Multicenter Prospective Observational Study Research Articles

Sepsis epidemiology and prognosis in cancer patients: Preliminary results of a multicenter prospective observational study

Sepsis epidemiology and prognosis in cancer patients: Preliminary results of a multicenter prospective observational study

SARS-CoV-2 vaccination in the first year after hematopoietic cell transplant or chimeric antigen receptor T cell therapy: A prospective, multicenter, observational study.

The optimal timing of vaccination with SARS-CoV-2 vaccines after cellular therapy is incompletely understood. The objectives of this study are to determine whether humoral and cellular responses after SARS-CoV-2 vaccination differ if initiated <4 months versus 4-12 months after cellular therapy. We conducted a multicenter prospective observational study at 30 cancer centers in the United States. SARS-CoV-2 vaccination was administered as part of routine care. We obtained blood prior to and after vaccinations at up to five time points and tested for SARS-CoV-2 spike (anti-S) IgG in all participants and neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains, as well as SARS-CoV-2-specific T cell receptors (TCRs), in a subgroup. We enrolled 466 allogeneic hematopoietic cell transplant (HCT; n=231), autologous HCT (n=170), and chimeric antigen receptor T cell (CAR-T cell) therapy (n=65) recipients between April 2021 and June 2022. Humoral and cellular responses did not significantly differ among participants initiating vaccinations <4 months vs 4-12 months after cellular therapy. Anti-S IgG ≥2,500 U/mL was correlated with high neutralizing antibody titers and attained by the last time point in 70%, 69%, and 34% of allogeneic HCT, autologous HCT, and CAR-T cell recipients, respectively. SARS-CoV-2-specific T cell responses were attained in 57%, 83%, and 58%, respectively. Pre-cellular therapy SARS-CoV-2 infection or vaccination were key predictors of post-cellular therapy immunity. These data support mRNA SARS-CoV-2 vaccination prior to, and reinitiation three to four months after, cellular therapies with allogeneic HCT, autologous HCT, and CAR-T cell therapy.

Efficacy and Safety of Surgical Peripheral Iridectomy, Goniosynechialysis, and Goniotomy for Advanced Primary Angle-closure Glaucoma without Cataract: One-year Results of a Multicenter Study.

The combination of surgical peripheral iridectomy, goniosynechialysis, and goniotomy is a safe and effective surgical approach for advanced primary angle-closure glaucoma without cataract. To evaluate the efficacy and safety of surgical peripheral iridectomy (SPI), goniosynechialysis (GSL), and goniotomy (GT) in advanced primary angle-closure glaucoma (PACG) eyes without cataract. A prospective multicenter observational study was performed for patients who underwent combined SPI, GSL, and GT for advanced PACG without cataract. Patients were assessed before and after the operation. Complete success was defined as achieving intraocular pressure (IOP) between 6-18mm Hg with at least a 20% reduction compared to baseline, without the use of ocular hypotensive medications or reoperation. Qualified success adopted the same criteria but allowed medication use. Factors associated with surgical success were analyzed using logistic regression. A total of 61 eyes of 50 advanced PACG were included. All participants completed 12 months of follow-up. Thirty-six eyes (59.0%) achieved complete success, and 56 eyes (91.8%) achieved qualified success. Preoperative and postsurgical at 12 months mean IOPs were 29.7±7.7 and 16.1±4.8mm Hg, respectively. The average number of ocular hypotensive medications decreased from 1.9 to 0.9 over 12 months. The primary complications included IOP spike (n=9), hyphema (n=7), and shallow anterior chamber (n=3). Regression analysis indicated that older age (odds ratio [OR]=1.09; P=0.043) was positively associated with complete success, while a mixed angle closure mechanism (OR=0.17; P=0.036) reduced success rate. The combination of SPI, GSL, and GT is a safe and effective surgical approach for advanced PACG without cataract. It has great potential as a first-line treatment option for these patients.

Impact of hyponatremia in patients hospitalized in Internal Medicine units: Hyponatremia in Internal Medicine units.

The aim of this study was to analyze the impact and the clinical and evolutionary characteristics of hypotonic hyponatremia in patients hospitalized in Internal Medicine units. Prospective multicenter observational study of patients with hypotonic hyponatremia (<135 mmol/L) in 5 hospitals in southern Spain. Patients were included according to point prevalence studies carried out every 2 weeks between March 2015 and October 2017, by assessing demographic, clinical, analytical, and management data; each patient was subsequently followed up for 12 months, during which time mortality and readmissions were assessed. A total of 501 patients were included (51.9% women, mean age = 71.3 ± 14.24 years), resulting in an overall prevalence of hyponatremia of 8.3%. The mean comorbidities rate was 4.50 ± 2.41, the most frequent diagnoses being heart failure (115) (23%), respiratory infections (65) (13%), and oncological pathologies (42) (6.4%). Of the total number of hyponatremia cases, 180 (35.9%) were hypervolemic, 164 (32.7%) hypovolemic, and 157 (31.3%) were euvolemic. A total of 87.4% did not receive additional diagnostic tests to establish the origin of the condition and 30% did not receive any treatment. Hospital mortality was 15.6% and the mean length of stay was 14.7 days. Euvolemic and admission hyponatremia versus hyponatremia developed during admission were significantly associated with lower mortality rates (P = .037). Mortality at 1 year and readmissions were high (31% and 53% of patients, respectively). Hyponatremia was common in Internal Medicine areas, with hypervolemic hyponatremia being the most frequent type. The mortality rate was high during admission and at follow-up; yet there is a margin for improvement in the clinical management of this condition.

Atrial fibrillation cryoablation guided by pressure waveform: a prospective multicentre registry

Abstract Background Cryoballoon ablation (CA) procedures require optimal occlusion of the pulmonary veins (PV), which is conventionally evaluated by iodine contrast injection through the catheter tip. This technique has some weaknesses such as risk of allergic reactions, nephrotoxicity, requirement of fluoroscopy (sometimes at high doses), requirement of a second operator, among others. PV pressure waveform assessment is an alternative method for confirming occlusion, however, multicentre assessment of periprocedural efficacy and safety is lacking. Purpose To describe the intra-procedural performance and safety of routine pressure-based CA. Methods In this independent prospective multicentre observational study, baseline and procedure data from consecutive pressure-guided CB ablations were collected. Operators were not required to have experience in pressure-guided CA for participating in the registry. They were asked to classify the pressure waveform curves into type 1 (presence of "a-wave" and/or symmetric "v-wave", meaning incomplete PV occlusion) and type 2 (absence of "a-wave" and asymmetric "v-wave", meaning complete PV occlusion), Figure 1. The primary endpoint was PV isolation in all veins without use of contrast. Procedure performance and adverse events were also analyzed. Results A total of 150 patients (mean age: 61 ± 10 y.) with paroxysmal (62%) or persistent AF (38%) were included and underwent pressure-guided CA in 9 centres from Spain. Complete PV isolation was achieved in 148 patients (98%). The operators switched to contrast use in 14 cases (9%), mainly to double check the occlusion. Total procedure and fluoroscopy time were 97 ± 39 and 19 ± 10 min respectively. There were 7 (4.7%) procedure related adverse events: 4 phrenic nerve palsy (3 of them were transient), 1 transient coronary ST elevation (before ablation), 1 gastroparesis and 1 femoral pseudoaneurysm. Most relevant results are summarized in Figure 2. Conclusion In this multicentre and multi-brand assessment, CA guided by pressure waveforms provided outstanding procedural outcomes, which were equivalent to those reported with the conventional approach. All operators could easily obtain and identify the waveform without a specific learning curve, avoiding the use of iodine contrast in most cases. The long-term efficacy of this approach will be presented in future analyses.Pressure waveforms types in cryoablationProcedural data

#226 Outcome of intermittent hemodialysis vs. continuous kidney replacement therapy for acute kidney injury: observational prospective multi-center study

Abstract Background and Aims Continuous hemodialysis in hemodynamically stable acute kidney injury (AKI) patients may impact outcome differently compared to intermittent hemodialysis, although this issue is controversial. We look at differences in AKI outcomes between patients treated with intermittent hemodialysis (IHD) and patients treated with continuous kidney replacement therapy (CKRT) modalities in in Kuwait. Method Clinically and hemodynamically stable adult inpatients with native kidneys (i.e., did not need inotropic support or mechanical ventilation) who received IHD or CKRT for AKI, in seven public hospitals in Kuwait between 1/January to 31/December 2021 were recruited. CKRT was selected due to lack of access to water treatment in patients wards in some of the participating hospitals. Demographics, comorbidities, dialytic and non-dialytic management data, and 30-day kidney and patient outcome data for, were prospectively collected and analyzed. Results Total number of AKI patients not on inotropic support and not mechanically ventilated who received dialysis during study period was 229 (age: 59.9 years; males: 60.3%; baseline eGFR: 56 ml/min). IHD (group 1) was performed in 27.1% of the cohort whereas CKRT (group 2) was performed in 72.9%. There was no statistically significant difference between the two groups in age (58.4 for IHD and 59.9 for CKRT, p=0.6), baseline eGFR (55 ml/min for IHD and 56.4 for CKRT, p=0.8), sex ratio, incidence of diabetes, hypertension or cardiovascular disease, or cause of AKI. However, renin angiotensin aldosterone system inhibitors (RAASi) were precipitating factors for AKI more significantly in the IHD group (25.8% vs. 6% for CKRT, P ≤ 0.001). Intensive care unit (ICU) contributed 21% of cases (14.5% for IHD and 23.4% for CKRT, insignificant p value of 0.1). Also, there was no statistically significant difference in receiving intravenous fluids between the two groups (71% for IHD vs. 71.5% for CKRT, p=0.8), however, more patients in the IHD group received diuretics (62.9% vs 43.1% for CKRT, p=0.008). Dialysis vascular access was right internal jugular vein in 59% (75.8% FOR IHD vs. 52.7% for CKRT) followed by femoral vein in 35% of cases (19.4%). Extracorporeal membrane oxygenation (ECMO) was used in only two cases in the CKRT group. Of the total cohort, 21.8% died, with no difference between the two groups (16.1% for IHD vs 24% for CKRT, p=0.2). Partial recovery was higher in IHD group (30.8% vs.17.3%, p=0.046) and complete recovery higher in CKRT group 33.1% vs 13.5%, p=0.009). eGFR at 30 days was 53.2 ml/min with no statistically significant difference between the two groups (44.6 for IHD vs 56.1 for CKRT, p=0.15). Conclusion The IHD group and the CKRT group were statistically similar in basic characteristics and received similar lines of management, except for the diuretics. At 30 days, they had similar death rates but CKRT group had higher rates of complete recovery than the IHD group. This is in line with published literature that suggest CKRT may not improve mortality but may improve kidney recovery.

#1323 Kidney health in children with X-linked hypophosphatemia: lessons from the prospective multicenter study in Germany and Switzerland

Abstract Background and Aims X-linked hypophosphatemia (XLH) is the most common genetic cause of hypophosphatemia. Mutations in the PHEX gene cause elevated circulating levels of fibroblast growth factor 23 (FGF23), phosphaturia, rickets and osteomalacia. Conventional treatment with phosphate salts and active vitamin D is associated with nephrocalcinosis and preclinical studies in mice have shown that a chronic high phosphate load causes proximal tubular injury and fibrosis. There is no detailed analysis on kidney health in XLH patients yet. Method We conduct a prospective observational multicenter study in Germany and Switzerland to evaluate kidney health in pediatric XLH patients. Patients receive conventional therapy or burosumab, a fully humanized anti-FGF23 antibody. Clinical and biochemical data, blood and urine samples are collected annually. Results To date, 137 patients (80 girls, mean age 10.5 years) from 40 centers are included. 22% of patients have been treated conventionally for 7.5 years, 78% of patients have received burosumab for 2.3 years with 3.7 years of conventional therapy beforehand. Children with XLH show increased systolic blood pressure and body mass index (BMI), and overweight (BMI &amp;gt;90th percentile) and hypertension (systolic blood pressure &amp;gt;95th percentile) were each found in 20% of patients. A reduced eGFR (&amp;lt;90 ml/min/1.73 m2) and/or nephrocalcinosis was noted in 7% and 28% of patients, respectively. Microalbuminuria is twice as prevalent in children with XLH as in healthy children (14% vs 7%). Urinary lithogenic substances (calcium, oxalate, glycolate) are increased in 1.8-22.8%, and citrate is decreased in 12.3% of XLH patients. Tubular injury markers neutrophil gelatinase-associated lipocalin (NGAL) and Dickkopf-3 (DKK3) are elevated in urine of children with XLH, Chitinase 3-like 1 (CHl3L1) is comparable to children with chronic kidney disease, while kidney injury molecule-1 (Kim-1), indicating proximal tubule cell injury, is within a normal range. The renal inflammation marker monocyte chemoattractant protein-1 (MCP-1) is elevated in children with XLH, and epidermal growth factor (EGF), a marker of tubular cell repair, is decreased compared to healthy adults. Conclusion Pediatric XLH patients on conventional or burosumab therapy show enhanced systolic blood pressure slightly associated with elevated BMI, and significant renal comorbidity, i.e. reduced eGFR, nephrocalcinosis, increased urinary lithogenic substances, elevated urinary markers of glomerular and tubular injury and inflammation. The impact of conventional versus burosumab treatment are still being investigated.

Antifungal Prophylaxis and Treatment of Breakthrough Invasive Fungal Diseases in High-Risk Hematology Patients: A Prospective Observational Multicenter Study

Antifungal Prophylaxis and Treatment of Breakthrough Invasive Fungal Diseases in High-Risk Hematology Patients: A Prospective Observational Multicenter Study

Local Excision for organ preservation in early REctal cancer with No Adjuvant treatment (LORENA Trial): prospective observational study protocol

IntroductionLocal resection (LR) is an alternative to total mesorectal excision (TME) that avoids its associated morbidity to the detriment of oncological radicality in early stages of rectal cancer. There are several conditioning factors for the success of this strategy, such as poor prognosis histological factors (PPHF), involvement of resection margins, clinical under staging, or complications that may lead to the indication for radical surgery with TME. Patients and methodAn international multicenter prospective observational open-label study has been designed. Consecutive patients diagnosed with early rectal cancer (cT1N0 on MRI +/− endorectal ultrasound) whose lower limit is a maximum of 2 cm proximal to the ano-rectal junction will be included. The primary objective of the study is to determine the overall prevalence of PPHF after LR and requiring TME or postoperative radio-chemotherapy. DiscussionThe prevalence of PPHF conditioning the success of LR in early distal rectal cancer has been scarcely studied in the literature, and there are very few prospective data. Considering the increasing interest in the watch and wait strategy in rectal cancer and its possible application in early-stage tumors, it seems necessary to know this information.The results of this study will help guide clinical practice in patients with early distal rectal cancer. It will also provide quality information for the design of future comparative studies to improve organ preservation success in these patients.Trial registration number: NCT05927584.

Real-life Achievements of MiniMed™ 780G Advanced Closed Loop System in Youth With Type 1 Diabetes: AWeSoMe Study Group Multi-Center Prospective Trial.

We assessed real-life glycemic outcomes and predictors of composite measures of optimal glycemic control in children and adolescents with type 1 diabetes (T1D) during their initial 12 months of the MiniMed™ 780G use. This prospective observational multicenter study collected demographic, clinical, and two-week 780G system data at five timepoints. Optimal glycemic control was defined as a composite glycemic control (CGC) score requiring the attainment of four recommended continuous glucose monitoring (CGM) targets, as well as the glycemia risk index (GRI) of hypoglycemia and hyperglycemia and composite CGM index (COGI). Outcome measures included longitudinal changes in multiple glycemic parameters and CGC, GRI, and COGI scores, as well as predictors of these optimal measures. The cohort included 93 children, 43% girls, with a median age of 15.1 years [IQR 12.9,17.0]. A longitudinal analysis adjusted for age and socioeconomic index yielded a significant improvement in glycemic control for the entire cohort (ptime<0.001) after the transition to 780G. The mean HbA1c (SE) was 8.65%(0.12) at baseline and dropped by more than 1% after one year to 7.54%(0.14) (ptime<0.001). Optimal glycemic control measures improved at 12 months post 780G; CGC improved by 5.6-fold (p<0.001) and was attained by 24% of the participants, the GRI score improved by 10-fold (p=0.009) and was achieved by 10% of them, and the COGI improved by 7.6-fold (p<0.001) and was attained by 20% of them. Lower baseline HbA1c levels and increased adherence to AHCL usage were predictors of achieving optimal glycemic control. The AHCL 780G system enhances glycemic control in children and adolescents with T1D, demonstrating improvements in HbA1c and CGM metrics, albeit most participants did not achieve optimal glycemic control. This highlights yet ongoing challenges in diabetes management, emphasizing the need for continued proactive efforts on the part of healthcare professionals, youth, and caregivers.

Snapshot Audit Early Onset Colorectal Cancer (EOCC) – What is the Current Situation in Switzerland?

Abstract Background Early onset colorectal cancer (EOCC), defined as colorectal cancer (CRC) ≤ 50 years, has seen an alarming rising incidence in western countries. Aims This research aims to determine the current state of incidence, symptoms, diagnostic methods, and treatment approach in EOCC compared to late onset CRC (LOCRC) in the extended Northwestern Switzerland. Methods Patients seeking care for CRC between April-November 2023 were enrolled in a prospective multicenter (11 hospitals within extended Northwestern Switzerland) observational cohort study. Information was collected using questionnaires and patient charts. Results We included 315 patients, thereof 38 (10.8%) EOCC. In total 211 (58.9%) patients were male, mean age was 42.5 and 71.2 years, respectively. Rectal bleeding was the main symptom in both groups (60.5% vs 37.0%), followed by change in bowel habits in EOCC and fatigue in LOCRC without reaching significance. Rectal bleeding and mucous, abdominal pain, change of bowel habits and bloating were significantly more often in EOCC. Significantly more LOCRC patients stated that their physical condition affected sexual erection and social interaction, whereas in EOCC, family life was significantly affected. For both groups, endoscopy was the leading diagnostic tool. EOCC had a diagnostic delay of 6.5 weeks compared to their counterparts. No difference in frequency of neoadjuvant treatment, surgical approach or need for emergency surgery was observed. In EOCC, a trend to more lymph node retrieval was observed and significantly more EOCC received an ostomy. Postoperatively, significantly more EOCC than LOCRC patients received adjuvant chemotherapy (55.6 % vs 28.6 %). Conclusion Our analysis illustrates the current standard-of-care of EOCC in the extended Northwestern Switzerland. EOCC compared to LOCRC patients present themselves differently to the medical community, leading to a different approach to their symptoms, which eventually results in a delayed diagnosis. Based on these results, it is time to foster awareness and start redefining national screening criteria.

Study protocol: the biologics in severe chronic rhinosinusitis with nasal polyps survey

IntroductionChronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent condition affecting approximately 2% of the population. Medical treatment consists long-term use of intranasal corticosteroids and short-term use of oral corticosteroids,...

Effects of incremental peritoneal dialysis with low glucose-degradation product neutral pH solution on clinical outcomes.

Incremental peritoneal dialysis (IPD) could decrease unfavorable glucose exposure results and preserve (RKF). However, there is no standardization of dialysis prescriptions for patients undergoing IPD. We designed a prospective observational multi-center study with a standardized IPD prescription to evaluate the effect of IPD on RKF, metabolic alterations, blood pressure control, and adverse outcomes. All patients used low GDP product (GDP) neutral pH solutions in both the incremental continuous ambulatory peritoneal dialysis (ICAPD) group and the retrospective standard PD (sPD) group. IPD patients started treatment with three daily exchanges five days a week. Control-group patients performed four changes per day, seven days a week. A total of 94 patients (47 IPD and 47 sPD) were included in this study. The small-solute clearance and mean blood pressures were similar between both groups during follow-up. The weekly mean glucose exposure was significantly higher in sPD group than IPD during the follow-up (p < 0.001). The patients with sPD required more phosphate-binding medications compared to the IPD group (p = 0.05). The rates of peritonitis, tunnel infection, and hospitalization frequencies were similar between groups. Patients in the sPD group experienced more episodes of hypervolemia compared to the IPD group (p = 0.007). The slope in RKF in the 6th month was significantly higher in the sPD group compared to the IPD group (65% vs. 95%, p = 0.001). IPD could be a rational dialysis method and provide non-inferior dialysis adequacy compared to full-dose PD. This regimen may contribute to preserving RKF for a longer period.

Machine learning with electrocardiograms to optimize mortality risk stratification in patients with suspected acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, and Blood Institute (NHLBI) and National Center for Advancing Translational Sciences (NCATS). Background The importance of risk stratification in patients with suspected acute coronary syndrome (ACS) extends beyond diagnosis and immediate treatment. It influences the precision of care delivery and the allocation of resources to those at highest risk of adverse events. Purpose We sought to evaluate the prognostic value of electrocardiogram (ECG) feature-based machine learning models to risk-stratify long-term mortality in those with suspected ACS. Methods This was a multicenter prospective observational cohort study of consecutive, non-traumatic patients evaluated at the emergency department for suspected ACS. The derivation cohort included 4,015 patients from a University Medical Center (age 59±16 years, 47% women, 80% training with 10-fold cross-validation and 20% testing). Ascertainment of all-cause death was based on numerous data sources, including the Centers for Disease Control and Prevention’s National Death Index registry. We trained six machine learning methods for survival analysis using 73 morphological ECG features from presenting prehospital 10-second 12-lead ECGs. We used predicted risk scores in a variational Bayesian Gaussian mixture model to define three risk groups corresponding to low, moderate, and high-risk and compared the resulting classification performance against the HEART score. The external testing cohort included 3,095 patients from a University (age 59±15 years, 44% women). Results The mortality rate was 20.3% in the derivation cohort after an average follow-up period of 3.53 years (IQR 1.75 - 5.32). Extra Survival Trees outperformed other forecasting models during cross-validation. In the internal testing cohort, the derived risk groups were significantly predictive of survival (Kaplan-Meier log-rank test statistic = 121.14, p&amp;lt;0.001), outperforming the classification performance using the HEART score (Figure 1). Our machine learning-based risk stratification model detected &amp;gt;90% of death events missed by low-risk HEART score (Figure 2). Ruling-out the low-risk group, it achieved a negative predictive value of 93.4% with a sensitivity of 85.9% (compared to 89.0% and 75.0%, respectively, for the HEART score). This classification performance generalized well to our external testing cohort. Compared to those in the low-risk group, patients at moderate (OR = 3.62 [1.35-9.74]) and high (OR = 6.12 [2.38-15.75]) risk had significantly higher odds of 30-day cardiovascular death (n=109, 3.5%). Conclusions Using only features from the 10-second 12-lead ECG, we derived and externally validated a machine learning model that stratifies the mortality risk of patients during long-term follow up. This model outperformed current standard of care based on the HEART score. Future work should validate the potential of this decision-support tool in influencing treatment plans and resource allocation.Figure 1.Clustering performanceFigure 2.Sankey diagram

Pre-Operative Group and Save in Elective and Emergency Laparoscopic Cholecystectomy: Necessity, Cost-Effectiveness, and Own Experience.

Background: Laparoscopic cholecystectomy is associated with a high safety profile. This study seeks to quantify the incidence of blood transfusion in both the elective and emergency settings, examine related patient outcomes, and investigate selection criteria for pre-operative Group and Save (G&S) sampling. Methods: A prospective multi-centre observational study was conducted to investigate patients undergoing either elective or emergency laparoscopic cholecystectomy in the UK between January 2020 and May 2021. Multivariate logistical regression models were used to identify patient factors associated with the risk of transfusion and explore outcomes linked to pre-operative G&S sampling. Results: This study comprised 959 patients, with 631 (65.8%) undergoing elective cholecystectomy and 328 (34.2%) undergoing emergency surgery. The median age was 48 years (range: 35-59), with 724 (75.5%) of the patients being female. Only five patients (0.5%) required blood transfusions, receiving an average of three units, with the first unit administered approximately six hours post-operatively. Among these cases, three patients (60%) had underlying haematological conditions. In adjusted models, male gender was significantly associated with the need for a blood transfusion (OR 11.31, p = 0.013), while the presence of a pre-operative Group and Save sample did not demonstrate any positive impact on patient outcomes. Conclusions: The incidence of blood transfusion following laparoscopic cholecystectomy is very low. Male gender and haematological conditions may present as independent risk factors. Pre-operative G&S sampling did not yield any positive impact on patient outcomes and could be safely excluded in both elective and emergency cases, although certain population subsets will warrant further consideration.

Prospective observational study comparing the perioperative outcomes of laparoscopic colectomy with or without epidural anesthesia: the Kanagawa Yokohama Colorectal Cancer Study Group (KYCC) 1806.

There have been no adequate comparisons of the efficacy, safety, and efficiency of analgesia after laparoscopic colorectal resection (LAC), with and without epidural anesthesia (EDA). This was a multicenter prospective observational study of patients undergoing LAC. The primary end point was the mean visual analog scale (VAS) score on postoperative days (PODs) 1-7. The secondary end points were the highest VAS, complication rate, days to first ambulation and fatigue, length of hospital stay, and time to commencement of surgery. We compared an EDA group (Group E, n = 48) and a no-EDA group (Group O, n = 48) after matching. The mean VAS was not significantly different between the groups (28.7 vs. 30.1, p = 0.288). On assessing the secondary end points, the highest VAS was not significantly different between the groups. In fact, the VAS was lower in Group E only on POD 2. There was no difference in the incidence of complications, the time to first postoperative evacuation was shorter in Group E, and postoperative hospitalization was similar. The time to surgery was shorter in Group O. These results suggest that LAC without EDA is a feasible option, but with the early and regular use of adjunctive measures to provide more stable analgesia.

Telemedicine in Nail Psoriasis: Validation of a New Tool to Monitor (In-Person, In-Picture, and In-Video) Nail Psoriasis Severity in Patients with Concurrent Onychophagia and Onychotillomania.

Since during the COVID-19 pandemic nail psoriasis was evaluated exclusively with teledermatology, dermatologists started to face the difficulty in rating it concurrent with other onycopathies (i.e., onychotillomania and onychophagy). Thus, we aimed to improve the existing severity scores and verify the value in different clinical settings (i.e., in person vs. teledermatology (video or picture)). This multicenter prospective observational study evaluated patients with nail psoriasis and screened them for onychophagy or onychotillomania in telemedicine from May2020 to January 2021. For therapeutic purposes patients with nail psoriasis were followed and rated with the Nijmegen-Nail psoriasis Activity Index tooL (N-NAIL) for 9months; at the same time, N-NAIL and a new dedicated index that monitor also the changes in nail dimension (Galeazzi-(G) N-NAIL) were tested for accuracy. We assessed inter- and intraobserver agreement for the three different settings (in person, video, and pictures). In our cohort of 382 patients with nail psoriasis after a clinical and dermatoscopic assessment we found 20 (5.24%) patients with onychophagy and 17 (4.45%) patients with onychotillomania. Analysis of the impact of nail psoriasis on patients revealed that onycholysis and crumbing, followed by subungual hyperkeratosis, were the clinical signs that prevalently bothered patients. N-NAIL score displayed moderate intra- and interobserver agreement. Over the 9months follow-up, N-NAIL vs. GN-NAIL displayed a solid correlation at all the examined time points, i.e., baseline and after 3, 6, and 9months. We created a new tool, the GN-NAIL capable of efficiently scoring nail psoriasis severity in complex cases, such as patients with onychotillomania and onychophagy, and monitor response to treatment during the COVID-19 pandemic.

Abstract PO1-23-04: The IBRAnet localisation study; a UK National multi-centre cohort study comparing the safety and effectiveness of guidewire, RFID, and magnetic seed- guided localisation for impalpable breast lesions

Abstract Background Wire-guided localisations (WGL) of breast cancers have been the gold-standard for pre-operative localisation of non-palpable breast cancers for many years but have significant limitations. Newer localisation techniques have been introduced including Radio Frequency ID tags (RFID) and magnetic seeds which aim to overcome these limitations. The UK iBRA-net group have designed a multi-centre platform study aiming to compare the safety and effectiveness of wire, RFID, magnetic seeds, and radar-based localisation. A second aim was the qualitative assessment of shared learning as users gained experience. Methods A UK national multi-centre prospective observational platform study was designed to compare a control arm of WGL for women undergoing breast conserving surgery with two interventional arms of RFID tags and magnetic seeds. Patient data were collected between August 2018 and July 2022 in UK centres. The primary outcome was accurate excision of the index lesion at the time of surgery. Secondary outcomes were defined as; resection margins, breast reoperation rate (planned and unplanned), complications, cancellation rate on day of surgery, and duration of the surgery. To account for lesion size in the assessment of excision weight, we used size as a denominator over two dimensions, reporting this as weight/size2, in g/mm2. Data was collected prospectively on a secure REDcap database following approval from local audit departments. To calculate the sample size a power calculation was employed, with n=950 patients per group the upper limit of the observed one-sided 95% confidence interval for the difference between identification rates (intervention vs WGL) is expected to be less than 0.9% with 80% power, assuming the two methods both have an expected identification rate of 99.4%. Simple summary statistics were calculated for each outcome and data were tested for distribution and differences between groups using unpaired t-tests, Mann-Whitney U tests, and Chi squared tests as appropriate. Analyses were conducted using Stata® IC version 14 (StataCorp, College Station, Texas, USA). Results Data were accrued from 3484 patients in 55 units. This included 1293 patients having WGL, 1188 RFID tags, and 1003 magnetic seeds. RFID had a lower rate of identification of the index lesion compared to magnetic seed and wire (97.9% vs. 99.8% vs. 99.1% respectively). When comparing the reasons behind failure of the primary outcome, the majority were not thought to be related to the modality of localisation. Data from 1560 patients with unifocal, unilateral breast lesions were included in subgroup analysis, excluding those having neo-adjuvant chemotherapy and those having therapeutic mammoplasty. Positive margins were lower in RFID excisions compared to wire (11.2% vs. 15% respectively, p&amp;lt; 0.05), whereas magnetic seed were equivalent (11.2 % vs 13.3%, P=0.22). Routine cavity shaves were performed in 64.5% of WGL vs 48.3% of RFID vs 64.3% of magnetic guided excisions. There was no difference in specimen weight/size2 (0.138 WGL vs. 0.131 RFID vs. 0.15 magnetic seed). Re-excision (for positive or close margins) was equivalent across the three groups (13.2% of wire vs 15% of RFID vs 12.3% of magnetic seed guided excisions, p=0.3). There have been four shared learning educational events focussing on three key themes relating to preoperative, intraoperative, and postoperative learning outcomes in addition to 130 database shared learning entries. This may aid other surgeons as they adopt these techniques. Conclusions All three localisation devices demonstrate high levels of localisation accuracy. There was a higher rate of device dislodgement in the RFID group, which was also identified in the shared learning events. However, re-excision rates were equivalent across the three groups. This study has demonstrated a robust platform for the comparative evaluation of new localisation technologies and of sharing learning and experience. Citation Format: Rachel Foster, James Harvey, Rajiv Dave, Anthony Maxwell, Senthurun Mylvaganam, Matthew Gardiner, Sue Down, Nicola Barnes, Mihir Chandarana, Shelley Potter, Yazan Masannat, Chris Holcombe, Tahir Masudi, Amtul Carmichael, Robert Milligan, Jenna Morgan. The IBRAnet localisation study; a UK National multi-centre cohort study comparing the safety and effectiveness of guidewire, RFID, and magnetic seed- guided localisation for impalpable breast lesions [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-23-04.

Abstract PO5-15-10: Plasticity marker FOXC1 expression accurately predicts efficacy of Adjuvant Tamoxifen + Chemotherapy in reducing all-cause mortality in ER+LN- Breast Cancer: Validation in the SCAN-B Prospective Study (NCT02306096)

Abstract INTRODUCTION: Despite the development and validation of multimarker gene panels like OncotypeDx®, Mammaprint® and EndoPredict®, an affordable and globally accessible biomarker approach that can predict increased risk of all-cause mortality in patients diagnosed with ER+LN- breast cancer, as well as the efficacy of adjuvant endocrine + chemotherapy in mitigating such elevated risk, continues to be an unmet medical need. Lack of such a pragmatic solution continues to be the cause of preventable recurrent/metastatic disease in patients diagnosed with ER+LN- breast cancer in resource-challenged settings around the world. We hypothesized that a predictive biomarker strategy that measures expression of the plasticity marker FOXC1, in combination with clinical parameters like tumor size (TS) and tumor grade (TG), may offer equivalent results to that of the above multimarker gene panels at a significantly lower economic cost without compromising accuracy of prediction results. METHODS: Pre-treatment tumor RNA data obtained from a training cohort (compendium of gene expression microarray datasets, n=2857) and a single large validation cohort (SCAN-B Prospective Multicenter Observational Study, n=3520) for patients diagnosed with ER+LN- breast cancer were analyzed for FOXC1 expression, tumor size (TS) and tumor grade (TG) and correlated with Recurrence-Free Survival (RFS) and Overall Survival (OS). Optimized biomarker cutoff values based on model area-under-curve were leave-one-out cross validated and Risk-of-Recurrence (ROR) prediction algorithm derived utilizing the (compendium) training dataset. The unmodified strategy was then validated in the independent (SCAN-B) validation dataset. RESULTS: A predetermined High ROR score calculated using FOXC1 expression, TS and TG (trained using the compendium dataset) predicted efficacy of adjuvant endocrine + chemotherapy over that of adjuvant endocrine therapy alone in ER+LN- patients in terms of statistically significant reduction in all-cause mortality at 8-years post-diagnosis in the SCAN-B validation dataset (4.66% vs 24.06%, n=326, OR=6.48, 95%CI [2.97-14.11], p&amp;lt; 0.0001). OncotypeDx® (5.7% vs 14.4%, n=762, OR=2.79, 95%CI [1.37-5.67], p=0.002), Mammaprint® (5.1% vs 18.4%, n=665, OR= 95%CI [2.04-8.43], p&amp;lt; 0.0001) and Endopredict® (4.8% vs 15.2%, n=923, OR=3.58 95%CI [1.78-7.21], p=0.0002) were also statistically significant predictors of the same. CONCLUSION: Pre-treatment tumor FOXC1 mRNA or protein expression (assessed using qRT-PCR or routine immunohistochemistry (IHC), respectively, when combined with TS and TG presents a unique and economical alternative solution to multimarker gene panel tests like OncotypeDx®, Mammaprint® or Endopredict®, for guiding therapy of patients diagnosed with ER+LN- breast cancer in resource challenged settings. Such an approach to identify elevated risk of recurrence in patients diagnosed with ER+LN- breast cancer and prevent the same by guiding adjuvant endocrine + chemotherapy decisions, could help to extend recurrence-free and overall survival. Such an approach merits testing in real world ER+LN- patient cohorts in resource-challenged settings to help support implementation of this FOXC1-driven predictive biomarker strategy in the clinic. Citation Format: Partha Ray, Tania Ray, Clive Taylor, Robert Hussa. Plasticity marker FOXC1 expression accurately predicts efficacy of Adjuvant Tamoxifen + Chemotherapy in reducing all-cause mortality in ER+LN- Breast Cancer: Validation in the SCAN-B Prospective Study (NCT02306096) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-15-10.

A prospective multicenter European observational study of a single incision sling (Altis®): A safe and effective treatment option for women

Introduction:Single-incision slings were introduced for female stress urinary incontinence (SUI) treatment to decrease surgery time, postoperative pain, and the amount of mesh used. Objective:This multicenter study aims to examine Altis® usage in real-world clinical practice, its effectiveness in treating SUI, patient satisfaction, quality of life, sexual function, and complication rates. Methods:Between 2015 and 2022, a prospective single-arm observational cohort study was conducted across 33 European centers involving 564 patients, investigating the clinical effectiveness of the Altis® sling. Patients were monitored for 36 months. The primary endpoint (success) was a positive impression of improvement and absence of serious/severe/Clavien Dindo (CD) ≥ III-related adverse events at 12 months. Secondary endpoints included effectiveness at 36 months, impact on quality of life, and risk factors for failure. Results:An Altis® was implanted in 564 women. At 12-months, 86.6% of patients achieved success, 97.2% endorsed the surgery, and 90.4% were satisfied with the outcomes. At 36 months, 83.0% reported significant improvement, 94.5% endorsed the surgery, and 89.9% were satisfied. Altis® demonstrated decreased daily pad usage and improved quality of life. Dyspareunia and sexual function largely remained unchanged. However, 11.3% reported pain, and there were instances of serious adverse events. Conclusion:The Altis® implant demonstrated substantial improvements in symptoms and overall quality of life for a majority of women with SUI. Potential complications such as mesh exposure, reoperation, voiding dysfunction, and urinary retention emphasize the importance of preoperative counseling. The Altis® implant is a viable option within the available surgical treatments of SUI.