Clinical validation of an artificial intelligence-enabled wound imaging mobile application in diabetic foot ulcers

There is a lifetime risk of 15% to 25% of development of diabetic foot ulcers (DFUs) in patients with diabetes mellitus. DFUs need to be followed up on and assessed for development of complications and/or resolution, which was traditionally performed using manual measurement. Our study aims to compare the intra- and inter-rater reliability of an artificial intelligence-enabled wound imaging mobile application (CARES4WOUNDS [C4W] system, Tetsuyu, Singapore) with traditional measurement. This is a prospective cross-sectional study on 28 patients with DFUs from June 2020 to January 2021. The main wound parameters assessed were length and width. For traditional manual measurement, area was calculated by overlaying traced wound on graphical paper. Intra- and inter-rater reliability was analysed using intra-class correlation statistics. A value of <0.5, 0.5–0.75, 0.75–0.9, and >0.9 indicates poor, moderate, good, and excellent reliability, respectively. Seventy-five wound episodes from 28 patients were collected and a total of 547 wound images were analysed in this study. The median wound area during the first clinic consultation and all wound episodes was 3.75 cm² (interquartile range [IQR] 1.40–16.50) and 3.10 cm² (IQR 0.60–14.84), respectively. There is excellent intra-rater reliability of C4W on three different image captures of the same wound (intra-rater reliability ranging 0.933–0.994). There is also excellent inter-rater reliability between three C4W devices for length (0.947), width (0.923), and area (0.965). Good inter-rater reliability for length, width, and area (range 0.825–0.934) was obtained between wound nurse measurement and each of the C4W devices. In conclusion, we obtained good inter-rater and intra-rater reliability of C4W measurements against traditional wound measurement. The C4W is a useful adjunct in monitoring DFU wound progress.     

Laser and electron‐beam powder‐bed additive manufacturing of metallic implants: A review on processes,materials and designs

Additive manufacturing (AM), also commonly known as 3D printing, allows the direct fabrication of functional parts with complex shapes from digital models. In this review, the current progress of two AM processes suitable for metallic orthopaedic implant applications, namely selective laser melting (SLM) and electron beam melting (EBM) are presented. Several critical design factors such as the need for data acquisition for patient‐specific design, design dependent porosity for osteo‐inductive implants, surface topology of the implants and design for reduction of stress‐shielding in implants are discussed. Additive manufactured biomaterials such as 316L stainless steel, titanium‐6aluminium‐4vanadium (Ti6Al4V) and cobalt‐chromium (CoCr) are highlighted. Limitations and future potential of such technologies are also explored. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:369–385, 2016.     

Cyclophilin D promotes tubular cell damage and the development of interstitial fibrosis in the obstructed kidney

Cyclophilin D (CypD) is an important component in mitochondrial‐dependent tubular cell death in acute kidney injury. However, it is not known whether CypD contributes to tubular cell damage in chronic interstitial fibrosis. We investigated this question in the unilateral ureter obstruction (UUO) model of renal interstitial fibrosis. Groups of CypD^?/? and wild type (WT) mice were killed 7 or 12 days after UUO surgery. The significant tubular cell apoptosis seen in WT UUO was significantly reduced in CypD^?/? UUO based on TUNEL and cleaved caspase 3 staining. Other markers of tubular cell damage; loss of E‐cadherin and AQP1 expression, were also reduced in the CypD^?/? UUO kidney. This reduced tubular damage was associated with less inflammation and a partial protection against loss of peritubular capillaries. The prominent accumulation of α‐SMA+ myofibroblasts and interstitial collagen deposition seen in WT UUO was significantly reduced in CypD^?/? UUO on day 12, but not day 7. Activation of several pro‐fibrotic signalling pathways (p38 MAPK, JNK and Smad3) was unaltered in CypD^?/? UUO, arguing that CypD acts independently to promote renal fibrosis. CypD deletion in cultured tubular cells attenuated oxidative stress‐induced pro‐inflammatory, pro‐fibrotic and apoptotic responses; however, responses to angiotensin II and LPS were unaffected. In contrast, CypD deletion in cultured renal fibroblasts did not affect PDGF‐induced proliferation or TGF‐β1‐induced collagen I expression, suggesting no direct role of CypD in the fibroblast response. In conclusion, we have identified a role for CypD in chronic tubular cell damage and in the development of renal interstitial fibrosis.     

Disease-directed design of biodegradable polymers: Reactive oxygen species and pH-responsive micellar nanoparticles for anticancer drug delivery

Herein, we report reactive oxygen species (ROS)- and pH-responsive biodegradable polyethylene glycol (PEG)-block-polycarbonate by installing thioether groups onto the polycarbonate and its self-assembled core/shell structured micelles for anticancer drug delivery. Oxidation of thioethers to sulfoxide and subsequently sulfone induces an increase in hydrophilicity, resulting in more hydrophilic micellar core. This phase-change caused the micelles to swell and enhance cargo release. Carboxylic acid groups have also been installed onto thioether-containing polycarbonate to promote loading of amine-containing anticancer doxorubicin through electrostatic interaction. Urea-functionalized thioether-containing PEG-block-polycarbonates were synthesized to mix with the acid-functionalized PEG-block-polycarbonate for stabilizing micelle structure through hydrogen-bonding interaction. The mixed micelles were 50?nm in diameter and had a 25?wt% loading capacity for doxorubicin. Enhanced drug release from the micelles was triggered by low pH and high content of ROS. Drug-encapsulated micelles accumulated in tumors through leaky tumor vasculature in PC-3 human prostate cancer xenograft mouse model.     

Osseointegrated implants in craniofacial application: current status

The success rates of craniofacial osseointegrated implants are not uniform throughout the craniofacial area. A better understanding of their clinical behaviour is needed. This article investigates current perspectives on the application of endosseous implants in the restoration of craniofacial defects. An online search was completed for the time period from 1966 to 2007, along with a manual search, to locate relevant peer-reviewed articles and textbooks published in English. A review of published reports of craniofacial application of endosseous implants in irradiated and nonirradiated tissue sites showed a strong correlation between anatomic sites and clinical success. Maxillofacial prosthetic considerations are also reviewed.     

Evaluating the preoperative breast cancer characteristics affecting the accuracy of axillary ultrasound staging

We evaluate the preoperative breast cancer (BC) characteristics that affect the diagnostic accuracy of axillary ultrasound (US) and determine the reliability of US in the different subgroups of BC patients. Axillary US assessments in women with invasive BC diagnosed between 2009 and 2016 in a single institution were retrospectively reviewed. The diagnostic accuracy of axillary US was obtained using surgical nodal histology as the gold standard. Preoperative breast tumor sonographic and histological factors affecting axillary US diagnostic accuracy were examined. Of the 605 newly diagnosed invasive BC cases reviewed, 251 (41.5%) had nodal metastases. Axillary US sensitivity was 75.7%, specificity 92.9%, positive predictive value 88.4%, negative predictive value 84.4%, and false‐negative rate 24.3%. Lower US sensitivity was seen with invasive lobular cancer (ILC) (P = .043), grade I/II, (P = .021), unifocal (P = .039), and smaller tumors (P < .001). US specificity was lower in grade III (P < .001), estrogen receptor (ER)‐negative (P < .001), progesterone receptor (PR)‐negative (P = .004), HER2‐positive (P = .015), triple‐negative (P = .001), and larger breast tumors (P < .001). US has moderate sensitivity and good specificity in detecting metastatic axillary lymph nodes. Based on preoperative cancer characteristics, US was less sensitive for nodal metastases from ILC, unifocal, lower grade, and smaller breast tumors. It was also less specific in grade III, ER‐negative, PR‐negative, HER2‐positive, triple‐negative, and larger breast tumors. Caution is suggested in interpreting the US axillary findings of patients with these preoperative tumor features.     

Outcomes of incisional negative pressure wound therapy following brachiobasilic transposition arteriovenous fistula creation: A 1:2 propensity score matched study

Incisional negative wound pressure therapy (iNPWT) use on closed incisions has been shown to improve wound outcomes, but no studies have evaluated the use of iNPWT following brachiobasilic transposition arteriovenous fistula (BBT‐AVF). We aim to investigate the efficacy of iNPWT vs conventional wound therapy in reducing surgical site infections (SSIs) for BBT‐AVF incisions. This is a retrospective cohort study of patients who underwent BBT‐AVF creation between January 2010 and December 2017. A 1:2 propensity score matching (PSM) was performed to reduce selection bias and address for confounding factors. Study outcomes included SSI and haematoma incidence, 30‐day readmission, and 30‐day mortality. A total of 154 patients were reviewed in this study: 47 (30.5%) had iNPWT and 107 (69.5%) had conventional wound therapy. The overall median age was 60.5 (interquartile range 54–69). PSM with a 1:2 ratio resulted in a total of 117 patients (39 iNPWT and 78 conventional wound therapy). In the unmatched cohort, SSI incidence was lower in the iNPWT group (n = 1/47 [2.1%] vs n = 14/107 [13.1%], P = .035). However, incidence of SSI was comparable between iNPWT and conventional wound therapy after matching (n = 1/39 [2.6%] vs n = 9/78 [11.5%], P = .102). There was no significant difference in 30‐day readmission and 30‐day mortality. Within our study population of patients with BBT‐AVF incisions, there is a non‐statistically significant reduction in SSI incidence for patients who received iNPWT as compared with conventional wound therapy. Further prospective randomised controlled studies should be conducted to validate these findings.