Three-dimensional computed tomography dose optimisation and image quality improvement of abdomen-pelvis using adaptive-iterative dose reduction

New development of computed tomography (CT) technology has made CT a versatile and efficient diagnostic modality. This has led to exponentially increased demand in clinical practice with increased risk of radiation exposure to the patients. Most research on CT optimisation concentrates on physical parameters, such as tube potential, tube current and pitch factor. Little research has been done on iterative reconstruction process in dose reduction without compromising image quality in clinical CT examination. Thus, this study investigates dose optimisation and image quality improvement using Adaptive-Iterative Dose Reduction Three-Dimensional (AIDR 3D) reconstruction, compared with conventional filtered back projection (FBP), in abdomen-pelvis CT. In a single-centre cohort study, 100 patients who underwent plain CT abdomen-pelvis using a 80-multidetector CT system were retrospectively analysed. Patients were divided into three groups according to the scanning protocol. Group 1 patients (n = 39) were scanned with 120 kVp standard dose FBP reconstruction. Iterative reconstruction was used for 120 kVp low dose group 2 (AIDR 3D standard, n = 28) and 100 kVp low dose group 3 (AIDR 3D strong, n = 33). Quantitative measures of radiation dose, objective image noise and signal to noise ratio (SNR) were obtained. The results were compared between all groups and correlated to body mass index (BMI). Subjective image quality evaluations were graded by two radiologists. The volume CT dose index (CTDIvol), dose length product (DLP), and effective dose (E) in low dose AIDR 3D studies (group 2 and group 3) were significantly lower than standard dose FBP CT (p < 0.05). Group 3 (100 kVp low dose AIDR 3D strong) obtained highest dose reduction with CTDIvol, DLP and E as low as 3.35 ± 1.04 mGy, 172.05 ± 63.32 mGy.cm and 2.58 ± 0.95 mSv respectively. In objective image quality analysis, group 2 and group 3 achieved significant image noise reduction (41.33% versus 52.62%) and SNR increment (62.25% versus 101.47%) compared to group 1. Subjective image noise, artifacts, sharpness and overall diagnostic confidence were greatly improved by AIDR 3D (group 2 and group 3). Moreover, AIDR 3D strong (group 3) was the most optimal iterative reconstruction to demonstrate fine anatomical structures. AIDR 3D could advance dose optimisation and improved image quality for wide range of BMI in the population. Thus, AIDR 3D is a useful algorithm to optimise scanning protocol and practicable in all routine CT examinations at the lowest radiation exposure

Acute Abdomen caused by Perforated Jejunal Diverticulitis

Jejunal diverticulum accounts for only 25% of small bowel diverticula, and approximately 7% of these will present as complicated jejunal diverticulitis or perforation. Here, we described a case of jejunal diverticular perforation presented as acute abdominal peritonitis. The computed tomography of the abdomen suggested small bowel perforation and therefore, emergency surgical exploration was performed. Intraoperatively, multiple jejunal diverticulae were found with one forming a localised diverticular abscess. Segmental resection of the diseased segment with primary anastomosis was performed. The patient made an uneventful post-operative recovery. Although complicated jejunal diverticulitis is rare, emergency surgery is often warranted if perforation occurs. Computed tomography is valuable in the diagnosis and preoperative planning especially in an emergency surgical conundrum when there is equivocal clinical peritonitis or perforation

Adaptive iterative dose reduction (AIDR) 3D in low dose CT abdomen-pelvis: effects on image quality and radiation exposure

The widespread use of computed tomography (CT) has increased the medical radiation exposure and cancer risk. We aimed to evaluate the impact of AIDR 3D in CT abdomen-pelvic examinations based on image quality and radiation dose in low dose (LD) setting compared to standard dose (STD) with filtered back projection (FBP) reconstruction. We retrospectively reviewed the images of 40 patients who underwent CT abdomen-pelvic using a 80 slice CT scanner. Group 1 patients (n=20, mean age 41 ± 17 years) were performed at LD with AIDR 3D reconstruction and Group 2 patients (n=20, mean age 52 ± 21 years) were scanned with STD using FBP reconstruction. Objective image noise was assessed by region of interest (ROI) measurements in the liver and aorta as standard deviation (SD) of the attenuation value (Hounsfield Unit, HU) while subjective image quality was evaluated by two radiologists. Statistical analysis was used to compare the scan length, CT dose index volume (CTDIvol) and image quality of both patient groups. Although both groups have similar mean scan length, the CTDIvol significantly decreased by 38% in LD CT compared to STD CT (p<0.05). Objective and subjective image quality were statistically improved with AIDR 3D (p<0.05). In conclusion, AIDR 3D enables significant dose reduction of 38% with superior image quality in LD CT abdomen-pelvis

Diameter-dependent release of a cisplatin pro-drug from small and large functionalized carbon nanotubes

The use of platinum-based chemotherapeutic drugs in cancer therapy still suffers from severe disadvantages, such as lack of appropriate selectivity for tumor tissues and insurgence of multi-drug resistance. Moreover, drug efficacy can be attenuated by several mechanisms such as premature drug inactivation, reduced drug uptake inside cells and increased drug efflux once internalized. The use of functionalized carbon nanotubes (CNTs) as chemotherapeutic drug delivery systems is a promising strategy to overcome such limitations due to their ability to enhance cellular internalization of poorly permeable drugs and thus increase the drug bioavailability at the diseased site, compared to the free drug. Furthermore, the possibility to encapsulate agents in the nanotubes’ inner cavity can protect the drug from early inactivation and their external functionalizable surface is useful for selective targeting. In this study, a hydrophobic platinum(IV) complex was encapsulated within the inner space of two different diameter functionalized multi-walled CNTs (Pt(IV)@CNTs). The behavior of the complexes, compared to the free drug, was investigated on both HeLa human cancer cells and RAW 264.7 murine macrophages. Both CNT samples efficiently induced cell death in HeLa cancer cells 72 hours after the end of exposure to CNTs. Although the larger diameter CNTs were more cytotoxic on HeLa cells compared to both the free drug and the smaller diameter nanotubes, the latter allowed a prolonged release of the encapsulated drug, thus increasing its anticancer efficacy. In contrast, both Pt(IV)@CNT constructs were poorly cytotoxic on macrophages and induced negligible cell activation and no pro-inflammatory cytokine production. Both CNT samples were efficiently internalized by the two types of cells, as demonstrated by transmission electron microscopy observations and flow cytometry analysis. Finally, the platinum levels found in the cells after Pt(IV)@CNT exposure demonstrate that they can promote drug accumulation inside cells in comparison with treatment with the free complex. To conclude, our study shows that CNTs are promising nanocarriers to improve the accumulation of a chemotherapeutic drug and its slow release inside tumor cells, by tuning the CNT diameter, without inducing a high inflammatory response

Reduced durability of hybrid immunity to SARS-CoV-2 in immunocompromised children

BackgroundIn endemic COVID-19, immunocompromised children are vulnerable until vaccinated but the optimal primary vaccination regime and need for booster doses remains uncertain.MethodsWe recruited 19 immunocompromised children (post-solid organ transplantation, have autoimmune disease or were on current or recent chemotherapy for acute lymphoblastic leukemia), and followed them from the start of primary vaccination with BNT162b2 mRNA SARS-CoV-2 until 1-year post-vaccination. We investigated the quality of vaccine immunogenicity, and longevity of hybrid immunity, in comparison to healthy children.ResultsImmunocompromised children failed to produce T cell and memory B cell (MBC) responses reaching thresholds of protection after 2 doses; a third dose however improved both responses. Initially robust hybrid immunity demonstrated significantly more decline in T cell and MBC responses in immunocompromised compared to healthy children, to levels below the protective threshold by month 12.DiscussionImmunocompromised children may benefit from a 3-dose primary vaccination regime, with yearly or twice-yearly booster doses for sustained immunity

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation &lt;92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p&lt;0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p&lt;0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research