Construction of 5-Amino-1,2-Selenazole Scaffolds through N-Selenocyanation/Cyclization of Enaminones Using KSeCN.

A metal-free and mild approach for constructing 5-amino-1,2-selenazole skeletons by NBS/KSeCN-mediated N-selenocyanation and nucleophilic cyclization of ß-enaminones has been developed. Various isoselenazole compounds and the isoselenazolyl derivatives of anti-inflammatory medicines, including isosepac, oxaprozin, and ibuprofen, have been obtained with good yields. This efficient, "one-pot", and atomic economy strategy may represent an alternative route for the construction of a 1,2-selenazole framework via the "+SeCN" pathway and provide new access to heterocycles containing a Se-N bond.

Changes in cardiovascular disease risk predicted by the Framingham risk model in the Hong Kong population between 2003-2005 and 2014-2015: data from Population Health Surveys.

INTRODUCTION: The Framingham risk model estimates a person's 10-year cardiovascular disease (CVD) risk. This study used this model to calculate the changes in sex- and age-specific CVD risks in the Hong Kong Population Health Survey (PHS) 2014/15 compared with two previous surveys conducted during 2003 and 2005, namely, PHS 2003/2004 and Heart Health Survey (HHS) 2004/2005. METHODS: This study included individuals aged 30 to 74 years from PHS 2014/15 (n=1662; n=4 445 868 after population weighting) and PHS 2003/2004 and HHS 2004/2005 (n=818; n=3 495 074 after population weighting) with complete data for calculating the risk of CVD predicted by the Framingham model. Sex-specific CVD risks were calculated based on age, total cholesterol and high-density lipoprotein cholesterol levels, mean systolic blood pressure, smoking habit, diabetic status, and hypertension treatment. Mean sex- and age-specific CVD risks were calculated; differences in CVD risk between the two surveys were compared by independent t tests. RESULTS: The difference in 10-year CVD risk from 2003-2005 to 2014-2015 was not statistically significant (10.2% vs 10.6%; P=0.29). After age standardisation according to World Health Organization world standard population data, a small decrease in CVD risk was observed, from 9.4% in 2003-2005 to 8.8% in 2014-2015. Analysis according to age-group showed that more participants aged 65 to 74 years were considered high risk in 2003 to 2005 (2003-2005: 66.8% vs 2014-2015: 53.1%; P=0.028). This difference may be due to the decrease in smokers among men (2003-2005: 30.5% vs 2014-2015: 24.0%; P<0.001). CONCLUSION: From 2003-2005 to 2014-2015, there was a small decrease in age-standardised 10-year CVD risk. A holistic public health approach simultaneously targeting multiple risk factors is needed to achieve greater decreases in CVD risk.

Determining the value of the abdominal core health quality collaborative to support regulatory decisions.

PURPOSE: The study objective is to document value created by real-world evidence from the Abdominal Core Health Quality Collaborative (ACHQC) for regulatory decisions. The ACHQC is a national effort that generates data on hernia repair techniques and devices. METHODS: Two retrospective cohort evaluations compared cost and time of ACHQC analyses to traditional postmarket studies. The first analysis was based on 25 reports submitted to the European Medicines Agency of 20 mesh products for post-market surveillance. A second analysis supported label expansion submitted to the Food and Drug Administration, Center for Devices and Radiological Health for a robotic-assisted surgery device to include ventral hernia repair. Estimated costs of counterfactual studies, defined as studies that might have been done if the registry had not been available, were derived from a model described in the literature. Return on investment, percentage of cost savings, and time savings were calculated. RESULTS: 45,010 patients contributed to the two analyses. The cost and time differences between individual 25 ACHQC analyses (41,112 patients) and traditional studies ranged from $1.3 to $2.2 million and from 3 to 4.8 years, both favoring use of the ACHQC. In the second label expansion analysis (3,898 patients), the estimated return on investment ranged from 11 to 461% with time savings of 5.1 years favoring use of the ACHQC. CONCLUSIONS: Compared to traditional postmarket studies, use of ACHQC data can result in cost and time savings when used for appropriate regulatory decisions in light of key assumptions.

A B7-H4-Targeting Antibody-Drug Conjugate Shows Antitumor Activity in PARPi and Platinum-Resistant Cancers with B7-H4 Expression.

PURPOSE: Platinum and PARP inhibitors (PARPi) demonstrate activity in breast and ovarian cancers, but drug resistance ultimately emerges. Here, we examine B7-H4 expression in primary and recurrent high-grade serous ovarian carcinoma (HGSOC) and the activity of a B7-H4-directed antibody-drug conjugate (B7-H4-ADC), using a pyrrolobenzodiazepine-dimer payload, in PARPi- and platinum-resistant HGSOC patient-derived xenograft (PDX) models. EXPERIMENTAL DESIGN: B7-H4 expression was quantified by flow cytometry and IHC. B7-H4-ADC efficacy was tested against multiple cell lines in vitro and PDX in vivo. The effect of B7-H4-ADC on cell cycle, DNA damage, and apoptosis was measured using flow cytometry. RESULTS: B7-H4 is overexpressed in 92% of HGSOC tumors at diagnosis (n = 12), persisted in recurrent matched samples after platinum treatment, and was expressed at similar levels across metastatic sites after acquired multi-drug resistance (n = 4). Treatment with B7-H4-ADC resulted in target-specific growth inhibition of multiple ovarian and breast cancer cell lines. In platinum- or PARPi-resistant ovarian cancer cells, B7-H4-ADC significantly decreased viability and colony formation while increasing cell-cycle arrest and DNA damage, ultimately leading to apoptosis. Single-dose B7-H4-ADC led to tumor regression in 65.5% of breast and ovarian PDX models (n = 29), with reduced activity in B7-H4 low or negative models. In PARPi and platinum-resistant HGSOC PDX models, scheduled B7-H4-ADC dosing led to sustained tumor regression and increased survival. CONCLUSIONS: These data support B7-H4 as an attractive ADC target for treatment of drug-resistant HGSOC and provide evidence for activity of an ADC with a DNA-damaging payload in this population. See related commentary by Veneziani et al., p. 1434.

Molybdenum(V)-mediated switching of the C(sp2)-Se bond of phenylselenyl-functionalized arenes or heterocycles under mild conditions.

Molybdenum(V)-mediated cleavage of C(sp2)-Se bond and C(sp2)-H bond as well as intramolecular oxidative C(sp2)-Se coupling reaction of phenylselenyl-functionalized arenes or heterocycles has been developed. Three kinds of benzoselenophene frameworks were constructed through this reaction with yields up to 94%. This new C(sp2)-Se bond-switching methodology may provide a new strategy for interesting applications of phenylselenyl-substituted aromatic compounds in the synthesis of selenium-containing heterocycles and natural products.

[Genetic diagnosis of microcephaly].

Objective: To explore the diagnostic value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in microcephaly. Methods: A total of 9 cases of microcephaly fetuses diagnosed by prenatal ultrasound or children with microcephaly diagnosed after birth were selected from the Sixth Affiliated Hospital of Guangzhou Medical University from January 2014 to August 2022.Karyotype analysis and/or CMA were used to detect. The cases with negative karyotype analysis and CMA results were further sequenced by trio-based WES (Trio-WES). Then the coding genes contained in the pathogenic copy number variation (CNV) fragments were analyzed by gene ontology (GO) enrichment. The genes related to the development of the central nervous system contained in the pathogenic CNV and the pathogenic genes found by Trio-WES were combined for gene interaction network analysis. Results: In this study, 9 cases of microcephaly were recruited, with the time of diagnosis ranged from 23 weeks of gestation to 7 years after birth, and the head circumference of fetus or children ranged from 18.3 to 42.5 cm (-7SD to -2SD). Karyotype analysis was detected in all 9 cases and no abnormality result was found. Eight cases were detected by CMA, and one abnormal was found. Five cases were detected by Trio-WES, and two cases were detected with likely pathogenic genes. The GO enrichment analysis of the coding gene in the 4p16.3 microdeletion (pathogenic CNV) region showed that: in biological process, it was mainly concentrated in phototransduction, visible light; in terms of molecular function, it was mainly concentrated in fibroblast growth factor binding; in terms of cell components, it was mainly concentrated in rough endoplasmic reticulum. Gene interaction network analysis suggested that CDC42 gene could interact with CTBP1, HTT and ASPM gene. Conclusions: CMA could be used as a first-line detection technique for microcephaly. When the results of chromosome karyotype analysis and/or CMA are negative, Trio-WES could improve the detection rate of pathogenicity of microcephaly.

Reductions and pronounced regional differences in morphine distribution in the United States.

OBJECTIVES: The purpose of this longitudinal study was to describe the temporal pattern of morphine distribution nationally and between states. METHODS: Drug weight was obtained from Report 5 of the US Drug Enforcement Administration's Automation of Reports and Consolidated Orders System (ARCOS) to characterize patterns in the distribution of morphine from 2012 to 2021. Morphine distribution amounts were separated by state and business type and corrected for population. States outside a 95% confidence interval relative to the national average were considered statistically significant. KEY FINDINGS: In 2012, there was a 4.6-fold difference in morphine distribution between the highest-prescribing state, Tennessee (180.2 mg/person), and the lowest-prescribing state, Texas (39.4 mg/person). By the end of 2021, national distribution of morphine had decreased by 59.9% when compared to the peak year 2012. In 2021, Tennessee (51.1 mg/person) remained the highest-prescribing state with a 3.0-fold difference relative to Texas (17.2 mg/person). The average hospital decrease (-73.9%) from 2012 to 2021 was larger than that of pharmacies (-58.2%). CONCLUSIONS: The national 59.9% decline in morphine in the last decade may be attributable to prioritization of the US opioid crisis as a public concern. Further research is necessary to understand the persistent regional difference between states.

The impact of coronary calcium score as an addition to myocardial perfusion imaging in altering clinical management (ICCAMPA trial).

INTRODUCTION: AIM: Myocardial perfusion imaging (MPI) is a key tool for the identification and risk stratification of patients with coronary artery disease. The use of a coronary calcium score further adds to prognostic data above MPI alone. In this study, our aim was to evaluate the extent to which the use of a coronary artery calcium (CAC) score, when co-reported with MPI, impacts changes in clinical management in patients without a history of coronary artery disease (CAD) undergoing functional imaging. METHODS: This is a multicenter international study which incorporated a standardized questionnaire to evaluate changes in clinician management after MPI results were given with and without the additional information of a CAC score. Calcium scoring on a SPECT-CT system was performed via a semiquantitative Shemesh score (0-12) with a 0-3 score from the left main, left anterior descending, left circumflex, and right coronary arteries. CT of the chest was read independently, and non-coronary findings were reported alongside the CAC score. RESULTS: A total of 281 patients were enrolled across 3 international centers (Brazil, Australia, New Zealand). Of the 281 patients, 133 (47%) had management altered after the clinician was made aware of the CAC score. The impact of the CAC in changing clinical management was significant, particularly in patients with a negative MPI (P < 0.0001), but also in MPI-positive patients (P = 0.0021). The most common management change was the addition or intensification of statin therapy. CONCLUSION: The addition of the CAC component to MPI yielded significant management changes in nearly half of all patients undergoing MPI for suspected CAD. This trend was observed across all centers in the three countries involved and was particularly evident in patient with a negative MPI.

Silver-catalysed three-component reactions of alkynyl aryl ketones, element selenium, and boronic acids leading to 3-organoselenylchromones.

An Ag-catalysed three-component reaction of alkynyl aryl ketones bearing an ortho-methoxy group, element selenium, and arylboronic acid, providing a facile route to selenofunctionalized chromone products has been developed. This protocol features high efficiency and high regioselectivity, and the use of selenium powder as the selenium source. Mechanistic experiments indicated that the combined oxidative effect of (bis(trifluoroacetoxy)iodo)benzene and oxygen in the air pushes the catalytic redox cycle of the Ag catalyst and the phenylselenium trifluoroacetate formed in situ is the key intermediate of the PIFA-mediated 6-endo-electrophilic cyclization and selenofunctionalization reaction of alkynyl aryl ketones.

Wafer scale manufacturing of high precision micro-optical components through X-ray lithography yielding 1800 Gray Levels in a fingertip sized chip.

We present a novel x-ray lithography based micromanufacturing methodology that offers scalable manufacturing of high precision optical components. It is accomplished through simultaneous usage of multiple stencil masks made moveable with respect to one another through custom made micromotion stages. The range of spectral flux reaching the sample surface at the LiMiNT micro/nanomanufacturing facility of Singapore Synchrotron Light Source (SSLS) is about 2 keV to 10 keV, offering substantial photon energy to carry out deep x-ray lithography. In this energy range, x-rays penetrate through resist materials with only little scattering. The highly collimated rectangular beam architecture of the x-ray source enables a full 4″ wafer scale fabrication. Precise control of dose deposited offers determined chain scission in the polymer to required depth enabling 1800 discrete gray levels in a chip of area 20 mm2 and with more than 2000 within our reach. Due to its parallel processing capability, our methodology serves as a promising candidate to fabricate micro/nano components of optical quality on a large scale to cater for industrial requirements. Usage of these fine components in analytical devices such as spectrometers and multispectral imagers transforms their architecture and shrinks their size to pocket dimension. It also reduces their complexity and increases affordability while also expanding their application areas. Consequently, equipment based on these devices is made available and affordable for consumers and businesses expanding the horizon of analytical applications. Mass manufacturing is especially vital when these devices are to be sold in large quantities especially as components for original equipment manufacturers (OEM), which has also been demonstrated through our work. Furthermore, we also substantially improve the quality of the micro-components fabricated, 3D architecture generated, throughput, capability and availability for industrial application. Manufacturing 1800 Gray levels or more through other competing techniques is either limited due to multiple process steps involved or due to unacceptably long time required owing to their pencil beam architecture. Our manufacturing technique presented here overcomes both these shortcomings in terms of the maximum number of gray levels that can be generated, and the time required to generate the same.

A randomised controlled trial of a novel tramadol chewable tablet: pharmacokinetics and tolerability in children.

Tramadol is a bitter atypical opioid analgesic drug and is prescribed to treat postoperative pain in children. However, in many countries there is no licensed paediatric tramadol formulation available. We have formulated a novel chewable chocolate-based drug delivery system for the administration of tramadol to children. This pilot, single-centre, open-label, randomised clinical study assessed the taste tolerability and comparative population pharmacokinetics of the novel tramadol chewable tablet against a compounded tramadol hydrochloride oral liquid, at a dose of 1 mg.kg-1 . A 5-point facial hedonic scale was used by the children, parents and nurses to assess tolerability. One hundred and forty-one children aged 3-16 years were given tramadol 30 min before general anaesthesia. Blood samples were taken following the induction of anaesthesia and for up to 5 h following tramadol administration. Tramadol and its active metabolite O-desmethyltramadol were analysed using reversed-phase high-performance liquid chromatography. A population pharmacokinetic model was built using non-linear mixed effects modelling. The relative bioavailability for the tablet was 1.25 times higher (95%CI 1.16-1.35) than for tramadol hydrochloride oral liquid, while the absorption rate constant for the tablet was significantly lower (1.97 h-1 vs. 3.34 h-1 , p < 0.001). Larger inter-individual variability in absorption rates were observed with the liquid tramadol. The tramadol chewable tablet was more acceptable in taste to children when assessed by the children, parents and nurses (all p < 0.001). We conclude that the novel tramadol chewable tablet has favourable acceptability and more reliable relative bioavailability in children compared with tramadol hydrochloride oral liquid.

Efficacy and Safety of Yangyin Shuxin Decoction-a Chinese Herbal Medicine Formula For Heart Failure with Preserved Ejection Fraction: A Randomized Controlled Trial.

Background: Heart failure with preserved ejection fraction (HFpEF) is a large subtype of heart failure (HF) characterized by exercise intolerance and reduced quality of life. Studies have shown that traditional Chinese medicine (TCM) combined with conventional Western medicine has a good effect on improving exercise tolerance and quality of life in patients with HFpEF, but the overall quality of evidence is low. This study aimed to determine the safety and efficacy of Yangyin Shuxin (YYSX) decoction in the treatment of HFpEF. Methods: A prospective, single-blind, single-center, randomized controlled clinical study was conducted. 64 patients with HFpEF were randomly assigned to receive oral YYSX decoction (150 ml, twice a day) combined with conventional Western treatment or conventional Western treatment alone at a ratio of 1 : 1. The course of treatment was 2 weeks, and the follow-up was 3 months. The primary outcome was peak oxygen uptake (peak VO2) measured by the cardiopulmonary exercise test (CPET). Furthermore, the safety of YYSX decoction was assessed. Results: 63 patients (31 in the YYSX group and 32 in the control group) were included in the full analysis set. The peak VO2 of the YYSX group was significantly higher than that of the control group (12.04 ± 3.41 vs. 11.02 ± 3.33, P = 0.013) after 2 weeks. The maximum voluntary ventilation (MVV) was significantly higher in the YYSX group compared with the control group (P < 0.05). The YYSX group had a higher EQ-visual analogue scale (EQ-VAS) score (71.13 ± 13.95 vs. 70.94 ± 13.70, P < 0.05) and a lower TCM Four-Dimensional Diagnostic Information Scale (TCMFDIS) score (49.74 ± 24.73 vs. 64.16 ± 27.15, P < 0.05) than the control group. There was no statistical difference between two groups (P = 0.160), although 51.61% of patients in the YYSX group showed a decrease in brain natriuretic peptide (BNP) levels of at least 30%, compared with 37.50% of patients in the control group. No serious adverse events were reported in either group, but systolic and diastolic blood pressure decreased and serum sodium levels increased slightly in the control group. Conclusion: The YYSX decoction combined with conventional Western treatment was superior to the conventional Western treatment alone in improving exercise tolerance, quality of life, and cardiopulmonary function of patients with HFpEF. YYSX decoction is safe and may prevent a drop in blood pressure and sodium retention. Trial Registration. Chinese Clinical Trial Registry (www.chictr.org/cn/, No. ChiCTR-IOR-17014206).

Induction of IL19 expression through JNK and cGAS-STING modulates DNA damage-induced cytokine production.

Cytokine production is a critical component of cell-extrinsic responses to DNA damage and cellular senescence. Here, we demonstrated that expression of the gene encoding interleukin-19 (IL-19) was enhanced by DNA damage through pathways mediated by c-Jun amino-terminal kinase (JNK) and cGAS-STING and that IL19 expression was required for the subsequent production of the cytokines IL-1, IL-6, and IL-8. IL19 expression was stimulated by diverse cellular stresses, including inhibition of the DNA replication checkpoint kinase ATR (ataxia telangiectasia and Rad3-related protein), oncogene expression, replicative exhaustion, oxidative stress, and DNA double-strand breaks. Unlike the production of IL-6 and IL-8, IL19 expression was not affected by abrogation of signaling by the IL-1 receptor (IL-1R) or the mitogen-activated protein kinase p38. Instead, the DNA damage­induced production of IL-1, IL-6, and IL-8 was substantially reduced by suppression of IL19 expression. The signaling pathways required to stimulate IL19 expression selectively depended on the type of DNA-damaging agent. Reactive oxygen species and the ASK1-JNK pathway were critical for responses to ionizing radiation (IR), whereas the cGAS-STING pathway stimulated IL19 expression in response to either IR or ATR inhibition. Whereas induction of IL1, IL6, and IL8 by IR depended on IL19 expression, the cGAS-STING­dependent induction of the immune checkpoint gene PDL1 after IR and ATR inhibition was independent of IL19. Together, these results suggest that IL-19 production by diverse pathways forms a distinct cytokine regulatory arm of the response to DNA damage.

HPLC-UV assay of tramadol and O-desmethyltramadol in human plasma containing other drugs potentially co-administered to participants in a paediatric population pharmacokinetic study.

Multimodal analgesia is employed in paediatric pain management to maximise analgesia and minimise side effects. Tramadol is dosed at 1-1.5 mg/kg to treat severe pain in children but the assay for tramadol in plasma samples for pharmacokinetic and toxicology studies does not often consider concurrently administered medications. In this study we developed and validated an HPLC-UV method to quantify tramadol and its main metabolite (O-desmethyltramadol) in human plasma in the presence of seven potentially interfering drugs. Sample preparation method was developed by combining liquid-liquid extraction and protein precipitation. Chromatographic separation was achieved on a BDS-Hypersil-C18 column (5 µm, 250 × 4.6 mm) using a double gradient method. The limit of quantification was 6.7 ng/ml for both tramadol and ODT. The precision and accuracy were in compliance with ICH guidelines. This method was successfully employed to analyse the blood samples of 137 paediatric participants in a tramadol pharmacokinetic trial.

SGLT2i as fourth-line therapy and risk of mortality, end-stage renal diseases and cardiovascular diseases in patients with type 2 diabetes mellitus.

AIM: Current guideline recommends insulin as fourth-line glucose-lowering medications. However, treatment effects of sodium glucose co-transporter-2 inhibitors (SGLT2i) on the risk of complications are uncertain. This study examines risks of all-cause mortality, cardiovascular diseases (CVD) and end-stage renal diseases (ESRD) in type 2 diabetes mellitus (T2DM) patients on triple oral glucose-lowering medications initiating SGLT2i, insulin or other oral medications. METHODS: A population-based retrospective cohort of patients with T2DM between 2006-2017 was extracted from Hong Kong Hospital Authority database. Patients who were initiated a fourth-line therapy with SGLT2i, insulin or other oral medications were included. Hazard ratios (HRs) for all-cause mortality, CVD and ESRD were assessed using Cox proportional hazard models. RESULTS: Over a median follow-up period of 18.5 months with 63,122 person-years, SGLT2i and insulin group had the lowest and highest incidence rate of all-cause mortality, CVD and ESRD (1.06, 0.65 and 0.61 vs 4.25, 5.58 and 4.39/100 person-years), respectively. Initiating SGLT2i as fourth-line medication had more benefits on CVD, in particular coronary heart disease and stroke. Insulin users had higher risks of CVD (HR=8.04, 95%CI=3.06-21.12) than SGLT2i users. SGLT2i was associated with insignificant reduction in ESRD (HR=4.62, 95%CI=0.73-29.09) and all-cause mortality (HR=3.06, 95%CI=0.75-12.45), and HF (HR=2.99, 95%CI=0.37-24.42) among patients without established HF. CONCLUSION: Among T2DM patients initiating fourth-line therapy, SGLT2i users had significant benefits in lowering risk of CVD, and potential benefits in lowering risks of ESRD and all-cause mortality. SGLT2i was the preferred fourth-line glucose-lowering medication least likely to be associated with complication risks.

[A case of difficult extubation after tracheotomy in a child with severe scald of oropharynx].

In November 4, 2016, a 1 year and 3 months old male patient with face and neck scald complicated with severe scald of oropharynx was admitted to Guangzhou Red Cross Hospital 1 hour after injury. The child developed upper respiratory tract obstruction 2 hours after injury, therefore tracheotomy and intubation were performed immediately to establish an artificial airway, and symptomatic treatments such as anti-infection, fluid replacement, and dressing change were conducted. On the 10th day after injury, the child had difficult breathing during the test tube blocking before extubation, and it was difficult to extubate. Symptomatic treatments such as ventilator assisted ventilation and strengthened anti-infection were continued. On the 17th day after injury, extubation plan was adjusted. Thirty minutes before extubation, phenobarbital was injected intramuscularly for sedation, and atropine was used to reduce airway secretions, after which extubation was successful. After 21 days of treatment, the child was cured and discharged. In the treatment of this case, high attention was paid to the important influence of children's mental factors among causes of difficult extubation, which provided a reference for clinical treatment of extubation in children with tracheal tube after tracheotomy.

Radiation therapy on primary tumour of synchronous metastatic head and neck squamous cell carcinomas.

PURPOSE: Patients with synchronous metastatic head and neck squamous cell carcinomas often present associated locoregional symptoms and a risk of life-threatening primary tumour progression. Few data have been published about the use of radiation therapy in the management of newly diagnosed metastatic disease associated with advanced locoregional disease. In this article, we aim to determine the role of radiation therapy of the primary tumour in the overall therapeutic strategy for these diseases. We further address radiation therapy modalities (technique, volumes, and fractionation) in such a context. MATERIAL AND METHODS: We conducted a literature survey on locoregional radiotherapy for newly diagnosed metastatic head and neck squamous cell carcinomas. RESULTS: Several retrospective studies have reported that locoregional radiotherapy is associated with improved overall survival of patients with synchronous metastatic head and neck squamous cell carcinomas. However, data about modalities such as timing of radiotherapy in the overall strategy, dose, fractionation and delineation volumes are scarce. Two schematic situations can be distinguished with respect to prognosis and treatment adaptations: polymetastatic/bulky or oligometastatic disease. In polymetastic/bulky disease associated with poor prognosis, standard-of-care is systemic therapy, but locoregional radiotherapy can be discussed either upfront, mainly for symptomatic palliation, or as consolidation after downsizing obtained by systemic therapy. As for oligometastatic disease, with the rise in use of efficacious and well-tolerated local ablative treatments of metastases, aggressive curative-intent locoregional radiotherapy can be considered with or without systemic therapy. CONCLUSION: Because locoregional disease is a major cause of disease failure in patients with synchronous metastatic head and neck squamous cell carcinomas, aggressive locoregional radiation therapy to the primary tumour may be discussed in the initial management of the disease where systemic therapy alone may not induce sufficient primary tumour reduction. With recent technological advances in radiotherapy, the delivery of radiotherapy is safe and feasible even in metastatic setting. Clinical trials assessing radiotherapy use for metastatic head and neck squamous cell carcinomas are warranted.