Effective Dose Research Articles

Measurement of radon gas activity concentration and physiochemical parameters (pH, TDS, conductivity) in marshes water in Dhi Qar governorate – southern Iraq

ABSTRACT Radon concentration measurements were conducted on 40 water samples taken from various marsh areas in the Dhi-Qar governorate, located in southern Iraq, using a RAD7-H2O detector. The results indicate that the activity concentration of 222Rn in BqL−1 varied from 0.058 to 0.802, with an average of 0.26 ± 0.17. In addition, the annual effective dose due to the ingestion of 222Rn has varied between 0.00015 mSvy−1 to 0.0021 mSvy−1, with an average of 0.0013 ± 0.003 mSvy−1. The average lifetime cancer risk (×10−4) was 0.029 ± 0.021, ranging from 0.006 to 0.081. On the other hand, physiochemical parameters such as pH, TDS, and EC were determined. No correlation was noted between radon concentration and pH. However, there is a weak correlation between radon and TDS and EC. 222Rn values in marsh water samples from this study were within the EPA limits; the maximum water radon concentration was 11.1 BqL−1. However, some samples exhibited 222Rn values above the 2008 WHO maximum drinking water limit of 0.4 BqL−1. Furthermore, all samples’ AED and lifetime cancer risk were below the healthy drinking water safety standard. Thus, it can be said that marsh water in the DhiQar governorate – of Iraq has minimal human health effects due to radioactive radon gas.

Author Correction: Reducing the effective dose of doxycycline using chitosan silver nanocomposite as a carriers on gram positive and gram-negative bacteria

Author Correction: Reducing the effective dose of doxycycline using chitosan silver nanocomposite as a carriers on gram positive and gram-negative bacteria

Radiation Dose Savings Associated with Personalized CT Scan Range in 18F-NaF Bone PET/CT.

A disadvantage of 18F-NaF PET/CT compared with other types of bone scintigraphy is the additional radiation dose from the standard whole-body CT scan for lesion localization and characterization (L/C). This study investigated whether the L/C CT region can be personalized to reduce CT radiation dose, according to uptake in the PET images. Methods: Attenuation-corrected 18F-NaF PET images were reviewed for the clinically required L/C CT range by 1 medical observer and 1 technologist observer in 25 patients with breast cancer scanned before neoadjuvant chemotherapy. For each patient, effective doses were estimated for whole-body L/C CT, personalized L/C CT, and whole-body CT for attenuation correction only. Dose savings for the personalized method incorporating both whole-body CT for attenuation correction and personalized L/C CT were expressed relative to standard whole-body L/C CT. The clinical impact of the personalized method was determined by evaluating whether lesions clinically requiring coverage had been missed from the L/C CT region. Results: Potential dose savings of 43%-54% were estimated for the personalized CT method, according to the observers. From the 25 patients reviewed, the medical observer did not miss any clinically significant lesions from the L/C CT region, whereas the technologist observer missed 2 clinically significant lesions of 61 suggestive lesions identified by medical observer follow-up. Conclusion: Mean CT dose could be reduced by around half in this patient group with personalized CT. Future work should further evaluate whether this method can be implemented in clinical practice without compromising clinical image evaluation.

Current state of natural and artificial radiation in the Eastern Black Sea Coast of Türkiye (Trabzon–Rize–Artvin) 38 years after Chernobyl

Abstract The aim of this study was to evaluate the artificial and natural radiation dose levels in the coastal areas of Trabzon–Rize–Artvin provinces 38 years after the Chernobyl nuclear accident. Radioactive 232Th, 238U, 40K and 137Cs concentrations were determined in 49 soil samples by HPGe gamma spectrometry. Average concentrations were 12 Bqkg−1 for 238U, 15 Bqkg−1 for 232Th, 162 Bqkg−1 for 40K and 37 Bqkg−1 for 137Cs. Annual effective dose equivalents and excess lifetime cancer risk values are below the world average. This study also presents the average 137Cs value measured in the same area from 1990–2004–2024.

A Bioassay Analysis of Uranium and Lead in Urine Samples from a High Natural Background Radiation Area in Indonesia

Heavy metal pollution is a major environmental concern due to the high toxicity of heavy metals in humans. High natural background radiation areas (HNBRAs) contain high concentrations of the radioactive element 238U, which decays into 206Pb, in their soil, crops, and water. Concentrations of the heavy metals lead (Pb) and uranium (U) are, thus, correlated with HNBRAs. Mamuju in Indonesia is a recently studied HNBRA where high concentrations of Pb and U in the soil have been reported. The present study analyzes Mamuju residents’ exposure to Pb and U. Two zones in the study area were selected for comprehensive assessment. North Botteng was chosen to represent the HNBRA, and Topoyo was selected as the control zone, with 22 urine samples collected from each zone. The samples were analyzed using a quadrupole inductively coupled plasma mass spectrometer (ICP-MS). The average concentrations of Pb measured in the urine samples were 1.31 mg L−1 and 0.77 mg L−1 in North Botteng and Topoyo, respectively. These values are higher than the urine Pb reference value of 5 µg L−1. The urine Pb concentrations in both studied zones were alarmingly high, which may have serious health effects on the population and should warrant action to reduce Pb exposure in this area. The committed effective dose from the ingestion of 238U in North Botteng was higher than in Topoyo, measuring 36.0 mSv and 8.9 mSv, respectively. The area most affected by the ingestion of 238U was the red bone marrow, followed by the bone surface.

Radiation Exposure in Operatively Treated Pediatric Femur Fracture Patients.

Children who sustain femur fractures are exposed to medical radiation as part of their treatment. In addition to standard radiographs and fluoroscopy, computerized tomography (CT) is a major source of ionizing radiation (IR). These patients frequently undergo CT scans during their treatment. The aim of the current study was to quantify the factors associated with greater IR exposure in children with operatively treated femur fractures and compare radiation exposure among those who received CT scans versus those who did not. Thirty-eight patients below 18 years old with operatively treated traumatic femur fractures were included in the study. They fell into one of 2 groups: 1 received 1 or more CT scans (CT group), and the other did not receive a CT scan (non-CT scan). The 2 groups were then compared by total quantitative radiation exposure, age, BMI, location of the femur fracture, open versus closed fracture, and the presence versus absence of fracture displacement. The effective dose of IR exposure that occurred within the operating room (OR) made up 75.7%±27.4% of the total IR exposure among all patients. Patients in the CT group had over a 5-fold greater quantitative cumulative IR exposure compared with the non-CT group (P<0.0001). Furthermore, patients in the CT group were significantly older than (P=0.004) and had a greater BMI (P=0.045) than the non-CT group. Children with pediatric femur fractures often exceed what is considered a low level of radiation. There is a significant difference in radiation exposure between pediatric femur fracture patients who receive 1 or more CT scans compared with those who do not receive a CT scan. Level III-retrospective cohort study.

Discovery of the bacterial HslV protease activators as lead molecules with novel mode of action

Abstract The HslVU enzyme complex, a proteasomal analog found in bacteria, consists of two components, i.e., the HslV protease and the HslU ATPase. These proteins come together to form a functional enzyme complex, where the C-terminal helix of each HslU subunit is inserted into the binding pocket of each HslV dimer. This interaction leads to the activation of the HslV protease through allosteric mechanisms, enabling its enzymatic function. This bacterial complex is reflected as an attractive target for drug development due to its presence in disease-causing microorganisms and concurrent absence in humans. The objective of this research was to identify certain promising drug candidates that could excessively stimulate the HslV protease, leading to uncontrolled protein breakdown in the pathogens. Four dihydropyrimidone derivatives have been identified as potential activators of HslV protease exhibiting high docking scores, favorable binding patterns, and significant in vitro activation capabilities. These compounds have demonstrated effective dose 50 values within the sub-micromolar range, i.e., 0.4–0.58 µM. Normal mode analysis investigations provided additional confirmation regarding the stability of the conformational interactions between the HslV protease and the active compounds. In addition, the predicted absorption, distribution, metabolism, excretion, and toxicity properties of these lead compounds remarkably demonstrated their considerable drug-like and non-toxic qualities. This study not only presents more potent small non-peptide activators of the HslV protease but also enhances the understanding regarding the mechanism of HslVU complex activation via small non-peptidic molecules.

The Effectiveness of Bougainvillea (Bougainvillea spectabilis willd) Extract on Reducing Blood Glucose in Hypercholesterolaemia White Rats

Bougainvillea leaves are often used by the public as a treatment by drinking boiled water, but their use as a blood sugar-lowering agent is not supported by scientific data. The purpose of this study was to determine the effect of reducing blood glucose levels and to determine the dose of extract that is effective in in white rats. The plant's herbal extract was prepared using the reflux method with 90% ethanol solvent. This study uses a laboratory experimental method to compare blood glucose levels in white rats before and after administration of herb extract at doses of 100, 200, and 300 mg/kg BW orally using high-fat feed induction and streptozotocin. Blood glucose levels were measured using a glucometer, and mice were declared positive for diabetes with fasting blood sugar levels above 126 mg/dL. The number of test animals used in this study was 30 mice, divided into 6 groups. A randomized block design was used as the research design. The study's findings revealed that administering Bougainville spectabilis willd herb extract at doses of 100, 200, and 300 mg/kg BW can reduce blood glucose in test animals with an effective dose of 200 mg/kg BW

Assessment of Occupational Radiation Exposure Among Various Medical Professions in Interventional Cardiology: A Five-Year Study (2018-2022)

Background: Occupational radiation exposure in medical settings is a growing concern, especially in interventional cardiology. This study aims to assess the occupational radiation exposure among medical personnel in interventional cardiology from 2018 to 2022. Methods: We conducted a retrospective analysis of the annual mean effective doses (AMED) and the average over a five-year period (MED-5y) among various medical professionals, including anesthesiologists, cardiologists, nurses, radiologists, and radiologic technologists. The effective doses were estimated using thermoluminescent dosimeters and analyzed to compute the AMED and MED-5y. Statistical significance was determined using T-tests and ANOVA, with subsequent Tukey Post-Hoc Tests for specific group comparisons. Results: The AMED varied significantly among professions, with cardiologists experiencing the highest exposure (3.469 ± 7.81 mSv in 2022). An overall increase in AMED doses was observed from 2018 to 2022. The results of the T-Test showed a significant difference in the radiation exposure across the years under study (p &lt; .001). The MED-5y were anesthesiologists (0.62 ± 0.30), cardiologists (3.23 ± 7.37), nurses (1.17 ± 0.56), radiologic technologists (1.13 ± 0.38), and radiologists (0.86 ± 0.26). The study also found significant differences in MED-5y across professions (F = 14.8, p &lt; .001). Gender-based analysis indicated significant differences in MED-5y, particularly among nurses and radiologists. Conclusion: The results of this study revealed that the annual effective dose received by anesthesiologists, cardiologists, nurses, radiologists, and radiologic technologists was below the recommended occupational dose limit of 20 mSv per year, as stipulated by both national and international standards.

Potential for reduction of radiation dose in the assessment of the lead orientation in directional deep brain stimulation electrodes.

Directional deep brain stimulation (dDBS) relies on electrodes steering the stimulation field in a specific direction. Post implantation, however, the intended and real orientation of the lead frequently deviates e.g. due to torque of the electrode. The orientation is assessed by postoperative imaging such as C-arm cone-beam CT (CBCT) using 3D rotational fluoroscopy and multi-slice CT (MSCT). The objective is to determine the effect of different X-ray systems such as CBCT and MSCT, and scan acquisition parameters on effective radiation doses. We retrospectively investigated the dose area product (DAP) and dose length product (DLP) of patients who underwent both CBCT and MSCT after dDBS surgery. These metrics were then converted into the effective dose by established conversion coefficients. For CBCT, the feasible dose optimization by collimation was virtually assessed. Univariate analysis was performed to determine differences. Among 88 patients median effective dose was 0.20±0.07mSv in CBCT and 2.11±0.33mSv in MSCT (p<0.001). The field of view (FOV) in CBCT can be collimated in craniocaudal orientation by 33.6% and mediolaterally by 60.8%. This optimized collimation implies an effective dose reduction of 76% (p<0.001). Comparison of the effective dose of MSCT vs. CBCT revealed a significant dose reduction by 90.3% (p<0.001), whereas optimal collimation by 97.7% (p<0.001). For assessment of dDBS orientation, CBCT had significantly lower radiation doses compared to MSCT. Optimized collimation in CBCT allows for a further substantial dose reduction. Moreover, the proposed approach is applicable on other neuroimaging procedures such as 3D visualization of treated intracranial aneurysm.

CT-based migration analysis of a tibial component compared to radiostereometric analysis : one-year results of a prospective single-group implant safety study.

Radiostereometric analysis (RSA) is considered the gold standard for in vivo migration analysis, but CT-based alternatives show comparable results in the shoulder and hip. We have previously validated a CT-based migration analysis method (CTMA) in a knee phantom compared to RSA. In this study, we validated the method in patients undergoing total knee arthroplasty (TKA). Our primary outcome measure was the difference in maximum total point motion (MTPM) between the differing methods. A total of 31 patients were prospectively studied having undergone an uncemented medial pivot knee TKA. Migrations were measured up to 12 months with marker-based and model-based RSA, and CT-RSA. Mean precision data for MTPM were 0.27 mm (SD 0.09) for marker-based RSA, 0.37 mm (SD 0.26) for model-based RSA, and 0.25 mm (SD 0.11) for CTMA. CTMA was as precise as both RSA methods (p = 0.845 and p = 0.156). At three months, MTPM showed a mean of 0.66 mm (95% CI 0.52 to 0.81) for marker-based RSA, 0.79 (95% CI 0.64 to 0.94) for model-based RSA, and 0.59 (95% CI 0.47 to 0.72) for CTMA. There was no difference between CTMA and marker-based RSA (p = 0.400), but CTMA showed lower migration than model-based RSA (p = 0.019). At 12 months, MTPM was 1.03 (95% CI 0.79 to 1.26) for marker-based RSA, 1.02 (95% CI 0.79 to 1.25) for model-based RSA, and 0.71 (95% CI 0.48 to 0.94) for CTMA. MTPM for CTMA was lower than both RSA methods (p < 0.001). Differences between migration increased between the methods from three to 12 months. Mean effective radiation doses per examination were 0.016 mSv (RSA) and 0.069 mSv (CT). Imaging time for performing RSA radiographs was 17 minutes 26 seconds (SD 7 mins 9 sec) and 4 minutes 24 seconds (SD 2 mins 3 sec) for CT. No difference in precision was found between CTMA and marker- or model-based RSA, but CTMA shows lower migration values of the tibial component at 12 months. CTMA can be used with low effective radiation doses, and CT image acquisition is faster to perform than RSA methods and may be suitable for use in ordinary clinical settings.

Effect of Different Doses of Intrathecal Nalbuphine as Adjuvant to Hyperbaric Bupivacaine on Characteristics of Subarachnoid Block in Pelvic and Lower Limb Orthopaedic Surgeries: A Randomised Clinical Study

Introduction: Hyperbaric bupivacaine 0.5% is most commonly used amide local anaesthetic drug in spinal anaesthesia. Various additives have been used as an adjuvant to hyperbaric bupivacaine 0.5% to modify its anaesthetic properties. Nalbuphine, a mix opioid with high efficacy kappa receptors agonism has also been used as an adjuvant to hyperbaric bupivacaine 0.5% at different doses. Aim: To compare and discover the effective dose of nalbuphine as adjuvant in subarachnoid block with hyperbaric bupivacaine in pelvic and lower limb orthopaedic surgeries in terms of onset and duration of sensory and motor block along with postoperative analgesia duration. Materials and Methods: This randomised clinical study was conducted in the Department of Anaesthesia, Shrimati Bhikhiben Kanjibhai Shah Medical Institute and Research Centre (SBKS MIRC), Piparia, Vadodara, Gujarat, India over a period of 18 months from February 2023 to August 2024 on 80 patients belonging to 20-60 years of age, American Soceity of Anaesthesiology (ASA) Grade I or II, of either gender undergoing elective pelvic and orthopaedic surgeries. Patients were randomly divided into two groups having 40 patients each. Group A received hyperbaric bupivacaine 12.5 mg+0.4 mg nalbuphine (total 3 mL) and Group B received hyperbaric bupivacaine 12.5 mg + 0.8 mg nalbuphine (total 3 mL). Sensory and motor block characteristics like their onset time, time to achieve highest sensory level, time to achieve bromage 3, time of two segment regression, duration of sensory and motor block, duration of postoperative analgesia and time for requirement of first rescue analgesia dose were observed and assessed. Haemodynamic parameters along with intraoperative and postoperative sideeffects were also observed. Results: Both the study groups had similar demographics and haemodynamic parameters. Time of two segment regression of sensory block was significantly longer in Group B (135.25±11.49 min) than A (120.95±16.98 min) with statistically significant prolonged duration of sensory block in Group B (228.25±21.91 min) than A (206.75±15.21 min) (p&lt;0.0001). Postoperative analgesia was also prolonged in Group B (294.75±19.15 min) than A (226.19±14.78 min) without significant increase the incidence of side-effects (p≥0.05). Conclusion: Study concluded that 0.8 mg nalbuphine as an adjuvant to 0.5% hyperbaric bupivacaine in subarachnoid block is more effective dose as it provides prolonged duration of sensory block and postoperative analgesia with good haemodynamic stability and minimal side-effects.

Efficacy of 5 µg and 10 µg Dexmedetomidine as Adjuvants to 3 mL 0.5% Hyperbaric Bupivacaine in Pelvic and Lower Limb Orthopaedic Surgeries: A Randomised Clinical Study

Introduction: Low-dose bupivacaine used in spinal anaesthesia results in speedy recovery. For lower limb orthopaedic surgeries, to provide sufficient anaesthesia and prolong postoperative analgesia in a less cumbersome way, author can add potent adjuvants like dexmedetomidine (an alpha-2 adrenergic receptor agonist) in effective and safer doses intrathecally. Aim: To compare the effects of intrathecal 5 µg dexmedetomidine versus 10 µg dexmedetomidine as adjuvants to 3 mL of 0.5% hyperbaric bupivacaine in pelvic and lower limb orthopaedic surgeries. Materials and Methods: This randomised clinical and singleblind study study was conducted at the Operation Theatre (OT) complex of Dheeraj Hospital, SBKS, and MIRC, Sumandeep Vidyapeeth, Vadodara, Gujarat, India in the Department of Anaesthesia over a period of 18 months, from September 2022 to March 2024 and total of 82 patients scheduled for lower limb and pelvic orthopaedic surgery who were to receive spinal anaesthesia were divided into Group D1 and D2. Group D1 (n=41) received 3 mL of bupivacaine (0.5% heavy) with 5 µg dexmedetomidine, totaling 3.1 mL, while group D2 (n=41) received 3 mL of bupivacaine (0.5% heavy) with 10 µg dexmedetomidine, also totaling 3.1 mL intrathecally. The onset and duration of sensory and motor blockade, as well as the duration of analgesia, were noted, along with the monitoring of haemodynamic parameters and any side effects. All observed data were analysed using statistical tests such as the unpaired t-test and Chi-square test. A p-value &lt;0.05 was considered statistically significant. Results: Demographic data were comparable in both groups and were non significant (p-value &gt;0.05). The onset of sensory block was earlier in group D2 (2.01±0.12 min) than in group D1 (2.87±0.36 min) (p-value &lt;0.05). The onset of motor block was also earlier in group D2 (2.63±0.26 min) compared to group D1 (3.36±0.43 min). The duration of sensory block was longer in group D2 (457.46±32.85 min) than in group D1 (318.02±32.27 min). The duration of motor block was also longer in group D2 (396.17±36.13 min) than in group D1 (257.37±25.02 min) (p-value &lt;0.05). The duration of analgesia and the time until the need for the first rescue analgesia was significantly longer in group D2 (364.29±43.64 min) compared to group D1 (219.51±23.39 min). Conclusion: Intrathecal bupivacaine with dexmedetomidine at a dose of 10 µg results in an earlier onset and longer duration of sensory and motor block compared to a dose of 5 µg. The duration of postoperative analgesia was longer, and the time until the need for the first rescue analgesia was extended with the 10 µg dosage. No significant side effects were observed in either group.

A duplicate diet survey for the assessment of the annual effective dose to the Irish adult population from the ingestion of natural radionuclides in food

A duplicate diet survey for the assessment of the annual effective dose to the Irish adult population from the ingestion of natural radionuclides in food

Optimization of Clozapine Treatment: Study of Variables Affecting Response in Uruguayan Patients With Schizophrenia.

Clozapine is the recommended drug for treatment-resistant schizophrenia. Drug response could be affected by numerous factors such as age, sex, body mass index, co-medication, consumption of xanthine-containing beverages, smoking, and genetic variants of the enzymes involved in clozapine metabolism (CYP1A2, CYP3A4, and, to a lesser extent, CYP2C19 and CYP2D6). This study evaluated genetic and nongenetic variables that may affect clozapine plasma concentrations in Uruguayan patients with schizophrenia. Demographic data including sex, age, ethnicity, body weight, smoking habit, concomitant medication, and xanthine consumption were collected through a data collection form. Clozapine and norclozapine concentrations were determined using an HPLC system equipped with a UV detector. Genetic variants were determined through next-generation sequencing using Illumina sequencing technology and a panel of DNA probes. Fifty patients were included in the study. After evaluation, only tobacco use and obesity had a significant impact on clozapine exposure (P < 0.05). The high prevalence of the genetic variant CYP1A2*1F may account for the significant impact that tobacco smoking has on clozapine concentrations. Some common adverse effects observed in this study depend on clozapine plasma concentrations, such as constipation and sialorrhea. These types of studies provide the clinician with tools to optimize clozapine therapy, attempting to use the minimum effective dose and attenuating the burden of concentration-dependent adverse reactions.

AGX101: A TM4SF1-directed tubulin inhibitor conjugate in ongoing first-in-human trial including GI cancers.

829 Background: TM4SF1 (Transmembrane-4 L-Six-Family-Member-1) is an endothelial marker with critical roles in angiogenesis, as well as a tumor cell antigen that contributes significantly to invasion and metastasis. TM4SF1 is upregulated 20-fold in angiogenic tumor vascular endothelium compared to normal vasculature endothelium and exhibits a unique nuclear internalization pathway. AGX101 is a novel tubulin inhibitor conjugate specifically directed against TM4SF1, delivering a potent maytansinoid payload directly to the nucleus of cells within the tumor microenvironment. Delivery to both the vascular and tumor cell compartments of the tumor results in three mechanisms of action (MoAs): (1) activation of tumor immune surveillance, (2) tumor blood supply deprivation, and (3) direct tumor cell killing. Methods: TM4SF1 expression was assessed using immunohistochemistry. Safety and pharmacokinetics of AGX101 were evaluated in non-human primates (NHP), with escalating doses to determine the highest non-severely toxic dose (HNSTD). Efficacy studies were also conducted in mouse models, enabling assessment of the minimum effective dose (MED) needed to engage each of the three MoAs. The combination of HNSTD and MED enables calculation of a therapeutic index (TI). The potential for synergy with immune checkpoint inhibitors (ICIs) was also investigated. A first-in-human study of AGX101 in patients with advanced solid tumors with the primary objective of safety and dose-limiting toxicities (DLTs) has initiated. Results: Notable cancers with high TM4SF1 scoring intensity include pancreatic adenocarcinoma, hepatocellular carcinoma, cholangiocarcinoma, and gastric cancer. In esophageal cancer, 20% of patients have a TM4SF1 copy number amplification, and these have worse prognosis. In NHP, AGX101 exhibited a favorable safety profile. In preclinical efficacy studies, monotherapy demonstrated robust efficacy through each of the three MoAs in syngeneic models in mice including CT26 colon carcinoma, and human tumor xenograft models including MIA PaCa-2 pancreatic cancer. Measured by exposure, TI was large. In syngeneic mouse models including CT26, the effects of ICIs were potentiated, suggesting a potential synergistic approach in cancer therapy. The first two dose levels of AGX101 monotherapy in humans has cleared without DLTs. Three patients with pancreatic adenocarcinoma have been treated thus far. Conclusions: AGX101, targeting the TM4SF1 antigen, represents a promising new approach in cancer therapy. The preclinical data suggest that AGX101 could provide a significant therapeutic benefit by novel and differentiated mechanisms of action, namely selectively targeting the tumor vasculature and potentiating immune-based therapies. Further clinical development of AGX101 is ongoing and initial outcome data will become available by the conference. Clinical trial information: NCT06440005 .

KRAS status in lung oligometastases treated with SBRT.

264 Background: Stereotactic Body Radiotherapy (SBRT) to lung metastases (LM) from colorectal cancer (CRC) has been applied to improve disease control in in the oligometastatic (OM) and oligoprogressive (OP) setting. The aim of this study is to assess the impact of KRAS mutational (KRASmut) status in the response to SBRT in LM. Methods: Data from a consecutive cohort of OM/OP CRC patients treated at our Institution with SBRT for LM from May 2019 to March 2024 were retrospectively reviewed. Patients (age, KRASmut in primary tumor, OM/OP disease, chemotherapy lines prior to SBRT) and treatment-related variables (dose regimen and Biologically Effective Dose: BED, toxicity) were collected. Local Control (LC) was defined as time from SBRT to local failure or last radiologic follow-up. Results: Sixty-two patients (median age: 74 years, range 49-85), accounting for 103 LM were included. LM were treated in the OM and OP setting in 65(63%) and 38(37%) cases, respectively. SBRT was delivered before chemotherapy (n=49,48%) or following first (n=31,30%) or further chemotherapy lines (n=23,22%). KRASmut was present ab initio in 49% of cases (n=50). Dose regimens included 48-60 Gy in 3-8 fractions, resulting in a median BED of 115.5 (range 76.8-151.2) Gy 10 : a BED&gt;100Gy 10 was delivered in 92% (n=95) of treatment courses. Median follow-up was 16 (range 2-45) months. Median LC was not reached; 1- and 3 years LC rates were 85% and 67% respectively. At multivariate analysis (MVA), only a BED≤100Gy 10 (p=0.029, HR 2.99, IC95% 1.1- 9.5) and prior second or further chemotherapy line (p=0.031, HR 3.2, IC95% 1.1- 8.1) were independently correlated with impaired LC. No grade &gt;2 toxicity was observed. Focusing on patients receiving no chemotherapy or first-line treatment before SBRT, 1- and 3 years LC rates were 92% and 77% respectively (median: NR). At MVA, while BED≤100Gy 10 (p=0.036, HR 6.96, IC95% 1.9-25.7) was associated with poorer LC, lack of KRASmut (p=0.037, HR 0.26, IC95% 0.07- 0.9) was independently correlated with improved LC. Conclusions: SBRT in LM from OM/OP CRC results in high LC rates, particularly with intensive regimens in non-heavily pretreated patients. No impact of KRASmut was observed. Due to possible occurrence of secondary mutations in the pretreated population, a subset analysis in the chemotherapy-naive/first-line subset suggests an impact of KRASmut in radioresistance that should be further explored in a dose-escalation perspective. Re-biopsy or liquid biopsy may be useful to identify de-novo mutations.

Pramipexole decreases allodynia and hyperalgesia via NF-κB in astrocytes in rats with Parkinson's disease.

Pain is one of the principal non-motor symptoms of Parkinson's disease (PD), negatively impacting the patient's quality of life. This study aimed to demonstrate whether an effective dose of pramipexole (PPX) can modulate the NF-κB/p-p65 activation in glial cells (astrocytes and microglia) and diminish the hypersensitivity (allodynia and hyperalgesia) in male Wistar rats with PD. For this, 2μl of 6-hydroxydopamine (6-OHDA, 8μg/μL/0.2μl/min) was administered unilaterally in the Substantia Nigra of the Pars Compacta (SNpc) to establish a PD model rat. Motor behavioral tests were used to validate the PD model, and von Frey filaments were used to evaluate allodynia and hyperalgesia. Immunohistochemical and immunofluorescence were used to analyze the level of tyrosine hydroxylase in SNpc and striatum as well as the expression of GFAP, Iba-1, NF-κB/p-65 in the L4-L6 spinal cord dorsal horn. Unilateral 6-OHDA-lesion reduces motor capacity and produces long-term allodynia and hyperalgesia in both hind paws. L4-L6 spinal cord dorsal horn astrocytes and microglia were active in these 6-OHDA-lesioned rats. Moreover, PPX (1 and 3mg/Kg, i.p./10days, n=10 per group) inhibited the bilateral mechanical hypersensitivity, and PPX (3mg/Kg/i.p./10days) reduced 6-OHDA-induced astrocyte and microglia activation, as well as reduced NF-κB/p-p65 expression only in astrocytes of dorsal horn spinal cord in the L5-L6. These findings suggest that PPX could alleviate pain by decreasing the activation of microglia and astrocytes through the NF-κB/p-p65 pathway in the dorsal horn spinal cord. Therefore, PPX could be considered an optional tool for improving pain hypersensitivity in PD patients.

Qualitative study of patients experiences and perceptions of stepping down asthma medication in primary care across England

BackgroundGuidelines recommend that asthma medication should be stepped down to the minimally effective dose that achieves symptom control. Stepping down aims to prevent adverse medication effects and unnecessary costs but...

Ultra-low-dose coronary CT angiography via super-resolution deep learning reconstruction: impact on image quality, coronary plaque, and stenosis analysis.

To exploit the capability of super-resolution deep learning reconstruction (SR-DLR) to save radiation exposure from coronary CT angiography (CCTA) and assess its impact on image quality, coronary plaque quantification and characterization, and stenosis severity analysis. This prospective study included 50 patients who underwent low-dose (LD) and subsequent ultra-low-dose (ULD) CCTA scans. LD CCTA images were reconstructed with hybrid iterative reconstruction (HIR) and ULD CCTA images were reconstructed with HIR and SR-DLR. The objective parameters and subjective scores were compared. Coronary plaques were classified into three components: necrotic, fibrous or calcified content, with absolute volumes (mm3) recorded, and further characterized by percentage of calcified content. The four main coronary arteries were evaluated for the presence of stenosis. Moreover, 48 coronary segments in 9 patients were evaluated for the presence of significant stenosis, with invasive coronary angiography as a reference. Effective dose decreased by 60% from LD to ULD CCTA scans (2.01 ± 0.84 mSv vs. 0.80 ± 0.34 mSv, p < 0.001). ULD SR-DLR was non-inferior or even superior to LD HIR in terms of image quality and showed excellent agreements with LD HIR on the plaque volumes, characterization, and stenosis analysis (ICCs > 0.8). Moreover, there was no evidence of a difference in detecting significant coronary stenosis between the LD HIR and ULD SR-DLR (AUC: 0.90 vs. 0.89; p = 1.0). SR-DLR led to significant radiation dose savings from CCTA while ensuring high image quality and excellent performance in coronary plaque and stenosis analysis. Question How can radiation dose for coronary CT angiography be reduced without compromising image quality or affecting clinical decisions? Finding Super-resolution deep learning reconstruction (SR-DLR) algorithm allows for 60% dose reduction while ensuring high image quality and excellent performance in coronary plaque and stenosis analysis. Clinical relevance Dose optimization via SR-DLR has no detrimental effect on image quality, coronary plaque quantification and characterization, and stenosis severity analysis, which paves the way for its implementation in clinical practice.