Plastic scintillator-based dosimeters for ultra-high dose rate (UHDR) electron radiotherapy.

This paper reports the development of dosimeters based on plastic scintillating fibers imaged by a charge-coupled device camera, and their performance evaluation through irradiations with the electron Flash research accelerator located at the Centro Pisano Flash Radiotherapy. The dosimeter prototypes were composed of a piece of plastic scintillating fiber optically coupled to a clear optical fiber which transported the scintillation signal to the readout systems (an imaging system and a photodiode). The following properties were tested: linearity, capability to reconstruct the percentage depth dose curve in solid water and to sample in time the single beam pulse. The stem effect contribution was evaluated with three methods, and a proof-of-concept one-dimensional array was developed and tested for online beam profiling. Results show linearity up to 10 Gy per pulse, and good capability to reconstruct both the timing and spatial profiles of the beam, thus suggesting that plastic scintillating fibers may be good candidates for low-energy electron Flash dosimetry.

Effects of perioperative low-dose naloxone on the immune system in patients undergoing laparoscopic-assisted total gastrectomy: a randomized controlled trial.

BACKGROUND: Low immune function after laparoscopic total gastrectomy puts patients at risk of infection-related complications. Low-dose naloxone (LDN) can improve the prognosis of patients suffering from chronic inflammatory diseases or autoimmune diseases. The use of LDN during perioperative procedures may reduce perioperative complications. The purpose of this study was to examine the effects of LDN on endogenous immune function in gastric cancer patients and its specific mechanisms through a randomized controlled trial. METHODS: Fifty-five patients who underwent laparoscopic-assisted total gastrectomy were randomly assigned to either a naloxone group (n = 23) or a nonnaloxone group (n = 22). Patients in the naloxone group received 0.05 µg/kg-1.h- 1naloxone from 3 days before surgery to 5 days after surgery via a patient-controlled intravenous injection (PCIA) pump, and patients in the nonnaloxone group did not receive special treatment. The primary outcomes were the rates of postoperative complications and immune function assessed by NK cell, CD3+ T cell, CD4+ T cell, CD8+ T cell, WBC count, neutrophil percentage, and IL-6 and calcitonin levels. The secondary outcomes were the expression levels of TLR4 (Toll-like receptor), IL-6 and TNF-α in gastric cancer tissue. RESULTS: Compared with the nonnaloxone group, the naloxone group exhibited a lower incidence of infection (in the incision, abdomen, and lungs) (P < 0.05). The numbers of NK cells and CD8+ T cells in the naloxone group were significantly greater than those in the nonnaloxone group at 24 h after surgery (P < 0.05) and at 96 h after surgery (P < 0.05). Compared with those in the nonnaloxone group, the CD3 + T-cell (P < 0.05) and CD4 + T-cell (P < 0.01) counts were significantly lower in the naloxone group 24 h after surgery. At 24 h and 96 h after surgery, the WBC count (P < 0.05) and neutrophil percentage (P < 0.05) were significantly greater in the nonnaloxone group. The levels of IL-6 (P < 0.05) and calcitonin in the nonnaloxone group were significantly greater at 24 h after surgery. At 24 h following surgery, the nonnaloxone group had significantly greater levels of IL-6 (P < 0.05) and calcitonin than did the naloxone group. Compared with those in the naloxone group, the expression levels of TLR4 (P < 0.05) in gastric cancer tissue in the naloxone group were greater; however, the expression levels of IL-6 (P < 0.01) and TNF-α (P < 0.01) in the naloxone group were greater than those in the nonnaloxone group. CONCLUSION: Laparoscopic total gastrectomy patients can benefit from 0.05 ug/kg- 1. h- 1 naloxone by reducing their risk of infection. It is possible that LDN alters the number of cells in lymphocyte subpopulations, such as NK cells, CD3 + T cells, and CD4 + T cells, and the CD4+/CD8 + T-cell ratio or alters TLR4 receptor expression in immune cells, thereby altering immune cell activity. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry on 24/11/2023 (ChiCTR2300077948).

Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial.

BACKGROUND: HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB. METHODS: This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events. DISCUSSION: Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986.

Influence of deep learning image reconstruction algorithm for reducing radiation dose and image noise compared to iterative reconstruction and filtered back projection for head and chest computed tomography examinations: a systematic review.

Background: The most recent advances in Computed Tomography (CT) image reconstruction technology are Deep learning image reconstruction (DLIR) algorithms. Due to drawbacks in Iterative reconstruction (IR) techniques such as negative image texture and nonlinear spatial resolutions, DLIRs are gradually replacing them. However, the potential use of DLIR in Head and Chest CT has to be examined further. Hence, the purpose of the study is to review the influence of DLIR on Radiation dose (RD), Image noise (IN), and outcomes of the studies compared with IR and FBP in Head and Chest CT examinations. Methods: We performed a detailed search in PubMed, Scopus, Web of Science, Cochrane Library, and Embase to find the articles reported using DLIR for Head and Chest CT examinations between 2017 to 2023. Data were retrieved from the short-listed studies using Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Results: Out of 196 articles searched, 15 articles were included. A total of 1292 sample size was included. 14 articles were rated as high and 1 article as moderate quality. All studies compared DLIR to IR techniques. 5 studies compared DLIR with IR and FBP. The review showed that DLIR improved IQ, and reduced RD and IN for CT Head and Chest examinations. Conclusions: DLIR algorithm have demonstrated a noted enhancement in IQ with reduced IN for CT Head and Chest examinations at lower dose compared with IR and FBP. DLIR showed potential for enhancing patient care by reducing radiation risks and increasing diagnostic accuracy.

Efficacy and safety of esketamine for pediatric gastrointestinal endoscopy: a meta-analysis and trial sequential analysis.

Objective: The role of esketamine in pediatric gastrointestinal endoscopy is still unclear. This study aims to evaluate the efficacy and safety of esketamine for pediatric gastrointestinal endoscopy. Methods: Clinical trials of esketamine for pediatric gastrointestinal endoscopy were searched in eight common databases, up to October 2023. These clinical trials were included in the meta-analysis and trial sequential analysis (TSA). The risk ratio (RR) and weighted mean difference (WMD) were used as the effect sizes for dichotomous variables and continuity variables, respectively. When the heterogeneity test showed I2 < 50%, the fixed effects model was used for the meta-analysis and TSA; Otherwise, the random effects model was used for them. Results: In terms of efficacy endpoints, the meta-analysis showed that compared with placebo or blank, esketamine significantly decreased recovery time by 2.34 min (WMD -2.34; 95% Confidence interval [CI] -3.65, -1.02; p = 0.0005) and propofol consumption by 0.70 mg/kg (WMD -0.70; 95% CI -0.98, -0.43; p < 0.00001), and increased mean heart rate by 4.77 beats/min (WMD 4.77; 95% CI 2.67, 6.87; p < 0.00001) and mean arterial pressure by 3.10 mmHg (WMD 3.10; 95% CI 1.52, 4.67; p = 0.0001), while induction time and mean blood oxygen remained comparable. TSA indicated conclusive evidence for these benefits. In terms of safety endpoints, the meta-analysis revealed that esketamine significantly reduced involuntary movements by 59% (RR 0.41; 95% CI 0.22, 0.76; p = 0.005) and choking by 51% (RR 0.49; 95% CI 0.26, 0.92; p = 0.03), while significantly increasing dizziness by 98% (RR 1.98; 95% CI 1.11, 3.56; p = 0.02) and there were no significant differences in total adverse events, respiratory depression, and vomiting. TSA demonstrated conclusive evidence for involuntary movements and dizziness. Low-dose analysis showed that esketamine at ≤0.3 mg/kg significantly reduced recovery time, propofol consumption and involuntary movements, and significantly increasing mean heart rate, with no increase in dizziness. The Begg's test (p = 0.327) and the Egger's test (p = 0.413) indicated no significant publication bias, yet the funnel plot suggested potential publication bias. Conclusion: Esketamine is an effective adjuvant anesthesia for children undergoing gastrointestinal endoscopy. However, the general dose of esketamine may increase the risk of dizziness, which can be avoided by administering a low dose (≤0.3 mg/kg).

Immune Cells Are Differentially Affected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virus-infected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105 PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Radiation Adverse Outcome pathways (AOPs): examining priority questions from an international horizon-style exercise.

PURPOSE: The Organisation for Economic Co-operation and Development (OECD) Adverse Outcome Pathway (AOP) Development Programme is being explored in the radiation field, as an overarching framework to identify and prioritize research needs that best support strengthening of radiation risk assessment and risk management strategies. To advance the use of AOPs, an international horizon-style exercise (HSE) was initiated through the Radiation/Chemical AOP Joint Topical Group (JTG) formed by the OECD Nuclear Energy Agency (NEA) High-Level Group on Low Dose Research (HLG-LDR) under the auspices of the Committee on Radiological Protection and Public Health (CRPPH). The intent of the HSE was to identify key research questions for consideration in AOP development that would help to reduce uncertainties in estimating the health risks following exposures to low dose and low dose-rate ionizing radiation. The HSE was conducted in several phases involving the solicitation of relevant questions, a collaborative review of open-ended candidate questions and an elimination exercise that led to the selection of 25 highest priority questions for the stated purpose. These questions were further ranked by over 100 respondents through an international survey. This final set of questions was judged to provide insights into how the OECD's AOP approach can be put into practice to meet the needs of hazard and risk assessors, regulators, and researchers. This paper examines the 25 priority questions in the context of hazard/risk assessment framework for ionizing radiation. CONCLUSION: By addressing the 25 priority questions, it is anticipated that constructed AOPs will have a high level of specificity, making them valuable tools for simplifying and prioritizing complex biological processes for use in developing revised radiation hazard and risk assessment strategies.

Dose-response associations between physical activity and sedentary time with functional disability in older adults with or without frailty: a prospective cohort study.

Purpose: Evidence regarding the dose-response curve shapes of physical activity (PA) and sedentary time (ST) in older adults with functional disability (FD) is extremely limited. Moreover, these associations may differ depending on with/without frailty. We examined the dose-response associations between moderate-to-vigorous PA (MVPA) and ST with FD among older adults with/without frailty. Methods: We included 7,480 initially nondisabled adults (3,795 men and 3,685 women) aged 65-84 years in Ota City, Tokyo, Japan. MVPA and ST were evaluated using the International Physical Activity Questionnaire-Short Form. FD was prospectively identified using a nationally unified database of the long-term care insurance system. Frailty was determined using Check-List 15, validated against Fried's frailty criteria. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of MVPA and ST for FD were calculated, and dose-response curves were examined using restricted cubic splines. Results: During 3.6 years of follow-up, 1,001 (13.4%) participants had FD. Among all participants, compared with no MVPA, the HRs for FD reduced linearly up to approximately 2000 metabolic equivalents (METs)■min/week of MVPA, and the lowest HR (HR: 0.61, 95% CI: 0.51-0.74) was reached at around 3,000-4,000 METs■min/week. Although the shape of this association was consistent regardless of with/without frailty, the magnitude of the association tended to be stronger in frail older adults than in non-frail older adults. Compared with those for the median (300 min/day) of ST, the HRs for FD increased linearly as ST reached approximately 600 min/day or more, independent of MVPA, with a maximum HR of 1.31 (95% CI: 1.01-1.71) for 1,080 min/day among all participants. This association was more pronounced among non-frail older adults but not statistically significant among frail older adults. Conclusion: Higher MVPA levels consistently reduced the incidence of FD regardless of frailty in a significant inverse nonlinear dose-response manner. A significant positive nonlinear dose-response association between ST and FD risk was identified among non-frail older adults but not among frail older adults. Increasing MVPA and reducing prolonged ST are important for preventing FD among non-frail older adults. However, reducing ST alone may be insufficient; increasing MVPA, even if by only small increments, is highly recommended for frail older adults.

Association of dietary selenium intake and all-cause mortality of Parkinson's disease and its interaction with blood cadmium level: a retrospective cohort study.

BACKGROUND: Parkinson's disease (PD) is a slowly progressive neurodegenerating disease that may eventually lead to disabling condition and pose a threat to the health of aging populations. This study aimed to explore the association of two potential risk factors, selenium and cadmium, with the prognosis of Parkinson's disease as well as their interaction effect. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 to 2015-2016 and National Death Index (NDI). Participants were classified as Parkinson's patients by self-reported anti-Parkinson medications usage. Cox regression models and restricted cubic spline models were applied to evaluate the association between PD mortality and selenium intake level as well as blood cadmium level. Subgroup analysis was also conducted to explore the interaction between them. RESULTS: A total of 184 individuals were included. In full adjusted cox regression model (adjusted for age, gender, race, hypertension, pesticide exposure, smoking status and caffeine intake), compared with participants with low selenium intake, those with normal selenium intake level were significantly associated with less risk of death (95%CI: 0.18-0.76, P = 0.005) while no significant association was found between low selenium intake group and high selenium group (95%CI: 0.16-1.20, P = 0.112). Restricted cubic spline model indicated a nonlinear relationship between selenium intake and PD mortality (P for nonlinearity = 0.050). The association between PD mortality and blood cadmium level was not significant (95%CI: 0.19-5.57, P = 0.112). However, the interaction term of selenium intake and blood cadmium showed significance in the cox model (P for interaction = 0.048). Subgroup analysis showed that the significant protective effect of selenium intake existed in populations with high blood cadmium but not in populations with low blood cadmium. CONCLUSION: Moderate increase of selenium intake had a protective effect on PD mortality especially in high blood cadmium populations.

Increasing the etanercept dose in a treat-to-target approach in juvenile idiopathic arthritis: does it help to reach the target? A post-hoc analysis of the BeSt for Kids randomised clinical trial.

BACKGROUND: Etanercept has been studied in doses up to 0.8 mg/kg/week (max 50 mg/week) in juvenile idiopathic arthritis (JIA) patients. In clinical practice higher doses are used off-label, but evidence regarding the relation with outcomes is lacking. We describe the clinical course of JIA-patients receiving high-dose etanercept (1.6 mg/kg/week; max 50 mg/week) in the BeSt for Kids trial. METHODS: 92 patients with oligoarticular JIA, RF-negative polyarticular JIA or juvenile psoriatic arthritis were randomised across three treat-to-target arms: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination-therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX + etanercept. In any treatment-arm, patients could eventually escalate to high-dose etanercept alongside MTX 10mg/m2/week. RESULTS: 32 patients received high-dose etanercept (69% female, median age 6 years (IQR 4-10), median 10 months (7-16) from baseline). Median follow-up was 24.6 months. Most clinical parameters improved within 3 months after dose-increase: median JADAS10 from 7.2 to 2.8 (p = 0.008), VAS-physician from 12 to 4 (p = 0.022), VAS-patient/parent from 38.5 to 13 (p = 0.003), number of active joints from 2 to 0.5 (p = 0.12) and VAS-pain from 35.5 to 15 (p = 0.030). Functional impairments (CHAQ-score) improved more gradually and ESR remained stable. A comparable pattern was observed in 11 patients (73% girls, median age 8 (IQR 6-9)) who did not receive high-dose etanercept despite eligibility (comparison group). In both groups, 56% reached inactive disease at 6 months. No severe adverse events (SAEs) occurred after etanercept dose-increase. In the comparison group, 2 SAEs consisting of hospital admission occurred. Rates of non-severe AEs per subsequent patient year follow-up were 2.27 in the high-dose and 1.43 in the comparison group. CONCLUSIONS: Escalation to high-dose etanercept in JIA-patients who were treated to target was generally followed by meaningful clinical improvement. However, similar improvements were observed in a smaller comparison group who did not escalate to high-dose etanercept. No SAEs were seen after escalation to high-dose etanercept. The division into the high-dose and comparison groups was not randomised, which is a potential source of bias. We advocate larger, randomised studies of high versus regular dose etanercept to provide high level evidence on efficacy and safety. TRIAL REGISTRATION: Dutch Trial Register; NTR1574; 3 December 2008; https://onderzoekmetmensen.nl/en/trial/26585 .

Breast Articles From 2023: Informing Practice Across the Continuum of Care.

With new investigations and clinical trials in breast oncology reported every year, it is critical that surgeons be aware of advances and insights into the evolving care paradigms and treatments available to their patients. This article highlights five publications found to be particularly impactful this past year. These articles report on efforts to select the minimal effective dose of tamoxifen for prevention, to challenge the existing age-based screening guidelines as they relate to race and ethnicity, to refine axillary management treatment standards, to optimize systemic therapy in multidisciplinary care settings, and to reduce the burden of breast cancer-related lymphedema after treatment. Taken together, these efforts have an impact on all facets of the continuum of care from prevention and screening through treatment and survivorship.

A novel method for rapid estimation of active bone marrow dose for radiotherapy patients in epidemiological studies.

BACKGROUND: In a dedicated effort to improve the assessment of clonal hematopoiesis (CH) and study leukemia risk following radiotherapy, we are developing a large-scale cohort study among cancer patients who received radiation. To that end, it will be critical to analyze dosimetric parameters of red bone marrow (ABM) exposure in relation to CH and its progression to myeloid neoplasms, requiring reconstruction method for ABM doses of a large-scale patients rapidly and accurately. PURPOSE: To support a large-scale cohort study on the assessment of clonal hematopoiesis and leukemia risk following radiotherapy, we present a new method for the rapid reconstruction of ABM doses of radiotherapy among cancer patients. METHODS: The key idea of the presented method is to segment patient bones rapidly and automatically by matching a whole-body computational human phantom, in which the skeletal system is divided into 34 bone sites, to patient CT images via 3D skeletal registration. The automatic approach was used to segment site-specific bones for 40 radiotherapy patients. Also, we segmented the bones manually. The bones segmented both manually and automatically were then combined with the patient dose matrix calculated by the treatment planning system (TPS) to derive patient ABM dose. We evaluated the performance of the automatic method in geometric and dosimetric accuracy by comparison with the manual approach. RESULTS: The pelvis showed the best geometric performance [volume overlap fraction (VOF): 52% (mean) with 23% (σ) and average distance (AD): 0.8 cm (mean) with 0.5 cm (σ)]. The pelvis also showed the best dosimetry performance [absorbed dose difference (ADD): 0.7 Gy (mean) with 1.0 Gy (σ)]. Some bones showed unsatisfactory performances such as the cervical vertebrae [ADD: 5.2 Gy (mean) with 10.8 Gy (σ)]. This impact on the total ABM dose, however, was not significant. An excellent agreement for the total ABM dose was indeed observed [ADD: 0.4 Gy (mean) with 0.4 Gy (σ)]. The computation time required for dose calculation using our method was robust (about one minute per patient). CONCLUSIONS: We confirmed that our method estimates ABM doses across treatment sites accurately, while providing high computational efficiency. The method will be used to reconstruct patient-specific ABM doses for dose-response assessment in a large cohort study. The method can also be applied to prospective dose calculation within a clinical TPS to support clinical decision making at the point of care.

Dosis­Wirkungs­Beziehung zwischen Alkoholkonsum und Psoriasis: Systematische Übersicht und Metaanalyse: Dose­response analysis between alcohol consumption and psoriasis: A systematic review and meta­analysis.

The association between psoriasis and alcohol consumption has been inconsistent across various studies. However, to the best of our knowledge, no dose-response meta-analysis has been performed to date. This study aims to investigate the association between alcohol consumption and psoriasis. The search was performed on July 27, 2021, using Embase and MEDLINE. The restricted cubic spline analysis was used to perform a dose-response analysis. We identified 3,904 studies, of which 48 studies with 1,702,847 individuals across 24 countries were included. Alcohol consumption was positively associated with psoriasis (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.27-1.70). In addition, a significantly increased OR for psoriasis was observed in males (OR, 1.84; 95% CI, 1.13-3.01) but not in females (OR, 1.22; 95% CI, 0.97-1.54). Based on eight studies, including three cohort and five case-control studies, the analysis revealed that with each additional gram of daily alcohol intake, the OR for psoriasis increased by 4%. We found a positive association between alcohol consumption and psoriasis. The association is more prominent in the group drinking more than 45 g of alcohol per day (3.2 alcoholic drink equivalent).

Combined Metronomic Chemo-immunotherapy (CMCI) in Head and Neck Cancers-An Experience from a Developing Country.

Head and neck squamous cell carcinomas (HNSCC) have proven to be inherently resistant to systemic treatments as a result of histological, molecular, and etiological heterogeneity, with limited responses seen after second-line therapy and beyond. With limited treatment options after progression on systemic chemotherapy in HNSCCs, immunotherapy has a role to play with improved results. In this prospective, observational, non-randomized, open-label study, a total of 12 patients with advanced, relapsed, or metastatic HNSCC received Inj. Nivolumab weight-based dose of 3 mg per kg, intravenously every 2 weeks along with low-dose capecitabine 500 mg twice a day, was prospectively assessed. The patient's clinical, hematological, and staging characteristics were described and the clinical benefit rate (CBR) was calculated. A total of 12 patients received the combined metronomic chemo-immunotherapy (CMCI). The majority of patients were belonging to ECOG-PS 1(66%), with all patients being in stage IV disease. Six, four, and two patients received immunotherapy as the 5th, 3rd, and 4th line of therapy, respectively. Nivolumab and low-dose capecitabine were used in all 12 patients. CBR was seen in 66% (8/12) of patients, one patient died due to hepatitis and hepatic encephalopathy, another patient died due to pneumonia and respiratory complications, two patients had progressive disease, and two patients with stable disease discontinued treatment because of financial constraints and kept on capecitabine alone. The majority tolerated therapy well with no grade 3/4 immune-related adverse events (IRAEs). Two patients required supportive therapy with packed red cell transfusion and albumin infusions. Six-month overall survival (OS) and progression-free survival (PFS) in the study population were 83.3% and 66.6%, respectively. In conclusion, nivolumab along with metronomic chemotherapy with low-dose capecitabine was very well tolerated and exhibited anti-tumor activity with a CBR of 66%, 6-month OS of 83.3%, and 6-month PFS of 66.6%, in extensively pretreated patients with HNSCCs. Additional studies of nivolumab and metronomic chemotherapy and immuno-immuno combination therapy in these diseases are ongoing.

Evaluation of radioactivity concentration in farm fresh milk and concomitant dose to consumer.

In this study, activity concentrations of natural radionuclides in 28 raw milk samples collected from different dairy farms in Dhaka city of Bangladesh were measured using a high-purity germanium (HPGe) detector for the first time. The activity concentration of 226Ra, 232Th, and 40K in the investigated fresh milk samples ranged from BDL (Below detection level) to 26 ± 1.6 Bq/kg, BDL to 11.7 ± 3.3 Bq/kg and 101 ± 17 to 384 ± 32 Bq/kg, respectively. No artificial radionuclides were found in the investigated samples. Present results show inline within the range of available data in the literature. Annual committed effective doses were estimated following the consumption characteristics of raw milk by city population, values are found within the limiting range recommended by international organizations due to consumption of foodstuffs. Additionally, real-time gamma-ray dose rate in the farms/sampling locations was found in the range of 0.12 ± 0.01-0.20 ± 0.01 µSv/h by using a digital gamma survey meter (Gamma Scout) and the calculated maximum annual effective dose due to outdoor absorbed dose was found to be 0.25 mSv/y, which shows lower than the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) recommended limit of 2.4 mSv/y. This study indicates that the concentration of radionuclides in the farm fresh milk of Dhaka city does not pose any unwanted risk to public health, and it is safe to consume by both children and adults with the current intake level.

The FLASH effect-an evaluation of preclinical studies of ultra-high dose rate radiotherapy.

FLASH radiotherapy (FLASH-RT) is a novel radiotherapy approach based on the use of ultra-high dose radiation to treat malignant cells. Although tumours can be reduced or eradicated using radiotherapy, toxicities induced by radiation can compromise healthy tissues. The FLASH effect is the observation that treatment delivered at an ultra-high dose rate is able to reduce adverse toxicities present at conventional dose rates. While this novel technique may provide a turning point for clinical practice, the exact mechanisms underlying the causes or influences of the FLASH effect are not fully understood. The study presented here uses data collected from 41 experimental investigations (published before March 2024) of the FLASH effect. Searchable databases were constructed to contain the outcomes of the various experiments in addition to values of beam parameters that may have a bearing on the FLASH effect. An in-depth review of the impact of the key beam parameters on the results of the experiments was carried out. Correlations between parameter values and experimental outcomes were studied. Pulse Dose Rate had positive correlations with almost all end points, suggesting viability of FLASH-RT as a new modality of radiotherapy. The collective results of this systematic review study suggest that beam parameter qualities from both FLASH and conventional radiotherapy can be valuable for tissue sparing and effective tumour treatment.

A study of hemodynamic effects, postoperative recovery, and safety of esketamine (right handed) during flexible bronchoscopy under general anesthesia.

OBJECTIVE: Flexible bronchoscopy during general anesthesia has become an indispensable tool. Anesthetics are widely utilized in flexible bronchoscopy (FB). This study delved into the application value of a subanesthetic dose of esketamine (ES) (right handed) in flexible bronchoscopy during general anesthesia. METHODS: A sample of 160 patients who underwent flexible bronchoscopy during general anesthesia were selected as study subjects and were equally divided into the control and ES groups, with clinical baseline data (age, sex, body mass index, American Society of Anesthesiologists grading) collected. Hemodynamic parameters (mean artery pressure, heart rate, pulse blood oxygen saturation) at different time points, the onset time of anesthesia, surgery time, analgesia maintenance time, anesthesia awakening time, and perioperative adverse reactions were recorded. Visual analogue scale (VAS), Mini-Mental State Examination (MMSE), and quality of recovery-40 (QoR-40) scales were utilized for assessing post-surgery satisfaction, cognitive function, and post-surgery early recovery quality. RESULTS: The hemodynamics were stable at each time point, but patients in the ES group were more stable than those in the control group. Patients in the ES group exhibited faster onset and awakening time of anesthesia, longer duration of analgesia, and lower total incidence of adverse reactions versus the control group. The patients' QoR-40 total scores in the ES group were improved versus the control group at 1 day after surgery. CONCLUSION: Compared with fentanyl, the use of ES (right handed) in flexible bronchoscopy during general anesthesia produces more stable hemodynamics, faster onset and recovery time of anesthesia, longer duration of analgesia, lower incidence of adverse reactions, and improved early postoperative recovery quality in patients.

Surface Dose measurement and Comparison between TLD and OSLD during Modified re constructive Mastectomy Irradiation.

The surface dose response of luminescent detectors (LD), in particular thermoluminescent dosimeter (TLD) and optically stimulated luminescent dosimeter (OSLD), during modified re constructive mastectomy (MRM) irradiation has been compared. The study utilized 100 MRM patients with LDs (n=500) for the irradiation of TLD (n=250) and OSLD (n=250) during irradiation from an Elekta Versa HD Linear accelerator.A more pronounced dose-response relationship was evident for both TLD and OSLD. These findings indicate a close adherence to the vendor-specified tolerance limits, affirming the suitability of these dosimeters, as substantiated by individual investigations on each type. While a minor difference in dose measurement was noted between TLD and OSLD, the study's outcomes support the applicability of both TLD and OSLD as effective dosimeters during MRM breast irradiation for surface dose evaluation. .

Parameter uncertainty analysis of the equivalent lung dose coefficient for the intake of radon in mines: A review.

Radon presents significant health risks due to its short-lived progeny. The evaluation of the equivalent lung dose coefficient is crucial for assessing the potential health effects of radon exposure. This review focuses on the uncertainty analysis of the parameters associated with the calculation of the equivalent lung dose coefficient attributed to radon inhalation in mines. This analysis is complex due to various factors, such as geological conditions, ventilation rates, and occupational practices. The literature review systematically examines the sources of radon and its health effects among underground miners. It also discusses the human respiratory tract model used to calculate the equivalent lung dose coefficient and the associated parameters leading to uncertainties in the calculated lung dose. Additionally, the review covers the different methodologies employed for uncertainty quantification and their implications on dose assessment. The text discusses challenges and limitations in current research practices and provides recommendations for future studies. Accurate risk assessment and effective safety measures in mining environments require understanding and mitigating parameter uncertainties.

Use of a 3D camera for automated patient positioning for chest-abdomen-pelvis CT scans: Effect on positioning accuracy and patient dose.

INTRODUCTION: 3D positioning cameras that automate the positioning of patients with respect to the CT isocentre have been developed and are in common use in CT departments. This study aimed to compare the performance of radiographers and a 3D camera system with respect to positioning accuracy and the effect on patient radiation dose for chest-abdomen-pelvis scans. METHODS: Patient positioning and dose data obtained from a dose management system was evaluated over a two-month period for patients positioned with (CAMon) and without (CAMoff) the positioning camera. Median vertical and lateral offset values were compared between the groups whilst doses were evaluated as a function of patient water equivalent diameter (WED) for the thorax and abdomen-pelvis acquisitions for both cohorts. RESULTS: Radiographers demonstrated high levels of positioning accuracy, however significant improvements in median vertical offset were identified for the CAMon cohort for both thorax (8 mm vs. 17 mm (p = 0.001)) and abdomen-pelvis (7 mm vs. 16 mm (p = 0.003)) scans. The percentage of patients positioned within 5 mm of the isocentre was 39.0% and 16.1% for the CAMon and CAMoff cohorts. For CAMoff scans, 77.4% of patients were positioned below the isocentre, but this was reduced to 45.8% for CAMon scans. No significant changes in dose as a function of WED were identified related to the camera use (thorax: p = 0.569, abdomen-pelvis: p = 0.760). CONCLUSION: Use of a 3D camera delivered significant improvements in the accuracy and reproducibility of patient positioning when compared with radiographers. IMPLICATIONS FOR PRACTICE: Improvements in positioning accuracy were observed at the research site and hence positioning camera use has the potential to become standard practice in CT to help ensure appropriate doses are delivered to patients according to their size.