The Kent and Canterbury Hospital, colloquially known among residents as the K+C, is a community hospital in Canterbury, Kent, England. It is managed by the East Kent Hospitals University NHS Foundation Trust.
Introduction. Patients with high-risk smoldering multiple myeloma (SMM) may benefit from early treatment. With SMM risk stratification advancement, post hoc analysis of the AQUILA study using IMWG 2020 (“20/2/20”) and other risk models was conducted to assess which patients benefited most from daratumumab. Safety and efficacy analyses by age and stem cell collection outcomes were also assessed. Methods. Patients with confirmed high-risk SMM per IMWG 2014 criteria were randomized to receive subcutaneous daratumumab or active monitoring for 39 cycles, 36 months, or until confirmed disease progression, whichever came first. The primary endpoint was progression-free survival (PFS); secondary endpoints included time to 1L treatment and overall survival. Outcomes were assessed by age, IMWG 2020 high-risk SMM criteria, and IMWG 2020 plus cytogenetic criteria. Results. Daratumumab showed PFS benefit across all IMWG 2020 subgroups (low-risk: HR=0.59; intermediate-risk: HR=0.70), with largest benefit in the high-risk subgroup; disease progression/death rate with active monitoring was ~1.6-fold greater than daratumumab (62.8% vs 37.5%; HR=0.36). Daratumumab benefit was durable, with 5-year PFS rates of 78.2% vs 71.6%, 56.2% vs 42.9%, and 60.4% vs 23.6% in IMWG 2020 low-, intermediate-, and high-risk groups, respectively. A favorable trend for daratumumab in time to 1L treatment was seen across all IMWG 2020 risk groups (low-risk HR=0.63; 95% CI, 0.22–1.80; intermediate-risk HR=0.57; 95% CI, 0.35–0.92; high-risk HR=0.39; 95% CI, 0.25–0.62). PFS benefit occurred regardless of age, in younger (<65y HR, 0.51; 95% CI, 0.32–0.79) vs older (≥65y, HR=0.50; 95% CI, 0.32–0.77) patients. Treatment-emergent adverse event (TEAE) incidence was consistent across the <65, 65 to <75, and ≥75 year subgroups (82.7%, 81.1%, and 87.5% with active monitoring; 96.2%, 98.5%, and 95.2% with daratumumab). Serious TEAEs were more frequently observed in older active monitoring patients (12.2%, 18.9%, and 50.0% with active monitoring; 24.8%, 35.8%, and 28.6% with daratumumab). In daratumumab and active monitoring arms, respectively, 23 (11.9%) and 41 (20.9%) patients received autologous stem cell transplant after active MM progression, with limited plerixafor use (daratumumab, 3 [1.6%] vs active monitoring, 9 [4.6%]). The median (range) CD34+ cell yield was 5.0 (2–20)×106 cells/kg body weight among 22 patients in the daratumumab arm and 5.1 (2–21)×106 cells/kg body weight among 39 patients in the active monitoring arm. Conclusions. Patients receiving daratumumab experienced long-term PFS benefits across IMWG 2020 subgroups, with the largest benefit seen in high-risk patients. No notable differences in PFS or safety were observed across age subgroups. Early daratumumab treatment for high-risk SMM did not have a detrimental impact on stem cell yield. These results support early intervention with daratumumab monotherapy among patients with high-risk SMM. ©American Society of Hematology (2025). Reused with permission
Objectives Primary objective: to determine whether prostate gland partial ablation (PA) has non‐inferior oncological treatment success vs radical treatment (RT) of localised intermediate‐risk prostate cancer (irPCa). Secondary objectives: to compare (i) participant‐reported urinary and sexual dysfunction side effects, (ii) short/medium term serious adverse events, (iii) health‐related quality of life (HRQoL), (iv) cost‐effectiveness; and to report (v) the need for repeat PA, (vi) accuracy of magnetic resonance imaging and biopsy protocols in determining suitability for PA, (vii) disease progression, local spread and metastases, (viii) medium‐term disease‐specific and overall mortality. Participants and Methods The ‘Partial prostate Ablation versus Radical Treatment’ (PART; International Standard Randomised Controlled Trial Number ISRCTN17249875) is a UK‐wide, multicentre, pragmatic, randomised controlled trial investigating whether PA (high‐intensity focused ultrasound [HIFU] or irreversible electroporation [IRE]) is non‐inferior to RT (radical prostatectomy, radical radiotherapy, or low‐dose‐rate brachytherapy [LDR‐B]) in treating localised irPCa. A Qualitative Research Integrated within Trials (QuinteT) Recruitment Intervention is included to optimise recruitment and informed consent. Primary outcome treatment success for PA will be determined by prostate biopsies and imaging, and for RT using standard definitions. Participants will receive treatment according to their randomised allocation, with HIFU or IRE for PA depending on lesion location, and radical prostatectomy, radical radiotherapy, or LDR‐B according to patient and physician preference for RT. Based on 95% and 85% oncological treatment success for RT and PA, respectively, with a non‐inferiority margin of 20%, at median 3 years of follow‐up, PART requires 275 recruited men (137 per group, randomised on a 1:1 basis), for 80% power, with a one‐sided alpha of 0.025. Allowing for a 10% total withdrawal or dropout rate, PART requires 306 recruited and randomised participants. Conclusions The PART trial will provide robust prospective data and high‐level randomised evidence to determine oncological treatment effectiveness of PA vs RT for localised irPCa, along with comparative side effect, HRQoL, and health economics evaluations, to inform clinical decision‐making.
Background: The rising consumption of herbal alcoholic beverages in Nigeria, driven by unverified health claims, poses growing public health risks and adds to the global disease burden.Aim: To evaluate the effects of ascorbate and alpha-tocopherol supplementation on hepatorenal biochemical parameters, histopathology, and expression of oxidative stress-related genes (Nrf2 and CYP2E1) in rats exposed to a herbal-based alcoholic beverage. Methods: Twenty-eight adult male Wistar rats were randomly assigned into four groups (n=7 per group) using a computer-generated randomisation, with all outcome assessments performed under blinded conditions. Group I consisted of the unexposed control rats. Group II rats received a daily oral dose of alcohol at 0.2 mL/kg/bw. Groups III and IV were also administered alcohol daily at 0.2 mL/kg/bw but were additionally treated with ascorbate (500 mg/kg) and alpha-tocopherol (300 mg/kg), respectively, for 28 days. Hepatorenal biochemical parameters, hepatic and renal Nrf2 and CYP2E1 expression, and histopathological changes were subsequently evaluated. Results: Supplementation with ascorbate (500 mg/kg) or alpha-tocopherol (300 mg/kg) was associated with significantly lower (p < 0.05) ALP, ALT, AST, creatinine, and urea levels compared with alcohol-exposed untreated rats. Vitamin supplementation was associated with the modulation of alcohol-induced overexpression of CYP2E1 and Nrf2, and partially restored the altered biochemical parameters. Histopathological examination further revealed mitigated alcohol-induced architectural disruptions in the liver and kidney, suggestive of the protective effects of antioxidant supplementation. Conclusion: Ascorbate and alpha-tocopherol supplementation were associated with attenuation of alcohol-induced hepatorenal biochemical alterations, partial normalisation of liver and kidney function parameters, and modulation of oxidative stress-related gene expression (CYP2E1, Nrf2), findings consistent with a potential adjunctive role of these vitamins in mitigating alcohol-related organ toxicity rather than indicating definitive therapeutic effects. Mechanistic conclusions are limited by the absence of direct oxidative stress marker measurements (lipid peroxidation, glutathione status, antioxidant enzyme activities), and interpretation is limited by the absence of pure ethanol and vitamin-only control groups and the lack of independent chemical verification of the test beverage.
BackgroundPulsed dye laser (PDL) therapy is the gold standard for treating port-wine stains (PWS) in children but frequently requires procedural analgosedation due to pain and the need for immobility. The optimal sedative agent for repeated outpatient procedures remains unclear.ObjectiveTo compare the safety and efficacy of propofol- versus ketamine-based analgosedation in children undergoing PDL therapy, with a primary focus on respiratory depression.MethodsIn this prospective, randomized, controlled study, children aged 1–18 years (ASA I–II) were assigned to receive propofol or ketamine for PDL therapy. Standardized monitoring included electrocardiography, noninvasive blood pressure, pulse oximetry, and end-tidal CO₂. The primary outcome was respiratory depression, defined by predefined clinical and capnographic criteria. Secondary outcomes included hemodynamic instability, adverse events, drug consumption, procedural duration, sedation depth, and recovery time. Receiver operating characteristic (ROC) analysis was used to identify predictors of respiratory depression.ResultsA total of 310 procedures were analyzed. Respiratory depression was significantly more frequent in the propofol group compared with the ketamine group (19.5% vs. 2.6%, p < 0.01). Ketamine was associated with higher rates of hypertension, tachycardia, psychomimetic effects, and postoperative nausea and vomiting (p < 0.01), whereas propofol was associated with more hypotension. Sedation and recovery times were longer with ketamine (p < 0.01), while sedation depth was comparable between groups. A procedural duration ≥13.5 min predicted respiratory depression in the propofol group (AUC 0.755).ConclusionBoth propofol and ketamine provide effective analgosedation for pediatric PDL therapy. Propofol is associated with a higher risk of respiratory depression, particularly during longer procedures, whereas ketamine offers greater respiratory stability but more other adverse effects. These findings support individualized anesthetic selection based on procedural duration and patient risk factors.
