Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU): Trial Satisfaction and Attitudes towards Future Clinical Trials.

BACKGROUND: Clinical trial satisfaction is increasingly important for future trial designs and is associated with treatment adherence and willingness to enroll in future research studies or to recommend trial participation. In this post-trial survey, we examined participant satisfaction and attitudes toward future clinical trials in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU). METHODS: We developed an anonymous, participant satisfaction survey tailored to participants enrolled in the DIAN-TU-001 double-blind clinical trial of solanezumab or gantenerumab and requested that all study sites share the survey with their trial participants. A total of 194 participants enrolled in the trial at 24 study sites. We utilized regression analysis to explore the link between participants' clinical trial experiences, their satisfaction, and their willingness to participate in upcoming trials. RESULTS: Survey responses were received over a sixteen-month window during 2020-2021 from 58 participants representing 15 study sites. Notably, 96.5% of the survey respondents expressed high levels of satisfaction with the trial, 91.4% would recommend trial participation, and 96.5% were willing to enroll again. Age, gender, and education did not influence satisfaction levels. Participants reported enhanced medical care (70.7%) and pride in contributing to the DIAN-TU trial (84.5%). Satisfaction with personnel and procedures was high (98.3%). Respondents had a mean age of 48.7 years, with most being from North America and Western Europe, matching the trial's demographic distribution. Participants' decisions to learn their genetic status increased during the trial, and most participants endorsed considering future trial participation regardless of the DIAN-TU-001 trial outcome. CONCLUSION: Results suggest that DIAN-TU-001 participants who responded to the survey exhibited high motivation to participate in research, overall satisfaction with the clinical trial, and willingness to participate in research in the future, despite a long trial duration of 4-7 years with detailed annual clinical, cognitive, PET, MRI, and lumbar puncture assessments. Implementation of features that alleviate barriers and challenges to trial participation is like to have a high impact on trial satisfaction and reduce participant burden.

Influence of meteorological variables and air pollutants on measurements from automatic pollen sampling devices.

This study examines the influence of meteorological factors and air pollutants on the performance of automatic pollen monitoring devices, as part of the EUMETNET Autopollen COST ADOPT-intercomparison campaign held in Munich, Germany, during the 2021 pollen season. The campaign offered a unique opportunity to compare all automatic monitors available at the time, a Plair Rapid-E, a Hund-Wetzlar BAA500, an OPC Alphasense, a KH-3000 Yamatronics, three Swisens Polenos, a PollenSense APS, a FLIR IBAC2, a DMT WIBS-5, an Aerotape Sextant, to the average of four manual Hirst traps, under the same environmental conditions. The investigation aimed to elucidate how meteorological factors and air pollution impact particle capture and identification efficiency. The analysis showed coherent results for most devices regarding the correlation between environmental conditions and pollen concentrations. This reflects on one hand, a significant correlation between weather and airborne pollen concentration, and on the other hand the capability of devices to provide meaningful data under the conditions under which measurements were taken. However, correlation strength varied among devices, reflecting differences in design, algorithms, or sensors used. Additionally, it was observed that different algorithms applied to the same dataset resulted in different concentration outputs, highlighting the role of algorithm design in these systems (monitor + algorithm). Notably, no significant influence from air pollutants on the pollen concentrations was observed, suggesting that any potential difference in effect on the systems might require higher air pollution concentrations or more complex interactions. However, results from some monitors were affected to a minor degree by specific weather variables. Our findings suggest that the application of real-time devices in urban environments should focus on the associated algorithm that classifies pollen taxa. The impact of air pollution, although not to be excluded, is of secondary concern as long as the pollution levels are similar to a large European city like Munich.

A comparison of the efficacy of trastuzumab deruxtecan in advanced HER2-positive breast cancer: active brain metastasis versus progressive extracranial disease alone.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) has demonstrated efficacy in patients with brain metastasis (BM), a group historically with poor outcomes. The prevalence of BMs in patients commencing T-DXd is currently unknown. No direct comparisons have been made of the activity of T-DXd in patients with active BM versus those with extracranial progression alone. This real-world study explored the prevalence of BMs in patients commencing T-DXd, the efficacy of T-DXd in active BM versus extracranial progression alone and the safety of T-DXd. PATIENTS AND METHODS: Patients with human epidermal growth factor receptor 2-positive advanced breast cancer treated with T-DXd between June 2021 and February 2023 at our specialist cancer hospital were identified and notes reviewed. Clinicopathological information, prior treatment, the presence or absence of central nervous system (CNS) disease, outcomes and treatment-emergent adverse events (TEAEs) were recorded. RESULTS: Twenty-nine female patients, with a median age of 52 years (interquartile range 44-62 years), were identified; the prevalence of BM was 41%. Median number of lines of prior therapy was 2 (range 2-6). At a median follow-up of 13.8 months, median progression-free survival (PFS) for the overall population was 13.9 months [95% confidence interval (CI) 12.4 months-not estimable (NE)], 16.1 months (95% CI 15.1 months-NE) for active BMs and 12.4 months (95% CI 8.3 months-NE) for progressive extracranial disease alone. The 12-month overall survival (OS) rate was 74% (95% CI 59% to 95%) in the overall population, and 83% (95% CI 58% to 100%) and 66% (95% CI 45% to 96%) for active BMs and extracranial disease only, respectively. Most common TEAEs were fatigue, alopecia, and constipation. In nine patients (31%, including two deaths), pneumonitis occurred. CONCLUSION: In this real-world population, we demonstrate T-DXd to be effective in patients with active BMs and those with progressive extracranial disease alone. PFS and OS were numerically longer in those with active BMs. These data demonstrate that patients with active BM treated with T-DXd have at least comparable outcomes to those with extracranial disease alone. The high rate of pneumonitis warrants further consideration.

Delivery of multipotent adult progenitor cells via a functionalized plasma polymerized surface accelerates healing of murine diabetic wounds.

Introduction: Stem cell therapies have been investigated as potential treatment modalities for chronic wounds however there has been limited success to date. Multipotent Adult Progenitor Cells (MAPCs©) have been identified as having potential as an allogenic stem cell product due to their high population doubling number and their characteristic dampening of T-cell proliferation. This helps to prevent autoimmunity and graft/cell rejection. Methods: We have developed a dressing, consisting of medical grade silicone coated with a heptylamine plasma polymer, which supports the growth and transfer of MAPCs to skin. To determine if the dressing can deliver functional stem cells into diabetic wounds, they were loaded with MAPCs and then placed over excisional wounds in both normal and diabetic mice. Results and discussion: Accelerated healing was observed in both the normal and diabetic wounds with wound gape being significantly smaller at day 3 when compared to controls. Wound analysis showed that treatment with the MAPC dressings dampened the inflammatory response with reduced numbers of neutrophils and macrophages observed. Additionally, an increase in pro-angiogenic VEGF and CD31 positive endothelial cells was observed indicating improved new blood vessel formation. The MAPC dressings had no effect on fibrosis with collagen I and III being equally affected in both control and treated wounds. Overall, the functionalized MAPC dressings improve healing responses particularly in diabetic mice with impaired healing responses and therefore, show potential for development as an advanced therapeutic approach for the treatment of chronic diabetic wounds.

Validation of an endoscopic anastomotic grading score as an intraoperative method for assessing stapled rectal anastomoses.

PURPOSE: Anastomotic leak is a dreaded complication of colorectal surgery. An endoscopic grading score of the perianastomotic mucosa has been previously developed at our institution (UCI) to assess colorectal anastomotic integrity. The objective of this study is to validate the UCI anastomotic score and determine its impact in anastomotic failure. METHODS: As a follow-up study of the UCI grading score implementation during 2011 to 2014, patients undergoing stapled colorectal anastomoses after sigmoidectomy or proctectomy at a single institution from 2015 to 2018 were retrospectively reviewed. Patients were grouped into three tiers based on endoscopic appearance (grade 1, circumferentially normal mucosa; grade 2, ischemia/congestion < 30% of circumference; grade 3, ischemia/congestion > 30% of circumference). RESULTS: On the basis of endoscopic mucosal evaluation, grade 1 anastomosis was observed in 299 patients (94%), grade 2 anastomosis in 14 patients (4.4%), and grade 3 anastomosis in 5 patients (1.6%). All grade 3 classifications were immediately and successfully revised intraoperatively with reclassification as a grade 1 anastomosis. The anastomotic leak rate of the follow-up study period from 2015 to 2018 was 6.4% which was lower compared to the anastomotic leak rate of 12.2% in the original study period from 2011 to 2014 (p = 0.07). Anastomotic leak rate for the entire patient series was 8.5%. A grade 2 anastomosis was associated with higher anastomotic leak rate compared to a grade 1 anastomosis (35.7% vs. 7.4%, p < 0.05). None of the five grade 3 anastomoses resulted in an anastomotic leak upon revision. CONCLUSION: This study further validates the anastomotic grading score and suggests that its systematic implementation can result in a reduction in anastomotic leaks.

Genome skimming elucidates the evolutionary history of Octopoda.

Phylogenies for Octopoda have, until now, been based on morphological characters or a few genes. Here we provide the complete mitogenomes and the nuclear 18S and 28S ribosomal genes of twenty Octopoda specimens, comprising 18 species of Cirrata and Incirrata, representing 13 genera and all five putative families of Cirrata (Cirroctopodidae, Cirroteuthidae, Grimpoteuthidae, Opisthoteuthidae and Stauroteuthidae) and six families of Incirrata (Amphitretidae, Argonautidae, Bathypolypodidae, Eledonidae, Enteroctopodidae, and Megaleledonidae) which were assembled using genome skimming. Phylogenetic trees were built using Maximum Likelihood and Bayesian Inference with several alignment matrices. All mitochondrial genomes had the 'typical' genome composition and gene order previously reported for octopodiforms, except Bathypolypus ergasticus, which appears to lack ND5, two tRNA genes that flank ND5 and two other tRNA genes. Argonautoidea was revealed as sister to Octopodidae by the mitochondrial protein-coding gene dataset, however, it was recovered as sister to all other incirrate octopods with strong support in an analysis using nuclear rRNA genes. Within Cirrata, our study supports two existing classifications suggesting neither is likely in conflict with the true evolutionary history of the suborder. Genome skimming is useful in the analysis of phylogenetic relationships within Octopoda; inclusion of both mitochondrial and nuclear data may be key.

Colorectal cancer care in the COVID-19 era: outcomes from a 'mixed site' model.

INTRODUCTION: The COVID-19 pandemic has presented many challenges to colorectal cancer (CRC) care. Many organisations opted to perform CRC resections in 'cold' sites. Infrastructure in Northumbria Healthcare NHS Foundation Trust (NHCT) necessitated co-locating CRC care with 'hot' COVID streams but with additional precautions. This study aimed to evaluate that approach for a consecutive series of CRC cases, diagnosed before and during the COVID-19 pandemic. METHODS: A prospectively populated data set of CRC patients diagnosed between 1 April 2019 and 30 September 2020 was used. Patients presenting before 1 April 2020 were considered 'pre-COVID' and those presenting subsequently as 'COVID era'. RESULTS: Some 344 cases were diagnosed in the 12 months 'pre-COVID' and 166 in the 6 months of the 'COVID era'. The median numbers of days from referral to diagnosis (21 vs 20, p=0.373) and operation (63 vs 61, p=0.208) were unchanged. The 'COVID era' saw an increase in the proportion of radiological diagnoses (39.5% vs 53.0%, p=0.004) with an associated decrease in endoscopic diagnoses (56.7% vs 45.8%, p=0.021). Rates of inoperable (1.5% vs 1.2%, p=0.821), obstructing (11.0% vs 16.2%, p=0.272) and perforated tumours (0.6% vs 1.5%, p=0.492) remained the same. One patient developed COVID-19 perioperatively. Rates of laparoscopic operation (59.5% vs 61.8%, p=0.751), anastomotic leak (6.4% vs 5.9%, p=0.891), re-operative surgery (10.4% vs 4.4%, p=0.138), primary stoma (40.5% vs 32.4%, p=0.244) and 90-day mortality (0.6% vs 1.5%, p=0.492) did not change. CONCLUSIONS: With appropriate infection control measures, it may be safe to continue providing standard elective and urgent CRC care without access to a 'COVID clean' site.

Rare anatomical variant of the spinal accessory nerve: case report and comprehensive review.

Historical studies of the anatomy of the spinal accessory nerve (SAN) have reported conflicting results regarding its relationship with the internal jugular vein (IJV). A literature review was undertaken to establish the prevalence of anatomical variations of the SAN encountered during routine neck dissection surgery, in order to increase awareness and reduce morbidity associated with iatrogenic SAN injury. The published literature was analysed by qualitative synthesis and nine articles were yielded following application of the inclusion and exclusion criteria. Incidences of the SAN lateral to the IJV and medial to the IJV ranged from 39.8% to 96.6%, and 2.6% to 57.4%, respectively. Five of the studies reported incidences of the SAN traversing the IJV, which occurred in 0.9% to 2.8% of cases. One study reported an isolated variant of the SAN dividing around the IJV, with a prevalence of 0.5%. We present a case report demonstrating the rare variant of the SAN traversing the IJV. Preoperative identification of rare anatomical association of the SAN and IJV may reduce perioperative injury to vital structures during neck dissection.

Local excision and treatment of early node-negative anal squamous cell carcinomas in a highly HIV prevalent population.

BACKGROUND: Anal squamous cell carcinoma (ASCC) is an uncommon cancer associated with human immunodeficiency virus (HIV) infection. There has been increasing interest in providing organ-sparing treatment in small node-negative ASCC's, however, there is a paucity of evidence about the use of local excision alone in people living with HIV (PLWH). The aim of this study was to evaluate the efficacy of local excision alone in this patient population. METHODS: We present a case series of stage 1 and stage 2 ASCC in PLWH and HIV negative patients. Data were extracted from a 20-year retrospective cohort study analysing the treatment and outcomes of patients with primary ASCC in a cohort with a high prevalence of HIV. RESULTS: Ninety-four patients were included in the analysis. Fifty-seven (61%) were PLWH. Thirty-five (37%) patients received local excision alone as treatment for ASCC, they were more likely to be younger (p = 0.037, ANOVA) and have either foci of malignancy or well-differentiated tumours on histology (p = 0.002, Fisher's exact test). There was no statistically significant difference in 5-year disease-free survival and recurrence between treatment groups, however, patients who had local excision alone and PLWH were both more likely to recur later compared to patients who received other treatments for ASCC. (72.3 months vs 27.3 months, p = 0.06, ANOVA, and 72.3 months vs 31.8 months, p = 0.035, ANOVA, respectively). CONCLUSIONS: We recommend that local excision be considered the sole treatment for stage 1 node-negative tumours that have clear margins and advantageous histology regardless of HIV status. However, PLWH who have local excision alone must have access to an expert long-term surveillance programme after treatment to identify late recurrences.

A systematic review of colorectal multidisciplinary team meetings: an international comparison.

BACKGROUND: Colorectal multidisciplinary teams (CR MDTs) were introduced to enhance the cancer care pathway and allow for early investigation and treatment of cancer. However, there are no 'gold standards' set for this process. The aim of this study was to review the literature systematically and provide a qualitative analysis on the principles, organization, structure and output of CR MDTs internationally. METHODS: Literature on the role of CR MDTs published between January 1999 and March 2020 in the UK, USA and continental Europe was evaluated. Historical background, structure, core members, education, frequency, patient-selection criteria, quality assurance, clinical output and outcomes were extracted from data from the UK, USA and continental Europe. RESULTS: Forty-eight studies were identified that specifically met the inclusion criteria. The majority of hospitals held CR MDTs at least fortnightly in the UK and Europe by 2002 and 2005 respectively. In the USA, monthly MDTs became a mandatory element of cancer programmes by 2013. In the UK, USA and in several European countries, the lead of the MDT meeting is a surgeon and core members include the oncologist, specialist nurse, histopathologist, radiologist and gastroenterologist. There were differences observed in patient-selection criteria, in the use of information technology, MDT databases and quality assurance internationally. CONCLUSION: CR MDTs are essential in improving the patient care pathway and should express clear recommendations for each patient. However, a form of quality assurance should be implemented across all MDTs.

Measuring quality of life in patients with abdominal wall hernias: a systematic review of available tools.

INTRODUCTION: Abdominal wall herniation (AWH) is an increasing problem for patients, surgeons, and healthcare providers. Surgical-site specific outcomes, such as infection, recurrence, and mesh explantation, are improving; however, successful repair still exposes the patient to what is often a complex major operation aimed at improving quality of life. Quality-of-life (QOL) outcomes, such as aesthetics, pain, and physical and emotional functioning, are less often and less well reported. We reviewed QOL tools currently available to evaluate their suitability. METHODS: A systematic review of the literature in compliance with PRISMA guidelines was performed between 1st January 1990 and 1st May 2019. English language studies using validated quality-of-life assessment tool, whereby outcomes using this tool could be assessed were included. RESULTS: Heterogeneity in the QOL tool used for reporting outcome was evident throughout the articles reviewed. AWH disease-specific tools, hernia-specific tools, and generic tools were used throughout the literature with no obviously preferred or dominant method identified. CONCLUSION: Despite increasing acknowledgement of the need to evaluate QOL in patients with AWH, no tool has become dominant in this field. Assessment, therefore, of the impact of certain interventions or techniques on quality of life remains difficult and will continue to do so until an adequate standardised outcome measurement tool is available.

Prolonged recovery time after eruptive disturbance of a deep-sea hydrothermal vent community.

Deep-sea hydrothermal vents are associated with seafloor tectonic and magmatic activity, and the communities living there are subject to disturbance. Eruptions can be frequent and catastrophic, raising questions about how these communities persist and maintain regional biodiversity. Prior studies of frequently disturbed vents have led to suggestions that faunal recovery can occur within 2-4 years. We use an unprecedented long-term (11-year) series of colonization data following a catastrophic 2006 seafloor eruption on the East Pacific Rise to show that faunal successional changes continue beyond a decade following the disturbance. Species composition at nine months post-eruption was conspicuously different than the pre-eruption 'baseline' state, which had been characterized in 1998 (85 months after disturbance by the previous 1991 eruption). By 96 months post-eruption, species composition was approaching the pre-eruption state, but continued to change up through to the end of our measurements at 135 months, indicating that the 'baseline' state was not a climax community. The strong variation observed in species composition across environmental gradients and successional stages highlights the importance of long-term, distributed sampling in order to understand the consequences of disturbance for maintenance of a diverse regional species pool. This perspective is critical for characterizing the resilience of vent species to both natural disturbance and human impacts such as deep-sea mining.

Localizing Fractional Quasiparticles on Graphene Quantum Hall Antidots.

We report localization of fractional quantum Hall (QH) quasiparticles on graphene antidots. By studying coherent tunneling through the localized QH edge modes on the antidot, we measured the QH quasiparticle charges to be approximately ±e/3 at fractional fillings of ν=±1/3. The Dirac spectrum in graphene allows large energy scales and robust quasiparticle localization against thermal excitation. The capability of localizing fractional quasiparticles on QH antidots brings promising opportunities for realizing anyon braiding and novel quantum electronics.

Assessing the effectiveness of laser fistulectomy for anal fistula: a retrospective cohort study.

BACKGROUND: Laser fistulectomy is a minimally invasive, sphincter-sparing procedure for treatment of anal fistula. In several studies, this method has been shown to be safe and effective, with reported success rates ranging from 40 to 88%. We hypothesized that with longer follow-up, these rates would decrease. METHODS: A retrospective case analysis assessing the effectiveness of laser fistulectomy in curing fistula-in-ano tracts within a cohort of patients at a single academic institution was conducted. All patients having laser ablation between March 2016 and July 2018 were analyzed. Cure of the fistula was determined by history and postoperative physical exam, and was defined as complete closure of fistula tract with resolution of symptoms. Secondary symptoms of fecal incontinence, infection, and pain were evaluated. RESULTS: Eighteen patients (10 males, mean age 41 ± 13 years) were analyzed. Transphincteric fistula was the most common type (67%, N = 12). The mean number of previous fistula procedures was 1.33 ± 1.64. There was a 22% (N = 4) success rate at an average postoperative follow-up period of 29 ± 8 months (range 18-46 months). Of those who failed, 64% (N = 9) had a subsequent fistula procedure. There were no cases of fecal incontinence, but 3 cases (17%) of postoperative infection were reported and 8 patients (44%) had a subjective increase in pain at first follow-up appointment. CONCLUSIONS: Our data showed a much higher failure rate of laser fistulectomy compared to those reported in the literature. However, the small sample size, a large amount of heterogeneity in our patient population with a mixture of fistula types present, and various laser techniques applied decreased the power of this study.

Postoperative chemotherapy improves survival in patients with resected high-risk Stage II colorectal cancer: results of a systematic review and meta-analysis.

AIM: The aim was to assess the benefit of adjuvant chemotherapy in high-risk Stage II colorectal cancer. METHOD: A systematic literature review and meta-analysis was performed comparing survival in patients with resected Stage II colorectal cancer and high-risk features having postoperative chemotherapy vs no chemotherapy. RESULTS: Of 1031 articles screened, 29 were included, reporting on 183 749 participants. Adjuvant chemotherapy significantly improved overall survival [hazard ratio (HR) 0.61, P < 0.0001], disease-specific survival (HR = 0.73, P = 0.05) and disease-free survival (HR = 0.59, P < 0.0001) compared to no chemotherapy. Adjuvant chemotherapy significantly increased 5-year overall survival (OR = 0.53, P = 0.0008) and 5-year disease-free survival (OR = 0.50, P = 0.001). Overall survival and disease-free survival remained significantly prolonged during subgroup analysis of studies published from 2015 onwards (HR = 0.60, P < 0.0001; HR = 0.65, P = 0.0001; respectively), in patients with two or more high-risk features (HR = 0.59, P = 0.0001; HR = 0.70, P = 0.03; respectively) and in colon cancer (HR = 0.61, P < 0.0001; HR = 0.51, P = 0.0001; respectively). Overall survival, disease-specific survival and disease-free survival during subgroup analysis of individual high-risk features were T4 tumour (HR = 0.58, P < 0.0001; HR = 0.50, P = 0.003; HR = 0.75, P = 0.05), < 12 lymph nodes harvested (HR = 0.67, P = 0.0002; HR = 0.80, P = 0.17; HR = 0.72, P = 0.02), poor differentiation (HR = 0.84, P = 0.35; HR = 0.85, P = 0.23; HR = 0.61, P = 0.41), lymphovascular or perineural invasion (HR = 0.55, P = 0.05; HR = 0.59, P = 0.11; HR = 0.76, P = 0.05) and emergency surgery (HR = 0.60, P = 0.02; HR = 0.68, P = 0.19). CONCLUSION: Adjuvant chemotherapy in high-risk Stage II colorectal cancer results in a modest survival improvement and should be considered on an individual patient basis. Due to potential heterogeneity and selection bias of the included studies, and lack of separate rectal cancer data, further large randomized trials with predefined inclusion criteria and standardized chemotherapy regimens are required.