Patterns of brain metastases response to immunotherapy with pembrolizumab.

PURPOSE: Central nervous system (CNS) metastases from lung cancers and melanoma, significantly contribute to morbidity and mortality. Despite advances in local therapies, there is a need for effective systemic treatments. Pembrolizumab, a PD-1 inhibitor, has shown promise for some patients with untreated brain metastases from melanoma and non-small cell lung cancer (NSCLC). This study aims to analyze the response of brain metastasis to pembrolizumab and associate characteristics like size and location with treatment outcome. METHODS: This retrospective study used imaging data from a phase II trial of pembrolizumab in melanoma or NSCLC patients with untreated brain metastases. MRI evaluations were conducted at 2 month intervals, with each brain metastasis treated as a distinct tumor for response assessment, based on modified RECIST criteria (maximum 5 lesions, 5 mm target lesions). RESULTS: Of 130 individual target metastases (> 5 mm), in 65 patients with NSCLC (90 metastases) and Melanoma (40 metastases), 32 (24.6%) demonstrated complete resolution, 24 (18.5%) had partial resolution, 32 (24.6%) were SD and 42 (32.3%) demonstrated PD. Those smaller than 10 mm were more likely to show complete resolution (p = 0.0218), while those ≥ 10 mm were more likely to have PR. There was no significant association between size, number or location (supratentorial vs. infratentorial) and lesion progression. The median time to metastatic lesion progression in the brain was 5.7-7 weeks. CONCLUSION: Pembrolizumab is effective in brain metastases from NSCLC and melanoma, showing response (CR + PR) in 43% and progression (PD) in 32% of metastases. With the median time to CNS progression of 5.7-7 weeks, careful radiographic monitoring is essential to guide timely local treatment decisions.

Rehabilitation Surgery for Peripheral Facial Nerve Injury after Facial Trauma.

Introduction Facial trauma can cause damage to the facial nerve, which can have negative effects on function, aesthetics, and quality of life if left untreated. Objective To evaluate the effectiveness of peripheral facial nerve direct end-to-end anastomosis and/or nerve grafting surgery for patients with facial nerve injury after facial trauma. Methods Fifty-nine patients with peripheral facial nerve paralysis after facial injuries underwent facial nerve rehabilitation surgery from November 2017 to December 2021 at Ho Chi Minh City National Hospital of Odontology. Results All 59 cases of facial trauma with damage to the peripheral facial nerve underwent facial nerve reconstruction surgery within 8 weeks of the injury. Of these cases, 25/59 (42.3%) had end-to-end anastomosis, 22/59 (37.3%) had nerve grafting, and 12/59 (20.4%) had a combination of nerve grafting and end-to-end anastomosis. After surgery, the rates of moderate and good recovery were 78.4% and 11.8%, respectively. All facial paralysis measurements showed statistically significant improvement after surgery, including the Facial Nerve Grading Scale 2.0 (FNGS 2.0) score, the Facial Clinimetric Evaluation (FaCE) scale, and electroneurography. The rate of synkinesis after surgery was 34%. Patient follow-up postoperatively ranged from 6 to > 36 months; 51 out of 59 patients (86.4%) were followed-up for at least 12 months or longer. Conclusion Nerve rehabilitation surgery including direct end-to-end anastomosis and nerve grafting is effective in cases of peripheral facial nerve injury following facial trauma. The surgery helps restore nerve conduction and improve facial paralysis.

In-line fiber optical sensor for detection of IgG aggregates in affinity chromatography.

Therapeutic monoclonal antibodies (mAbs) are critical for treatment of a wide range of diseases. Immunoglobulin G (IgG) is the most predominant form of mAb but is prone to aggregation during production. Detection and removal of IgG aggregates are time-consuming and laborious. Chromatography is central for purification of biopharmaceuticals in general and essential in the production of mAbs. Protein purification systems are usually equipped with detectors for monitoring pH, UV absorbance, and conductivity, to facilitate optimization and control of the purification process. However, specific in-line detection of the target products and contaminating species, such as aggregates, is currently not possible using convectional techniques. Here we show a novel fiber optical in-line sensor, based on localized surface plasmon resonance (LSPR), for specific detection of IgG and IgG aggregates during affinity chromatography. A flow cell with a Protein A sensor chip was connected to the outlet of the affinity column connected to three different chromatography systems operating at lab scale to pilot scale. Samples containing various IgG concentrations and aggregate contents were analyzed in-line during purification on a Protein A column using both pH gradient and isocratic elution. Because of avidity effects, IgG aggregates showed slower dissociation kinetics than monomers after binding to the sensor chips. Possibilities to detect aggregate concentrations below 1 % and difference in aggregate content smaller than 0.3 % between samples were demonstrated. In-line detection of aggregates can circumvent time-consuming off-line analysis and facilitate automation and process intensification.

Bone turnover markers reference database in five Southeast Asian countries.

Osteoporosis is highly prevalent, particularly in developing countries. However, bone turnover marker reference ranges for management of osteoporosis in Asian population are yet to be explored and established. Thus, this study aims to develop a regional bone turnover markers (BTMs) reference database by combining country-specific reference database from five ASEAN countries: Malaysia, the Philippines, Singapore, Thailand, and Vietnam. We established a healthy reference population of 746 healthy premenopausal women aged 20 to 44 years old. Serum Procollagen 1 N-Terminal Propeptide (P1NP), Osteocalcin (OC), and Beta-Crosslaps (CTX) concentrations were measured using an automated immunoassay analyzer system, the cobas® modular analyzer systems (Roche Diagnostic Gmbh). The reference interval was defined as the central 95 % range. The estimated reference interval for CTX was 128 to 811 ng/L, OC was 9.0 to 33.0 µg/L, and for P1NP, the range was 22.8 to 96.5 µg/L. Comparison across countries showed that Singaporeans had the highest levels of median CTX along with Thais and Filipinos, who had significantly higher levels of P1NP and OC. Exploratory analysis on the associations with age showed that BTMs decreased with increasing age at 20 to 29 years old and plateaued after 30 years old. When excluding participants in their 20s, the reference interval estimated were CTX: 117-678 ng/L, P1NP: 21.6-85.8 µg/L and OC: 3.5-27.0 µg/L respectively. To the best of our knowledge, this is the first study to report BTMs reference intervals based on a healthy premenopausal Southeast Asian population which will contribute to the appropriate assessment and monitoring of bone turnover rate in the evaluation and management of osteoporosis in the Southeast Asian region. LAY SUMMARY: Osteoporosis is a common health issue, especially in developing countries. However, there is a lack of information on bone health markers specific to the Southeast Asian population. This study aimed to fill this gap by creating a reference database for bone turnover markers (BTMs) in Southeast Asian countries, including Malaysia, the Philippines, Singapore, Thailand, and Vietnam. The researchers studied 746 healthy women aged 20 to 44 years and measured blood markers related to bone health. The reference interval, representing the normal range, was determined. For example, the normal range for CTX was found to be 128 to 811 ng/L, for Osteocalcin was 9.0 to 33.0 µg/L, and for P1NP, the range was 22.8 to 96.5 µg/L. When excluding participants in their 20s, the reference intervals estimated were CTX: 117-678 ng/L, P1NP: 21.6-85.8 µg/L and OC: 3.5-27.0 µg/L respectively. Comparing the results across countries, Singaporeans, Thais, and Filipinos showed variations in their biochemical bone marker levels. Additionally, the study observed changes in the levels with age, with a decrease in BTMs observed after the age of 30. This groundbreaking study provides the first-ever reference intervals for BTMs in a healthy premenopausal Southeast Asian population. These findings will help in the proper assessment and monitoring of bone health, contributing to the management of osteoporosis in the Southeast Asian region.

The phosphate-solubilising fungi in sustainable agriculture: unleashing the potential of fungal biofertilisers for plant growth.

Phosphate-solubilising fungi (PSF) are beneficial microorganisms that play a pivotal role in plant growth by increasing the availability of phosphorus (P) in soil. Although phosphorus is an essential nutrient for plants, it often becomes inaccessible as it binds into insoluble forms. PSF effectively facilitate the release of this bound phosphorus through diverse mechanisms. Numerous fungal species demonstrate the ability to solubilise various types of phosphate compounds. Among the commonly researched PSF are Penicillium, Aspergillus, Rhizopus, Fusarium, Trichoderma, and Sclerotium. Moreover, yeasts such as Saccharomyces cerevisiae can potentially be leveraged as PSF. PSF secrete organic acids that chelate phosphate ions, thereby increasing their solubility in the soil. Moreover, PSF contribute to the decomposition of organic phosphorus compounds in soil by employing enzymes such as phosphatases, phytases, and phosphonatases. Furthermore, PSF can interact with other soil microorganisms, including nitrogen-fixing bacteria and arbuscular mycorrhizal fungi (AM-fungi), fostering synergistic effects that further enhance plant growth and nutrient absorption. The utilisation of PSF as biofertilisers offers numerous advantages over chemical fertilisers, including environmental friendliness, cost-effectiveness, and enhanced fertiliser utilisation efficiency. Furthermore, PSF can prove beneficial in challenging environments characterised by high phosphate sorption. Hence, this review serves as an updated study aimed at broadening the understanding of PSF and its potential applications in P solubilisation. This review also focuses on the diversity of PSF, the mechanisms underlying solubilisation, ecological roles of PSF in soil microbiome, and the benefits of sustainable agriculture. By delving into the ecological roles of PSF and their potential as biofertilisers, this study contributes to a deeper understanding of sustainable agriculture practices and addresses challenges in phosphate-scarce environments.

GMP production of [18F]FE-PE2I on a TRACERLab FX2 N synthesis module, a radiotracer for in vivo PET imaging of the dopamine transport.

BACKGROUND: Parkinson's disease is a neurodegenerative disorder that is characterized by a degeneration of the dopaminergic system. Dopamine transporter (DAT) positron emission tomography (PET) imaging has emerged as a powerful and non-invasive method to quantify dopaminergic function in the living brain. The PET radioligand, [18F]FE-PE2I, a cocaine chemical derivative, has shown promising properties for in vivo PET imaging of DAT, including high affinity and selectivity for DAT, excellent brain permeability, and favorable metabolism. The aim of the current study was to scale up the production of [18F]FE-PE2I to fulfil the increasing clinical demand for this tracer. RESULTS: Thus, a fully automated and GMP-compliant production procedure has been developed using a commercially available radiosynthesis module GE TRACERLab FX2 N. [18F]FE-PE2I was produced with a radiochemical yield of 39 ± 8% (n = 4, relative [18F]F- delivered to the module). The synthesis time was 70 min, and the molar activity was 925.3 ± 763 GBq/µmol (250 ± 20 Ci/µmol). The produced [18F]FE-PE2I was stable over 6 h at room temperature. CONCLUSION: The protocol reliably provides a sterile and pyrogen-free GMP-compliant product.

Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities.

Discovered as inflammatory cytokines, MIF and DDT exhibit widespread expression and have emerged as critical mediators in the response to infection, inflammation, and more recently, in cancer. In this comprehensive review, we provide details on their structures, binding partners, regulatory mechanisms, and roles in cancer. We also elaborate on their significant impact in driving tumorigenesis across various cancer types, supported by extensive in vitro, in vivo, bioinformatic, and clinical studies. To date, only a limited number of clinical trials have explored MIF as a therapeutic target in cancer patients, and DDT has not been evaluated. The ongoing pursuit of optimal strategies for targeting MIF and DDT highlights their potential as promising antitumor candidates. Dual inhibition of MIF and DDT may allow for the most effective suppression of canonical and non-canonical signaling pathways, warranting further investigations and clinical exploration.

A serotype-specific and tiled amplicon multiplex PCR method for whole genome sequencing of dengue virus.

Dengue fever, a mosquito-borne viral disease of significant public health concern in tropical and subtropical regions, is caused by any of the four serotypes of the dengue virus (DENV1-4). Cutting-edge technologies like next-generation sequencing (NGS) are revolutionizing virology, enabling in-depth exploration of DENV's genetic diversity. Here, we present an optimized workflow for full-genome sequencing of DENV 1-4 utilizing tiled amplicon multiplex PCR and Illumina sequencing. Our assay, sequenced on the Illumina MiSeq platform, demonstrates its ability to recover the full-length dengue genome across various viral abundances in clinical specimens with high-quality base coverage. This high quality underscores its suitability for precise examination of intra-host diversity, enriching our understanding of viral evolution and holding potential for improved diagnostic and intervention strategies in regions facing dengue outbreaks.

Boosting Urea-Assisted Natural Seawater Electrolysis in 3D Leaf-Like Metal-Organic Framework Nanosheet Arrays Using Metal Node Engineering.

Metal node engineering, which can optimize the electronic structure and modulate the composition of poor electrically conductive metal-organic frameworks, is of great interest for electrochemical natural seawater splitting. However, the mechanism underlying the influence of mixed-metal nodes on electrocatalytic activities is still ambiguous. Herein, a strategic design is comprehensively demonstrated in which mixed Ni and Co metal redox-active centers are uniformly distributed within NH2-Fe-MIL-101 to obtain a synergistic effect for the overall enhancement of electrocatalytic activities. Three-dimensional mixed metallic MOF nanosheet arrays, consisting of three different metal nodes, were in situ grown on Ni foam as a highly active and stable bifunctional catalyst for urea-assisted natural seawater splitting. A well-defined NH2-NiCoFe-MIL-101 reaches 1.5 A cm-2 at 360 mV for the oxygen evolution reaction (OER) and 0.6 A cm-2 at 295 mV for the hydrogen evolution reaction (HER) in freshwater, substantially higher than its bimetallic and monometallic counterparts. Moreover, the bifunctional NH2-NiCoFe-MIL-101 electrode exhibits eminent catalytic activity and stability in natural seawater-based electrolytes. Impressively, the two-electrode urea-assisted alkaline natural seawater electrolysis cell based on NH2-NiCoFe-MIL-101 needs only 1.56 mV to yield 100 mA cm-2, much lower than 1.78 V for alkaline natural seawater electrolysis cells and exhibits superior long-term stability at a current density of 80 mA cm-2 for 80 h.

MIF and CD74 as Emerging Biomarkers for Immune Checkpoint Blockade Therapy.

Immune checkpoint blockade (ICB) therapy is used to treat a wide range of cancers; however, some patients are at risk of developing treatment resistance and/or immune-related adverse events (irAEs). Thus, there is a great need for the identification of reliable predictive biomarkers for response and toxicity. The cytokine MIF (macrophage migration inhibitory factor) and its cognate receptor CD74 are intimately connected with cancer progression and have previously been proposed as prognostic biomarkers for patient outcome in various cancers, including solid tumors such as malignant melanoma. Here, we assess their potential as predictive biomarkers for response to ICB therapy and irAE development. We provide a brief overview of their function and roles in the context of cancer and autoimmune disease. We also review the evidence showing that MIF and CD74 may be of use as predictive biomarkers of patient response to ICB therapy and irAE development. We also highlight that careful consideration is required when assessing the potential of serum MIF levels as a biomarker due to its reported circadian expression in human plasma. Finally, we suggest future directions for the establishment of MIF and CD74 as predictive biomarkers for ICB therapy and irAE development to guide further research in this field.

Vascular mimicry as a facilitator of melanoma brain metastasis.

Melanoma has the highest propensity among solid tumors to metastasize to the brain. Melanoma brain metastases (MBM) are a leading cause of death in melanoma and affect 40-60% of patients with late-stage disease. Therefore, uncovering the molecular mechanisms behind MBM is necessary to enhance therapeutic interventions. Vascular mimicry (VM) is a form of neovascularization linked to invasion, increased risk of metastasis, and poor prognosis in many tumor types, but its significance in MBM remains poorly understood. We found that VM density is elevated in MBM compared to paired extracranial specimens and is associated with tumor volume and CNS edema. In addition, our studies indicate a relevant role of YAP and TAZ, two transcriptional co-factors scarcely studied in melanoma, in tumor cell-vasculogenesis and in brain metastasis. We recently demonstrated activation of the Hippo tumor suppressor pathway and increased degradation of its downstream targets YAP and TAZ in a metastasis impaired cell line model. In the current study we establish the utility of anti-YAP/TAZ therapy in mouse models of metastatic melanoma whereby treatment effectively inhibits VM and prolongs survival of mice with MBM. The data presented herein suggest that VM may be an important and targetable mechanism in melanoma and that VM inhibition might be useful for treating MBM, an area of high unmet clinical need, thus having important implications for future treatment regimens for these patients.

Mental health impact on healthcare workers from COVID-19 in Vietnam: Suggestions for a preventive program.

The COVID-19 pandemic has had a negative impact on the mental health of healthcare workers participating in the prevention and control of the pandemic, thereby reducing their quality of life and affecting the quality of patient outcomes. This study aims to explore and deeply understand the mental health problems among healthcare workers participating in the prevention and control of COVID-19 in Ho Chi Minh City, Vietnam. A mixed methods study was undertaken with a descriptive cross-sectional survey of 2870 healthcare workers who have been participating in the prevention and control of COVID-19 in Ho Chi Minh City in 2021, followed by a qualitative descriptive phenomenological study comprised of in-depth interviews with a purposively sampled subset of 40 healthcare workers. Results showed that of the 2870 survey participants, the majority (60.6%) were female, and the average age was 35.1 (SD = 8.6). The prevalence of stress, anxiety and depression was 17.2%, 20.8%, and 17.6%, respectively. The findings from in-depth interviews revealed that the participants were under extreme mental health issues such as worries, stress, and negative emotions. The worrying was related to risk of infection, being shunned, stigmatised, or assaulted by the community. Stress was due to excessive pressure from work. Negative emotions were identified as sadness, self-pity, feelings of loneliness, entrusting fate, feelings of guilt, anxiety, confusion, obsession, disorientation, physical and mental exhaustion. Promoting mental health among healthcare workers who participated in the crisis is necessary and urgent.

Prevalence, determinants, intervention strategies and current gaps in addressing childhood malnutrition in Vietnam: a systematic review.

BACKGROUND: Childhood malnutrition in all forms is a major public health issue worldwide. This review systematically examined the prevalence and determinants and identify the potential interventions and current gap in addressing malnutrition including undernutrition, overnutrition and micronutrient deficiencies (MNDs) in Vietnamese children aged 0-18 years old. METHODS: Embase, Scopus, PubMed, and Web of Science were systematically searched through June 2022 to identify relevant articles published within the past 25 years. Study selection and data extraction were performed by one reviewer and checked for accuracy by the other two reviewers in accordance with PRISMA guideline. Risk of publication bias was assessed using American Dietetic Association Quality Criteria Checklist. RESULTS: Seventy-two studies that met the inclusion criteria were included. Undernutrition has decreased over time but still 22.4%, 5.2% and 12.2% of children under 5 were stunted, wasted and underweight, respectively. Anaemia, iron, zinc, and vitamin D deficiencies were the more common forms of MNDs, the prevalence varied by age, region, and socioeconomic group. Population-based surveys reported that 11% and 48% of children aged 0-11 years old were iron and vitamin D deficient, respectively. Zinc deficiency affected almost one-quarter of the children and adolescents. Retinol deficiency was of less concern (< 20%). However, more evidence on MNDs prevalence is needed. Overweight and obesity is now on the rise, affecting one-third of school-aged children. The key determinants of undernutrition included living in rural areas, children with low birth weight, and poor socio-economic status, whereas living in urban and affluent areas, having an inactive lifestyle and being a boy were associated with increased risk of overweight and obesity. Nutrition specific intervention studies including supplementation and food fortification consistently showed improvements in anthropometric indices and micronutrient biomarkers. National nutrition-sensitive programmes also provided nutritional benefits for children's growth and eating behaviours, but there is a lack of data on childhood obesity. CONCLUSION: This finding highlights the need for effective double duty actions to simultaneously address different forms of childhood malnutrition in Vietnam. However, evidence on the potential intervention strategies, especially on MNDs and overnutrition are still limited to inform policy decision, thus future research is warranted.

South East Asian Nutrition Surveys (SEANUTS) II - a multi-country evaluation of nutrition and lifestyle indicators in children aged 12 years and below: Rationale and Design.

OBJECTIVE: To assess the nutritional status, growth parameters and lifestyle behaviours of children between 0.5-12 years in nationally representative samples in Malaysia, Indonesia, Thailand, and Vietnam. DESIGN: A cross-sectional study was conducted in the four countries, between May 2019 and April 2021. Data collected can be categorized into four categories: (1) Growth - anthropometry, body composition, development disorder, (2) Nutrient intake and dietary habits - 24-hour dietary recall, child food habits, breast feeding and complementary feeding, (3) Socio-economic status - food insecurity and child health status/environmental, and (4) Lifestyle behaviours - physical activity patterns, fitness, sunlight exposure, sleep patterns, body image and behavioural problems. Blood samples were also collected for biochemical and metabolomic analyses. With the pandemic emerging during the study, a COVID-19 questionnaire was developed and implemented. SETTING: Both rural and urban areas in Malaysia, Indonesia, Thailand, and Vietnam. PARTICIPANTS: Children who were well, with no physical disability or serious infections/injuries and between the age of 0.5-12 years old were recruited. RESULTS: The South East Asian Nutrition Surveys II recruited 13,933 children. Depending on the country, data collection from children were conducted in schools and commune health centres, or temples, or sub-district administrative organizations. CONCLUSIONS: The results will provide up-to-date insights into nutritional status and lifestyle behaviours of children in the four countries. Subsequently, these data will facilitate exploration of potential gaps in dietary intake among Southeast Asian children and enable local authorities to plan future nutrition and lifestyle intervention strategies.

Acquisition Duration Optimization Using Visual Grading Regression in [68Ga]FAPI-46 PET Imaging of Oncologic Patients.

Fibroblast activation protein is a promising target for oncologic molecular imaging with radiolabeled fibroblast activation protein inhibitors (FAPI) in a large variety of cancers. However, there are yet no published recommendations on how to set up an optimal imaging protocol for FAPI PET/CT. It is important to optimize the acquisition duration and strive toward an acquisition that is sufficiently short while simultaneously providing sufficient image quality to ensure a reliable diagnosis. The aim of this study was to evaluate the feasibility of reducing the acquisition duration of [68Ga]FAPI-46 imaging while maintaining satisfactory image quality, with certainty that the radiologist's ability to make a clinical diagnosis would not be affected. Methods: [68Ga]FAPI-46 PET/CT imaging was performed on 10 patients scheduled for surgical resection of suspected pancreatic cancer, 60 min after administration of 3.6 ± 0.2 MBq/kg. The acquisition time was 4 min/bed position, and the raw PET data were statistically truncated and reconstructed to represent images with an acquisition duration of 1, 2, and 3 min/bed position, additional to the reference images of 4 min/bed position. Four image quality criteria that focused on the ability to distinguish specific anatomic details, as well as perceived image noise and overall image quality, were scored on a 4-point Likert scale and analyzed with mixed-effects ordinal logistic regression. Results: A trend toward increasing image quality scores with increasing acquisition duration was observed for all criteria. For the overall image quality, there was no significant difference between 3 and 4 min/bed position, whereas 1 and 2 min/bed position were rated significantly (P < 0.05) lower than 4 min/bed position. For the other criteria, all images with a reduced acquisition duration were rated significantly inferior to images obtained at 4 min/bed position. Conclusion: The acquisition duration can be reduced from 4 to 3 min/bed position while maintaining satisfactory image quality. Reducing the acquisition duration to 2 min/bed position or lower is not recommended since it results in inferior-quality images so noisy that clinical interpretation is significantly disrupted.

Natural history of undifferentiated pleomorphic sarcoma: Experience from the US Sarcoma Collaborative.

BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) is a relatively rare but aggressive neoplasm. We sought to utilize a multi-institutional US cohort of sarcoma patients to examine predictors of survival and recurrence patterns after resection of UPS. METHODS: From 2000 to 2016, patients with primary UPS undergoing curative-intent surgical resection at seven academic institutions were retrospectively reviewed. Epidemiologic and clinicopathologic factors were reviewed by site of origin. Overall survival (OS), recurrence-free survival (RFS), time-to-locoregional (TTLR), time-to-distant recurrence (TTDR), and patterns of recurrence were analyzed. RESULTS: Of the 534 UPS patients identified, 53% were female, with a median age of 60 and median tumor size of 8.5 cm. The median OS, RFS, TTLR, and TTDR for the entire cohort were 109, 49, 86, and 46 months, respectively. There were no differences in these survival outcomes between extremity and truncal UPS. Compared with truncal, extremity UPS were more commonly amenable to R0 resection (87% vs. 75%, p = 0.017) and less commonly associated with lymph node metastasis (1% vs. 6%, p = 0.031). R0 resection and radiation treatment, but not site of origin (extremity vs. trunk) were independent predictors of OS and RFS. TTLR recurrence was shorter for UPS resected with a positive margin and for tumors not treated with radiation. CONCLUSION: For patients with resected extremity and truncal UPS, tumor size >5 cm and positive resection margin are associated with worse survival OS and RFS, irrespectively the site of origin. R0 surgical resection and radiation treatment may help improve these survival outcomes.

Improved survival of patients receiving immunotherapy and chemotherapy following curative-intent resection of colorectal liver metastases.

BACKGROUND: Despite significant advancements in the treatment of patients with colorectal liver metastases (CRLMs), only a minority will experience long-term survival. This study aimed to determine the effect of chemotherapy (CT) and immunotherapy (IT) compared with that of CT alone on patient survival after surgical resection. METHODS: Patients undergoing curative-intent liver resection followed by adjuvant systemic therapy for stage IV colon cancer were identified using the National Cancer Database. Patients were stratified into type of therapy (CT alone vs CT + IT) and microsatellite status. Propensity score-weighted analysis was performed through 1:1 matching based on the nearest neighbor method. RESULTS: Of 9943 patients who underwent resection of CRLMs, 7971 (80%) received systemic adjuvant therapy. Of 7971 patients, 1432 (18%) received a combination of CT and IT. Microsatellite status was not associated with overall survival (OS). Adjuvant CT + IT was associated with increased 3-year OS compared with that of CT alone in both the unmatched cohort (55% vs 48%, respectively; P < .001) and matched cohort (52% vs 48%, respectively; P = .050). On multivariate analysis, older age, positive resection margins, and KRAS mutation were independent predictors of poor survival, whereas the administration of adjuvant CT + IT was an independent predictor of improved survival. CONCLUSION: IT combined with CT was associated with improved survival compared with that of CT alone after curative-intent resection of CRLMs, regardless of microsatellite instability status. Clinical trials to determine optimal patient selection, IT regimen, and long-term efficacy to improve outcomes of patients with CRLMs are warranted.

Endothelial and inflammatory pathophysiology in dengue shock: New insights from a prospective cohort study in Vietnam.

Dengue shock (DS) is the most severe complication of dengue infection; endothelial hyperpermeability leads to profound plasma leakage, hypovolaemia and extravascular fluid accumulation. At present, the only treatment is supportive with intravenous fluid, but targeted endothelial stabilising therapies and host immune modulators are needed. With the aim of prioritising potential therapeutics, we conducted a prospective observational study of adults (≥16 years) with DS in Vietnam from 2019-2022, comparing the pathophysiology underlying circulatory failure with patients with septic shock (SS), and investigating the association of biomarkers with clinical severity (SOFA score, ICU admission, mortality) and pulmonary vascular leak (daily lung ultrasound for interstitial and pleural fluid). Plasma was collected at enrolment, 48 hours later and hospital discharge. We measured biomarkers of inflammation (IL-6, ferritin), endothelial activation (Ang-1, Ang-2, sTie-2, VCAM-1) and endothelial glycocalyx breakdown (hyaluronan, heparan sulfate, endocan, syndecan-1). We enrolled 135 patients with DS (median age 26, median SOFA score 7, 34 required ICU admission, 5 deaths), together with 37 patients with SS and 25 healthy controls. Within the DS group, IL-6 and ferritin were associated with admission SOFA score (IL-6: ßeta0.70, p<0.001 & ferritin: ßeta0.45, p<0.001), ICU admission (IL-6: OR 2.6, p<0.001 & ferritin: OR 1.55, p<0.001) and mortality (IL-6: OR 4.49, p = 0.005 & ferritin: OR 13.8, p = 0.02); both biomarkers discriminated survivors and non-survivors at 48 hours and all patients who died from DS had pre-mortem ferritin ≥100,000ng/ml. IL-6 most strongly correlated with severity of pulmonary vascular leakage (R = 0.41, p<0.001). Ang-2 correlated with pulmonary vascular leak (R = 0.33, p<0.001) and associated with SOFA score (ß 0.81, p<0.001) and mortality (OR 8.06, p = 0.002). Ang-1 was associated with ICU admission (OR 1.6, p = 0.005) and mortality (OR 3.62, p = 0.006). All 4 glycocalyx biomarkers were positively associated with SOFA score, but only syndecan-1 was associated with ICU admission (OR 2.02, p<0.001) and mortality (OR 6.51, p<0.001). This study highlights the central role of hyperinflammation in determining outcomes from DS; the data suggest that anti-IL-1 and anti-IL-6 immune modulators and Tie2 agonists may be considered as candidates for therapeutic trials in severe dengue.

Human Epidermal Growth Factor Receptor 2 (HER2) PET Imaging of HER2-Low Breast Cancer with [68Ga]Ga-ABY-025: Results from a Pilot Study.

Patients with HER2-low metastatic breast cancer (mBC), defined as an immunohistochemistry (IHC) score of 1+ or 2+ without HER2 gene amplification, may benefit from HER2 antibody-drug conjugates. Identifying suitable candidates is a clinical challenge because of spatial and temporal heterogeneity in HER2 expression and discrepancies in pathologic reporting. We aimed to investigate the feasibility and safety of HER2-specific PET imaging with [68Ga]Ga-ABY-025 for visualization of HER2-low mBC. Methods: A prospective pilot study was done with 10 patients who had HER2-low mBC, as part of a phase 2 basket imaging study with [68Ga]Ga-ABY-025 in HER2-expressing solid tumors. Patients were recruited at the Breast Clinic at the Karolinska University Hospital, Stockholm, Sweden. PET/CT images were acquired 3 h after injection of 200 MBq of [68Ga]Ga-ABY-025. The SUVmax was used to quantify tracer uptake. Ultrasound-guided tumor biopsies were guided by results from the HER2 PET. The main outcome-the safety and feasibility of HER2 PET in patients with HER2-low mBC, measured the occurrence of possible procedure-related adverse events. Results: Ten patients with HER2-low mBC underwent [68Ga]Ga-ABY-025 PET/CT with paired tumor biopsies. No adverse events occurred. In all patients, [68Ga]Ga-ABY-025-avid lesions with substantial intra- and interindividual heterogeneity in tracer uptake were noted. In 8 of 10 patients with ABY-025-avid lesions, the HER2-low status of the corresponding lesions was confirmed by IHC or in situ hybridization. Two patients had an IHC score of 0 in the tumor biopsies:1 in a cutaneous lesion with a low SUVmax and 1 in a liver metastasis with a high SUVmax but a "cold" core. Conclusion: The visualization of HER2-low mBC with [68Ga]Ga-ABY-025 PET/CT was feasible and safe. Areas of tracer uptake showed varying levels of HER2 expression on IHC. The observed intra- and interindividual heterogeneity in [68Ga]Ga-ABY-025 uptake suggested that HER2 PET might be used as a tool for the noninvasive assessment of disease heterogeneity and has the potential to identify patients in whom HER2-targeted drugs can have a clinical benefit.

The impacts of telemedicine on assisted reproduction: a systematic review and meta-analysis.

Telemedicine is being applied in assisted reproduction technology (ART) to provide remote consultations, monitoring and support for patients. This study aimed to evaluate the potential advantages of telemedicine in ART treatment in the form of virtual consultations. Studies in which patients were using telemedicine during ART treatment were identified from four scientific databases (PudMed, EMBASE, Scopus, Web of Science). The success of fertility treatments was compared between telemedicine and in-office care, and patient satisfaction with ART through telemedicine was assessed. Eleven studies, comprising 4697 patients, were identified. Quality assessment (Joanna Briggs Institute Critical Appraisal and revised Cochrane risk-of-bias tools) revealed an acceptable risk of bias for both randomized controlled trials and observational studies. Using a fixed-effects model, telemedicine was comparable to in-person care regarding the pregnancy rate achieved (odds ratio 1.02, 95% confidence intervals 0.83-1.26, P = 0.83). A Q-test suggested that all the included studies were homogeneous. Patients who received telemedicine during fertility treatment reported a high level of satisfaction (91%, 95% confidence intervals 80-96%). Egger's test confirmed that no publication bias was found. Telemedicine could serve as a complementary tool during fertility treatment to facilitate patients' satisfaction and overcome some practical problems without compromising treatment outcomes. Future studies should continue exploring the potential applications of telemedicine in assisted reproduction.