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Background: Hyaluronidase remains the mainstay treatment for impending filler-induced facial skin necrosis. Complete resolution of impending skin necrosis following hyaluronidase injection is estimated to be around 77.8%. Current practices are varied but most involve flooding 1500 international units (IU) of hyaluronidase into the suspect area. Image-guided hyaluronidase administration has shown improved outcomes with lower doses of hyaluronidase; however, no reviews have been conducted., Objectives: To characterize and establish the proportion of patients treated successfully with ultrasound-guided hyaluronidase for impending filler-induced facial skin necrosis., Methods: This systematic review and meta-analysis queried four international databases from inception until September 2024 for sources including two or more patients receiving ultrasound-guided hyaluronidase for impending filler-induced facial skin necrosis. Random-effects (DerSimonian and Laird) meta-analyses were conducted. The primary outcome was the pooled proportion of complete scar resolution after ultrasound-guided hyaluronidase. The Joanna Briggs Institute checklists were utilized to assess intra-study risk of bias, and the certainty of evidence rated using the GRADE approach., Results: Four studies totaling 55 patients were included in the analysis. The pooled proportion of complete scar resolution after ultrasound-guided hyaluronidase is probably 94.6% (95%-CI 80.6-98.7%, 4 studies, 55 patients, p egger  = 0.06, moderate certainty). Two of four studies utilized image-guided hyaluronidase after failure of conventional flooding with 1500 IU. There was no statistical difference between ultrasound-guided injection of hyaluronidase intra-arterially and into hyaluronic acid deposits (p = 0.36)., Conclusion: Ultrasound-guided hyaluronidase represents a compelling step forward for complete resolution of impending filler-induced facial skin necrosis. Clinicians may wish to consider ultrasound-guided hyaluronidase as a first-line intervention considering the significant increase in the proportion of patients with better outcomes compared to non-image-guided intervention. More studies and higher-powered analyses are required to further confirm our findings., Protocol Registration: CRD42024585657., Level of Evidence I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266., Competing Interests: Declarations. Conflict of interest: Jonathan Jia En Boey declares no competing interests in the domain explored in this review. Justin Jia Jun Boey declares no competing interests in the domain explored in this review. This author has received honoraria as a consultant in the same domain but not identical to the topic from Galderma Pte Ltd. Zhang Chen declares no competing interests in the domain explored in this review. Taige Cao declares no competing interests in the domain explored in this review. Alexander Sheng Ming Tan declares no competing interests in the domain explored in this review. Zhi Yang Ng declares no competing interests in the domain explored in this review and is the corresponding author for this paper. Patient Consent: Not applicable. Permission to Reproduce Material From Other Sources: Not applicable., (© 2025. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Objectives: To evaluate the at-risk organs that require protection during percutaneous cryoablation (PCA) of renal tumours and the correlation with patient and target lesion characteristics, type of protective measure used and postoperative outcomes., Materials and Methods: Single-centre retrospective review of patients with renal tumours who underwent PCA between 2008 and 2020. Final analysis included 374 tumours. Patient, tumour, and procedure technical details were extracted and analysed. At-risk organs were classified according to tumour location relative to kidney side, pyelic axis, and polar lines., Results: There were 171 (46.0%) tumours in the left kidney, and 194 (52.0%) in the right. Cryoprotection was required for 272 (272/374; 73.0%) tumours, with hydrodissection (216/374; 58.0%) being the most common technique. Protective measures were used for 82 (82/93; 88.0%) tumours in under/normal-weight patients and 143 (143/196; 73.0%) in overweight/obese ones (P = 0.004). In the left kidney, colon was the most common at-risk organ (63/171; 37.0%), followed by spleen (21/171; 12.3%), small bowel (21/171; 12.3%), ureter (19/171; 11.1%), abdominal wall (15/171; 8.8%), psoas muscle (10/171; 5.8%), and pancreas (9/171; 5.3%). In the right kidney, common at-risk organs were the colon (67/194; 35.0%), liver (50/194; 25.7%), ureter (15/194; 15.5%), diaphragm (16/194; 8.2%), abdominal wall (14/194; 7.2%), and duodenum (12/194; 6.1%). No cryoinjuries to at-risk organs occurred., Conclusion: Hydrodissection is the most common cryoprotective measure used for renal tumour PCA. Under/normal-weight patients are more likely to require cryoprotection. The colon is the most common adjacent at-risk organ requiring protection for both right- and left-sided tumours., Competing Interests: Declarations. Conflict of interest: Roberto Luigi CAZZATO, Julien GARNON, and Afshin GANGI received consultancy fees from Boston Scientific. Ethical approval: Institutional Review Board approval was obtained., (© 2025. Italian Society of Medical Radiology.)

Purpose: To evaluate the feasibility and accuracy of a robotic system to integrate and map computed tomography (CT) and robotic coordinates, followed by automatic trajectory execution by a robotic arm. The system was hypothesized to achieve a targeting error of <5 mm without significant influence from variations in angulation or depth., Materials and Methods: An experimental study was conducted using a robotic system (Automated Needle Targeting device for CT [ANT-C]) for needle insertions into a phantom model on both moving patient table and moving gantry CT scanners. Eight spherical markers were registered as targets for 90 insertions at different trajectories. After a single ANT-C registration, the closed-loop software targeted multiple markers via the insertion of robotically aligned 18-gauge needles. Accuracy (distance from the needle tip to the target) was assessed by postinsertion CT scans. Similar procedures were repeated to guide 10 needle insertions into a porcine lung. A regression analysis was performed to test the effect of needle angulation and insertion depth on the accuracy of insertion., Results: In the phantom model, all needle insertions (median trajectory depth, 64.8 mm; range, 46.1-153 mm) were successfully performed in single attempts. The overall accuracy was 1.36 mm ± 0.53, which did not differ between the 2 types of CT scanners (1.39 mm ± 0.54 [moving patient table CT] vs 1.33 mm ± 0.52 [moving gantry CT]; P = .54) and was not significantly affected by the needle angulation and insertion depth. The accuracy for the porcine model was 9.09 mm ± 4.21., Conclusions: Robot-assisted needle insertion using the ANT-C robotic device was feasible and accurate for targeting multiple markers in a phantom model., (Copyright © 2022 SIR. Published by Elsevier Inc. All rights reserved.)

Serial passaging of the human fungal pathogen Candida albicans in the gastrointestinal tract of antibiotics-treated mice selects for virulence-attenuated strains. These gut-evolved strains protect the host from infection by a wide range of pathogens via trained immunity. Here, we further investigated the molecular and cellular mechanisms underlying this innate immune memory. Both Dectin-1 (the main receptor for β-glucan; a well-described immune training molecule in the fungal cell wall) and Nod2 (a receptor described to mediate BCG-induced trained immunity), were redundant for the protection induced by gut-evolved C. albicans against a virulent C. albicans strain, suggesting that gut-evolved C. albicans strains induce trained immunity via other pathways. Cytometry by time of flight (CyTOF) analysis of mouse splenocytes revealed that immunization with gut-evolved C. albicans resulted in an expansion of neutrophils and a reduction in natural killer (NK) cells, but no significant numeric changes in monocytes, macrophages or dendritic cell populations. Systemic depletion of phagocytes or neutrophils, but not of macrophages or NK cells, reduced protection mediated by gut-evolved C. albicans . Splenocytes and bone marrow cells of mice immunized with gut-evolved C. albicans demonstrated metabolic changes. In particular, splenic neutrophils displayed significantly elevated glycolytic and respiratory activity in comparison to those from mock-immunized mice. Although further investigation is required for fully deciphering the trained immunity mechanism induced by gut-evolved C. albicans strains, this data is consistent with the existence of several mechanisms of trained immunity, triggered by different training stimuli and involving different immune molecules and cell types., Competing Interests: EN is a co-founder, advisor and shareholder of ImmunoScape Pte. Ltd. EN is an advisor for Neogene Therapeutics and Nanostring Technologies. NP is employed by F. Hoffmann-La Roche AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Reales-Calderon, Tso, Tan, Hor, Böhme, Teng, Newell, Singhal and Pavelka.)

The desmoplastic nature of the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) prevents the infiltration of T cells and the penetration of chemotherapeutic drugs, posing a challenge to the validation of targeted therapies, including T cell immunotherapies. We present an in vitro 3D PDAC-TME model to observe and quantify T cell infiltration across the vasculature. In a three-channel microfluidic device, PDAC cells are cultured in a collagen matrix in the central channel surrounded, on one side, by endothelial cells (ECs) to mimic a blood vessel and, on the opposite side, by pancreatic stellate cells (PSCs) to simulate exocrine pancreas. The migration of T cells toward the tumor is quantified based on their activation state and TME composition. The presence of EC-lining drastically reduces T cell infiltration, confirming the essential role of the vasculature in controlling T cell trafficking. We show that activated T cells migrate ∼50% more than the not-activated ones toward the cancer cells. Correspondingly, in the absence of cancer cells, both activated and not-activated T cells present similar migration toward the PSCs. The proposed approach could help researchers in testing and optimizing immunotherapies for pancreatic cancer.

The human fetal immune system begins to develop early during gestation; however, factors responsible for fetal immune-priming remain elusive. We explored potential exposure to microbial agents in utero and their contribution toward activation of memory T cells in fetal tissues. We profiled microbes across fetal organs using 16S rRNA gene sequencing and detected low but consistent microbial signal in fetal gut, skin, placenta, and lungs in the 2 nd trimester of gestation. We identified several live bacterial strains including Staphylococcus and Lactobacillus in fetal tissues, which induced in vitro activation of memory T cells in fetal mesenteric lymph node, supporting the role of microbial exposure in fetal immune-priming. Finally, using SEM and RNA-ISH, we visualized discrete localization of bacteria-like structures and eubacterial-RNA within 14 th weeks fetal gut lumen. These findings indicate selective presence of live microbes in fetal organs during the 2 nd trimester of gestation and have broader implications toward the establishment of immune competency and priming before birth., Competing Interests: Declaration of interests The authors declare no competing interests., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether congenital diaphragmatic hernia repair outcomes are better before or after decannulation in infants requiring extracorporeal membrane oxygenation (ECMO). A total of 884 papers were found using the reported search, of which 9 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that infants with congenital diaphragmatic hernia requiring ECMO should undergo a trial of weaning and aim for post-decannulation repair, as this has been associated with improved survival, shorter ECMO duration and fewer bleeding complications. However, if weaning of ECMO is unsuccessful, the patient should ideally undergo early on-ECMO repair (within 72 h of cannulation), which has been associated with improved survival, less bleeding, shorter ECMO duration and fewer circuit changes compared to late on-ECMO repair. Anticoagulation protocols including perioperative administration of aminocaproic acid or tranexamic acid, as well as close perioperative monitoring of coagulation parameters have been associated with reduced bleeding risk with on-ECMO repairs., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Graduate medical education in Singapore recently underwent significant restructuring, leading to the accreditation of residency programs by the Accreditation Council for Graduate Medical Education-International (ACGME-I). In radiology, this involved a change in teaching and quality assurance of plain film (PF) reporting. PF reported by junior residents (postgraduate year 1-3) are subject to a 50% random audit. To date, national data on junior resident performance in PF reporting have not been published., Objective: We reviewed performance in PF reporting under the current teaching and audit framework., Methods: Retrospective review of junior resident reported PF audit data from all 3 radiology residency programs in Singapore. The number of residents audited, number of PF reported and audited, and major discrepancy rates were analyzed., Results: On average, 86 440 PF were audited annually nationwide from an estimated 184 288 junior resident-reported PF. Each program trained between 4 to 24 junior residents annually (mean 15), averaging about 44 each year nationwide. A mean of 28 813 PF were audited annually in each program (range 4355-50 880). An estimated mean of 4148 PF (range 1452-9752) were reported per junior resident per year, about 346 PF per month. The major discrepancy rate ranged from 0.04% to 1.13% (mean 0.34%). One resident required remediation in the study period., Conclusions: Structured residency training in Singapore has produced a high level of junior resident competency in PF interpretation., Competing Interests: Conflict of interest: The authors declare they have no competing interests., (Accreditation Council for Graduate Medical Education 2020.)

Macrophages are abundant in the tumor microenvironment (TME), serving as accomplices to cancer cells for their invasion. Studies have explored the biochemical mechanisms that drive pro-tumor macrophage functions; however the role of TME interstitial flow (IF) is often disregarded. Therefore, we developed a three-dimensional microfluidic-based model with tumor cells and macrophages to study how IF affects macrophage migration and its potential contribution to cancer invasion. The presence of either tumor cells or IF individually increased macrophage migration directedness and speed. Interestingly, there was no additive effect on macrophage migration directedness and speed under the simultaneous presence of tumor cells and IF. Further, we present an in silico model that couples chemokine-mediated signaling with mechanosensing networks to explain our in vitro observations. In our model design, we propose IL-8, CCL2, and β-integrin as key pathways that commonly regulate various Rho GTPases. In agreement, in vitro macrophage migration remained elevated when exposed to a saturating concentration of recombinant IL-8 or CCL2 or to the co-addition of a sub-saturating concentration of both cytokines. Moreover, antibody blockade against IL-8 and/or CCL2 inhibited migration that could be restored by IF, indicating cytokine-independent mechanisms of migration induction. Importantly, we demonstrate the utility of an integrated in silico and 3D in vitro approach to aid the design of tumor-associated macrophage-based immunotherapeutic strategies., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aneuploidy is common both in tumor cells responding to chemotherapeutic agents and in fungal cells adapting to antifungal drugs. Because aneuploidy simultaneously affects many genes, it has the potential to confer multiple phenotypes to the same cells. Here, we analyzed the mechanisms by which Candida albicans, the most prevalent human fungal pathogen, acquires the ability to survive both chemotherapeutic agents and antifungal drugs. Strikingly, adaptation to both types of drugs was accompanied by the acquisition of specific whole-chromosome aneuploidies, with some aneuploid karyotypes recovered independently and repeatedly from very different drug conditions. Specifically, strains selected for survival in hydroxyurea, an anticancer drug, acquired cross-adaptation to caspofungin, a first-line antifungal drug, and both acquired traits were attributable to trisomy of the same chromosome: loss of trisomy was accompanied by loss of adaptation to both drugs. Mechanistically, aneuploidy simultaneously altered the copy number of most genes on chromosome 2, yet survival in hydroxyurea or caspofungin required different genes and stress response pathways. Similarly, chromosome 5 monosomy conferred increased tolerance to both fluconazole and to caspofungin, antifungals with different mechanisms of action. Thus, the potential for cross-adaptation is not a feature of aneuploidy per se; rather, it is dependent on specific genes harbored on given aneuploid chromosomes. Furthermore, pre-exposure to hydroxyurea increased the frequency of appearance of caspofungin survivors, and hydroxyurea-adapted C. albicans cells were refractory to antifungal drug treatment in a mouse model of systemic candidiasis. This highlights the potential clinical consequences for the management of cancer chemotherapy patients at risk of fungal infections., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Gut microbes live in symbiosis with their hosts, but how mutualistic animal-microbe interactions emerge is not understood. By adaptively evolving the opportunistic fungal pathogen Candida albicans in the mouse gastrointestinal tract, we selected strains that not only had lost their main virulence program but also protected their new hosts against a variety of systemic infections. This protection was independent of adaptive immunity, arose as early as a single day postpriming, was dependent on increased innate cytokine responses, and was thus reminiscent of "trained immunity." Because both the microbe and its new host gain some advantages from their interaction, this experimental system might allow direct study of the evolutionary forces that govern the emergence of mutualism between a mammal and a fungus., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Candida albicans is a resident fungus of the human intestinal microflora. Commonly isolated at low abundance in healthy people, C. albicans outcompetes local microbiota during candidiasis episodes. Under normal conditions, members of the human gastrointestinal (GI) microbiota were shown to keep C. albicans colonization under control. By releasing weak organic acids (WOAs), bacteria are able to moderate yeast growth. This mechanism displays a synergistic effect in vitro with the absence of glucose in medium of culture, which underlines the complex interactions that C. albicans faces in its natural environment. Inactivation of the transcriptional regulator MIG1 in C. albicans results in a lack of sensitivity to this synergistic outcome. To decipher C. albicans transcriptional responses to glucose, WOAs, and the role of MIG1 , we performed RNA sequencing (RNA-seq) on four biological replicates exposed to combinations of these three parameters. We were able to characterize the (i) glucose response, (ii) response to acetic and butyric acid, (iii) MIG1 regulation of C. albicans , and (iv) genes responsible for WOA resistance. We identified a group of six genes linked to WOA sensitivity in a glucose- MIG1 -dependent manner and inactivated one of these genes, the putative glucose transporter HGT16 , in a SC5314 wild-type background. As expected, the mutant displayed a partial complementation to WOA resistance in the absence of glucose. This result points toward a mechanism of WOA sensitivity in C. albicans involving membrane transporters, which could be exploited to control yeast colonization in human body niches., (Copyright © 2017 Cottier et al.)