A machine-learning-enabled smart neckband for monitoring dietary intake.

The increasing need for precise dietary monitoring across various health scenarios has led to innovations in wearable sensing technologies. However, continuously tracking food and fluid intake during daily activities can be complex. In this study, we present a machine-learning-powered smart neckband that features wireless connectivity and a comfortable, foldable design. Initially considered beneficial for managing conditions such as diabetes and obesity by facilitating dietary control, the device's utility extends beyond these applications. It has proved to be valuable for sports enthusiasts, individuals focused on diet control, and general health monitoring. Its wireless connectivity, ergonomic design, and advanced classification capabilities offer a promising solution for overcoming the limitations of traditional dietary tracking methods, highlighting its potential in personalized healthcare and wellness strategies.

Mapping cutaneous field carcinogenesis of nonmelanoma skin cancer using mesoscopic imaging of pro-inflammation cues.

Nonmelanoma skin cancers remain the most widely diagnosed types of cancers globally. Thus, for optimal patient management, it has become imperative that we focus our efforts on the detection and monitoring of cutaneous field carcinogenesis. The concept of field cancerization (or field carcinogenesis), introduced by Slaughter in 1953 in the context of oral cancer, suggests that invasive cancer may emerge from a molecularly and genetically altered field affecting a substantial area of underlying tissue including the skin. A carcinogenic field alteration, present in precancerous tissue over a relatively large area, is not easily detected by routine visualization. Conventional dermoscopy and microscopy imaging are often limited in assessing the entire carcinogenic landscape. Recent efforts have suggested the use of noninvasive mesoscopic (between microscopic and macroscopic) optical imaging methods that can detect chronic inflammatory features to identify pre-cancerous and cancerous angiogenic changes in tissue microenvironments. This concise review covers major types of mesoscopic optical imaging modalities capable of assessing pro-inflammatory cues by quantifying blood haemoglobin parameters and hemodynamics. Importantly, these imaging modalities demonstrate the ability to detect angiogenesis and inflammation associated with actinically damaged skin. Representative experimental preclinical and human clinical studies using these imaging methods provide biological and clinical relevance to cutaneous field carcinogenesis in altered tissue microenvironments in the apparently normal epidermis and dermis. Overall, mesoscopic optical imaging modalities assessing chronic inflammatory hyperemia can enhance the understanding of cutaneous field carcinogenesis, offer a window of intervention and monitoring for actinic keratoses and nonmelanoma skin cancers and maximise currently available treatment options.

Influence of Selective Carbon 1s Excitation on Auger-Meitner Decay in the ESCA Molecule.

Two-dimensional spectral mapping is used to visualize how resonant Auger-Meitner spectra are influenced by the site of the initial core-electron excitation and the symmetry of the core-excited state in the trifluoroethyl acetate molecule (ESCA). We observe a significant enhancement of electron yield for excitation of the COO 1s → π* and CF3 1s → σ* resonances unlike excitation at resonances involving the CH3 and CH2 sites. The CF3 1s → π* and CF3 1s → σ* resonance spectra are very different from each other, with the latter populating most valence states equally. Two complementary electronic structure calculations for the photoelectron cross section and Auger-Meitner intensity are shown to effectively reproduce the site- and state-selective nature of the resonant enhancement features. The site of the core-electron excitation and the respective final state hole locality increase the sensistivity of the photoelectron signal at specific functional group sites. This showcases resonant Auger-Meitner decay as a potentially powerful tool for selectively probing structural changes at specific functional group sites of polyatomic molecules.

Psychiatric Polygenic Risk Scores Across Youth With Bipolar Disorder, Youth at High Risk for Bipolar Disorder, and Controls.

OBJECTIVE: There is a pronounced gap in knowledge regarding polygenic underpinnings of youth bipolar disorder (BD). This study aimed to compare polygenic risk scores (PRSs) in youth with BD, youth at high clinical and/or familial risk for BD (HR), and controls. METHOD: Participants were 344 youths of European ancestry (13-20 years old), including 136 youths with BD, 121 HR youths, and 87 controls. PRSs for BD, schizophrenia, major depressive disorder, and attention-deficit/hyperactivity disorder were constructed using independent genome-wide summary statistics from adult cohorts. Multinomial logistic regression was used to examine the association between each PRS and diagnostic status (BD vs HR vs controls). All genetic analyses controlled for age, sex, and 2 genetic principal components. RESULTS: The BD group showed significantly higher BD-PRS than the control group (odds ratio = 1.54, 95% CI = 1.13-2.10, p = .006), with the HR group numerically intermediate. BD-PRS explained 7.9% of phenotypic variance. PRSs for schizophrenia, major depressive disorder, and attention-deficit/hyperactivity disorder were not significantly different among groups. In the BD group, BD-PRS did not significantly differ in relation to BD subtype, age of onset, psychosis, or family history of BD. CONCLUSION: BD-PRS derived from adult genome-wide summary statistics is elevated in youth with BD. Absence of significant between-group differences in PRSs for other psychiatric disorders supports the specificity of BD-PRS in youth. These findings add to the biological validation of BD in youth and could have implications for early identification and diagnosis. To enhance clinical utility, future genome-wide association studies that focus specifically on early-onset BD are warranted, as are studies integrating additional genetic and environmental factors. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Rapid Self-Healing Hydrogel with Ultralow Electrical Hysteresis for Wearable Sensing.

Self-healing hydrogels are in high demand for wearable sensing applications due to their remarkable deformability, high ionic and electrical conductivity, self-adhesiveness to human skin, as well as resilience to both mechanical and electrical damage. However, these hydrogels face challenges such as delayed healing times and unavoidable electrical hysteresis, which limit their practical effectiveness. Here, we introduce a self-healing hydrogel that exhibits exceptionally rapid healing with a recovery time of less than 0.12 s and an ultralow electrical hysteresis of less than 0.64% under cyclic strains of up to 500%. This hydrogel strikes an ideal balance, without notable trade-offs, between properties such as softness, deformability, ionic and electrical conductivity, self-adhesiveness, response and recovery times, durability, overshoot behavior, and resistance to nonaxial deformations such as twisting, bending, and pressing. Owing to this unique combination of features, the hydrogel is highly suitable for long-term, durable use in wearable sensing applications, including monitoring body movements and electrophysiological activities on the skin.

Engineering Improved CAR T Cell Products with A Multi-Cytokine Particle Platform for Hematologic and Solid Tumors.

Despite the remarkable clinical efficacy of chimeric antigen receptor (CAR) T cells in hematological malignancies, only a subset of patients achieves a durable complete response (dCR). DCR has been correlated with CAR T cell products enriched with T cells memory phenotypes. Therefore, reagents that consistently promote memory phenotypes during the manufacturing of CAR T cells have the potential to significantly improve clinical outcomes. A novel modular multi-cytokine particle (MCP) platform is developed that combines the signals necessary for activation, costimulation, and cytokine support into a single "all-in-one" stimulation reagent for CAR T cell manufacturing. This platform allows for the assembly and screening of compositionally diverse MCP libraries to identify formulations tailored to promote specific phenotypes with a high degree of flexibility. The approach is leveraged to identify unique MCP formulations that manufacture CAR T cell products from diffuse large B cell patients   with increased proportions of memory-like phenotypes MCP-manufactured CAR T cells demonstrate superior anti-tumor efficacy in mouse models of lymphoma and ovarian cancer through enhanced persistence. These findings serve as a proof-of-principle of the powerful utility of the MCP platform to identify "all-in-one" stimulation reagents that can improve the effectiveness of cell therapy products through optimal manufacturing.

Heteronanostructured Field-Effect Transistors for Enhancing Entropy and Parameter Space in Electrical Unclonable Primitives.

Hardware security is not a new problem but is ever-growing in consumer and medical domains owing to hyperconnectivity. A physical unclonable function (PUF) offers a promising hardware security solution for cryptographic key generation, identification, and authentication. However, electrical PUFs using nanomaterials or two-dimensional (2D) transition metal dichalcogenides (TMDCs) often have limited entropy and parameter space sources, both of which increase the vulnerability to attacks and act as bottlenecks for practical applications. We report an electrical PUF with enhanced entropy as well as parameter space by incorporating 2D TMDC heteronanostructures into field-effect transistors (FETs). Lateral heteronanostructures of 2D molybdenum disulfide and tungsten disulfide serve as a potent entropy source. The variable feature of FETs is further leveraged to enhance the parameter space that provides multiple challenge-response pairs, which are essential for PUFs. This combination results in stably repeatable yet highly variable FET characteristics as alternative electrical PUFs. Comprehensive PUF performance analyses validate the bit uniformity, reproducibility, uniqueness, randomness, false rates, and encoding capacity. The 2D material heteronanostructure-driven electrical PUFs with strong FET-to-FET variability can potentially be augmented as an immediately deployable and scalable security solution for various hardware devices.

In Situ Spray Polymerization of Conductive Polymers for Personalized E-textiles.

E-textiles, also known as electronic textiles, seamlessly merge wearable technology with fabrics, offering comfort and unobtrusiveness and establishing a crucial role in health monitoring systems. In this field, the integration of custom sensor designs with conductive polymers into various fabric types, especially in large areas, has presented significant challenges. Here, we present an innovative additive patterning method that utilizes a dual-regime spray system, eliminating the need for masks and allowing for the programmable inscription of sensor arrays onto consumer textiles. Unlike traditional spray techniques, this approach enables in situ, on-the-fly polymerization of conductive polymers, enabling intricate designs with submillimeter resolution across fabric areas spanning several meters. Moreover, it addresses the nozzle clogging issues commonly encountered in such applications. The resulting e-textiles preserve essential fabric characteristics such as breathability, wearability, and washability while delivering exceptional sensing performance. A comprehensive investigation, combining experimental, computational, and theoretical approaches, was conducted to examine the critical factors influencing the operation of the dual-regime spraying system and its role in e-textile fabrication. These findings provide a flexible solution for producing e-textiles on consumer fabric items and hold significant implications for a diverse range of wearable sensing applications.

Improving physician wellness through the Applied Mindfulness Program for Medical Personnel: findings from a prospective qualitative study.

BACKGROUND: Physicians play a critical role across health care delivery systems, yet their own well-being is often overlooked; mindfulness has been widely recommended as a promising modality to support physician wellness. We sought to explore how physicians experience and engage with a 5-week applied mindfulness program and how they perceive its impact on their personal well-being in the context of their daily lives. METHOD: We delivered the Applied Mindfulness Program for Medical Personnel (AMP-MP) at a tertiary care hospital in downtown Toronto, Canada. This prospective qualitative study consists of a thematic analysis of post-program interviews with physicians, from across different specialties, who participated in the AMP-MP. The program includes 2-hour sessions, delivered once a week over 5 weeks, and is based on the teachings of Thích Nhat Hanh. RESULTS: We interviewed 28 physicians after they completed the AMP-MP. Our data show that a 5-week training was sufficient for physicians to develop a foundational level of mindfulness that integrated into their daily life. Two themes were identified: mindfulness encourages behavioural and cognitive changes that facilitate well-being, and mindfulness improves communication with patients and colleagues. INTERPRETATION: Our results show applied mindfulness to be well received by physicians as an effective modality to increase their perceived sense of wellness and enhance communication with their patients and colleagues. Further research is necessary to better understand the individual and systemic implications of mindfulness training, and how this modality can complement other efforts being made to address and maintain physician wellness.

Association of polygenic risk for bipolar disorder with grey matter structure and white matter integrity in youth.

There is a gap in knowledge regarding the polygenic underpinnings of brain anomalies observed in youth bipolar disorder (BD). This study examined the association of a polygenic risk score for BD (BD-PRS) with grey matter structure and white matter integrity in youth with and without BD. 113 participants were included in the analyses, including 78 participants with both T1-weighted and diffusion-weighted MRI images, 32 participants with T1-weighted images only, and 3 participants with diffusion-weighted images only. BD-PRS was calculated using PRS-CS-auto and was based on independent adult genome-wide summary statistics. Vertex- and voxel-wise analyses examined the associations of BD-PRS with grey matter metrics (cortical volume [CV], cortical surface area [CSA], cortical thickness [CTh]) and fractional anisotropy [FA] in the combined sample, and separately in BD and HC. In the combined sample of participants with T1-weighted images (n = 110, 66 BD, 44 HC), higher BD-PRS was associated with smaller grey matter metrics in frontal and temporal regions. In within-group analyses, higher BD-PRS was associated with lower CTh of frontal, temporal, and fusiform gyrus in BD, and with lower CV and CSA of superior frontal gyrus in HC. In the combined sample of participants with diffusion-weighted images (n = 81, 49 BD, 32 HC), higher BD-PRS was associated with lower FA in widespread white matter regions. In summary, BD-PRS calculated based on adult genetic data was negatively associated with grey matter structure and FA in youth in regions implicated in BD, which may suggest neuroimaging markers of vulnerability to BD. Future longitudinal studies are needed to examine whether BD-PRS predicts neurodevelopmental changes in BD vs. HC and its interaction with course of illness and long-term medication use.

Association of polygenic risk for bipolar disorder with resting-state network functional connectivity in youth with and without bipolar disorder.

Little is known regarding the polygenic underpinnings of anomalous resting-state functional connectivity (rsFC) in youth bipolar disorder (BD). The current study examined the association of polygenic risk for BD (BD-PRS) with whole-brain rsFC at the large-scale network level in youth with and without BD. 99 youth of European ancestry (56 BD, 43 healthy controls [HC]), ages 13-20 years, completed resting-state fMRI scans. BD-PRS was calculated using summary statistics from the latest adult BD genome-wide association study. Data-driven independent component analyses of the resting-state fMRI data were implemented to examine the association of BD-PRS with rsFC in the overall sample, and separately in BD and HC. In the overall sample, higher BD-PRS was associated with lower rsFC of the salience network and higher rsFC of the frontoparietal network with frontal and parietal regions. Within the BD group, higher BD-PRS was associated with higher rsFC of the default mode network with orbitofrontal cortex, and altered rsFC of the visual network with frontal and occipital regions. Within the HC group, higher BD-PRS was associated with altered rsFC of the frontoparietal network with frontal, temporal and occipital regions. In conclusion, the current study found that BD-PRS generated based on adult genetic data was associated with altered rsFC patterns of brain networks in youth. Our findings support the usefulness of BD-PRS to investigate genetically influenced neuroimaging markers of vulnerability to BD, which can be observed in youth with BD early in their course of illness as well as in healthy youth.

mHealth hyperspectral learning for instantaneous spatiospectral imaging of hemodynamics.

Hyperspectral imaging acquires data in both the spatial and frequency domains to offer abundant physical or biological information. However, conventional hyperspectral imaging has intrinsic limitations of bulky instruments, slow data acquisition rate, and spatiospectral trade-off. Here we introduce hyperspectral learning for snapshot hyperspectral imaging in which sampled hyperspectral data in a small subarea are incorporated into a learning algorithm to recover the hypercube. Hyperspectral learning exploits the idea that a photograph is more than merely a picture and contains detailed spectral information. A small sampling of hyperspectral data enables spectrally informed learning to recover a hypercube from a red-green-blue (RGB) image without complete hyperspectral measurements. Hyperspectral learning is capable of recovering full spectroscopic resolution in the hypercube, comparable to high spectral resolutions of scientific spectrometers. Hyperspectral learning also enables ultrafast dynamic imaging, leveraging ultraslow video recording in an off-the-shelf smartphone, given that a video comprises a time series of multiple RGB images. To demonstrate its versatility, an experimental model of vascular development is used to extract hemodynamic parameters via statistical and deep learning approaches. Subsequently, the hemodynamics of peripheral microcirculation is assessed at an ultrafast temporal resolution up to a millisecond, using a conventional smartphone camera. This spectrally informed learning method is analogous to compressed sensing; however, it further allows for reliable hypercube recovery and key feature extractions with a transparent learning algorithm. This learning-powered snapshot hyperspectral imaging method yields high spectral and temporal resolutions and eliminates the spatiospectral trade-off, offering simple hardware requirements and potential applications of various machine learning techniques.

Hashimoto's thyroiditis and renal transplant rejection.

PURPOSE: Hashimoto's thyroiditis (HT) is a common autoimmune thyroid disorder that can disrupt thyroid function and homeostasis. As HT results from a dysregulated immune system, we hypothesized that these patients might be more susceptible to transplant failure; however, literature on this association is limited. The purpose of this study is to examine the association of HT with the risk of renal transplant failure. METHODS: We utilized the United States Renal Database System dataset collected from 2005 to 2014 and compared the time from first renal transplant to transplant failure in end-stage renal disease (ESRD) patients with a HT diagnosis to ESRD patients without a HT diagnosis that underwent renal transplant. RESULTS: A total of 144 ESRD patients had International Classification of Disease-9 claim codes for HT prior to renal transplant, amongst a total cohort of 90,301 renal transplant patients aged 18-100 and meeting criteria. Patients with HT were significantly more likely to be female, white, and to have a diagnosis of cytomegalovirus compared to patients without. ESRD patients with a HT diagnosis that underwent renal transplant had a significantly increased risk of renal transplant failure compared to those ESRD renal transplant patients without an HT diagnosis. There was a significantly increased adjusted hazard ratio for graft failure in patients with a HT diagnosis compared to those without. CONCLUSION: Thyroid health and HT may play a significant role in the development of the increased risk of renal transplant failure observed in this study. Additional studies are needed to investigate the underlying mechanisms for this association.

CTC-5: A novel digital pathology approach to characterise circulating tumour cell biodiversity.

Metastatic progression and tumor evolution complicates the clinical management of cancer patients. Circulating tumor cell (CTC) characterization is a growing discipline that aims to elucidate tumor metastasis and evolution processes. CTCs offer the clinical potential to monitor cancer patients for therapy response, disease relapse, and screen 'at risk' groups for the onset of malignancy. However, such clinical utility is currently limited to breast, prostate, and colorectal cancer patients. Further understanding of the basic CTC biology of other malignancies is required to progress them towards clinical utility. Unfortunately, such basic clinical research is often limited by restrictive characterization methods and high-cost barrier to entry for CTC isolation and imaging infrastructure. As experimental clinical results on applications of CTC are accumulating, it is becoming clear that a two-tier system of CTC isolation and characterization is required. The first tier is to facilitate basic research into CTC characterization. This basic research then informs a second tier specialised in clinical prognostic and diagnostic testing. This study presented in this manuscript describes the development and application of a low-cost, CTC isolation and characterization pipeline; CTC-5. This approach uses an established 'isolation by size' approach (ScreenCell Cyto) and combines histochemical morphology stains and multiparametric immunofluorescence on the same isolated CTCs. This enables capture and characterization of CTCs independent of biomarker-based pre-selection and accommodates both single CTCs and clusters of CTCs. Additionally, the developed open-source software is provided to facilitate the synchronization of microscopy data from multiple sources (https://github.com/CTC5/). This enables high parameter histochemical and immunofluorescent analysis of CTCs with existing microscopy infrastructure without investment in CTC specific imaging hardware. Our approach confirmed by the number of successful tests represents a potential major advance towards highly accessible low-cost technology aiming at the basic research tier of CTC isolation and characterization. The biomarker independent approach facilitates closing the gap between malignancies with poorly, and well-defined CTC phenotypes. As is currently the case for some of the most commonly occurring breast, prostate and colorectal cancers, such advances will ultimately benefit the patient, as early detection of relapse or onset of malignancy strongly correlates with their prognosis.

Therapeutic drug monitoring and TB treatment outcomes in patients with diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) increases the risk of TB disease and poor treatment outcomes such as delayed sputum culture conversion due to inadequate drug exposure. Therapeutic drug monitoring (TDM) has improved these outcomes in some settings.METHODS: To compare treatment outcomes in programs with routine TDM vs. programs that did not use TDM, we conducted a retrospective study among people with DM and TB at health departments in four US states.RESULTS: A total of 170 patients were enrolled (73 patients in the non-TDM group and 97 patients in the TDM group). Days to sputum culture conversion and total treatment duration were significantly shorter in the TDM group vs. the non-TDM group. In adjusted analyses, patients who underwent TDM were significantly more likely to achieve sputum culture conversion at 2 months (P = 0.007).CONCLUSION: TDM hastened microbiological cure from TB among people with DM and a high risk for poor treatment outcomes in the programmatic setting.

MIF is a common genetic determinant of COVID-19 symptomatic infection and severity.

BACKGROUND: Genetic predisposition to coronavirus disease 2019 (COVID-19) may contribute to its morbidity and mortality. Because cytokines play an important role in multiple phases of infection, we examined whether commonly occurring, functional polymorphisms in macrophage migration inhibitory factor (MIF) are associated with COVID-19 infection or disease severity. AIM: To determine associations of common functional polymorphisms in MIF with symptomatic COVID-19 or its severity. METHODS: This retrospective case-control study utilized 1171 patients with COVID-19 from three tertiary medical centers in the USA, Hungary and Spain, together with a group of 637 pre-pandemic, healthy control subjects. Functional MIF promoter alleles (-794 CATT5-8,rs5844572), serum MIF and soluble MIF receptor levels, and available clinical characteristics were measured and correlated with COVID-19 diagnosis and hospitalization. Experimental mice genetically engineered to express human high- or low-expression MIF alleles were studied for response to coronavirus infection. RESULTS: In patients with COVID-19, there was a lower frequency of the high-expression MIF CATT7 allele when compared to healthy controls [11% vs. 19%, odds ratio (OR) 0.54 [0.41-0.72], P < 0.0001]. Among inpatients with COVID-19 (n = 805), there was a higher frequency of the MIF CATT7 allele compared to outpatients (n = 187) (12% vs. 5%, OR 2.87 [1.42-5.78], P = 0.002). Inpatients presented with higher serum MIF levels when compared to outpatients or uninfected healthy controls (87 ng/ml vs. 35 ng/ml vs. 29 ng/ml, P < 0.001, respectively). Among inpatients, circulating MIF concentrations correlated with admission ferritin (r = 0.19, P = 0.01) and maximum CRP (r = 0.16, P = 0.03) levels. Mice with a human high-expression MIF allele showed more severe disease than those with a low-expression MIF allele. CONCLUSIONS: In this multinational retrospective study of 1171 subjects with COVID-19, the commonly occurring -794 CATT7MIF allele is associated with reduced susceptibility to symptomatic SARS-CoV-2 infection but increased disease progression as assessed by hospitalization. These findings affirm the importance of the high-expression CATT7MIF allele, which occurs in 19% of the population, in different stages of COVID-19 infection.

The Effect of a Plastic Barrier Drape on Resuscitation Performance and Provider Contamination: A Randomized Controlled Simulation-Based Pilot Trial.

BACKGROUND: Patient barriers to protect health care workers from COVID-19 exposure have been studied for airway management. Few are tested for cardiopulmonary resuscitation (CPR). We sought to determine whether a plastic drape barrier affects resuscitation performance and contamination risks for a simulated cardiopulmonary arrest scenario. METHODS: This pilot trial randomized in-hospital resuscitation teams of 4 to 6 participants to a plastic drape or without a drape in an in situ cardiopulmonary arrest simulation. The mannequin's airway emanated simulated virus particles (GloGerm, Moab, UT), detectable through UV light. Primary outcomes included airway management and CPR quality measures. Secondary outcomes included visible contamination on personal protective equipment (PPE). We used the Non-Technical Skills (NO-TECHS) instrument to measure perceived team performance and the NASA Task Load Index (NASA-TLX) to measure individual workload. Outcome variables were analyzed using an analysis of covariance (ANCOVA) with participant number as a covariate. RESULTS: Seven teams were allocated to the intervention (plastic drape) group and 7 to the control. Intubation and ventilation performance (η 2 = 0.09, P > 0.3) and chest compression quality (η 2 = 0.03-0.19, P > 0.14) were not affected by the plastic drape. However, mean contaminated PPE per person decreased with the drape (2.8 ± 0.3 vs. 3.7 ± 0.3, partial η 2 = 0.29, P = 0.05). No differences in perceived workload nor team performance were noted ( P > 0.09). CONCLUSIONS: In this pilot study, the use of a plastic drape barrier seems not to affect resuscitation performance on simulated cardiopulmonary arrest but decreases health care worker contamination risk. Further implementation trials could characterize the true risk reduction and any effect on resuscitation outcomes.

Local Anaesthesia for Enzymatic Debridement of Cutaneous Burns: A Prospective Analysis of 27 Cases.

Enzymatic debridement (ED) is increasingly used for cutaneous burns. Compared with surgical debridement, ED has better preservation of viable dermis, less blood loss and autografting, however ED is painful. Current recommendations suggest local anaesthesia (LA) is useful for minor burns, but the evidence base is minimal. In our centre, we routinely use LA with good analgesic effect. This study was a single-centre, prospective analysis conducted at the Queen Victoria Hospital (UK). Patients had at least superficial partial thickness burns and received subcutaneous LA prior to ED during a 1-year period (October 2019-September 2020). Pain was assessed using a numeric scale of 1-10, recorded before, during and after the procedure. In total, 27 patients were included (n=17 males) with a median age of 47 (18-88 years). The mean total burn surface area was 1.5% (0.3-5.0). Treated sites included head and neck (1), trunk (5), upper limb (9) and lower limb (16). The most used LAwas bupivacaine 0.25% (n=25), followed by lidocaine 1% (n=2). Some required additional oral analgesia (n=8) or a regional blockade (n=2). Average pain score during debridement was 1.9 We have found LA effective, with favourable pain scores in comparison to previous studies with oral analgesia or regional blockade. LA is quick and easy to perform, as opposed to nerve blocks, which require trained personnel with ultrasound guidance. LA is a useful analgesic for patients with minor cutaneous burns undergoing ED. In some cases, it is sufficient without additional oral analgesia or regional blockade.

Le débridement enzymatique (DE) des brûlures est de plus en plus utilisé, ayant l'avantage d'être moins hémorragique et plus respectueux des tissus sains que la chirurgie, au prix d'une douleur plus importante. Les recommandations actuelles suggèrent l'utilisation de l'anesthésie locale (AL) sur les petites zones, avec un niveau de preuve minime. Dans notre centre, nous utilisons régulièrement l'AL, avec un bon effet analgésique. Cette étude a été conduite dans le CTB de l'hôpital Queen Vicoria (Royaume Uni). Durant 1 année (octobre 2019- septembre 2020), les patients devant bénéficier d'un DE recevaient préalablement une AL par infiltration. La douleur a été évaluée par échelle numérique (0 à 10) avant, pendant et après la procédure. Nous avons étudié 27 patients dont 17 hommes, d'âge médian 47 ans (18 à 88), brûlés en moyenne sur 1,5% (0,3 à 5), sur le cou (1), le tronc (5), le membre supérieur (9) et le membre supérieur (16). La bupivacaïne 0,25% a été la plus utilisée (25 fois), la lidocaïne 1% l'étant anecdotiquement (2 fois). Une analgésie complémentaire a été 10 fois nécessaire : orale 8 fois, régionale 2 fois. La douleur procédurale était cotée à 1,9 en moyenne. Nous estimons que l'AL est efficace, avec des scores de douleur favorables comparativement aux analgésies orale ou régionale. À la différence des analgésies régionales qui nécessitent un personnel entraîné et un écho- guidage, l'AL est facile et rapide. Elle peut être suffisante à elle seule pour le DE de brûlures minimes.

Characterisation of the immune microenvironment of primary breast cancer and brain metastasis reveals depleted T-cell response associated to ARG2 expression.

BACKGROUND: Immune checkpoint inhibition is an established treatment in programmed death-ligand 1 (PD-L1)-positive metastatic triple-negative (TN) breast cancer (BC). However, the immune landscape of breast cancer brain metastasis (BCBM) remains poorly defined. MATERIALS AND METHODS: The tumour-infiltrating lymphocytes (TILs) and the messenger RNA (mRNA) levels of 770 immune-related genes (NanoString™, nCounter™ Immuno-oncology IO360) were assessed in primary BCs and BCBMs. The prognostic role of ARG2 transcripts and protein expression in primary BCs and its association with outcome was determined. RESULTS: There was a significant reduction of TILs in the BCBMs in comparison to primary BCs. 11.5% of BCs presented a high immune infiltrate (hot), 46.2% were altered (immunosuppressed/excluded) and 34.6% were cold (no/low immune infiltrate). 3.8% of BCBMs were hot, 23.1% altered and 73.1% cold. One hundred and twelve immune-related genes including PD-L1 and CTLA4 were decreased in BCBM compared to the primary BCs (false discovery rate <0.01, log2 fold-change >1.5). These genes are involved in matrix remodelling and metastasis, cytokine-chemokine signalling, lymphoid compartment, antigen presentation and immune cell adhesion and migration. Immuno-modulators such as PD-L1 (CD274), CTLA4, TIGIT and CD276 (B7H3) were decreased in BCBMs. However, PD-L1 and CTLA4 expression was significantly higher in TN BCBMs (P = 0.01), with CTLA4 expression also high in human epidermal growth factor receptor 2-positive (P < 0.01) compared to estrogen receptor-positive BCBMs. ARG2 was one of four genes up-regulated in BCBMs. High ARG2 mRNA expression in primary BCs was associated with worse distant metastasis-free survival (P = 0.038), while ARG2 protein expression was associated with worse breast-brain metastasis-free (P = 0.027) and overall survival (P = 0.019). High transcript levels of ARG2 correlated to low levels of cytotoxic and T cells in both BC and BCBM (P < 0.01). CONCLUSION: This study highlights the immunological differences between primary BCs and BCBMs and the potential importance of ARG2 expression in T-cell depletion and clinical outcome.

Protocol of trans-Tasman feasibility randomised controlled trial of the Younger Women's Wellness After Breast Cancer (YWWACP) lifestyle intervention.

BACKGROUND: Younger women (defined as those < 50 years who are likely pre-menopausal at time of diagnosis) with breast cancer often experience persistent treatment-related side effects that adversely affect their physical and psychological wellbeing. The Women's Wellness After Cancer Program (WWACP) was adapted and piloted in Australia to address these outcomes in younger women. The aims of this feasibility study are to determine (1) the potential to translate the Younger WWACP (YWWACP) intervention to a broader population base in Aotearoa/New Zealand and Australia, and (2) the potential for success of a larger, international, phase ΙΙΙ, randomised controlled trial. METHODS: This bi-national, randomised, single-blinded controlled trial involves two main study sites in Aotearoa/New Zealand (Kowhai study) and Australia (EMERALD study). Young women aged 18 to 50 years who completed intensive treatment (surgery, chemotherapy, and/or radiotherapy) for breast cancer in the previous 24 months are eligible. The potential to translate the YWWACP to women in these two populations will be assessed according to several feasibility outcomes. These include examining intervention accessibility, acceptability and uptake; intervention sustainability and adherence; the prevalence components of the intervention in the control group; intervention efficacy; participants' perception of measurement burden; the effectiveness of planned recruitment strategies; and trial methods and procedures. The studies collectively aim to enrol 60 participants in the intervention group and 60 participants in the control group (total = 120 participants). DISCUSSION: Ethical approval has been received from the Southern Health and Disability Ethics Committee (Kowhai ref: 19/STH/215), and UnitingCare Human Research Ethics Committee (EMERALD ref: 202103). This study will provide important data on the feasibility of the refined YWWACP in the trans-Tasman context. This study will account for and harmonise cross-country differences to ensure the success of a proposed international grant application for a phase ΙΙΙ randomised controlled trial of this program to improve outcomes in younger women living with breast cancer. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): Kowhai ACTRN12620000260921 , registered on 27 February 2020. EMERALD ACTRN12621000447853 , registered on 19 April 2021.