prevention or treatment of proteinuric kidney disease.

The multiscale organization of protein-based fibrillar materials is a hallmark of many organs, but the recapitulation of hierarchal structures down to fibrillar scales, which is a requirement for withstanding physiological loading forces, has been challenging. We present a microfluidic strategy for the continuous, large-scale formation of strong, handleable, free-standing, multicentimeter-wide collagen sheets of unprecedented thinness through the application of hydrodynamic focusing with the simultaneous imposition of strain. Sheets as thin as 1.9 μm displayed tensile strengths of 0.5–2.7 MPa, Young’s moduli of 3–36 MPa, and modulated the diffusion of molecules as a function of collagen nanoscale structure. Smooth muscle cells cultured on engineered sheets oriented in the direction of aligned collagen fibrils and generated coordinated vasomotor responses. The described biofabrication approach enables rapid formation of ultrathin collagen sheets that withstand physiologically relevant loads for applications in tissue engineering and regenerative medicine, as well as in organ-on-chip and biohybrid devices.

With a firm understanding of the mechanistic underpinning of this rare phenomenon, otolaryngologic surgeons can be better prepared for its occurrence.

Complete surgical cytoreduction (R0 resection) is the single most important prognosticator in epithelial ovarian cancer (EOC). Explainable Artificial Intelligence (XAI) could clarify the influence of static and real-time features in the R0 resection prediction. We aimed to develop an AI-based predictive model for the R0 resection outcome, apply a methodology to explain the prediction, and evaluate the interpretability by analysing feature interactions. The retrospective cohort finally assessed 571 consecutive advanced-stage EOC patients who underwent cytoreductive surgery. An eXtreme Gradient Boosting (XGBoost) algorithm was employed to develop the predictive model including mostly patient- and surgery-specific variables. The Shapley Additive explanations (SHAP) framework was used to provide global and local explainability for the predictive model. The XGBoost accurately predicted R0 resection (area under curve [AUC] = 0.866; 95% confidence interval [CI] = 0.8–0.93). We identified “turning points” that increased the probability of complete cytoreduction including Intraoperative Mapping of Ovarian Cancer Score and Peritoneal Carcinomatosis Index < 4 and <5, respectively, followed by Surgical Complexity Score > 4, patient’s age < 60 years, and largest tumour bulk < 5 cm in a surgical environment of optimized infrastructural support. We demonstrated high model accuracy for the R0 resection prediction in EOC patients and provided novel global and local feature explainability that can be used for quality control and internal audit.

Introduction Anemia's effect on head and neck surgical complications is unknown. Methods Head and neck cancer operations were acquired from the 2006 to 2013 American College of Surgeons National Surgical Quality Improvement Program databases. Anemia was defined as <39% or <36% hematocrit in men and women, respectively. Multivariable logistic regression analyses were performed. Results Major head and neck surgery patients had a 44.2% anemia incidence (n = 527 of 1193). Anemic patients had increased complication rates (27.1%) and mortality (2.1%) vs non‐anemic patients at 19.8% (P = .003) and 0.5% (P = .009), respectively. There was a significant difference in morbidity odds with hematocrit >27% (odds ratio [OR] = 1.09) vs <27% (OR = 4.22). Complication odds were further increased with hematocrit between 24% and 27% (OR = 8.94). There were increased rates of wound dehiscence (6.6% vs 2.7%, P < .001), pneumonia (8.5% vs 4.7%, P = .006), and myocardial infarction (1.7% vs 0.3%, P = .01) in anemic vs non‐anemic patients. Conclusion Anemia was associated with increased morbidity at hematocrit <27%. An inverse dose‐dependent effect of decreasing hematocrit was observed for overall morbidity.

The CST significantly reduces OT for BM procedures compared to the SST without increasing complication rates. While time-savings was < 50% and may not be ideal for every patient, the CST offers an alternative BM approach potentially best-suited for large TBW patients and those undergoing axillary procedures.

The placement of a left atrial appendage occlusion (LAAO) device can be a technically challenging transcatheter‐based procedure. Key challenges include accurate pre‐procedural device sizing and proper device positioning at the LAA ostium to ensure sufficient device anchoring and avoid peri‐device leaks. To address these challenges, 3D printing (3DP) of LAA models has recently emerged in the literature, first being described in 2015. We present a review of the benefits and drawbacks of employing this technology for LAAO procedures. Pre‐procedurally the use of 3DP can consistently and accurately determine LAAO device size over standard of care approaches. Intra‐procedurally 3DP's impact entailed a statistically significant decrease in the number of devices used per procedure, as well as in the fluoroscopic time and dose. Post‐procedurally, there is some evidence that 3DP could reduce the rate of peri‐device leaks, with limited data on its effect on complication rates. Based on existing evidence, we recommend the focused application of 3DP to cases of complex LAA anatomy and for the training of proceduralists. Lastly, we address the emergence of next generation LAAO devices and AR/VR systems that could limit even this narrow window of clinical benefit afforded by 3DP.

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