Author: Jason Curtis

259 Shortened High-dose Palliative Radiotherapy (SHiP-Rt) for Lung Cancer - a Single-arm, Multi-centre, Phase-II Study (NCT06483308) (2025)

Posted on by

Type of publication:

Conference abstract

Author(s):

Raj S.; Ellanna G.; Vicky S.; Jo H.; Matthew J.; Louise H.; Manreet T.; Apurna J.; Qamar G.; *Anirban C.; Charles P.; Jane R.; Bleddyn J.; Janet D.

Citation:

Lung Cancer. Conference: 23rd Annual British Thoracic Oncology Group Conference 2025. Belfast Ireland. 200(Supplement 1) (no pagination), 2025. Article Number: 108368. Date of Publication: 01 Feb 2025.

Abstract:

Introduction Significant advances in systemic therapy have improved survival for patients with advanced-stage non-small cell lung cancer (NSCLC). However, current treatment strategies and dose-fractionation for high-dose palliative radiotherapy (RT) are based on trials from the 1990s, when RT planning was simple, typically parallel-pair or 3-dimensional conformal, with less precise delivery. Contemporary lung RT uses 4D-CT, volumetric modulated arc radiotherapy (VMAT), aided by online cone beam CT verification, which enable greater accuracy, better target volume coverage, whilst reducing doses to normal organs at risk. Methods and Results: The SHiP-Rt study aims to evaluate the safety and efficacy of reducing the number of RT fractions and RT duration, using contemporary planning, verification, and delivery techniques. This single-arm, multi-centre, phase-II study will evaluate the shortened hypofractionated accelerated palliative RT regimen of 30 Gy in 6 alternate-day fractions, with strict normal tissue dose constraints. We aim to recruit 37 patients, across 4 sites within the West Midlands. The RTTQA will support quality assurance for the RT. Patients with locally-advanced or metastatic NSCLC, who are candidates for high-dose palliative RT, before or after first-line systemic therapy are eligible for recruitment. The primary objective of this study is to assess the safety of the proposed dose-fractionation. Secondary objectives include evaluating toxicity profiles, patient-reported outcome measures (PROMS), Time to Progression (TTP), feasibility and the NHS cost-saving. Developed in collaboration with the Warwick CTU, this study was favourably reviewed by NCRI CTRad, NCRI lung CSG, and the RTTQA. Funding was awarded by the UHCW Charity and Coventry Hospitals Charity. Conclusion This study is open to recruitment. The potential advantages from this regimen include RT given in fewer fractions and hospital visits, resulting in cost-savings for the NHS and opportunity benefits for other patients. If successful, this study will support a phase-III randomised controlled trial to assess efficacy.

Glycerol intoxication syndrome in young children, following the consumption of slush ice drinks (2025)

Posted on by

Type of publication:

Journal article

Author(s):

Brothwell, Shona Lc; Fitzsimons, Patricia E; Gerrard, Adam; Schwahn, Bernd C; Stockdale, Christopher; Bowron, Ann; Anderson, Mark; Hart, Claire E; Hannah, Romanie; Ritchie, Francesca; *Deshpande, Sanjeev A; Sreekantam, Srividya; Watts, Gemma; Yap, Sufin; Mundy, Helen; Veiraiah, Aravindan; Collins, Abigail; Cozens, Alison; Morris, Andrew A; Crushell, Ellen.

Citation:

Archives of Disease in Childhood. 2025 Mar 11. [epub ahead of print]

Abstract:

INTRODUCTION: Slush ice drinks are commonly available refreshments, aimed at children and young people. Glycerol is used to maintain the slush effect in the absence of a high sugar content.

OBJECTIVE: To describe a series of children who became acutely unwell shortly after consuming a slush ice drink; their presentation mimics specific inherited metabolic diseases (IMDs).

METHODS: A retrospective case review of 21 children who presented to centres across the UK and Ireland from 2009 through 2024 was carried out.

RESULTS: Almost all of the children (93%) became unwell within 60 min of slush ice drink consumption. None had any relevant past medical history. The median age at presentation was 3 years 6 months (range 2 years – 6 years 9 months). Presenting features include acute decrease in consciousness (94%), hypoglycaemia (95%), metabolic (lactic) acidosis (94%), pseudohypertriglyceridaemia (89%) and hypokalaemia (75%). Glyceroluria was present in all acute urine organic acid samples. No underlying IMD was found in the 14 patients who underwent further enzymatic or genetic testing. The majority (95%) subsequently avoided slush ice drinks and did not have reoccurrence.

CONCLUSION: Consumption of slush ice drinks containing glycerol may cause a clinical syndrome of glycerol intoxication in young children, characterised by decreased consciousness, hypoglycaemia, lactic acidosis, pseudohypertriglyceridaemia and hypokalaemia. This mimics inherited disorders of gluconeogenesis and glycerol metabolism. Clinicians and parents should be alert to the phenomenon, and public health bodies should ensure clear messaging regarding the fact that younger children,
especially those under 8 years of age, should avoid slush ice drinks containing glycerol.

Link to full-text [open access - no password required]

Alopecia Areata: Understanding the Pathophysiology and Advancements in Treatment Modalities (2025)

Posted on by

Type of publication:

Journal article

Author(s):

Abarca, Yozahandy A; Scott-Emuakpor, Renee; Tirth, Jhanavi; Moroz, Oksana; Thomas, George Pandarakalam; *Yateem, Dana; Golbari, Rebecca; Aphia, Ninigail; Lysak, Yuliya; Narasimhan, Niketa; Siddiqui, Humza F.

Citation:

Cureus. 17(1):e78298, 2025 Jan.

Abstract:

Alopecia areata (AA) is an autoimmune condition that presents with non-scarring hair loss affecting multiple patients worldwide during their lifetime. It ranges from well-defined patchy to diffuse total hair loss, impacting all hair-bearing areas of the body. AA most commonly predominantly manifests on the scalp. The pathophysiology of AA is complex and multi-faceted. The findings of our review article were consistent with the recent literature, delineating autoimmunity, genetic susceptibility, and environmental aspects to be the contributing factors. One of the main causes of AA is believed to be the disruption in the immune privilege of the hair follicles. Multiple genetic loci involved in hair follicle maturation and immune process have been linked to the development of AA as evidenced by several studies. It has been postulated that psychological stressors, smoking, alcohol consumption, sleep disturbances, gut microbiota, and drugs play a role in the pathogenesis of AA by exacerbating the immune response against the hair follicles. AA is a clinically diagnosed disorder. Topical, intra-lesional, and oral corticosteroids, topical and oral minoxidil, cyclosporine, and other immune therapy drugs are widely accepted first-line treatment options, although incomplete remission and relapses are common. Recently JAK-2 inhibitors and mesenchymal stem cell exosomes have shown promising results, potentially treating severe and refractory hair loss. AA has a bidirectional relationship with psychological symptoms as it can lead to social anxiety and depression, which in turn can aggravate hair loss. Hence, it is crucial to implement a holistic approach to managing AA including topical and systemic therapies, psychological counseling, and lifestyle modifications. It is imperative to fully declinate the pathophysiological mechanisms of the disease and formulate therapies in future research to help clinicians and dermatologists devise definitive guidelines to treat the condition for long-term remission.

Link to full-text [open access - no password required]

Cardiovascular disease morbidity is associated with social deprivation in  subjects with familial hypercholesterolaemia (FH): A retrospective cohort  study of individuals with FH in UK primary care and the UK Simon Broome  register, linked with national hospital records (2025)

Posted on by

Type of publication:

Journal article

Author(s):

Iyen, B; Qureshi, N; Kai, J; *Capps, N; Durrington, P N; Cegla, J; Soran, H; Schofield, J; Neil, H A W; Humphries, S E.

Citation:

Atherosclerosis. 403:119142, 2025 Feb 18.

Abstract:

BACKGROUND: Social deprivation is associated with higher cardiovascular disease (CVD) morbidity and mortality. We examined whether this is also observed in people with Familial Hypercholesterolaemia (FH).

METHODS: Subjects with FH and linked secondary care records in Hospital Episode Statistics (HES) were identified from UK Clinical Practice Research Datalink (CPRD) and the Simon Broome (SB) adult FH register. Cox proportional hazards regression estimated hazard ratios (HR) for composite CVD outcomes (first HES outcome of coronary heart disease, myocardial infarction, angina, stroke, transient ischaemic attack, peripheral vascular disease, heart failure, coronary revascularisation interventions (PCI and CABG)) in Index of Multiple Deprivation (IMD) quintiles.

RESULTS: We identified 4309 patients with FH in CPRD (1988-2020) and 2956 in the SB register. Both cohorts had considerably fewer subjects in the most deprived compared to the least deprived quintile (60 % lower in CPRD and 52 % lower in SB). In CPRD, the most deprived individuals had higher unadjusted HRs for composite CVD (HR 1.71 [CI 1.22-2.40]), coronary heart disease (HR 1.63 [1.11-2.40]) and mortality (HR 1.58 [1.02-2.47]) compared to the least deprived but these became insignificant after adjusting for age, sex, smoking and alcohol consumption. In the SB register, hazard ratios for composite CVD increased with increasing deprivation quintiles and remained significant after adjustment for age, sex, smoking and
alcohol consumption (adjusted HR in quintile 5 vs quintile 1 = 1.83 [1.54-2.17]).

CONCLUSIONS: Strikingly fewer individuals with FH are identified from lower socioeconomic groups, though the most deprived FH patients have the highest risk of CVD and mortality. In CPRD, this risk was largely explained by smoking and alcohol consumption, but not in the SB register. More effective strategies to detect FH and optimise risk factor management, are needed in lower socioeconomic groups.

Link to full-text [open access - no password required]

Embracing qualitative approaches in gastroenterology research: a call to action (2025)

Posted on by

Type of publication:

Journal article

Author(s):

Little S.; Tawn J.; Khalil G.; Hardasani R.; Radford S.; Das D.; Peerally M.F.;

Citation:

Frontline Gastroenterology. (no pagination), 2025. Article Number: flgastro-2024-102952. Date of Publication: 2025 [epub ahead of print]

Abstract:

Link to full-text [NHS OpenAthens account required]

A multi-centred retrospective cohort study comparing JAK inhibitor therapies in moderate to severe ulcerative colitis (2025)

Posted on by

Type of publication:

Conference abstract

Author(s):

Kumar A.; Baxter J.; Rimmer P.; Noble B.; Makki M.; Chikhlia A.; Cheesbrough J.; Disney B.; *Muir J.; Karova M.; *Butterworth J.; Bower J.; Sagar N.; Al-Talib I.; Nahal J.; Hatta A.; Ali N.; Sagar V.; Varyani F.; Smith S.; Bourne S.; Hsu Y.K.; Eltahir A.; De silva S.; Harvey P.;

Citation:

Journal of Crohn's and Colitis. Conference: 20th Congress of ECCO. Berlin Germany. 19(Supplement 1) (pp i2143), 2025. Date of Publication: 01 Jan 2025.

Abstract:

Background: Tofacitinib, filgotinib and upadacitinib are JAK inhibitors (JAKi) that are licensed for treatment in moderate to severe ulcerative colitis (UC). Whilst these drugs have demonstrated efficacy against placebo, there is no head-to-head data. This study aims to compare the clinical efficacy between these drugs.

Method(s): This is a multi-centred, retrospective cohort study with data collected from January 2018 to June 2024. Patients with UC were recruited on their first JAKi, irrespective of previous advanced therapies. Clinical remission (faecal calprotectin (FCP) <250, Mayo 1, UCEIS 1, pMayo 2, SCCAI 2) and response (50% reduction in FCP from baseline, reduction in partial Mayo or UCEIS by 3 or more, or sustained <3) was measured at 3- and 6-months. If a patient stopped taking JAKi, they were considered to have failed both response and remission. Data was non-parametric and outcome measures were compared using Chi-squared tests.

Result(s): There was a total of 266 patients included in the final analysis. 70 (26%) were on upadacitinib, 47 (18%) on filgotinib and 149 (56%) on tofacitinib (Table 1). At least 87% (129/149) on tofacitinib had exposure to a previous biologic compared to 80% (56/70) for upadacitinib and 66% (31/47) for filgotinib. At 3-months, clinical response in upadacitinib, filgotinib and tofacitinib was demonstrated in 83%, 74% and 75% patients, respectively and clinical remission was seen in 69%, 64% and 52%, respectively. At 6-months, clinical response was demonstrated in 79%, 65% and 63%, respectively and remission was seen in 75%, 61% and 51%, respectively. Upadacitinib demonstrated significantly higher 3-months remission rate (p=0.019) and 6-months response (p=0.010) and remission rates (p= 0.001) compared to tofacitinib. In the bio-exposed cohorts, upadacitinib demonstrated greater 6-months remission rates (71%) compared to 64% on filgotinib (p=NS) and 52% tofacitinib (p= 0.022). In bio-naive cohorts (n=50), upadacitinib demonstrated greater 6-months remission rates (93%) compared to 56% on filgotinib (p=0.024) and 50% tofacitinib (p= 0.009). Combining the JAKi, 90% of patients were not on steroids at 3-months and 94% were not on steroids at 6-months. A total of 26 patients had a colectomy at the time of their JAKi, 17 on tofacitinib, 5 on filgotinib and 4 on upadacitinib.

Conclusion(s): This study demonstrates that upadacitinib is more likely to achieve 3- and 6-month remission compared to tofacitinib. In a small subgroup of bio-naive patients Upadacitinib was more likely to achieve 6-month remission compared to filgotinib and tofacitinib. JAKi were associated with minimal adverse events and importantly, the efficacy of JAKi does not appear diminished by prior biologic use.

Link to full-text [no password required]

Serious infections hospital admissions and mortality in patients with early inflammatory arthritis: results from the National Early Inflammatory Arthritis Audit (2024)

Posted on by

Type of publication:

Conference abstract

Author(s):

Adas M.; Bechman K.; Russell M.; Karafotias I.; Nagra D.; Patel S.; Gallagher S.; Price E.; *Garton M.; Rutherford A.; Cope A.; Norton S.; Galloway J.;

Citation:

Rheumatology. Conference: British Society for Rheumatology Annual Conference, BSR 2024. Liverpool United Kingdom. 63(Supplement 1) (pp i12), 2024. Date of Publication: 01 Apr 2024.

Abstract:

Background/Aims To identify the risk of serious infections (SI) according to initial treatment strategy, using conventional synthetic disease modifying antirheumatic drugs (csDMARD) and corticosteroids, in patients recruited to the National Early Inflammatory Arthritis Audit (NEIAA). Methods An observational cohort study design was used. The population included adults in England with a new onset rheumatoid arthritis (RA), fulfilling ACR/EULAR 2010 criteria, between April 2018-March 2021. Outcomes studied were SI, defined by infections requiring hospitalisation (primary admission diagnosis/nosocomial acquisition) or death (SI stated on death certificate), identified using NHS Digital linkage. Patients' characteristics were tabulated by treatment strategies. Hazard ratios (HR) were calculated using single failure Cox proportional-hazards models, with confounders- adjusted models (age, gender, smoking status, comorbidities, social deprivation) and fully-adjusted models including disease factors (seropositivity, DAS28). Individuals were considered at risk from the date of RA diagnosis, and censored at SI event, death, or March 2021 (whichever was earliest). Results 20,060 patients with RA were included. Initial DMARD therapy was known for 19,572 patients, of whom 11,966 were on methotrexate/ MTX based strategies (mono or combo), 5,059 on csDMARD combination strategies (other than MTX) and 2,547 on no DMARD strategy. 15,319 patients were on corticosteroids at baseline. Mean age 59.5 years (+/-15); 63% female; smoking status (20% current; 30% ex-smokers); comorbidities (21% hypertension; 10% diabetes; and 12% lung disease). Rheumatoid Factor/CCP antibodies were positive in 68%. At presentation, median disease scores were 5.1 (interquartile range [IQR]: 4.0-5.9) for DAS28, 1.1 (IQR: 0.6-1.7) for health assessment questionnaire (HAQ) and 24 (IQR: 16.0-33.0) for musculoskeletal health questionnaire (MSKHQ).There were 519 SI admissions and 17 SI deaths, corresponding to incidence rates per 100 person-years for admissions: 3.19 (95% CI: 2.93-3.48) and deaths: 0.10 (95% CI: 0.06-0.16). In fullyadjusted models, increasing age predicted both SI admissions and deaths. Being a smoker, having a comorbidity, higher disease activity (DAS28), symptom burden (MSKHQ) and disability (HAQ) at presentation associated with more SI admissions. For each 1 unit increase in DAS28, the risk of SI increased by 8% (HR 1.08 [95% CI:1.01-1.16]). Seropositivity did not associate with SI. MTX-based strategies 0.75 (95% CI:0.62-0.91) and csDMARD combination therapy 0.70 (95% CI:0.53-0.94) associated with fewer SI admissions compared to no DMARD. In unadjusted models, corticosteroid associated with more SI admissions 1.29 (95% CI:1.10 -1.62); however, in fully-adjusted models this association was no longer statistically significant. csDMARD strategies did not associated with SI deaths in any of the models. Conclusion Patient and disease factors at diagnosis appear to be important predictors of admissions and mortality for serious infections. Infection risk appears to be greatest in those with higher RA disease activity. An important limitation is that NEIAA does not capture data on treatment changes over time and steroid use beyond baseline.

Link to full-text

The changing landscape of traumatic brain injuries at a district general hospital in a trauma network (2025)

Posted on by

Type of publication:

Journal article

Author(s):

Abualsaud, Suhaib; Elmahdi, Ahmed; *Youssef, Mohamed; Jayakumar, Nithish; Lahart, Ian; Ashwood, Neil.

Citation:

British Journal of Neurosurgery. 1-6, 2025 Feb 22.

Abstract:

BACKGROUND: Major trauma networks were introduced in 2012 onwards with a major trauma centre (MTC) linked to district general hospitals (DGH). Most traumatic brain injuries (TBI) are managed in DGHs, without on-site neurosurgical services. It is unclear whether the characteristics of TBIs at DGHs have differed since the network was introduced. We compare outcomes of TBI patients pre- (2008-2012) and post-MTC (2013-2021) network implementation.

METHODS: We conducted a retrospective analysis of TBI patients admitted to a 500-bedded DGH, before and after the introduction of a trauma network. We compared the characteristics of patients, including age, mechanism of injury, imaging findings, and length of stay. All statistical analyses were carried out in SPSS v29 (IBM).

RESULTS: Overall, 876 patients (males = 56.1%; median age 67 years) were included. Mean yearly cases pre-MTC was 76 compared to 55 in the post-MTC period. Mean age was significantly higher, and patients had more co-morbidities, in the post-MTC period (p < 0.001). Mean GCS at presentation was not significantly different between the pre- and post-MTC periods (13.7 vs 13.8, respectively). Referrals to the regional neurosurgical centre were significantly higher in the post-MTC period. The overall mortality rate was 33.7%. Increasing age (OR = 1.072), higher comorbidities (OR = 1.243) and intracerebral haematoma (OR = 6.269) were associated with a higher risk of death. The post-MTC period was associated with a lower risk of death (OR = 0.501).

CONCLUSIONS: Fewer patients with less severe mechanisms of injury, and a more elderly population are now being managed at our DGH in the post-MTC period. Mortality was similar to published literature but the introduction of the trauma system was associated with lower risk of death. Although fewer TBIs help to optimise service delivery by maintaining orthopaedic bed capacity, the reduced exposure to these patients may lead to lowered expertise in managing these complex cases.

Doctor when can I drive? A systematic review and meta-analysis of brake reaction time in patients returning to driving after hip arthroscopy for femoroacetabular impingement (FAI) (2025)

Posted on by

Type of publication:

Journal article

Author(s):

*Patel, Ravi; Sokhal, Balamrit Singh; Fenton, Carl; Omonbude, Daniel; Banerjee, Robin; Nandra, Rajpal.

Citation:

Hip International, 2025 Feb 24.[epub ahead of print]

Abstract:

BACKGROUND: A common question from patients undergoing hip arthroscopy for femoroacetabular impingement (FAI) is when they may return to driving.

PURPOSE: We aimed to perform a formal systematic review and meta-analysis to address this issue.

METHODS: A systematic review and meta-analysis followed PRISMA guidelines. Databases searched included OVID, EMBASE, and COCHRANE through July 2024 for articles with keywords and MeSH terms like "Hip arthroscopy," "Femoroacetabular Impingement," "total brake response time," and "reaction time" related to driving. Titles and full articles were reviewed for quality and relevance. Statistical analysis was done using Review Manager Version 5.4.A total of 39 articles were reviewed, with 5 meeting inclusion criteria. All selected articles used brake reaction time (BRT) as an outcome measure. A meta-analysis compared pre- and postoperative BRT values. Data were analysed for the right and left hips combined, followed by a subgroup analysis by laterality. BRT values were divided into preoperative and 2, 4, 6, and 8 weeks postoperative periods.

RESULTS: The studies assessed 160 patients, with 142 undergoing hip arthroscopy for FAI. The mean age was 32.75 +/- 9.4 years, with a male-to-female ratio of 73:69. The right hip was affected in 68% of
patients. Preoperative BRT ranged from 566 to 1960 milliseconds, while postoperative BRT ranged from 567 to 1860 milliseconds between week 2 and week 12.

CONCLUSIONS: BRTs returned to baseline or control values and continued to improve 4 weeks post-surgery for FAI. It is safe to recommend a return to driving at 4 weeks after hip arthroscopy for FAI.

Severe hypocalcemia and hypophosphatemia following Denosumab administration in a multi-comorbidity patient (2025)

Posted on by

Type of publication:

Journal article

Author(s):

*Sagdeo, Anuja; *Elshehawy, Mahmoud; Rakieh, Chadi; Ball, Patrick; Morrissey, Hana.

Citation:

Medicine & Pharmacy Reports. 98(1):144-148, 2025 Jan.

Abstract:

The case is presented of an elderly patient (DCP) with extensive medical history, including osteoporosis, who developed hypocalcaemia and hypophosphataemia whilst treated with denosumab, while prescribed concomitant calcium and vitamin D therapies. The management of this complex case involved a multidisciplinary team (MDT) approach, incorporating the patient's wishes. It included discontinuation of denosumab and intravenous (IV) and oral mineral supplementation that yielded gradual amelioration of calcium and phosphate levels. This case demonstrates the importance of vigilant monitoring and appropriate management in patients receiving denosumab, particularly those with multiple comorbidities. It carries important considerations for using denosumab for osteoporosis treatment in patients with complex medical backgrounds. Ethical clearance waiver was granted by the Trust Research Ethics Committee on 18/01/2024.

Link to full-text [open access - no password required]