St George's, University of London

Background Risk scores have been used to assess stroke risk in atrial fibrillation (AF) for reducing ischemic stroke and bleeding risk. Information gain ratio (IGR) is an entropy-based parameter that shows which clinical score is more informative for prediction of the clinical endpoint. Objective Herein, we aimed to generate and validate a stroke risk score based on the TuRkish Atrial Fibrillation (TRAF) data. Methods We used a split-sample approach to develop and internally validate the new stroke risk score. Based on multivariate logistic regression analysis, we generated CHADS-F in the anticoagulation naïve TRAF cohort (274,631 patients). CHADS-F stands for Cardiac failure (1 point), hypertension (1 point), age (≥ 65–69 = 1 point, ≥ 70–74 = 2 points ≥ 75 = 3 points), diabetes (1 point), stroke (2 points), and older female (1 point) (≥ 65). External validation was performed in the “Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF)” Registry. Informative capacity and accuracy of the CHADS-F score was compared with CHADS2 and CHA2DS2-VASc scores. Results In anticoagulation naïve cohort, CHADS-F (IGR for all cohort: 0.7526) outperforms both the CHADS2 (IGR for all cohort: 0.6340) and CHA2DS2-VASc (IGR for all cohort: 0.6969) in terms of the IGR for ischemic stroke and systemic embolism. Receiver operating characteristic curves revealed highest accuracy for the CHADS-F score [area under curve for CHADS-F: 0.743, CHADS2: 0.722, and CHA2DS2-VASc: 0.722]. CHADS-F had good discriminative abilities at predicting clinical endpoints in the GARFIELD-AF registry. Conclusion The CHADS-F score had higher informative capacity and accuracy than the current CHADS2 and CHA2DS2-VASc scores for predicting stroke and systemic embolism. Graphical abstract

Background Mechanical thrombectomy (MT) is the standard treatment for large vessel occlusion (LVO) stroke. However, a substantial proportion of patients experience poor functional outcomes despite successful reperfusion, namely futile recanalization (FR). This study aimed to evaluate the predictive value of inflammatory biomarkers, measured on admission and at 24 h, in identifying the risk of FR and to assess age‐specific differences influencing this outcome. Methods This international, multicenter, observational study included patients with anterior circulation LVO stroke treated with MT. Strict inclusion criteria were applied to minimize confounding factors related to inflammation. Inflammatory biomarkers were assessed at admission and 24 h post‐procedure. Inverse probability weighting (IPW) was utilized to balance baseline characteristics between patients with FR and effective recanalization (ER). Least absolute shrinkage and selection operator (LASSO) regression was applied to identify independent predictors, and restricted cubic splines were used to determine optimal biomarker cut‐offs. Results Among 885 patients, 470 (53%) experienced FR. In multivariate analysis, 24‐h CRP (OR 1.01, 95% CI 1.01–1.02, p = 0.018) and 24‐h NLR (OR 1.11, 95% CI 1.02–1.22, p = 0.019) were significant predictors of FR, with cut‐offs of 8.55 and 4.58, respectively. In patients aged < 80 years, 24‐h CRP and NLR were most predictive (cut‐offs: 17.09 and 5.59). In patients aged ≥ 80 years, admission SIRI emerged as the most significant predictor (OR 1.24, 95% CI 1.06–1.50, p = 0.015), with an optimal cut‐off value of 2.53. Conclusions Inflammatory biomarkers exhibit significant predictive value for FR following MT, with distinct age‐specific patterns. These findings underscore the importance of tailoring predictive models and interventions to optimize clinical outcomes.

Rectal MRI studies used to stage and guide surgical or nonsurgical management of rectal cancer may harbor incidental findings (IFs) of varying significance. St George's Hospital uses a four-sequence MRI protocol which does not employ diffusion-weighted imaging (DW-MRI). Objectives To determine the frequency and significance of incidental findings identified when using a rectal MRI protocol which does not employ DW-MRI. Methods Retrospective analysis of rectal MRI study reports for IFs and stratifying their significance. Medical records were reviewed to clarify IFs of interest. Results One hundred thirty-four studies met the inclusion criteria for the study (75 men, mean age 65). 51/134 (38%) of studies had IFs. Fifteen percent (n = 7/46) of baseline studies for a new cancer had significant IFs. The commonest IF was diverticular disease (n = 10); however, a bladder malignancy was also identified. Conclusion Clinically significant IFs exist in 12% of patients undergoing rectal MRI, and any type of IFs exist in 38% of patients undergoing rectal MRI studies. The rate of significant IFs is comparable with other authors both in rectal and prostate MRI but with fewer overall IFs, possibly due to the lack of DW-MRI sequences in our local protocol. Our study is the first to assess IFs using a rectal MRI protocol which does not employ DW-MRI, and the results should be considered by centers when planning their rectal MRI protocol.

Constitutional or germline pathogenic variants (GPVs) in protection of telomeres 1 (POT1 ) are associated with a variety of tumours resulting in the recognition of POT1-tumour predisposition syndrome (POT1-TPDS). These tumours may include cutaneous melanoma, angiosarcoma, haematological malignancy and brain tumours. Due to the rarity of POT1 GPVs and limited available data, the overall lifetime cancer risks for individuals with POT1-TPDS are unclear. Furthermore, there is scant evidence to support the role of surveillance in early cancer detection in this patient group. A recent international publication suggested a surveillance protocol similar to that used in Li-Fraumeni Syndrome (LFS) could be offered to POT1 pathogenic variant carriers, particularly where there are LFS-like features. However, current evidence for POT1-TPDS is not supportive of an equivalent lifetime cancer risk. Given the inclusion of POT1 in the National Test Directory in England and the need for UK-based guidance, an expert group undertook a literature review to assess the phenotypic spectrum of POT1-TPDS and to provide lifetime risk estimates of POT1 -associated cancers. The available evidence was shared with a small working group of experts that included clinical geneticists, dermatologists, sarcoma specialists, haematologists and radiologists to cover all aspects of the cancers most commonly associated with POT1-TPDS. Following structured expert group discussions, we achieved consensus on best practice recommendations for a POT1-TPDS UK management protocol.

Background Cataract surgery is common procedure globally. Among its adverse effects is pseudophakic bullous keratopathy (PBK), a corneal disorder characterized by stromal edema and the formation of epithelial and subepithelial bullae due to endothelial cell loss and decompensation. This case series examines the outcomes of using the topical Rho kinase inhibitor Ripasudil for managing pseudophakic bullous keratopathy (PBK) in three patients treated at Hadassah Medical Center. Clinical data, including visual acuity, intraocular pressure, central corneal thickness (CCT), and endothelial cell count, were extracted from electronic medical records before and after treatment. Patients were treated with topical Ripasudil for periods ranging from three to eleven months, three times daily, with adjustments based on disease severity. Case presentation The first case involved a 66-year-old Jewish female, who presented with persistent corneal edema in the left eye. Following three months of Ripasudil therapy, the patient exhibited notable improvement in best-corrected visual acuity (BCVA), a reduction in central corneal thickness (CCT), and decreased central stromal edema. Similarly, the second case featured a 58-year-old Jewish male with a history of cataract surgery in the right eye performed 3 years prior at an external institution. After 3 months of Ripasudil treatment, the patient demonstrated measurable improvements in both BCVA and CCT, mirroring the therapeutic trend observed in the first case. In parallel, the third case described a 69-year-old Jewish male who presented with a 6-month history of blurred vision. In total, 11 months of Ripasudil administration led to resolution of stromal haze and corneal edema, along with a significant reduction in CCT and an enhancement in BCVA. Conclusion These findings suggest that Ripasudil has potential as an effective treatment option for PBK, possibly delaying or avoiding the need for corneal transplantation. Further studies are required to confirm the long-term efficacy and safety of Ripasudil for PBK.

Maternal uterine spiral arteries (SpA) undergo significant structural changes in early pregnancy, resulting in increased blood flow to the developing fetus. Endothelial cells (EC) and vascular smooth muscle cells (VSMC) are lost from the SpA wall and are replaced by trophoblasts. We have previously shown that matrix metalloproteinase 10 (MMP‐10) and Heparin binding‐EGF like growth factor (HB‐EGF) gene expression is increased in a 3D EC/VSMC co‐culture system in response to trophoblast secreted factors. This study investigated trophoblast mediated MMP‐10 and HB‐EGF expression and determined if there was a relationship between the secretion of MMP‐10 and the release of soluble HB‐EGF (sHB‐EGF) from EC. MMP‐10 was widely expressed in first trimester decidual tissue including trophoblast, and EC, but not VSMC. MMP‐10 expression was significantly lower in decidual tissue from pregnancies at increased risk of developing pre‐eclampsia compared to low‐risk pregnancies. In vitro, SGHEC‐7 cells, a human EC line, but not SGHVMC‐9, a human VSMC cell line, secreted MMP‐10 in response to trophoblast conditioned medium (TCM). TCM contains several growth factors and cytokines, but only interleukin‐1β (IL1β) significantly stimulated MMP‐10 secretion by SGHEC‐7 cells. Interleukin‐1 receptor antagonist (IL‐1Ra) significantly inhibited TCM‐induced MMP‐10 secretion. Interrogation of intracellular pathways established the involvement of MEK and JNK in TCM and IL‐1β stimulated MMP‐10 secretion. Although IL‐1β also significantly increased sHB‐EGF, inhibition of MMP‐10 activity using a broad spectrum MMP inhibitor had no effect on sHB‐EGF. Western blot analysis indicated that MMP‐10 secreted by EC in response to IL‐1β stimulation was the enzymatically inactive pro form.

Background Complete mesocolic excision (CME) is a surgical approach for right-sided colon cancer, involving the resection of the primary tumour along with an intact mesocolon, central vascular ligation, and exposure of the superior mesenteric vein. It has been postulated to improve oncologic outcomes such as disease-free survival and reduce local recurrence compared to standard right colectomy. However, the clinical benefits are still debated. Objective This systematic review and meta-analysis, sponsored by the European Association for Endoscopic Surgery, aims to compare the oncologic outcomes of CME with standard right colectomy for right-sided colon cancer, with the ultimate objective to inform clinical practice recommendations. Methods We followed the PRISMA 2020 reporting standards. A comprehensive literature search was conducted to identify relevant studies published from 2008 onwards, focusing on randomised trials and matched cohort studies comparing CME with standard right hemicolectomy. The GRADE methodology was used to assess the certainty of evidence, and minimal important differences were calculated to inform clinical relevance. Results Thirteen studies, amongst which three randomised trials, were included. No difference was found between CME and standard colectomy in terms of 30-day mortality, major peri-operative morbidity, or major blood loss. However, patients who underwent CME showed improved overall survival (HR = 0.67, 95%CI [0.48 – 0.93], low certainty of evidence) and disease-free survival (HR = 0.78, 95% CI [0.63 – 0.96], low certainty of evidence) compared to those who underwent standard colectomy, though certainty of the evidence was low due to the high risk of bias in the observational studies. Conclusion Complete mesocolic excision may offer survival benefits over standard right colectomy for right-sided colon cancer. However, the evidence remains of low certainty, mainly due to the predominance of observational data with significant risk of bias. Future high-quality randomized trials are needed to confirm these findings and standardize surgical techniques to reduce heterogeneity and improve clinical outcomes.

Background Functional cognitive disorder is an increasingly recognised subtype of functional neurological disorder for which treatment options are currently limited. We have developed a brief online group acceptance and commitment therapy (ACT)-based intervention. Aims To assess the feasibility of conducting a randomised controlled trial of this intervention versus treatment as usual (TAU). Method The study was a parallel-group, single-blind randomised controlled trial, with participants recruited from cognitive neurology, neuropsychiatry and memory clinics in London. Participants were randomised into two groups: ACT + TAU or TAU alone. Feasibility was assessed on the basis of recruitment and retention rates, the acceptability of the intervention, and signal of efficacy on the primary outcome measure (Acceptance and Action Questionnaire II (AAQ-II)) score, although the study was not powered to demonstrate this statistically. Outcome measures were collected at baseline and at 2, 4 and 6 months post-intervention, including assessments of quality of life, memory, anxiety, depression and healthcare use. Results We randomised 44 participants, with a participation rate of 51.1% (95% CI 40.8–61.5%); 36% of referred participants declined involvement, but retention was high, with 81.8% of ACT participants attending at least four sessions, and 64.3% of ACT participants reported being ‘satisfied’ or ‘very satisfied’ compared with 0% in the TAU group. Psychological flexibility as measured using the AAQ-II showed a trend towards modest improvement in the ACT group at 6 months. Other measures (quality of life, mood, memory satisfaction) also demonstrated small to modest positive trends. Conclusions It has proven feasible to conduct a randomised controlled trial of ACT versus TAU.

OBJECTIVES In this study, we compare digital and underwater seal drainage systems following cardiac surgery and assess postoperative outcomes. METHODS Between August 2017 and August 2018, cardiac surgical patients at our hospital were managed postoperatively using underwater seal drainage systems, and between August 2022 and August 2023 using digital drainage systems. Propensity score matching was used to estimate the effect of drainage system on various postoperative parameters (continuous and binary outcome modelling). Primary outcomes were postoperative atrial fibrillation, reoperation for bleeding or tamponade and pleural effusion requiring intervention. Secondary outcomes were hourly and cumulative drain output within 24 postoperative hours. RESULTS 347 patients met the entry criteria for the study. One hundred ninety patients were managed using an underwater seal drainage system, and 157 patients were managed using a digital drainage system. Three hundred fourteen patients from the original 333 patient cohort were matched according to the drainage system used. After matching, the odds of developing postoperative atrial fibrillation were 0.57 (95% CI 0.32–0.99, P = 0.046) times lower in the digital drainage group. There was no difference in the rates of reoperation for bleeding or tamponade, pleural effusion requiring intervention or cumulative drain volume within 24 h. CONCLUSIONS In this analysis, the odds of developing postoperative atrial fibrillation were lower in patients managed with digital drainage devices than underwater seal. However, there was no difference in rates of reoperation for bleeding, tamponade, pleural effusion, drain duration or overall length of stay. Digital drainage systems could therefore be considered as part of an enhanced recovery after cardiac surgery pathway.

The recently published Alzheimer's Association Workgroup diagnostic criteria for Alzheimer disease and consensus-based workflows for the use of diagnostic biomarkers in neurocognitive disorders promote further normalization of purely biological approaches to neurocognitive disorders. In this commentary, we reflect on the dangers of biological reductionist positions lacking solid scientific evidence and proven cost-effectiveness benefits, in particular its inability to offer a meaningful formulation for the large number of people with functional cognitive disorders. This, alongside the current lack of standardization, limited accuracy, and environmental consequences, means that the normalization of biomarkers as standard-of-care tests in all neurocognitive presentations does not represent responsible innovation. We emphasize the need for pluralism when considering technological developments, such that clinical judgment and biopsychosocial formulation continue to be accepted as a sound foundation for cognitive assessment.

Objective This study aimed to explore the knowledge, beliefs, and attitudes toward parenthood following gamete donation among the general population in Italy. Background In Western societies, where genetic continuity often defines kinship, couples using gamete donation to conceive may face societal stigma and lack of acknowledgment, potentially impacting their well‐being. As openness about donor conception is encouraged in donor‐conceived families' social networks, research on public perceptions of parenthood after gamete donation is necessary. Method Six hundred twenty‐four participants completed an online survey exploring their beliefs toward parenthood after gamete donation. Participants also assessed hypothetical parental abilities in five randomly presented scenarios depicting couples having a child using different conception methods. Results Participants showed limited knowledge of donor conception pathways and positive beliefs about parenthood following donor conception. Greater concerns were expressed regarding parenting abilities in spontaneously conceiving couples compared to those using donor and nondonor assisted reproduction technologies and concerns about the stability of relationships in donor‐conceiving couples. Conclusion Couples using donor assisted reproduction technologies are perceived as more committed to parenthood despite concerns about genetic asymmetry and limited understanding of donor conception. Implications The societal unawareness of donor conception may present challenges for families in legitimizing their family building within their social contexts.

Rectal cancer represents approximately 35% of colorectal cancer cases in the European Union. Early-stage tumors may be treated with less invasive techniques, such as endoscopic submucosal dissection (ESD) and transanal endoscopic microsurgery (TEM). This systematic review and meta-analysis evaluates the comparative efficacy and safety of ESD versus TEM for early-stage rectal cancer. A literature search was conducted in PubMed, Scopus, Embase, and Cochrane databases up to October 2024. Studies comparing ESD and TEM outcomes in adult patients with rectal tumors were included. Outcomes assessed included the rates of en-bloc resection, recurrence, overall complications, R0 resection rates, postoperative bleeding, reoperation rates, perforation rates, operative time, and length of hospital stay. Statistical analyses were performed using both fixed and random effects models. Seven retrospective studies involving 671 patients were included. Pooled analyses showed that ESD achieved higher en-bloc resection rates [odds ratio (OR) = 0.29, 95% confidence interval (CI): 0.10–0.83, P = 0.02), lower tumor recurrence rates (OR = 0.29, 95% CI: 0.12–0.70, P = 0.006) and lower overall complication rate (OR = 0.50, 95% CI: 0.31–0.81, P = 0.005). No significant differences were observed in terms of R0 resection rates, operative time, postoperative bleeding, and reoperation rates. ESD achieves favorable outcomes over TEM for early-stage rectal cancer by achieving higher en-bloc resection rates, lower rates of recurrence, and complications. Despite ESD’s technical complexity, its superior precision and lower complication profile make it a promising option for early-stage rectal cancer, though clinician expertise and available resources should guide treatment selection.

Aims This post-hoc analysis of the ATHENA trial assessed whether dronedarone (400 mg twice daily) improved cardiovascular outcomes compared with placebo in patients with early atrial fibrillation/atrial flutter (AF) and cardiovascular comorbidities, based on EAST-AFNET 4 inclusion criteria and outcomes. Methods and results The co-primary outcomes were (i) a composite of cardiovascular death, stroke, or hospitalisation due to worsening of heart failure (HF) or acute coronary syndrome (ACS) and (ii) nights spent in hospital per year. Sinus rhythm (SR) at 12 months was a secondary outcome. The primary safety outcome was a composite of death, stroke, or pre-specified serious adverse events of special interest (AESIs) related to rhythm control therapy. 1810 patients with early AF were identified. Patients receiving dronedarone had fewer deaths from cardiovascular causes, strokes, or hospitalisations due to worsening of HF or ACS compared with patients receiving placebo [dronedarone (n = 924), 87 patients with ≥1 event; placebo (n = 886), 117 patients with ≥1 event; hazard ratio 0.71; 95% confidence interval 0.54–0.94; P = 0.014]. Number of nights spent in hospital did not differ between treatment groups. More patients receiving dronedarone (69.2%) were in SR at 12 months compared with placebo (60.8%). Primary safety events comprising death, stroke, or pre-specified serious AESIs related to rhythm control therapy were not different (dronedarone vs. placebo: 60 vs. 71 patients with ≥1 event). Conclusion These data support the use of dronedarone for early rhythm control therapy in selected patients with early AF. Trial registration ATHENA: ClinicalTrials.gov identifier NCT00174785. EAST-AFNET 4: ClinicalTrials.gov identifier NCT01288352.

Objective: Therapeutic lateral neck dissection is recommended for papillary thyroid cancer with metastatic lymph nodes detected on palpation or on preoperative imaging. Current guidelines recommend systematic dissection of levels IIA, III, IV and VB in these patients. Despite this recommendation, management of level V remains controversial due to a varying degree of clinical and occult lymph node involvement reported in published retrospective studies, but also due to the functional risk involved in level V dissection in which the spinal accessory nerve may be temporarily or permanently injured. The aim of this review was to address the issues involved in level VB dissection and to provide our view of surgical management of level VB. Method: Narrrative review. Result: We propose a new concept of a partial or “super-superselective” level VB dissection in patients with clinical disease in levels IIA, III and IV.