Retinoic Acid-Mediated Control of Energy Metabolism Is Essential for Lung Branching Morphogenesis.

Lung branching morphogenesis relies on intricate epithelial-mesenchymal interactions and signaling networks. Still, the interplay between signaling and energy metabolism in shaping embryonic lung development remains unexplored. Retinoic acid (RA) signaling influences lung proximal-distal patterning and branching morphogenesis, but its role as a metabolic modulator is unknown. Hence, this study investigates how RA signaling affects the metabolic profile of lung branching. We performed ex vivo lung explant culture of embryonic chicken lungs treated with DMSO, 1 µM RA, or 10 µM BMS493. Extracellular metabolite consumption/production was evaluated by using 1H-NMR spectroscopy. Mitochondrial respiration and biogenesis were also analyzed. Proliferation was assessed using an EdU-based assay. The expression of crucial metabolic/signaling components was examined through Western blot, qPCR, and in situ hybridization. RA signaling stimulation redirects glucose towards pyruvate and succinate production rather than to alanine or lactate. Inhibition of RA signaling reduces lung branching, resulting in a cystic-like phenotype while promoting mitochondrial function. Here, RA signaling emerges as a regulator of tissue proliferation and lactate dehydrogenase expression. Furthermore, RA governs fatty acid metabolism through an AMPK-dependent mechanism. These findings underscore RA's pivotal role in shaping lung metabolism during branching morphogenesis, contributing to our understanding of lung development and cystic-related lung disorders.

Impact of polyurethane versus acellular dermal matrix coating on prepectoral reconstruction outcomes: Interface does matter.

BACKGROUND: Interfaces continue to be used in prepectoral breast reconstruction to refine breast appearance, but more clinical data are required to assess their effectiveness. This study compares the rates of capsular contracture, breast esthetics, and patient satisfaction between two commonly used interface materials, acellular dermal matrix (ADM) and polyurethane (PU) foam. METHODS: A cross-sectional assessment was conducted on all patients who underwent prepectoral direct-to-implant reconstruction with an interface material between June 2018 and June 2022. We compared capsular contracture rates (assessed in-person), esthetic outcomes (evaluated by a three-member panel using a specially designed scale), and patient satisfaction (measured using the Breast-Q questionnaire) among the members of the interface groups. RESULTS: Among the 79 reconstructed breasts (20 bilateral cases), 35 were reconstructed using ADM and 44 using PU implants. The ADM group had a significantly higher frequency of Baker III/IV capsular contracture compared with the PU group (14.3% vs. 0%, p = 0.014) and lower ratings from the panel in terms of capsular contracture (median 3.7 vs. 4.0, p < 0.001). PU reconstructions scored worse in implant visibility (median 2.3 vs. 3.3, p < 0.001) and rippling (median 3.0 vs. 3.7, p < 0.001). However, after appropriate adjustment for confounders, no significant differences in overall appearance and patient satisfaction were found. CONCLUSIONS: ADM reconstructions are prone to capsular contracture with all their related esthetic issues, but PU implants have certain cosmetic flaws, such as implant visibility and malposition. Since each technique has its own limitations, neither the experienced surgeons nor patients exhibited a clear preference for either approach.

Heterotopic ossification - A rare donor site complication after iliac crest free flap.

Iliac crest free flap is still essential as a source of vascularized bone tissue, having a definite role in osseous reconstruction of the face and other small bone defects. Some of its drawbacks include laborious dissection and donor site morbidity. We report a case of a patient that presented to our follow-up consultation ten years after iliac crest free flap harvest with new complaints of pain, gait disturbance and swelling in the right hip. Imaging exams revealed a heterotopic bone formation and helped with the diagnosis of heterotopic ossification (HO) of the right iliacus bone. Surgical intervention was needed for debridement of the heterotopic bone, with resolution of the symptoms. To our knowledge, this is the first report of HO after iliac crest free flap harvest. This rare condition adds to an already well-known number of donor zone complications of this flap. Plastic surgeons should be aware of this complication, as it can cause disability many years after the original surgery.

A Comparative Study of Deep Learning Methods for Multi-Class Semantic Segmentation of 2D Kidney Ultrasound Images.

Ultrasound (US) imaging is a widely used medical imaging modality for the diagnosis, monitoring, and surgical planning for kidney conditions. Thus, accurate segmentation of the kidney and internal structures in US images is essential for the assessment of kidney function and the detection of pathological conditions, such as cysts, tumors, and kidney stones. Therefore, there is a need for automated methods that can accurately segment the kidney and internal structures in US images. Over the years, automatic strategies were proposed for such purpose, with deep learning methods achieving the current state-of-the-art results. However, these strategies typically ignore the segmentation of the internal structures of the kidney. Moreover, they were evaluated in different private datasets, hampering the direct comparison of results, and making it difficult to determination the optimal strategy for this task. In this study, we perform a comparative analysis of 7 deep learning networks for the segmentation of the kidney and internal structures (Capsule, Central Echogenic Complex (CEC), Cortex and Medulla) in 2D US images in an open access multi-class kidney US dataset. The dataset includes 514 images, acquired in multiple clinical centers using different US machines and protocols. The dataset contains the annotation of two experts, but 321 images with complete segmentation of all 4 classes were used. Overall, the results demonstrate that the DeepLabV3+ network outperformed the inter-rater variability with a Dice score of 78.0% compared to 75.6% for inter-rater variability. Specifically, DeepLabV3Plus achieved mean Dice scores of 94.2% for the Capsule, 85.8% for the CEC, 62.4% for the Cortex, and 69.6% for the Medulla. These findings suggest the potential of deep learning-based methods in improving the accuracy of kidney segmentation in US images.Clinical Relevance- This study shows the potential of DL for improving accuracy of kidney segmentation in US, leading to increased diagnostic efficiency, and enabling new applications such as computer-aided diagnosis and treatment, ultimately resulting in improved patient outcomes and reduced healthcare costs.1.

Diaphragmatic hernia repair porcine model to compare the performance of biodegradable membranes against Gore-Tex®.

BACKGROUND: Patch repair of congenital diaphragmatic hernia (CDH) using Gore-Tex® is associated with infection, adhesions, hernia recurrence, long-term musculoskeletal sequels and poor tissue regeneration. To overcome these limitations, the performance of two novel biodegradable membranes was tested to repair CDH in a growing pig model. METHODS: Twelve male pigs were randomly assigned to 3 different groups of 4 animals each, determined by the type of patch used during thoracoscopic diaphragmatic hernia repair (Gore-Tex®, polycaprolactone electrospun membrane-PCLem, and decellularized human chorion membrane-dHCM). After 7 weeks, all animals were euthanized, followed by necropsy for diaphragmatic evaluation and histological analysis. RESULTS: Thoracoscopic defect creation and diaphragmatic repair were performed without any technical difficulty in all groups. However, hernia recurrence rate was 0% in Gore-Tex®, 50% in PCLem and 100% in dHCM groups. At euthanasia, Gore-Tex® patches appeared virtually unchanged and covered with a fibrotic capsule, while PCLem and dHCM patches were replaced by either floppy connective tissue or vascularized and floppy regenerated membranous tissue, respectively. CONCLUSION: Gore-Tex® was associated with a higher survival rate and lower recurrence. Nevertheless, the proposed biodegradable membranes were associated with better tissue integration when compared with Gore-Tex®.

Intraluminal chloride regulates lung branching morphogenesis: involvement of PIEZO1/PIEZO2.

BACKGROUND: Clinical and experimental evidence shows lung fluid volume as a modulator of fetal lung growth with important value in treating fetal lung hypoplasia. Thus, understanding the mechanisms underlying these morphological dynamics has been the topic of multiple investigations with, however, limited results, partially due to the difficulty of capturing or recapitulating these movements in the lab. In this sense, this study aims to establish an ex vivo model allowing the study of lung fluid function in branching morphogenesis and identify the subsequent molecular/ cellular mechanisms. METHODS: Ex vivo lung explant culture was selected as a model to study branching morphogenesis, and intraluminal injections were performed to change the composition of lung fluid. Distinct chloride (Cl-) concentrations (5.8, 29, 143, and 715 mM) or Cl- channels inhibitors [antracene-9-carboxylic acid (A9C), cystic fibrosis transmembrane conductance regulator inhibitor172 (CFTRinh), and calcium-dependent Cl- channel inhibitorA01 (CaCCinh)] were injected into lung lumen at two timepoints, day0 (D0) and D2. At D4, morphological and molecular analyses were performed in terms of branching morphogenesis, spatial distribution (immunofluorescence), and protein quantification (western blot) of mechanoreceptors (PIEZO1 and PIEZO2), neuroendocrine (bombesin, ghrelin, and PGP9.5) and smooth muscle [alpha-smooth muscle actin (α-SMA) and myosin light chain 2 (MLC2)] markers. RESULTS: For the first time, we described effective intraluminal injections at D0 and D2 and demonstrated intraluminal movements at D4 in ex vivo lung explant cultures. Through immunofluorescence assay in in vivo and ex vivo branching morphogenesis, we show that PGP9.5 colocalizes with PIEZO1 and PIEZO2 receptors. Fetal lung growth is increased at higher [Cl-], 715 mM Cl-, through the overexpression of PIEZO1, PIEZO2, ghrelin, bombesin, MLC2, and α-SMA. In contrast, intraluminal injection of CFTRinh or CaCCinh decreases fetal lung growth and the expression of PIEZO1, PIEZO2, ghrelin, bombesin, MLC2, and α-SMA. Finally, the inhibition of PIEZO1/PIEZO2 by GsMTx4 decreases branching morphogenesis and ghrelin, bombesin, MLC2, and α-SMA expression in an intraluminal injection-independent manner. CONCLUSIONS: Our results identify PIEZO1/PIEZO2 expressed in neuroendocrine cells as a regulator of fetal lung growth induced by lung fluid.

Comparing Polyurethane and Acellular Dermal Matrix Implant Cover in Prepectoral Breast Reconstruction: Short-term Complications.

Implant covering with an interface material is the standard in prepectoral breast reconstruction. Acellular dermal matrix (ADM) is frequently used, but it is expensive and associated with complications. Alternatively, we have been using integrated devices consisting of a silicone implant coated with polyurethane (PU) foam. We aimed to compare both techniques in terms of acute complications. Methods: The authors retrospectively reviewed patients undergoing prepectoral direct-to-implant reconstruction from June 2018 to January 2022. Two cohorts were defined based on the interface material used: ADM versus PU. Total drainage volume, time to drain removal, and acute complications (hematoma, seroma, infection, and explantation) were analyzed. Results: Forty-four breast reconstructions were performed in 35 patients (10 bilateral); implants were covered with ADM in 23 cases and with PU foam in 21. Median total drainage volume (500 versus 515 cc for ADM and PU, respectively) and time to drain removal (9 versus 8 days) were not affected by the interface material used, but seromas and infections occurred exclusively in the ADM cohort (seromas in four of 23 of cases, P = 0.109; infections in three of 23 cases, P = 0.234). Overall complications occurred more often in cases reconstructed with ADM, but the difference was nonsignificant (P = 0.245). Conclusions: The use of interface materials is generally considered a prerequisite for state-of-the-art prepectoral breast reconstruction for a variety of reasons, including the prevention of capsular contracture. In this study, PU coating tended to be associated with fewer short-term complications than ADM, including seroma and infection.

Comparative study of e-cigarette aerosol and cigarette smoke effect on ex vivo embryonic chick lung explants.

Electronic cigarette usage has significantly expanded among young people and pregnant women in the last decade. Although there are already some data regarding the short- and long-term consequences of e-cigarettes on human health, their effect on embryo and lung development still needs to be fully disclosed. In this sense, this study describes, for the first time, the impact of electronic cigarette aerosol on early lung development. For this purpose, ex vivo chick (Gallus gallus) embryonic lungs were cultured in vitro for 48 h in e-cigarette aerosol exposed-medium or unexposed medium. Chick lung explants were also cultured in a cigarette smoke-exposed medium for comparison purposes. Lung explants were morphologically analyzed to assess the impact on lung growth. Additionally, TNF-α levels were determined in the supernatant as a marker of pro-inflammatory response. The results suggest that electronic cigarette aerosol impairs lung growth and promotes lung inflammation. However, its impact on early lung growth seems less detrimental than conventional cigarette smoke. This work provides significant data regarding the impact of e-cig aerosol, adding to the efforts to fully understand its effect on embryo development. The validation of these effects may eventually lead to new tobacco control recommendations for pregnant women.

Analysis of Current Deep Learning Networks for Semantic Segmentation of Anatomical Structures in Laparoscopic Surgery.

Semantic segmentation of anatomical structures in laparoscopic videos is a crucial task to enable the development of new computer-assisted systems that can assist surgeons during surgery. However, this is a difficult task due to artifacts and similar visual characteristics of anatomical structures on the laparoscopic videos. Recently, deep learning algorithms have been showed promising results on the segmentation of laparoscopic instruments. However, due to the lack of large public datasets for semantic segmentation of anatomical structures, there are only a few studies on this task. In this work, we evaluate the performance of five networks, namely U-Net, U-Net++, DynUNet, UNETR and DeepLabV3+, for segmentation of laparoscopic cholecystectomy images from the recently released CholecSeg8k dataset. To the best of our knowledge, this is the first benchmark performed on this dataset. Training was performed with dice loss. The networks were evaluated on segmentation of 8 anatomical structures and instruments, performance was quantified through the dice coefficient, intersection over union, recall, and precision. Apart from the U-Net, all networks obtained scores similar to each other, with the U-Net++ being the network with the best overall score with a mean Dice value of 0.62. Overall, the results show that there is still room for improvement in the segmentation of anatomical structures from laparoscopic videos. Clinical Relevance- The results of this study show the potential of deep neural networks for the segmentation of anatomical structures in laparoscopic images which can later be incorporated into computer-aided systems for surgeons.

Ultrasound-Guided Selective Bronchial Intubation: A Feasibility Study in Pediatric Animal Model.

Objective: Selective one-lung ventilation used to optimize neonatal and pediatric surgical conditions is always a demanding task for anesthesiologists, especially during minimally invasive thoracoscopic surgery. This study aims to introduce an ultrasound-guided bronchial intubation and exclusion technique in a pediatric animal model. Methods: Seven rabbits were anesthetized and airway ultrasound acquisitions were done. Results: Tracheal tube progression along the trachea to the right bronchus and positioning of the bronchial blocker in the left bronchus were successfully done with consistent ultrasound identification of relevant anatomical structures. Conclusion: The study provided a new application of ultrasound in airway management. More advanced experimental studies are needed since this technique has the potential for translation to pediatric anesthesia.

Characterization of technical skill progress in a standardized rabbit model for training in laparoscopic duodenal atresia repair.

BACKGROUND: Laboratory skills training is an essential step before conducting minimally invasive surgery in clinical practice. Our main aim was to develop an animal model for training in clinically highly challenging laparoscopic duodenal atresia repair that could be useful in establishing a minimum number of repetitions to indicate safe performance of similar interventions on humans. MATERIALS AND METHODS: A rabbit model of laparoscopic duodenum atresia surgery involving a diamond-shaped duodeno-duodenostomy was designed. This approach was tested in two groups of surgeons: in a beginner group without any previous clinical laparoscopic experience (but having undergone previous standardized dry-lab training, n = 8) and in an advanced group comprising pediatric surgery fellows with previous clinical experience of laparoscopy (n = 7). Each participant performed eight interventions. Surgical time, expert assessment using the Global Operative Assessment of Laparoscopic Skills (GOALS) score, anastomosis quality (leakage) and results from participant feedback questionnaires were analyzed. RESULTS: Participants in both groups successfully completed all eight surgeries. The surgical time gradually improved in both groups, but it was typically shorter in the advanced group than in the beginner group. The leakage rate was significantly lower in the advanced group in the first two interventions, and it reached its optimal level after five operations in both groups. The GOALS and participant feedback scores showed gradual increases, evident even after the fifth surgery. CONCLUSIONS: Our data confirm the feasibility of this advanced pediatric laparoscopic model. Surgical time, anastomosis quality, GOALS score and self-assessment parameters adequately quantify technical improvement among the participants. Anastomosis quality reaches its optimal value after the fifth operation even in novice, but uniformly trained surgeons. A minimum number of wet-lab operations can be determined before surgery can be safely conducted in a clinical setting, where the development of further non-technical skills is also required.

Developmental Pathways Underlying Lung Development and Congenital Lung Disorders.

Lung organogenesis is a highly coordinated process governed by a network of conserved signaling pathways that ultimately control patterning, growth, and differentiation. This rigorously regulated developmental process culminates with the formation of a fully functional organ. Conversely, failure to correctly regulate this intricate series of events results in severe abnormalities that may compromise postnatal survival or affect/disrupt lung function through early life and adulthood. Conditions like congenital pulmonary airway malformation, bronchopulmonary sequestration, bronchogenic cysts, and congenital diaphragmatic hernia display unique forms of lung abnormalities. The etiology of these disorders is not yet completely understood; however, specific developmental pathways have already been reported as deregulated. In this sense, this review focuses on the molecular mechanisms that contribute to normal/abnormal lung growth and development and their impact on postnatal survival.

Minimally Invasive Neck Surgery: An Animal Model Study.

Background: Minimally invasive surgery (MIS) is replacing conventional surgery as the "gold standard" in different surgical areas. Although cervical MIS is already accepted in the adult population, its use in children is still new and controversial. The natural obstacles to this approach are the absence of a natural cavity, with the inherent complications of creating one artificially, and the limited existing workspace especially in pediatric patients. All endoscopic techniques in the field of neck surgery try to live up to the high cosmetic expectations and the transoral cervical approach as a natural orifice surgery technique excels at it. Aim: Besides the goal of feasibility, we aim to report on the pitfalls of this approach, by using an experimental rabbit model for minimally invasive thyroidectomy. Materials and Methods: Transoral endoscopic thyroidectomies using a vestibular approach were performed in 10 anesthetized rabbits. All surgeries were video recorded. The surgical time, anatomy identified, difficulties, and intraoperative complications were documented. Results: Through one trocar in the vestibular area and two lateral stab incisions, it was possible to create a working space and to reach the peritracheal area. Total thyroidectomies were completed in the 10 animals with a mean operative time of 51 minutes. In all of them we were able to identify the fascial spaces of the neck and the major vessels. During surgery, the lack of space required surgical gestures to be very precise, soft, and gentle. There were 2 cases with a small amount of bleeding and one mild trachea laceration during the procedure, but none of them required suspension or conversion to an open procedure. Animals were euthanized immediately after the surgical procedure. Conclusions: The vestibular approach seems to be a feasible technique to access pediatric neck pathology. Despite the differences in the cervical anatomy, the limited workspace of the rabbit model perfectly matches the requirements of a pediatric training model.

First-trimester miscarriage: A histopathological classification proposal.

BACKGROUND: Histopathology of first-trimester abortion products may be useful in document an intrauterine pregnancy, identifying an important pathology affecting the mother or the embryo and diagnosing conditions that are likely to recur in future pregnancies or that explain the adverse fetal outcome. Relevant information provided by histology is essential to determine the cause and to guide the patients with early pregnancy failure. AIMS: Histopathological classification proposal in first-trimester miscarriage. METHODS: Published pathological criteria in first-trimester abortion specimens were collected, standardized and focused into a comprehensive diagnosis. The idea was to create a comprehensive classification related to major pathophysiological processes. Thus, the histological criteria were grouped into 7 categories: i. Changes suggesting aneuploidy (CSA) or metabolic storage disease; ii. Embryo anomaly (EA); iii. Multifactorial (MF) causes; iv. Maternal causes (MC); v. Gestational trophoblastic disease, such as hydatidiform mole (HM) and non neoplastic lesions and neoplasms; vi. Ectopic pregnancy; vii. Other. So, a 6-years retrospective study of first-trimester spontaneous miscarriage were reviewed. Two groups were created: i. Study group include specimens with pathological diagnosis; ii. Control group incorporate specimens with pathological diagnosis and additional genetic study in order to validate pathological criteria. RESULTS: Pathological criteria concordance between inter-observers was generally good, with an excellent correlation in EA and HM categories. Despite greater inter-observer disagreement in the CSA and MC categories the correlation with the genetic results was very positive. CONCLUSION: A standardized, reproducible and biologically comprehensive histopathological classification may improve fetal follow-up and couple's management.

ASSOCIATION OF SERUM VASOGENIC AND PROINFLAMMATORY FACTORS WITH CLINICAL RESPONSE TO ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR FOR DIABETIC MACULAR EDEMA.

PURPOSE: To study the role of serum biomarkers as prognostic factors for qualitative and quantitative response to anti-vascular endothelial growth factor injections for diabetic macular edema (DME). METHODS: Sixty-seven eyes with DME were treated with intravitreal bevacizumab during a 12-month follow-up period. All cases underwent a baseline workup consisting of 12 inflammatory, metabolic and prothrombotic factors. The following outcomes were evaluated at 3-month intervals until 1 year of follow-up: visual acuity, central subfield thickness (CST), macular volume (MV), % of change from baseline in CST, occurrence of a CST change < 10%, a CST change >20%, and a CST <330 µm, achieving an improvement ≥2 lines of visual acuity, achieving visual acuity ≥20/40. RESULTS: A significant improvement in CST and visual acuity was seen from third month onwards. Twenty-eight (48.1%) cases were classified as "early responders," 24 (35.8%) as "late responders", and 15 (22.4%) as "poor responders." Serum vascular endothelial growth factor-A levels were significantly lower in "poor responders" (P = 0.006). C-reactive protein (hsCRP) was associated with a limited anatomic response (<10% CST change) (P = 0.002, OR = 1.845, cutoff value of hsCRP = 1.84 mg/L). hsCRP was also negatively associated with obtaining a final CST <330 µm (P = 0.04, r2 = 0.112, OR = 0.643). Baseline visual acuity was significantly associated with 12th month visual acuity (P < 0.001, r2 = 0.602) and also with an improvement ≥2 visual acuity lines (P = 0.009, OR = 20.54). CONCLUSION: Increased high-sensitivity C-reactive protein was associated with limited anatomic response to anti-vascular endothelial growth factor treatment and persistent DME. Poor responders had significantly lower values of serum vascular endothelial growth factor-A, suggesting an alternative pathogenic pathway for persisting DME.

Effects of testosterone replacement on serotonin levels in the prostate and plasma in a murine model of hypogonadism.

Benign prostate hyperplasia is a dysfunctional disease with an elevated prevalence. Despite the accepted impact of aging and testosterone (TES) in its pathophysiology, its aetiology remains unknown. Recent studies described that serotonin (5-HT) inhibits benign prostate growth through the modulation of the androgen receptor, in the presence of TES. Accordingly, this work aimed to determine the impact of castration and TES replacement in plasmatic and prostatic 5-HT regulation. C57BL/6 mice were submitted to surgical castration and divided into three groups, continually exposed to either vehicle or different TES doses for 14 days. Plasmatic 5-HT concentration was measured before and after castration, and after TES reintroduction. Finally, total prostatic weight and intra-prostatic 5-HT were determined in the different groups. Our results demonstrate that mice prostate exhibits high 5-HT tissue levels and that intra-prostatic total 5-HT was independent of castration or TES reintroduction, in all studied groups. Also, 5-HT plasmatic concentration significantly increased after castration and then normalized after TES administration. Our findings revealed that mice prostate has a high 5-HT content and that total prostatic 5-HT levels do not depend on androgens' action. On the other hand, castration induced a significant increase in plasmatic 5-HT concentration, raising the hypothesis that androgens might be regulating the production of extra-prostatic 5-HT.

Advancing spinal fusion: Interbody stabilization by in situ foaming of a chemically modified polycaprolactone.

Spinal fusion (SF) surgery relies on medical hardware such as screws, cages and rods, complemented by bone graft or substitute, to stabilize the interventioned spine and achieve adequate bone ingrowth. SF is technically demanding, lengthy and expensive. Advances in material science and processing technologies, proposed herein, allowed the development of an adhesive polymeric foam with the potential to dismiss the need for invasive hardware in SF. Herein, 3D foams of polycaprolactone doped with polydopamine and polymethacrylic acid (PCL pDA pMAA) were created. For immediate bone stabilization, in situ hardening of the foam is required; therefore, a portable high-pressure device was developed to allow CO2 foaming within bone defects. Foams were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Adhesive properties of PCL pDA pMAA outperformed PCL when tested using glass surfaces (p < 0.001) or spinal plugs (p < 0.05). No cytotoxicity was observed, and bioactivity was confirmed by the CaP layer formed upon 7 days immersion in simulated body fluid. As proof of concept, PCL pDA pMAA was extruded in-between ex vivo porcine vertebrae, and micro-computed tomography revealed similar properties to those of trabecular bone. This novel system presents great promise for instrumentation-free interbody fusion.

Technical Note: Assessment of electromagnetic tracking systems in a surgical environment using ultrasonography and ureteroscopy instruments for percutaneous renal access.

PURPOSE: Electromagnetic tracking systems (EMTSs) have been proposed to assist the percutaneous renal access (PRA) during minimally invasive interventions to the renal system. However, the influence of other surgical instruments widely used during PRA (like ureteroscopy and ultrasound equipment) in the EMTS performance is not completely known. This work performs this assessment for two EMTSs [Aurora® Planar Field Generator (PFG); Aurora® Tabletop Field Generator (TTFG)]. METHODS: An assessment platform, composed by a scaffold with specific supports to attach the surgical instruments and a plate phantom with multiple levels to precisely translate or rotate the surgical instruments, was developed. The median accuracy and precision in terms of position and orientation were estimated for the PFG and TTFG in a surgical environment using this platform. Then, the influence of different surgical instruments (alone or together), namely analogic flexible ureterorenoscope (AUR), digital flexible ureterorenoscope (DUR), two-dimensional (2D) ultrasound (US) probe, and four-dimensional (4D) mechanical US probe, was assessed for both EMTSs by coupling the instruments to 5-DOF and 6-DOF sensors. RESULTS: Overall, the median positional and orientation accuracies in the surgical environment were 0.85 mm and 0.42° for PFG, and 0.72 mm and 0.39° for TTFG, while precisions were 0.10 mm and 0.03° for PFG, and 0.20 mm and 0.12° for TTFG, respectively. No significant differences were found for accuracy between EMTSs. However, PFG showed a tendency for higher precision than TTFG. AUR, DUR, and 2D US probe did not influence the accuracy and precision of both EMTSs. In opposition, the 4D probe distorted the signal near the attached sensor, making readings unreliable. CONCLUSIONS: Ureteroscopy- and ultrasonography-assisted PRA based on EMTS guidance are feasible with the tested AUR or DUR together with the 2D probe. More studies must be performed to evaluate the probes and ureterorenoscopes' influence before their use in PRA based on EMTS guidance.

Serum pro-inflammatory factors as predictors of persistent diabetic macular oedema with limited anatomic response to anti-VEGF: association with intravitreal injection treatment profiles in real-world setting.

PURPOSE: To study the role of serum levels of pro-inflammatory factors in the identification of persistent diabetic macular oedema (DME) cases with limited anatomic response to anti-VEGF. Additionally, possible predictive associations between serum factors and intravitreal treatment profiles were analysed. METHODS: Cases with DME were treated with monthly bevacizumab (BVZ). After the sixth month of follow-up, if the change in central foveal thickness (CFT) was <20% of baseline, combination treatment with triamcinolone was initiated. All cases underwent a baseline laboratory workup including inflammatory, metabolic and prothrombotic factors. The following outcome parameters were evaluated: percentage of CFT change from baseline, occurrence of persistent DME with <20% change in CFT, achieving CFT <330 µm with ≤6 BVZ injections, total number of intravitreal injections (IVI), number of IVI after the 6th month and number of triamcinolone acetonide (TCA) injections. RESULTS: A total of 58 cases were included receiving a mean of 7.23 ± 1.55 IVI in 12 months, resulting in a significant improvement of visual acuity (VA) and CFT. No significant differences were found for baseline CFT, baseline LogMAR VA, diabetic retinopathy grade, age or duration of DM2 between cases initiating TCA and those treated only with anti-VEGF. Significant correlations were found between total number of IVI and the following serum factors: high-sensitivity C-reactive protein (hsCRP) (p = 0.004, r = 0.395), creatinine (p = 0.023, r = 0.338) and homocysteine (p = 0.037, r = 0.309). Regression analysis revealed that hsCRP was a significant predictor of TCA treatment (p = 0.028, r2  = 0.350). Cases requiring ≤6 IVI had significantly lower values of hsCRP (1.33 ± 1.07 versus 2.46 ± 2.18 mg/l, p = 0.016) and creatinine (0.71 ± 0.28 versus 0.94 ± 0.19 mg/dl, p = 0.003). CONCLUSIONS: Serum markers of microvascular damage (hsCRP, homocysteine and creatinine) were associated with a higher frequency of IVI due to persistent DME, suggesting a role for such biomarkers in the identification of limited responders to anti-VEGF monotherapy.