• The impact of facial prosthesis on quality of life for people with congenital defects : a systematic review

  Spooner, Katie; Chandler, Grace; Harding, Sam; Coward, Trevor (2025-05-07)

  Purpose: Congenital defects can often cause segregation from society due to aesthetical stigma and subjective opinion by the individual wearing the facial prosthesis, decreasing their overall Quality of Life (QoL). The aim of this systematic review is to collate and subsequently synthesise research reporting the impact of extra-oral facial prostheses on QoL for individuals with a congenital facial defect. Materials and Methods: A systematic review was undertaken following the Joanna Briggs Institute and PRISMA guidelines. The protocol was registered with the International Prospective Register of Systematic Reviews (CRD42023403545), and searches were performed in six databases from inception to June 4th 2025. Results: 1215 records were retrieved after review three articles were retained for inclusion. Four QoL measures were used across the study’s with the majority reporting QoL as a secondary outcome. A total of 22 people were represented across the study’s and were equally divided with 11 males and 11 females with an age range of 16–85. Despite the fact, numerous methodologies and QoL measures were used, statistically significant improvement in QoL was found following the fitting of a facial prostheses. Conclusions: All three studies suggest that a prosthesis influences patient QoL, however due to the small number of studies and the variety of QoL measures used, definitive conclusions regarding the impact of prosthetics on congenital facial deformities cannot be drawn. Future research should use standardized, prosthesis-specific QoL measures for clearer comparisons.
• The impact of extra-oral facial prosthesis on quality of life for people with aquired defects : a systematic review

  Spooner, Katie; Chandler, Grace; Harding, Sam; Coward, Trevor (2025-05-07)

  Purpose: Acquired facial defects caused by traumatic injury or malignancy are likely to affect one’s physical wellbeing. They may lead to segregation from society due to the stigma and the subjective opinions of the individual, decreasing their overall quality-of-life (QoL). Facial prostheses are suitable forms of rehabilitation for people with acquired facial defects. Recently, QoL has been receiving attention important in evaluating patient outcomes. The aim of this systematic review was to synthesise research reporting the impact of extra-oral facial prostheses on QoL for individuals with an acquired facial defect. Materials and methods: A systematic review was undertaken following Joanna Briggs Institute and PRISMA guidelines. The protocol was registered (CRD42024403538), and the searches were performed in six databases from inception to 5th August 2024. Results: 1291 records were retrieved after review ten articles were retained for inclusion. The papers were grouped into those assess people with acquired facial defects in either the auricular, nasal, or orbital regions. A total of 363 people were represented. Six QoL measures were used. Across all three groups, QoL improved post-prosthesis. Although nasal prosthesis users reported lower physical and social functioning than those with auricular prostheses. Conclusions: All ten studies reported positive impact on QoL of prosthesis, however their generalizability is limited by varying methodologies and QoL measures, none of which are designed for use with prosthesis users. Despite these limitations, QoL improvements were seen regardless of follow-up duration or prior prosthetic experience. Future research should use standardized, prosthesisspecific QoL measures for clearer comparisons.
• Operative times of 7 common Orthopaedic Trauma procedures: is there a difference between trainees and consultants?

  Gbejuade, Herbert; Pereira, Mira Odeessa (2025)

  Background Surgical training in the UK is under increasing pressure with a high demand for service provision. This raises concerns about the resultant negative impact this is having on training opportunities for surgical trainees in theatre due to a high demand for surgical procedures to be performed expediently by consultants. This is due to the assumption that trainee take significantly longer time to operate in theatre and thus result in a slow progress of theatre lists. Objective We evaluated the differences in operative time between orthopaedic trainees and orthopaedic consultants, as well as provided realistic timings for each stage encompassed within the entire duration a patient is in theatre. Methods From our trauma unit electronic theatre database, we retrospectively collected data for six Joint Committee of Surgical Training (JCST) mandatory procedures. Information collected included patients’ ASA grading, total surgical time and grade of surgeons. Results A total of 956 procedures were reviewed, 71.8% hip procedures, 14.2% intramedullary nail fixations and 14.2% ankle fixations. 46.2% and 53.8% of the procedures were performed by consultants and trainees as first surgeon, respectively. Conclusion On average, consultants were found to be 13 minutes quicker in performing the hip procedures and this difference was found to be statistically significant (p < 0.05). However, trainees were found to be quicker in performing intramedullary femoral nailing and simple ankle fixations, but consultants were faster at performing intramedullary tibial nailing and complex ankle fixations. The differences were not found to be statistically significant (p > 0.05).
• Expression of programmed cell death Ligand 1 and mismatch repair status in ovarian carcinomas

  Hariprasad, M.; Rao, M.; Elhence, P.A.; Bharti, J.N.; Singh, P.; Yadav, G.; Nalwa, A.; Ramalingam, H.; Goel, A. D. (2025-07)

  Background: Ovarian carcinoma is the third most common gynecological malignancy among women in India, with a poor prognosis despite advancements in treatment modalities. Immunotherapy, particularly the use of programd cell death ligand 1 (PD-L1) checkpoint inhibitors, has emerged as a promising approach. This study investigates the relationship between PD-L1 expression, mismatch repair (MMR) status, and clinicopathological features in epithelial ovarian carcinoma (EOC). Materials and Methods: A cohort of 50 EOC cases was analyzed for PD-L1 expression in tumor cells and tumor-infiltrating lymphocytes (TILs) using immunohistochemistry (IHC). MMR status was also assessed through IHC. Statistical correlations between PD-L1 expression, MMR deficiency (dMMR), and clinicopathological parameters were evaluated. Results: PD-L1 expression in tumor cells and TILs was observed in 20% and 14% of cases, respectively. PD-L1 expression in tumor cells was absent in most advanced-stage tumors (stages III and IV) and cases with extraovarian spread. dMMR was identified in 30% (n = 15) of cases, predominantly in higher-stage tumors with extraovarian spread and significant TIL presence (P = 0.007). However, PD-L1 expression in tumor cells and TILs was absent in 86.7% and 80% of dMMR cases, respectively. No significant association was found between dMMR status and PD-L1 expression in EOC. Conclusion: PD-L1 expression in tumor cells is predominantly observed in early-stage EOC, suggesting its potential as a prognostic marker and therapeutic target. Although dMMR status correlates with advanced-stage disease and TIL presence, it does not significantly influence PD-L1 expression in EOC. These findings highlight the importance of routinely assessing PD-L1 and MMR status to guide immunotherapeutic strategies in ovarian carcinoma.
• The activity of Protectin DX, 17 HDHA and Leukotriene B4 is correlated with Interleukin-1beta (IL-1beta) and Interleukin-1 Receptor Antagonist (IL-1Ra) in the early subacute phase of stroke

  Kotlęga, Dariusz; Drozd, Arleta; Zembron-Lacny, Agnieszka; Morawin, Barbara; Ryterska, Karina; Szczuko, Malgorzata (2025)

  Ischemic stroke is a leading cause of mortality and disability in adults. The inflammatory cascade is driven by various inflammatory molecules, such as interleukin-1β (IL-1β), and counteracted by its antagonist, interleukin-1 receptor antagonist (IL-1Ra). Eicosanoids are inflammatory derivatives of free fatty acids. Arachidonic acid (AA) derivatives exhibit pro-inflammatory activity, while eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derivatives, known as specialized pro-resolving mediators, have anti-inflammatory properties. This study aimed to analyze potential associations between eicosanoids and key inflammatory molecules, including IL-1β and its antagonist IL-1Ra. In this prospective study, we investigated inflammatory molecules in 73 ischemic stroke patients. We analyzed interactions between IL-1β, IL-1Ra, and eicosanoids as follows: resolvin E1, prostaglandin E2, resolvin D1, lipoxin A4 (5S, 6R, 15R), protectin DX, maresin 1, leukotriene B4, 18RS-HEPE, 13S-HODE, 9S-HODE, 15S-HETE, 17 HDHA, 12S-HETE, 5-oxo-ETE, and 5-HETE. In 73 ischemic stroke patients, mean IL-1β was 1.31 ± 1.54 pg/mL and IL-1Ra 810.8 ± 691.0 pg/mL. Spearman correlations showed positive associations between IL-1β and protectin DX (ρ = 0.56, p < 0.001), and 17 HDHA (ρ = 0.26, p < 0.05) and 5-oxo-ETE (ρ = 0.27, p < 0.05). IL-1Ra correlated negatively with protectin DX (ρ = −0.58, p < 0.001) and 17 HDHA (ρ = −0.29, p < 0.05), and positively with leukotriene B4 (ρ = 0.34, p < 0.005). After multivariable adjustment, associations with IL-1β lost statistical significance, whereas the inverse relationships between IL-1Ra and protectin DX/17 HDHA remained significant (p < 0.005). Despite the known anti-inflammatory roles of protectin DX and 17 HDHA, and the pro-inflammatory role of leukotriene B4, their activity in the early subacute phase of ischemic stroke appears to be influenced by complex interplays, possibly mediated by IL-1β and IL-1Ra. The activity of protectin DX, 17 HDHA, and leukotriene B4 is correlated with IL-1β and IL-1Ra levels in the early subacute phase of stroke.
• Use of End-of-Life care pathways in hospitalized stroke patients: a retrospective study of the AMBER care and dying adults in the last days of life approaches

  Kotlęga, Dariusz (2025)

  Background: Stroke-related deaths often follow rapid deterioration, making end-of-life (EOL) care decisions particularly challenging in acute settings. Although national guidelines support structured approaches to end-of-life care, there is limited evidence of how these pathways are applied in routine stroke practice. Objective: To evaluate the use of structured end-of-life care pathways, including the AMBER Care Bundle and Dying Adults in the Last Days of Life (DALDL), in stroke patients who died during admission at a general hospital stroke center. Methods: This retrospective, single-center cohort study included 123 patients with confirmed stroke (73.2% ischemic, 26.8% hemorrhagic) who died in hospital during 2023. Clinical characteristics, the timing of care pathway decisions, palliative care involvement, withdrawing of medical procedures, and outcomes were analyzed. Descriptive statistics, Mann–Whitney U tests, Spearman correlations, chi-square tests, and a multivariate regression model were performed. Results: Of 123 patients, 101 (82.1%) entered the DALDL pathway a median of 14.8 days after admission, with a subsequent median survival of 2.9 days. Anticipatory medications were prescribed in 100% of DALDL patients versus 0% of non-DALDL. Do Not Attempt Cardiopulmonary Resuscitation orders were documented in 99%, and 67.3% received specialist palliative care input. Nasogastric tube insertion correlated with a higher National Institutes of Health Stroke Scale (NIHSS) and higher rate of infections. Conclusions: Most patients had access to structured EOL care, but variability in timing and interventions highlights the need for earlier palliative engagement and consistent implementation of pathways to improve the quality of EOL care in stroke patients. We detected areas that could be improved, such as access to a palliative care team and the anticipatory medication use in dying stroke patients.
• Effect of Digoxin versus Bisoprolol for heart rate control in atrial fibrillation with heart failure on quality of life: a prospective randomised comparative study.

  Sarwar, Muhammad; Nahar, Noor Un; Amin, Hajra; Iqbal, Maheen; Bader, Aymen (2025)

  Introduction Atrial fibrillation (AF) and heart failure (HF) often co-exist, exerting synergistic adverse effects on patients’ morbidity, quality of life (QOL) and mortality. This also poses a unique management challenge of heart failure in the AF population as compared to the sinus rhythm population. While beta blockers such as bisoprolol have been preferred treatment options for patients with heart failure, digoxin remains a cost-effective yet underrated alternative. However, its overall effect on QOL remains debated, especially in the South Asian population that carries a higher burden of heart failure than any other ethnicity. Objective The objective of this study was to compare the short-term effect of bisoprolol versus digoxin on quality of life in patients with permanent AF and concurrent HF in the South Asian population. Methods This single-centred prospective randomised comparative study was conducted at the outpatient department of Punjab Institute of Cardiology, Lahore, from March to September 2022. A total of 80 patients with permanent AF and established HF were enrolled and randomised in two groups to receive either digoxin (62.5-250 mcg/day) or bisoprolol (1.25-15 mg/day). The 36-Item Short Form Health Survey (SF-36) was administered at baseline and after three months to assess changes in QOL. Data were analysed using SPSS v25.0 (IBM Corp., Armonk, NY, USA), with significance at p ≤ 0.05. Results Both treatment groups significantly improved SF-36 QoL scores after three months (p < 0.001). However, the digoxin group reported significantly greater improvement compared to the bisoprolol group (mean QoL score: 76.68 ± 9.37 vs. 70.90 ± 8.00; p = 0.004). No serious adverse events or digoxin-related toxicities were reported in either group. Conclusion In patients with permanent AF and HF, digoxin resulted in a statistically significant improvement in short-term quality of life compared to bisoprolol. These findings suggest that digoxin may serve as a viable and possibly superior alternative to bisoprolol in patients with permanent AF and HF, with a potential role for digoxin as a first-line agent in select populations. It also highlights the need to re-evaluate current treatment preferences, especially in resource-limited settings. Further multicentric and multi-ethnic studies are needed to substantiate these findings and evaluate long-term clinical outcomes.
• Advanced vascular ultrasound prior to radial artery cannulation on the intensive care unit: a feasibility service evaluation

  Smith, Matthew; Momoh, Rabiu; Wilkinson, Jonny; Olusanya, Olusegun; Underwood, Rachel; Abdulla, Naziya; Basset, Paul; Parulekar, Prashant (2025)

  Background: Radial arterial catheters are frequently used for monitoring and blood sampling in critical care patients. Ischaemic complications are rare but can cause significant morbidity. The use of vascular ultrasound in critical care is becoming increasingly commonplace. This service evaluation aims to assess the feasibility of training novices in advanced vascular ultrasound assessment, prior to radial arterial cannulation. Methods: Over a 4-month period, data was collected from patients admitted to the intensive care unit at the William Harvey Hospital, Ashford, Kent. Ultrasound was used to assess for the presence, size and flow of the radial and ulnar arteries. The assessments were performed by two novice residents in intensive care, who were trained in advanced ultrasound assessment of the radial and ulnar arteries, by an intensive care consultant with expertise in vascular ultrasound. Results: One hundred and five limbs were assessed in 53 patients. Novices were deemed to be sufficiently competent, after performing scans on 15 patients over a 2-week period. Satisfactory images were acquired in 100% of patients. The most common finding was a small diameter ulnar artery, present in 30 limbs (29%), while only 1 patient (1%) was found to have an absent ulnar artery. Thirty-two limbs had a radial arterial catheter in-situ. There were no ischaemic complications. Conclusion: This service evaluation demonstrates that the training of novices in advanced ultrasound assessment of the radial and ulnar arteries by an intensive care consultant, is feasible. Moreover, this modality may identify patients at risk of critical limb ischaemia. This particular investigation may be considered for incorporation into existing vascular ultrasound assessments.
• Study of treatment modalities and clinical outcomes of screen-detected cancers at a Tertiary Care Unit in the UK

  Hashmi, Junaid Zia; Khattak, Muhammad Ali; Ghafoor, Ammarah; Abdulrasheed, Habeeb; Abbasy, Jibran; Malik, Adnan; Malik, Amman (2025)

  Introduction Breast cancer is the most common type of cancer in women worldwide, and early detection plays a key role in improving survival and treatment outcomes. National breast screening programs help identify both invasive and non-invasive cancers, such as ductal carcinoma in situ (DCIS). This study aimed to compare the one-year outcomes of screen-detected invasive breast cancer and DCIS in women diagnosed through a regional screening program. Methods A retrospective cohort study was conducted at our tertiary center in the UK. Patients diagnosed with screen-detected breast cancers from January 1, 2023, to December 31, 2024, were followed for one year post-surgery. A total of 216 patients were included: 108 with invasive breast cancer (Group A) and 108 with DCIS (Group B). Data on demographics, tumor characteristics, surgical procedures, postoperative complications, and oncological outcomes were collected using electronic records. Comparative statistical analyses were performed using SPSS version 26 (IBM Corp., Armonk, USA). Chi-square and independent t-tests were used for categorical and continuous variables, and odds ratios (ORs) with 95% confidence intervals were calculated to assess the strength of associations. Statistical significance was set at p < 0.05. Results The mean age was similar between groups (Group A: 57.6 ± 10.8 years; Group B: 58.1 ± 11.5 years). Estrogen and progesterone receptor (ER/PR) positivity was high in both groups (70.4% vs. 75%, p = 0.431). Human epidermal growth factor receptor 2 (HER2) positivity was more frequent in Group A (17.6% vs 11.1%, p = 0.173). Multifocality (24.1% vs 13%, p = 0.038), positive margins (17.6% vs 6.5%, p = 0.015), and nodal involvement (23.1% vs 0%, p < 0.001) were significantly more common in invasive cancers. Postoperative complications (hematoma, wound infection, seroma, flap necrosis) were similar in both groups. However, local recurrence was higher in Group A (9.3% vs 2.8%, p = 0.044), and one-year disease-free survival was lower (85.2% vs 97.2%, p = 0.002). Chemotherapy was given only to patients in Group A (59.3%). Conclusion In our study, we found that screen-detected in situ breast cancer had better short-term outcomes than invasive cancer, with fewer recurrences and higher one-year disease-free survival. Both groups were similar in demographics, but invasive cancer had more multifocality and required more aggressive surgery. Re-excision was more common in the in situ group. The results suggest avoiding overtreatment of DCIS and using risk tools to balance treatment with quality of life. Improving patient education, collaboration, and standardizing surgical decisions is important. The study highlights the need for evidence-based approaches in treatment planning.
• Role of genetics in early-onset cardiovascular disease

  Meer, Muhammad; Meer, Muhsina; Mumtaz, Mahnoor; Jawed, Umar (2025)

  Genetics increasingly comes to the front with early-onset cardiovascular disease (CVD) since researchers investigate the complex interplay of hereditary factors that promote an early manifestation of the disease. CVD is one of the most general causes of morbidity and mortality worldwide, presenting unique challenges when it arises in younger populations many times due to genetic predispositions. The various etiologies in the pathogenesis of early-onset CVD involve genetic factors, including the monogenic disorders of familial hypercholesterolemia (FH) and hypertrophic cardiomyopathy (HCM) of these diseases showing the simple Mendelian patterns of inheritance. These may be mediated through gene variations, including Low-Density Lipoprotein Receptor (LDLR), Apolipoprotein B (APOB), Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), and Myosin Heavy Chain 7 (MYH7). Disrupted lipid metabolism, myocardial function, or vascular integrity due to mutations could lead to adverse clinical consequences. Moreover, polygenic risk score (PRS) has now become helpful in identifying individuals who are at elevated risk due to the cumulative effect of several genetic variants. Knowledge about gene-environment interactions, epigenetic influences, and complex regulatory networks contributes to understanding the importance of genetic contributions to early-onset CVD. However, the genetic variation is population-specific and underlines the need for research inclusive of diverse genetic backgrounds in developing more inclusive and effective predictive models. Whole genome and exome sequencing have revolutionized early detection, making personalized treatment plans possible, including targeted therapeutic interventions like PCSK9 inhibitors. On the other hand, such scientific progress also provides a lot of ethical challenges, such as utilizing personal data, informed consent, and equal access to genetic services. This review summarizes the genetic basis underlying early-onset CVD, with detailed discussions of monogenic and polygenic contributions, important genetic pathways, and emerging advances in genetic testing and personalized medicine approaches. By highlighting the integration of genetic insights with preventive and therapeutic strategies, this review aims to bring into focus the use of genetic insight in the betterment of outcomes in patients and inform future research in cardiovascular genetics.
• Robot-assisted radical nephroureterectomy for locally advanced upper tract urothelial carcinoma: a multicenter study by the Junior ERUS/YAU Working Group on Robot-assisted Surgery

  Di Maida, F; Bravi, C.A; De Groote, R; Piramide, F.; Turri, F.; Wenzel, M; Sharma, G.; Wurnschimmel, C; Andras, I.; Lambert, E.; et al. (2025-11)

  Introduction Aim of the study was investigate outcomes of patients affected by locally advanced (pT3-pT4 and/or pN+) upper tract urothelial carcinoma (UTUC) and treated with robot-assisted radical nephroureterectomy (RNU). Materials and methods Clinical and surgical data of newly-diagnosed UTUC patients referring to 9 high-volume centres from January 2019 to March 2023 undergoing RNU were collected. Results 191 patients showed locally advanced disease. Da Vinci and Hugo RAS ™ System were employed in 95.8 % and 4.2 % of cases, respectively. Bladder cuff removal was carried out in 161 (84.3 %) patients, by using either an intravesical and extravesical approach in 50 (31.1 %) and 111 (68.9 %) respectively. Open and robotic approaches for bladder cuff removal were preferred in 107 (66.5 %) and 54 (33.5 %) patients, respectively. Lymph node dissection was performed in 55 % of patients. Median follow up was 19 (IQR 10–23) months and 31 (16.4 %) patients experienced bladder recurrence. On multivariate analysis, in those patients receiving RNU and bladder cuff removal, the approach for bladder cuff management (extravesical vs intravesical) was the only independent predictor of bladder recurrence (hazard ratio [HR]: 1.34; 95 % confidence interval [CI] 1.12–2.11; p = 0.03). Surgical approach for bladder cuff management (open vs robot) was not independently associated with bladder recurrence or tumor progression (both p > 0.05) Conclusions In experienced hands, the robotic approach showed satisfactory survival outcomes also for the surgical treatment of pathological locally advanced UTUC. Extravesical approach for bladder cuff management may be burdened by a higher risk for bladder recurrence in locally advanced disease.
• Redefining urogynaecology services: the impact of nurse-physiotherapist triage clinics on reducing delays and improving patient care

  Banerjee, I.; Thakur, Y.A.; Oo, E.W.; Chanda, A.; Lawrence, S.; Shirsalkar, N. (2025)

  Introduction and Hypothesis This project aimed to evaluate the impact of a nurse-physiotherapist triage clinic (NPTC) on service delivery within a urogynaecology department. The NPTC model was designed to be the first point of contact for urogynaecology referrals to supplement a consultant-led model and was run by specialist nurses and pelvic floor physiotherapists. The project period spanned one year before and one year after the NPTC’s introduction. Methods This was a service evaluation project registered with the local clinical governance team (reference number GYNAE374). A retrospective review of 200 case notes compared patients referred before the NPTC’s establishment, pre-NPTC or group 1 (100 new patients), with those referred afterwards, post-NPTC or group 2 (100 new patients), with ensured comparability of primary reasons for referral between both groups. The patient selection for group 1 was conducted using statistical software R version 4.4.2 (R Foundation for Statistical Computing, Vienna, Austria). Results The process measure for the project was to determine whether implementation of the NPTC reduced time intervals between general practitioner (GP) referral to first appointment and from the first visit to treatment completion. In both analyses, the NPTC showed significant reduction in the time intervals. The time interval between GP referral and first appointment was significantly reduced in group 2, with a p value of < 0.001. Similarly, the time interval from the first visit to treatment completion was shorter for group 2, with a p value of < 0.001, demonstrating the NPTC’s efficiency in accelerating the care process and reducing treatment timelines. The balance measure was to investigate patient satisfaction, using feedback forms, which was overwhelmingly positive; 95% of respondents rated the clinic’s service as ‘excellent’, and 5% rated it as ‘good’. Conclusions The NPTC model provides an effective, resource-efficient solution to urogynaecological service delivery, demonstrating its potential as a benchmark for modern urogynaecological practice. This was a successful quality improvement journey that can lead the way for adaptation of the same approach by different units.
• Real-world clinical outcomes of patients with moderate-to-severe rheumatoid arthritis initiating upadacitinib in the United Kingdom: final analysis from a prospective observational cohort study (ENDEAVOUR)

  Taylor, James; Srirangan, Srinivasan; Bukhari, Marwan; Bilgrami, Syed; Nisar, Muhammad K.; McDonald, Stephen; Goodson, Nicola; Allard, Andrew; Kinder, Alison; Green, Michael; et al. (2025)

  Objective Upadacitinib is recommended by National Institute for Health and Care Excellence in the UK in adults with moderate-to-severe rheumatoid arthritis (RA). This observational study assessed real-world clinical outcomes and patient-reported outcomes (PROs) in patients receiving upadacitinib for 6 months in the UK. Methods Patients from 14 centres in whom the decision to initiate upadacitinib had already been made were enrolled. Baseline data were retrospectively collected from patient records. Clinician-reported data were collected at routine clinic visits 3 and 6 months after upadacitinib initiation. Patient-reported data were collected directly from patients using an app (electronic PROs, ePROs). The primary end-point was proportion of patients achieving clinical remission (DAS28 CRP <2.6) after 6 months of upadacitinib. Results Data are available for 63 patients at all three datapoints and for 53 patients for the primary end-point. At 6 months, 40% (21/53) of patients achieved clinical remission and 21% (11/53) achieved low disease activity. Response was seen at 3 months for all efficacy end-points. ePROs allowed the capture of early patient-reported data which demonstrated clinically important improvements in pain and fatigue within 10 days and other PROs within 2 months. Improvements were also seen in metrics of activity, work and quality of life (QOL). Conclusion Patients in ENDEAVOUR showed similar early effectiveness with upadacitinib to that observed in clinical trials. Use of ePROs demonstrated rapid onset of action and meaningful improvements in QOL providing a potential opportunity to reduce outpatient visits for early responders, thus reducing the burden on rheumatology services.
• Real world multi-centre UK review of Nivolumab Monotherapy in metastatic endometrial cancer with mismatch repair deficiency during COVID-19

  McGrane, J.; Eastlake, L.; Hadjiyiannakis, D.; Lalondrelle, S.; Bowen, R.; Trent, S.; Obeid, M.; Hudson, E.; Agarwal, R; Gandhi, S.; et al. (2025)

  Introduction Immunotherapy checkpoint inhibition has shown improvement in efficacy and survival in patients with mismatch repair deficient (MMRd) advanced endometrial cancer (mEC) compared to chemotherapy. This is combined with chemotherapy in the first-line setting or as monotherapy in later lines of therapy. Objective To assess the efficacy, survival and toxicity of nivolumab monotherapy in metastatic endometrial cancer (mEC) in both first and later lines of therapy as used in the NICE COVID-19 systemic anti-cancer (SACT) guidelines. Methods A multi-centre retrospective review of mEC patients with associated MMRd who received nivolumab as per NICE COVID NG161 at 10 NHS cancer centres. Patient demographics, molecular classification and previous treatments were recorded in addition to treatment responses, duration of response, overall survival, progression-free survival and toxicities. Kaplan-Meier curves analyse the survival data. Results 52 patients were identified. Median age was 67 (37–81) years. 87.5% of patients had endometrioid histology and 75% were oestrogen receptor (ER) positive. 10.4% patients were p53 mutated. 33.3% of mEC patients were stage IV at diagnosis. 30 (62.5%) patients received nivolumab as first-line mEC therapy. 33 (68.8%) patients received nivolumab 4-weekly. Treatment response was clinician-observed in 34 (70.8%) patients, with 7 (14.5%) more having stable disease. 52%, 45% and 36% of patients were progression-free at 12, 18 and 24months, respectively. 75%, 55% and 47% of patients were alive at 12, 18 and 24 months. There was no significant difference between survival or response whether nivolumab was given in the first line or subsequent lines. 29 (60.4%) patients have discontinued treatment with 23 (44.2%) being due to progressive disease or death. 18 (37.5%) patients developed G1-2 toxicity, and 3 (6.25%) patients discontinued due to G3 toxicity. Conclusions This retrospective cohort shows that nivolumab monotherapy has good real-world disease control of mEC patients with MMR deficiency. Toxicity rates were low, and checkpoint monotherapy may be a viable option for selected first-line MMRd mEC patients.
• Persistent pulmonary hypertension among infants undergoing therapeutic hypothermia for Hypoxic Ischemic Encephalopathy: a systematic review and meta-analysis

  Javed, Rashida; Van Hasselt, T.J.; Rao, N.; Gowda, H. (2025)

  To perform a systematic review and meta-analysis to examine the association between persistent pulmonary hypertension (PPHN) and receipt of therapeutic hypothermia (TH), compared to those who did not receive TH, among infants with moderate or severe hypoxic-ischemic encephalopathy (HIE). Systematic review and meta-analysis based on Ovid, Medline, Embase and Cochrane central searches from 01/01/2000 to 31/03/2025. We included only randomized control trials for meta-analysis and followed international guidelines for conducting systematic reviews. The primary outcome of the study was PPHN in infants undergoing TH for moderate to severe HIE. Among 185 articles identified using search strategy, 19 articles were assessed for eligibility. Eight randomized control trials (RCTs) met the inclusion criteria, and seven were included in meta-analysis. A random effects model used for the outcome of PPHN, comparing TH with NT or usual care, involving a pooled population of 1006 infants across seven studies. The relative risk of PPHN for TH versus NT was 1.13 (95% confidence interval 0.81 to 1.57). We noted risk of bias in the blinding of participants across included RCTs. We assessed nine observational studies and performed a narrative review. We noted that a considerable number of infants developed PPHN across TH and NT groups. We did not find evidence of an association between TH and PPHN in infants with moderate to severe HIE, although a considerable number of infants developed PPHN across both groups. We suggest that clinicians should be aware of the risk of PPHN to allow prompt investigation and management.
• Pathobiology and molecular pathways implicated in Osteosarcoma Lung Metastasis: a scoping review

  Bashir, A.; Ismail, A; Mavadia, A; Ghose, A; Ovsepian, S. V.; Boussios, S (2025)

  Osteosarcoma (OS) is the most common primary bone malignancy, with lung metastasis being the leading cause of mortality. The metastatic process is driven by complex biological mechanisms, including tumor cell-specific adaptations of growth pathways, immune modulation within the tumor microenvironment, and reactivation of metastatic cells from dormancy. This scoping review captures overlooked and under researched pathways, supporting mainstream therapeutic targets while shedding light on novel ones, reinforcing and revising conclusions drawn in previous literature, and guiding future research. MEDLINE, Embase, and Cochrane CENTRAL were searched with a publication date limit from 2019 onwards using relevant MeSH terms combined with Boolean operators, truncations, and keyword searches. The search culminated in 43 reports, including 30 in vivo, 8 in vitro, and 5 observational studies. This study conforms to the PRISMA-ScR guidelines. Tumor cell adaptations, including epithelial-mesenchymal transition (EMT) and enhanced migratory and proliferative signaling via JAK/STAT and TGF-β pathways, are critical drivers of OS lung metastasis. Manipulated upstream ligand-driven signaling promotes transcriptional changes that increase cell cycle proteins and mesenchymal markers, conferring chemoresistance and advancing OS cells toward a metastatic state. The tumor microenvironment also plays a key role; interactions between OS cell-derived cytokines and tumor-infiltrating immune cells lead to tumor associated macrophages and neutrophils (TAMs/TANs), which help establish a pre-metastatic niche and provoke immune remodeling. However, the impact of TAMs on OS survival remains ambiguous due to their dual pro- and anti-tumor roles. Lung-induced dormancy links tumor intrinsic and immune-driven mechanisms, allowing tumor cells to evade immunity or pause progression. Inflammatory pathways and immune activation can reverse dormancy, promoting further OS dissemination. The reviewed evidence supports targeting intracellular signaling and immune pathways to mitigate OS metastasis. The paucity of longitudinal data on lung dormancy warrants caution, emphasizing integrated approaches and better controlled studies with focus on combinatorial therapies for more conclusive outcomes.
• Oncologic outcomes of template versus radioguided salvage lymph node dissection for node-only recurrent prostate cancer on prostate-specific membrane antigen Positron emission tomography scan: results from a multi-institutional collaboration.

  Bravi, C. A; Knipper, S.; Heidenreich, A.; Fossati, N.; Gandaglia, G.; Dell'Oglio, P; Suardi, N.; Osmonov, D.; Juenemann, K.P.; Karnes, J.; et al. (2025)

  In patients treated with salvage lymph node dissection (sLND) for nodal recurrence of prostate cancer, whether radioguided surgery (RGS) might improve oncologic outcomes as compared with template sLND remains unknown. This study included 259 patients who experienced a prostate-specific antigen (PSA) rise and nodal-only recurrence after radical prostatectomy and underwent pelvic sLND at 11 tertiary referral centers between 2012 and 2022. Lymph node recurrence was documented by prostate-specific membrane antigen positron emission tomography scans. The outcomes included biochemical recurrence (BCR) and clinical recurrence (CR) after sLND. The probability of freedom from each outcome was calculated using Kaplan-Meier analyses. A Cox regression analysis was used to test the hypothesis that surgical technique for sLND (template vs RGS) might be associated with oncologic outcomes. Overall, 80 (31%) and 179 (69%) patients received template and radioguided sLND, respectively. PSA level at sLND was higher in the template than in the radioguided group (median: 1.3 vs 0.6 ng/ml; p < 0.0001), whereas the number of positive nodes on final pathology did not differ between the groups (p = 0.13). The first postoperative PSA level was higher in the template than in the radioguided group (median: 0.5 vs 0.1 ng/ml; p < 0.0001). Overall, there were 181 cases of BCR and 76 cases of CR after sLND. The median follow-up for survivors was 21 mo (interquartile range: 7, 36). The 2-yr BCR-free survival rate for patients in the template versus RGS sLND group was 18% (95% confidence interval [CI]: 9%, 29%) versus 30% (95% CI: 22%, 37%). The 2-yr CR-free survival rate for the template versus RGS sLND group was 51% (95% CI: 35%, 65%) versus 73% (95% CI: 65%, 80%). On multivariable analyses, we did not find evidence of a statistically significant difference between the groups with respect to BCR after sLND (p = 0.7), whereas men treated with RGS had a lower risk of CR after sLND than those receiving template sLND (hazard ratio: 0.51; 95% CI: 0.29, 0.92; p < 0.026). Results of the sensitivity analyses were generally consistent with our main findings. Our data suggest that, in men with node-recurrent prostate cancer treated with sLND, RGS may offer important surgical guidance for surgeons, and this may eventually translate into improved oncologic outcomes. Awaiting further evidence on long-term outcomes of RGS, our study represents the most solid comparative data on different techniques for sLND and provides relevant data for counseling patients with node-only recurrent prostate cancer.
• Novel finding of pulmonary embolism following tirzepatide (Manjaro) use in a young adult without risk factors of venous thromboembolic events

  Alsararatee, H. H. (2025)

  A woman in her early 40s presented with pleuritic chest pain and shortness of breath, which had progressively worsened over 20 days following initiation of tirzepatide (Manjaro). Her D-dimer level was elevated at 1340 ng/mL, prompting a CT pulmonary angiogram that confirmed right main pulmonary artery pulmonary embolism (PE). The patient had no identifiable provoked or unprovoked risk factors for venous thromboembolisms (VTEs). To our knowledge, this is the first reported case of PE that might be associated with the use of tirzepatide worldwide. The relationship between tirzepatide and VTEs events remains unclear. This case highlights the need for further research to explore the incidence and underlying mechanisms of VTEs in patients receiving tirzepatide.
• How to approach and manage ocular emergencies

  Alsararatee, H. H.; Abdul Rahim, A. N. (2025-07-02)

  Ocular emergencies require immediate recognition and intervention to prevent vision loss and other serious complications. A thorough history, clinical examination, and appropriate management can have a significant impact on patient outcomes. This article explores various ophthalmic emergencies, including traumatic and non-traumatic conditions, with emphasis on their clinical presentations, diagnostic approaches, and evidence-based management.
• Ethical principles and challenges in end-of-life care for frail older adults

  Alsararatee, H. H.; Mukhtar, M.; Musawar, A. (2025-06-05)

  Providing end-of-life care to frail, older adults with multiple comorbidities can be ethically complex. As frailty differs from single terminal illness, end-of-life care requires a carefully considered, ethically informed approach. The four core ethical principles of autonomy, beneficence, nonmaleficence and justice need to be applied within this context; they involve challenges specific to frail patients, including fluctuating mental capacity, the risks of aggressive interventions and equitable access to resources. Key ethical issues include do not attempt cardiopulmonary resuscitation orders, confidentiality, mental capacity assessments and palliative sedation. Health professionals require a structured framework for decision-making. By balancing patient dignity, quality of life and legal considerations, practitioners can understand ethical obligations and practical decision-making strategies. For frail, older adults, a compassionate, patient-centred approach that prioritises comfort and dignity, especially as people approach the end of life, ensures care is provided in line with both ethical and legal standards.

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