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Background Radar-guided localization (RGL) offers a wire-free, nonradioactive surgical guidance method consisting of a small percutaneously-placed radar reflector and handheld probe. This study investigates the feasibility, timing, and outcomes of RGL for melanoma metastasectomy. Methods We retrospectively identified patients at our cancer center who underwent RGL resection of metastatic melanoma between December 2020-June 2023. Data pertaining to patients’ melanoma history, management, reflector placement and retrieval, and follow-up was extracted from patient charts and analyzed using descriptive statistics. Results Twenty-three RGL cases were performed in patients with stage III-IV locoregional or oligometastatic disease, 10 of whom had reflectors placed prior to neoadjuvant therapy. Procedures included soft tissue nodule removals (8), index lymph node removals (13), and therapeutic lymph node dissections (2). Reflectors were located and retrieved intraoperatively in 96% of cases from a range of 2 to 282 days after placement; the last reflector was not able to be located during surgery via probe or intraoperative ultrasound. One retrieved reflector had migrated from the index lesion, thus overall success rate of reflector and associated index lesion removal was 21 of 23 (91%). All RGL-localized and retrieved index lesions that contained viable tumor (10) had microscopically negative margins. There were no complications attributable to reflector insertion and no unexpected complications of RGL surgery. Conclusion In our practice, RGL is a safe and effective surgical localization method for soft tissue and nodal melanoma metastases. The inert nature of the reflector enables implantation prior to neoadjuvant therapy with utility in index lymph node removal. Plain language summary There are a variety of tools available to localize melanoma that had spread to deep layers of the skin or lymph nodes that can guide surgeons to the cancer when the tumor cannot be felt. We evaluated a marker that reflects radar signals that has been studied in breast surgery but not in melanoma. The marker was placed in the tumor before surgery and was located during surgery using a handheld probe, guiding the surgeon to the correct location. An advantage of the radar-reflecting marker we studied is that since it is safe to stay in the body, it can be placed ahead of the use of cancer medications and can keep track of the tumor as it responds to treatment. In a review of 23 surgeries in which the radar-reflecting marker was used, there was one case where the marker migrated away from the tumor and one case where the marker was not able to be located. Monitoring or alternative definitive treatment was provided in each of these cases. Overall, we found the marker to be an effective tumor localization tool for surgeons and safe for patients. Other marker options available are unable or less suitable to be placed a long time in advance of surgery due to either technical or safety reasons, so the radar-reflecting marker is especially useful when it is placed in a tumor ahead of medical treatment leading up to planned surgical treatment.

Deregulation of metabolism and disruption of genome integrity are hallmarks of cancer 1 . Increased levels of the metabolites 2-hydroxyglutarate, succinate and fumarate occur in human malignancies owing to somatic mutations in the isocitrate dehydrogenase-1 or -2 ( IDH1 or IDH2 ) genes, or germline mutations in the fumarate hydratase ( FH ) and succinate dehydrogenase genes ( SDHA , SDHB , SDHC and SDHD ), respectively 2 – 4 . Recent work has made an unexpected connection between these metabolites and DNA repair by showing that they suppress the pathway of homology-dependent repair (HDR) 5 , 6 and confer an exquisite sensitivity to inhibitors of poly (ADP-ribose) polymerase (PARP) that are being tested in clinical trials. However, the mechanism by which these oncometabolites inhibit HDR remains poorly understood. Here we determine the pathway by which these metabolites disrupt DNA repair. We show that oncometabolite-induced inhibition of the lysine demethylase KDM4B results in aberrant hypermethylation of histone 3 lysine 9 (H3K9) at loci surrounding DNA breaks, masking a local H3K9 trimethylation signal that is essential for the proper execution of HDR. Consequently, recruitment of TIP60 and ATM, two key proximal HDR factors, is substantially impaired at DNA breaks, with reduced end resection and diminished recruitment of downstream repair factors. These findings provide a mechanistic basis for oncometabolite-induced HDR suppression and may guide effective strategies to exploit these defects for therapeutic gain. Metabolites that are elevated in tumours inhibit the lysine demethylase KDM4B, resulting in aberrant hypermethylation of histone 3 lysine 9 and decreased homology-dependent DNA repair.

Background Accurate growth assessment of preterm infants is essential in guiding medical care and suitable nutritional interventions. Currently, different growth references are used across hospitals in the United Arab Emirates (UAE). This study aims to compare the INTERGROWTH-21st standards with Fenton growth references regarding birth size classification and at the time of discharge in a sample of preterm infants in the UAE. Methods A retrospective single-center evaluation of medical records of infants born < 37 weeks of gestation was conducted using data from 2018 to 2020. Anthropometric measurements (weight, length, and head circumference) were obtained at birth and at the time of discharge, and then converted to percentiles according to the two reference standards. Results A total of 1537 infants with a median birth gestation of 35.3 weeks, and a median birthweight of 2320 g were included. The rates of SGA, AGA, and LGA at birth were 11.5%, 80.42%, and 9.08% using INTERGROWTH-21st growth charts compared to 9.5%, 83.2%, and 7.3% respectively according to Fenton charts. The findings indicated statistically significant differences between the two growth charts classifying of preterm infants based on weight, length, and head circumference ( p  < 0.05). For every 5 cases assessed as SGA at discharge according to Fenton charts, only 3 were classified as SGA by INTERGROWTH-21st curves. Conclusions Differences exist between the two growth charts with only moderate agreement. Thus, there is a need for harmonizing growth assessment standards. Misclassification of these vulnerable infants would affect their in-hospital and post-discharge nutrition and medical care plan.

Abstract Background The bivalent COVID-19 mRNA boosters became available in fall 2022 and were recommended alongside the seasonal influenza vaccine. However, the immunogenicity of concurrent vs separate administration of these vaccines remains unclear. Methods Here, we analyzed antibody responses in health care workers who received the bivalent COVID-19 booster and the influenza vaccine on the same day or on different days through systems serology. Antibody-binding and functional responses were characterized at peak responses and after 6 months following vaccination. Results IgG1 and neutralization responses to SARS-CoV-2 XBB.1.5 were higher at peak and after 6 months following concurrent administration as compared with separate administration of the COVID-19 and influenza vaccines. While similar results were not observed for influenza responses, no interference was noted with concurrent administration. Conclusions These data suggest that concurrent administration of these vaccines may yield higher and more durable SARS-CoV-2 neutralizing antibody responses while maintaining responses against influenza.

Potentially untreatable Plasmodium falciparum malaria threatens the Greater Mekong subregion. A previous series of pilot projects in Myanmar, Laos, Cambodia, and Vietnam suggested that mass drug administration was safe, and when added to provision of early diagnosis and treatment, could reduce the reservoir of P falciparum and interrupts transmission. We examined the effects of a scaled-up programme of this strategy in four townships of eastern Myanmar on the incidence of P falciparum malaria. The programme was implemented in the four townships of Myawaddy, Kawkareik, Hlaingbwe, and Hpapun in Kayin state, Myanmar. Increased access to early diagnosis and treatment of malaria was provided to all villages through community-based malaria posts equipped with rapid diagnostic tests, and treatment with artemether–lumefantrine plus single low-dose primaquine. Villages were identified as malarial hotspots (operationally defined as >40% malaria, of which 20% was P falciparum) with surveys using ultrasensitive quantitative PCR either randomly or targeted at villages where the incidence of clinical cases of P falciparum malaria remained high (ie, >100 cases per 1000 individuals per year) despite a functioning malaria post. During each survey, a 2 mL sample of venous blood was obtained from randomly selected adults. Hotspots received targeted mass drug administration with dihydroartemisinin–piperaquine plus single-dose primaquine once per month for 3 consecutive months in addition to the malaria posts. The main outcome was the change in village incidence of clinical P falciparum malaria, quantified using a multivariate, generalised, additive multilevel model. Malaria prevalence was measured in the hotspots 12 months after mass drug administration. Between May 1, 2014, and April 30, 2017, 1222 malarial posts were opened, providing early diagnosis and treatment to an estimated 365 000 individuals. Incidence of P falciparum malaria decreased by 60 to 98% in the four townships. 272 prevalence surveys were undertaken and 69 hotspot villages were identified. By April 2017, 50 hotspots were treated with mass drug administration. Hotspot villages had a three times higher incidence of P falciparum at malarial posts than neighbouring villages (adjusted incidence rate ratio [IRR] 2·7, 95% CI 1·8–4·4). Early diagnosis and treatment was associated with a significant decrease in P falciparum incidence in hotspots (IRR 0·82, 95% CI 0·76–0·88 per quarter) and in other villages (0·75, 0·73–0·78 per quarter). Mass drug administration was associated with a five-times decrease in P falciparum incidence within hotspot villages (IRR 0·19, 95% CI 0·13–0·26). By April, 2017, 965 villages (79%) of 1222 corresponding to 104 village tracts were free from P falciparum malaria for at least 6 months. The prevalence of wild-type genotype for K13 molecular markers of artemisinin resistance was stable over the three years (39%; 249/631). Providing early diagnosis and effective treatment substantially decreased village-level incidence of artemisinin-resistant P falciparum malaria in hard-to-reach, politically sensitive regions of eastern Myanmar. Targeted mass drug administration significantly reduced malaria incidence in hotspots. If these activities could proceed in all contiguous endemic areas in addition to standard control programmes already implemented, there is a possibility of subnational elimination of P falciparum. The Bill & Melinda Gates Foundation, the Regional Artemisinin Initiative (Global Fund against AIDS, Tuberculosis and Malaria), and the Wellcome Trust.

BackgroundThe optimal time to initiate adjuvant immune checkpoint inhibitors (ICI) following resection remains undefined. Herein, we investigated the impact of time to adjuvant ICI on survival in patients with stage III melanoma.MethodsPatients with resected stage III melanoma receiving adjuvant immune therapy were identified within a multi-institutional retrospective cohort. Patients were stratified by time to adjuvant ICI: within 6 weeks, 6–12 weeks, and greater than 12 weeks from surgery. Recurrence-free survival (RFS) was compared among time strata with Kaplan-Meier and Cox proportional hazards methods in the multi-institutional cohort.ResultsAltogether, 626 patients were identified within the multi-institutional cohort: 39% of patients initiated adjuvant ICI within 6 weeks, 42.2% within 6–12 weeks, and 18.8% greater than 12 weeks from surgery. In a multivariate Cox model, adjusting for histology, nodal tumor burden, and pathologic stage, we found that increased time to adjuvant ICI was associated with improved RFS. Patients who initiated adjuvant ICI within 6 weeks of surgery had worse RFS. These findings were preserved in a conditional landmark analysis and separate subgroups of patients with (1) new melanoma diagnoses, (2) occult stage III disease, and (3) those receiving anti-PD-1 monotherapy.ConclusionsOutcomes for patients with stage III melanoma are not compromised when adjuvant ICI is initiated beyond 6 weeks from resection. Additional work is needed to better understand the underlying mechanisms and implications of timing of adjuvant ICI on long-term outcomes.

Background Self‐harm and suicide related behaviours are increasing in young people, and clinical support is not adequately meeting needs. Improved approaches to assessment and the clinical management of self‐harm will result from codesign processes and include greater shared decision‐making between young people and practitioners. The CaTS‐App (an adapted digital version of the existing Card‐Sort Task for Self‐harm research tool) aims to facilitate a collaborative understanding of adolescent self‐harm and support decision‐making within clinical settings. The codevelopment of a digital, clinical tool which meets the needs of multiple stakeholders requires careful consideration. Methods We present a case‐study describing the participatory aspects of the development of the CaTS‐App, which included comprehensive patient involvement, research activities and coproduction with diverse young people aged 17–24 with lived experience of self‐harm. We share our processes and activities to deliver safe, engaging, sustainable, ethical and responsible participatory practice and co‐created knowledge, in the codevelopment of the CaTS‐App. Results Activities spanned a 48‐month period in both face‐to‐face and online settings. Example processes and activities are provided in narrative, tabular and diagrammatic form, alongside discussion of the rationale for choices made. A summary methodology is also shared to stimulate continued discussion and development of participatory approaches in digital mental health. Conclusions The paper contributes important insight and practical detail for the delivery of genuine participatory processes in digital mental health development when working with a population who may be considered vulnerable. We discuss a case‐study and working methodology for meaningful, safe and responsible involvement in the early Planning and Discovery phase of the development of a novel assessment and intervention app for self‐harm—the CaTS‐App This paper contributes to important discussions about the process and value of centering and evaluating participatory processes in the development of digital mental health interventions for self‐harm.

Antibodies represent a primary mediator of protection against respiratory viruses such as SARS-CoV-2. Serum neutralizing antibodies (NAbs) are often considered a primary correlate of protection. However, detailed antibody profiles including characterization of antibody functions in different anatomic compartments are not well understood. Here we show that antibody correlates of protection against SARS-CoV-2 challenge are different in systemic versus mucosal compartments in rhesus macaques. In serum, neutralizing antibodies were the strongest correlate of protection and were linked to Spike-specific binding antibodies and other extra-neutralizing antibody functions that create a larger protective network. In contrast, in bronchiolar lavage (BAL), antibody-dependent cellular phagocytosis (ADCP) proved the strongest correlate of protection rather than NAbs. Within BAL, ADCP was linked to mucosal Spike-specific IgG, IgA/secretory IgA, and Fcγ-receptor binding antibodies. Our results support a model in which antibodies with different functions mediate protection at different anatomic sites. The correlation of ADCP and other Fc functional antibody responses with protection in BAL suggests that these antibody responses may be critical for protection against SARS-CoV-2 Omicron challenge in mucosa.

The bivalent COVID-19 mRNA boosters became available in fall 2022 and were recommended alongside the seasonal influenza vaccine. However, the immunogenicity of concurrent versus separate administration of these vaccines remains unclear. Here, we analyzed antibody responses in healthcare workers who received the bivalent COVID-19 booster and the influenza vaccine on the same day or different days. IgG1 responses to SARS-CoV-2 Spike were higher at peak immunogenicity and 6 months following concurrent administration compared with separate administration of the COVID-19 and influenza vaccines. These data suggest that concurrent administration of these vaccines may yield higher and more durable SARS-CoV-2 antibody responses.