Changes in ADC and T2-weighted MRI-derived radiomic features in patients treated with focal salvage HDR prostate brachytherapy for local recurrence after previous external-beam radiotherapy

PurposeTo explore the changes in T2-weighted (T2w) and apparent diffusion coefficient (ADC) magnetic resonance imaging -derived radiomic features of the gross tumor volume (GTV) from focal salvage high-dose-rate prostate brachytherapy (HDRB) and to correlate with clinical parameters.Materials and MethodsEligible patients included those with biopsy-confirmed local recurrence that correlated with MRI (T2w, ADC). Patients received 27 Gy in 2 fractions separated by 1 week to a quadrant consisting of the GTV. The MRI was repeated 1 year after HDRB. GTVs, planning target volumes, and normal prostate tissue control volumes were identified on the pre- and post-HDRB MRIs. Radiomic features from each GTV were extracted, and principle component analysis identified features with the highest variance.ResultsPre- and post-HDRB MRIs were obtained from 14 trial patients. Principle component analysis showed that 18 and 17 features contributed to 93% and 86% of the variance observed in the T2w and ADC data, respectively. Sixteen T2w features and 1 ADC GTV feature were different from the control volumes in the pre-HDRB images (p < 0.05). Ten T2w and 7 ADC GTV post-HDRB features were different from those of pre-HDRB (p < 0.05).ConclusionsExploratory analysis reveals several radiomic features in the T2w and ADC image GTVs that distinguish the GTV from healthy prostate tissue and change significantly after salvage HDRB.     

Increase in the effectiveness of somatodendritic 5-HT-1A receptors in a rat model of tardive dyskinesia

The present study concerns responsiveness of pre- and postsynaptic 5-hydroxytryptamine (5-HT)-1A receptors in a rat model of tardive dyskinesia (TD). Vacuous chewing movements (VCMs) in rats are widely accepted as an animal model of TD. Results show that haloperidol injected at a dose of 1 mg/kg twice a day for 5 weeks elicited VCMs, which increased in a time dependent manner following the drug administration for 3-5 weeks. Tolerance was produced in motor coordination during the potentiation of VCMs. Exploratory activity in an open field and in an activity box decreased in haloperidol treated animals. The effects of 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT; 0.5 mg/kg) were monitored 48-h after withdrawal from repeated administration of haloperidol. 8-OH-DPAT-induced locomotion was greater in haloperidol treated rats. 5-HT synthesis increased in haloperidol treated animals, while 8-OH-DPAT-induced decreases of 5-HT synthesis were greater in repeated haloperidol than repeated saline injected animals. The results suggest that an increase in the effectiveness of somatodendritic 5-HT-1A receptors may decrease the inhibitory influence of 5-HT on the activity of dopaminergic neurons to precipitate VCMs. The 5-HT-1A agonist may help to alleviate neuroleptic-induced TD.     

Adaptation of Quality by Design-Based Development of Isradipine Nanostructured–Lipid Carrier and Its Evaluation for In Vitro Gut Permeation and In Vivo Solubilization Fate

The present study demonstrated the systematic adaptation of quality by design-integrated approach for the development of novel nanostructured lipid carrier (NLC) of an anti-hypertensive drug isradipine (ISD) to address the inherent challenges such as low solubility and low oral bioavailability. Plackett-Burman design was used for preliminary screening of significant process and formulation variables (p <0.05), which were further processed using Box-Behnken design for the attainment of optimization goal that is, mean particle size (85.7 ± 7.3 nm), drug entrapment efficiency (87.4 ± 3.29%), and in vitro drug release characteristics (92.89 ± 5.47%). The optimized ISD-NLC formulation also demonstrated well-dispersed uniform-shaped particles (polydispersity index 0.207 ± 0.029), high gastrointestinal fluid stability (zeta potential ?10.17 ± 0.59 mV), and higher in vitro gut permeation (21.69 ± 2.38 μg/cm² of ISD-NLC as compared to 11.23 ± 1.74 μg/cm² in ISD suspension). Furthermore, lipolysis studies were performed for the purpose of in vivo fate, and significantly higher drug content of ISD from ISD-NLC in aqueous phase was found (72.34 ± 4.62%) as compared to drug suspension (3.01 ± 0.91%). Relative bioavailability of ISD-NLC and ISD suspension was increased by 4.2-fold and 1.78-fold in the absence and presence of cycloheximide which is a lymphatic uptake inhibitor revealing lymphatic uptake of ISD-NLC in bioavailability improvement. Hence, systematic adaptation of quality by design integrated approach improved gut permeation and potential solubilizaton fate (dynamic lipolysis) of ISD-NLC, which further improved the lymphatic uptake and biodistribution of drug thereby promisingits in vivo prospect and clinical efficacy.     

Beyond bone biology: Lessons from team science

Today, research in biomedicine often requires the knowledge and technologies in diverse fields. Therefore, there is an increasing need for collaborative team science that crosses traditional disciplines. Here, we discuss our own lessons from both interdisciplinary and transdisciplinary teams, which ultimately ushered us to expand our research realm beyond bone biology.     

Coronary arterial disease in systemic lupus erythematosus: Quantification of degrees of narrowing in 22 necropsy patients (21 women) aged 16 to 37 years

The degrees of cross-sectional area luminal narrowing by atherosclerotic plaques of each 5 mm long segment of each of the four major (right, left main, left anterior descending and left circumflex) epicardial coronary arteries in 22 necropsy patients (age 16 to 37 years, 21 women) with systemic lupus erythematosus (SLE) was determined, and the findings were compared to those in 13 control subjects. Of 623 coronary segments (5 mm long) in the patients with SLE, 80 (13 percent) were narrowed 76 to 100 percent (controls = 0 of 431 segments); 125 (20 percent), 51 to 75 percent (controls = 6 percent); 273 (44 percent), 26 to 50 percent (controls = 63 percent) and 145 (23 percent), 0 to 25 percent (controls = 31 percent). Of the 22 patients with SLE, 10 had one or more of the four major coronary arteries narrowed 76 to 100 percent in cross-sectional area, and 12 patients had lesser degrees of narrowing similar to that in the 13 control subjects. The 10 patients with SLE and severe coronary narrowing compared to the 12 patients with SLE and no severe (> 75 percent) coronary narrowing had significantly higher (1) mean values of total serum cholesterol (382 versus 290 mg/dl), (2) mean systolic/diastolic systemic arterial pressures (175/119 versus 151/93 mm Hg), (3) frequencies of mitral valvular disease (seven of 10 patients versus none of 12 patients) and (4) frequencies of pericardial adhesions (seven of 10 patients versus three of 12 patients).     

Normal coronary angiograms: financial victory from the brink of clinical defeat?

OBJECTIVE: To examine the hypothesis that, in patients undergoing coronary angiography for suspected ischaemic heart disease, a normal angiographic result is associated with a fall in consumption of health care resources following the angiogram. DESIGN: Retrospective cost-benefit analysis comparing the 12 month periods before and after coronary angiography. SETTING: Tertiary cardiac referral centre. SUBJECTS: 69 consecutive patients investigated in the financial year 1991-92 whose angiograms were normal. MAIN OUTCOME MEASURES: Drug and hospital admission costs in the 12 month periods before and after angiography; urgent and elective consultations with general practitioner in that time. RESULTS: The mean cost of care per patient in the year before investigation was 656.89 pounds. A highly significant fall in all indices of resource consumption was observed in the year following investigation, the mean resulting difference in the cost of care being 35.15 pounds per month. The cost of coronary angiography would, if this fall were maintained, be recouped in a mean time of 18 months. CONCLUSIONS: Patients suspected on clinical grounds to have coronary atherosclerosis who are found at angiography to have normal coronary arteries are heavy consumers of health care resources. Early investigation for these patients is safe and has beneficial resource consequences in the medium term.     

COVID-19: mobilising CT as a frontline management tool

As the COVID-19 pandemic has spread across the globe, questions have arisen about the approach healthcare systems should adopt in order to optimally manage patient influx. With a focus on the impact of COVID-19 on the NHS, we describe the frontline experience of a severely affected hospital in close proximity to London. We highlight a protocol-driven approach, incorporating the use of CT in the rapid triage, assessment and cohorting of patients, in an environment where there was a lack of readily available, onsite RT-PCR testing facilities. Furthermore, the effects of the protocol on the effective streamlining of patient flow within the hospital are discussed, as are the resultant improvements in clinical management decisions within the acute care service. This model may help other healthcare systems in managing this pandemic whilst assessing their own needs and resources.