Multicenter Prospective Observational Cohort Study Research Articles

Long-term outcomes of the first prospective study of active surveillance for prostate cancer in Japan.

Active surveillance for prostate cancer was initiated in the early 2000s. We assessed the long-term outcomes of active surveillance in Japan. This multicenter prospective observational cohort study enrolled men aged 50-80years with stage cT1cN0M0 prostate cancer in 2002 and 2003. The eligibility criteria included serum prostate-specific antigen level ≤ 20ng/mL, ≤ 2 positive cores per 6-12 biopsy samples, Gleason score ≤ 6, and cancer involvement < 50% in the positive core. Patients were encouraged to undergo active surveillance. Prostate-specific antigen levels were measured bimonthly for 6months and every 3months thereafter. Triggers for recommending treatment were prostate-specific antigen doubling time of < 2years and pathological progression on repeat biopsy. Among 134 patients, 118 underwent active surveillance. The median age, prostate-specific antigen level at diagnosis, and maximum cancer occupancy were 70years, 6.5ng/mL, and 11.2%, respectively. Ninety-one patients had only one positive cancer core. The median observation period was 10.7years. At 1year, 65.7% underwent a repeat biopsy, and 37% of patients experienced pathological progression. The active surveillance continuation rates at 5, 10, and 15years were 28%, 9%, and 4%, respectively. One prostate cancer-related death occurred in a patient who refused treatment despite pathological progression at the one-year repeat biopsy. Active surveillance according to this study protocol was associated with conversion to the next treatment without delay, when indicated, despite the selection criteria and follow-up protocols being less rigorous than those recommended in current international guidelines.

Root causes of first-case start time delays for elective surgical procedures: a prospective multicenter observational cohort study in Ethiopia

BackgroundDelays in surgery start times can lead to poor patient outcomes and considerable increases in healthcare expenditures. This is especially true in developing countries that often face systemic inefficiencies, such as a shortage of operating rooms and trained surgical personnel. With substantial effects on patient outcomes, healthcare efficiency, and resource allocation, identifying delays in first-case elective surgery is a crucial area of research.MethodsA multicenter observational study was conducted at three comprehensive and specialized hospitals in the Amhara region of Ethiopia from May 1 to October 30, 2023. The primary aim of the study was to determine the occurrence of late first-case start times, defined as a patient being in the operating room at or after the hospital’s incision time of 2:30 a.m. The secondary aim was to discover potential root causes of delayed first-case start times. All patients scheduled for elective surgery as the first case on the operating list throughout the study period were included in the study. Every emergency, day case, after-hours case, and canceled case was excluded.ResultsA total of 530 surgical patients were included during the study window from May 1 to October 1, 2023. Of these, 41.5% were general surgeries, 20.4% were gynecology and obstetrics surgeries, and 13.2% were orthopedic surgery procedures. Before the procedure started, nine (1.7%) of the participants had prolonged discussion with a member of the surgical team. Patients who arrived in the operating room waiting area at or after 2:30 a.m. were 2.5 times more likely to experience a first-case start time delay than those who arrived before or at 2:00 a.m. (AOR = 2.50; 95% CI: 1.13–5.14). Furthermore, participants with abnormal investigation results were 2.4 times more likely to have a late first-case start time (AOR = 2.41; 95% CI: 1.06, 5.50). Moreover, the odds of a late first-case start time were increased by 10.53 times with the surgeon being in the operating room at or after 2:30 a.m. (AOR = 10.53; 95% CI: 5.51, 20.11).ConclusionThe research highlights a significant occurrence of delayed start times for the first elective surgical procedures. Therefore, directing attention to aspects such as ensuring patients and surgical teams arrive promptly (by or before 2:00 a.m.) and timely evaluation and communication of investigative findings before the scheduled surgery day could facilitate efforts to maximize operating room efficiency and enhance patient health outcomes.

Females have lower salivary flow than males, before and after radiation therapy for head/neck cancer.

To compare salivary flow rates between females and males, before and after radiation therapy (RT) for head and neck cancer (HNC). Prospective observational multicenter cohort study (OraRad). Stimulated whole salivary flow was measured before RT and at 6 and 18 months after RT. Mean (95% confidence interval) salivary flow in g/min before RT was 0.81 (0.71, 0.90) in females (n = 107) and 1.20 (1.15, 1.25) in males (n = 391) (p < 0.001); at 6 months was 0.34 (0.24, 0.44) in females and 0.50 (0.44, 0.55) in males (p = 0.01); at 18 months was 0.49 (0.38, 0.59) in females and 0.70 (0.64, 0.75) in males (p < 0.001). Median nadir salivary flow after RT was 0.22 in females and 0.35 in males (p < 0.001). A lower nadir salivary flow in females, but not males, was associated with an increased risk for tooth failure (p = 0.02). Females with HNC have lower stimulated whole salivary flow than males, before and after RT. Low salivary flow after RT may be a risk factor for tooth failure among females. The lower pre-RT salivary flow rates in females, combined with prior literature in other populations, indicates that, in general, females have lower stimulated salivary flow than males.

Usefulness of the one-step technique in functional end-to-end anastomosis for colonic surgery: results of a prospective multicentre cohort study from the Japanese KYCC group.

Although functional end-to-end anastomosis (FEEA) using a stapler in the colorectal field has been recognised worldwide, the technique varies by surgeon, and the safety of anastomosis using different techniques is unknown. This multicentre prospective observational cohort study was conducted by the KYCC Study Group in Yokohama, Japan, and included patients who underwent colonic resection at seven centres between April 2020 and March 2022. This study compared the incidence of surgery-related abdominal complications (SAC: anastomotic leakage [AL], anastomotic bleeding, intra-abdominal abscess, enteritis, ileus, surgical site infection, and other abdominal complications) between two different methods of FEEA (one-step [OS] method: simultaneous anastomosis and bowel resection; two-step [TS] method: anastomosis after bowel resection). Complications of Clavien-Dindo classification grade2 or higher were assessed. Among 293 eligible cases, the OS and TS methods were used in 194 (66.2%) and 99 (33.8%) patients, respectively. The baseline characteristics were similar between the groups. The OS method used fewer staplers (three vs. four staplers, p < 0.00001). There were no significant differences in SAC rate between the OS (19.1%) and the TS (16.2%) groups (p = 0.44). The OS group had four cases (2.1%) of AL (two patients; grade3, two patients; grade2) while the TS group had one case (1.0%) of grade2 AL (p = 0.67). Multivariate logistic regression analysis showed that male sex (odds ratio [OR] 3.95; p < 0.00001), an open surgical approach (OR 2.36; p = 0.03), and longer operative duration (OR,2.79; p = 0.002) were independent predictors of complications, whereas the OS method was not an independent predictor (OR 1.17; p = 0.66). The OS and the TS technique for stapled colonic anastomosis in a FEEA had a similar postoperative complication rate. UMIN000039902 (registration date 23 March 2020).

Associations of early changes in lung ultrasound aeration scores and mortality in invasively ventilated patients: a post hoc analysis

BackgroundLung ultrasound (LUS) in an emerging technique used in the intensive care unit (ICU). The derivative LUS aeration score has been shown to have associations with mortality in invasively ventilated patients. This study assessed the predictive value of baseline and early changes in LUS aeration scores in critically ill invasively ventilated patients with and without ARDS (Acute Respiratory Distress Syndrome) on 30- and 90-day mortality.MethodsThis is a post hoc analysis of a multicenter prospective observational cohort study, which included patients admitted to the ICU with an expected duration of ventilation for at least 24 h. We restricted participation to patients who underwent a 12-region LUS exam at baseline and had the primary endpoint (30-day mortality) available. Logistic regression was used to analyze the primary and secondary endpoints. The analysis was performed for the complete patient cohort and for predefined subgroups (ARDS and no ARDS).ResultsA total of 442 patients were included, of whom 245 had a second LUS exam. The baseline LUS aeration score was not associated with mortality (1.02 (95% CI: 0.99 – 1.06), p = 0.143). This finding was not different in patients with and in patients without ARDS. Early deterioration of the LUS score was associated with mortality (2.09 (95% CI: 1.01 – 4.3), p = 0.046) in patients without ARDS, but not in patients with ARDS or in the complete patient cohort.ConclusionIn this cohort of critically ill invasively ventilated patients, the baseline LUS aeration score was not associated with 30- and 90-day mortality. An early change in the LUS aeration score was associated with mortality, but only in patients without ARDS.Trial registrationClinicalTrials.gov, ID NCT04482621.

Cost-effectiveness and safety of continuous pulse oximetry for management of undiagnosed obstructive sleep apnea in bariatric surgery: a nationwide cohort study

BackgroundUndetected obstructive sleep apnea (OSA) is highly prevalent in patients undergoing bariatric surgery and increases perioperative risks. Screening for OSA using preoperative polygraphy (PG) with subsequent continuous positive airway pressure (CPAP) is costly and time-consuming. Postoperative continuous pulse oximetry (CPOX) is less invasive, and is hypothesized to be a safe and cost-effective alternative. ObjectivesThis nationwide multicenter prospective observational cohort study compared CPOX monitoring with OSA-screening using PG. SettingsHigh-volume bariatric centers. MethodsPatients were either postoperatively monitored using CPOX without pre-operative OSA-screening, or underwent pre-operative PG and CPAP treatment when OSA was diagnosed. Cohort placement was based on local hospital protocols. Cost-effectiveness was analyzed using quality adjusted life years (QALY) and healthcare costs. Surgical outcomes were also analyzed. Propensity score matching was used in sensitivity analyses. ResultsA total of 1390 patients was included. QALYs were similar between groups at baseline and one-year postoperatively. Postoperative complications, ICU-admissions and admissions, particularly OSA-related, did not differ between groups. Mean costs per patient/year in the CPOX group was €3,094 vs. €3,680 in the PG group; mean difference €-586 (95% CI €-933 to €-242). Following propensity score matching, 1090 of 1390 included patients remained, and similar findings for cost-effectiveness, complications and ICU admissions were observed. ConclusionCPOX monitoring without pre-operative OSA-screening was not associated with higher complication or readmission rates compared to PG. CPOX resulted in lower costs from a healthcare perspective and can therefore be considered a cost-effective alternative to routine OSA-screening in patients undergoing bariatric surgery.

Preliminary results from the Polish Infective Endocarditis Registry (POL-ENDO): Time to change clinical practice?

Infective endocarditis (IE) is a severe valvular disease associated with high morbidity and mortality. This preliminary study aimed to evaluate patient profiles and treatment outcomes of IE in Poland and compare them with European IE characteristics. We conducted a prospective multicenter observational cohort study - the POL-ENDO registry - in IE patients from 134 hospitals in Poland recruited between August 2022 and August 2023. We evaluated demographic, clinical, imaging, and treatment outcome data. A comparison of the Polish patients with those assessed in the EURO-ENDO registry between January 2016 and March 2018 was performed. Of a total of 880 IE patients, 622 were male (70.7%). The POL-ENDO participants were older (61.4 [16.7] years vs. 59.25 [18.03] years; P = 0.001). Native-valve IE occurred more often in Poland (82.3% vs. 56.6%; P <0.001). Transthoracic echocardiography was performed more frequently in Poland (93.6% vs. 89.8%; P <0.001). New imaging techniques (computed tomography/magnetic resonance imaging/positron emission tomography/single-photon emission computed tomography) were less frequently used in Poland (computed tomography: 41.3% vs. 53.2%; P <0.001; magnetic resonance imaging: 6.4% vs. 18.7%; P <0.001). Heart failure occurred more often in Poland as an in-hospital complication (31.4% vs. 14.1%; P <0.001). Surgical treatment was less frequently performed in Poland (36.9% vs. 51.2%; P <0.001). In-hospital mortality was higher in Poland (21% vs. 17%; P = 0.008). Polish IE patients were significantly older and had more comorbidities. New imaging techniques are less frequently used in Poland. Echocardiography was performed more frequently in Poland as the diagnostic mainstay. Surgical treatment was significantly less frequent in Poland. In-hospital mortality in Poland is higher.

Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron sublineage JN.1 in critically ill COVID-19 patients: a prospective, multicenter cohort study in France, November 2022 to January 2024

BackgroundA notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early 2024. However, no clinical data are available regarding critically-ill JN.1 COVID-19 infected patients.MethodsThe current study is a substudy of the SEVARVIR prospective multicenter observational cohort study. Patients admitted to any of the 40 participating ICUs between November 17, 2022, and January 22, 2024, were eligible for inclusion in the SEVARVIR cohort study (NCT05162508) if they met the following inclusion criteria: age ≥ 18 years, SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR) in nasopharyngeal swab samples, ICU admission for acute respiratory failure. The primary clinical endpoint of the study was day-28 mortality. Evaluation of the association between day-28 mortality and sublineage group was conducted by performing an exploratory multivariable logistic regression model, after systematically adjusting for predefined prognostic factors previously shown to be important confounders (i.e. obesity, immunosuppression, age and SOFA score) computing odds ratios (OR) along with their corresponding 95% confidence intervals (95% CI).ResultsDuring the study period (November 2022–January 2024) 56 JN.1- and 126 XBB-infected patients were prospectively enrolled in 40 French intensive care units. JN.1-infected patients were more likely to be obese (35.7% vs 20.8%; p = 0.033) and less frequently immunosuppressed than others (20.4% vs 41.4%; p = 0.010). JN.1-infected patients required invasive mechanical ventilation support in 29.1%, 87.5% of them received dexamethasone, 14.5% tocilizumab and none received monoclonal antibodies. Only one JN-1 infected patient (1.8%) required extracorporeal membrane oxygenation support during ICU stay (vs 0/126 in the XBB group; p = 0.30). Day-28 mortality of JN.1-infected patients was 14.6%, not significantly different from that of XBB-infected patients (22.0%; p = 0.28). In univariable logistic regression analysis and in multivariable analysis adjusting for confounders defined a priori, we found no statistically significant association between JN.1 infection and day-28 mortality (adjusted OR 1.06 95% CI (0.17;1.42); p = 0.19). There was no significant between group difference regarding duration of stay in the ICU (6.0 [3.5;11.0] vs 7.0 [4.0;14.0] days; p = 0.21).ConclusionsCritically-ill patients with Omicron JN.1 infection showed a different clinical phenotype than patients infected with the earlier XBB sublineage, including more frequent obesity and less immunosuppression. Compared with XBB, JN.1 infection was not associated with higher day-28 mortality.

Association of Prenatal Exposure to Antiseizure Medications With Creative and Executive Function at Age 4.5 Years.

Neurodevelopmental effects of fetal antiseizure medication (ASM) exposure on creativity and executive functions are poorly understood. We previously found fetal valproate exposure to adversely affect measures of creativity and executive functions. In this study, we examine fetal exposure of newer ASMs on these functions in children of women with epilepsy (WWE) compared with children of healthy women (HW). The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study is a multicenter NIH-funded prospective observational cohort study of WWE and HW enrolled in pregnancy and their offsprings. This report examines blindly assessed creativity and executive functions in 4.5-year-old children of WWE vs HW. In addition, exposure-dependent ASM effects during the third trimester were examined in children of WWE, using a ratio of maximum observed ASM concentrations and ratio of defined daily dose (ratio DDD). For polytherapy, ratios were summed across ASMs. Linear regression models adjusted for multiple potential confounding factors were conducted for all analyses. The primary outcome for 4.5-year-old children was the Torrance Test of Creative Thinking-Figural Creativity Index. Secondary outcomes included the Global Executive Composite Score from the Behavior Rating Inventory of Executive Function-Preschool Version and subscales and other indexes of both measures. The primary analysis included 251 children of WWE and 73 of HW. No differences in creativity or executive function were found between children of WWE vs HW. No ASM exposure-dependent effects were found for the creativity measures, but exposure-dependent effects for executive function were present for ratio ASM concentration and ratio DDD. Our findings at 4.5 years show no differences in creative thinking between children of WWE vs HW (-3.2 [-9.0 to 2.7], p = 0.286) or associations with fetal exposure to ASMs (-2.6 [-11.0 to 5.7], p = 0.530). Secondary analyses revealed fetal exposure-dependent effects for executive function in children of WWE (7.0 [2.9-11.2], p = 0.001), which are most marked for levetiracetam (12.9 [4.2-21.6], p = 0.004). Our findings suggest that even for relatively safe ASMs, dosing needs to be adjusted to concentrations that prevent seizures, but balance risks to the fetus that high concentrations may pose. The study is registered at ClinicalTrials.gov as NCT01730170.

Exploring Health-Related Quality of Life in Children With Hypertrophic Cardiomyopathy and Relationship to Physical Activity.

Hypertrophic cardiomyopathy is a burdensome condition that inflicts both physical and psychological impairment on those with the disease, negatively impacting health-related quality of life (HRQoL). Given the abundance of evidence suggesting a role of physical activity (PA) in modulating HRQoL in healthy populations of children, we sought to determine the relationship between HRQoL and PA in children diagnosed with hypertrophic cardiomyopathy. A multicenter prospective observational cohort study was conducted, with patients with hypertrophic cardiomyopathy aged 10 to 19 years being provided a wrist-worn activity tracker (Fitbit Charge HR) to wear for 14 days. Patients self-reported on Pediatric Quality of Life 4.0 quality of life inventory items, which were associated with PA metrics following covariate adjustment using linear regression. A total of 56 participants were recruited to the study. The median age at enrollment was 15.5 years (interquartile range, 13.8-16.8), and 16 out of 56 (29%) of the cohort were girls. The cohort reported decreased metrics of physical, psychosocial, and total summary scores compared with health reference populations, with scores comparable with that of published populations with chronic disease. Increased physical HRQoL scores were significantly associated with increased daily steps taken, distance traveled, and flights of stairs climbed. These results show that impaired PA correlates with reduced HRQoL in children with hypertrophic cardiomyopathy, suggesting PA may partially mediate HRQoL in this population.

Is the sFlt-1/PlGF ratio efficient in predicting adverse neonatal outcomes in small-for-gestational-age newborns? A prospective observational multicenter cohort study.

Fetuses with growth abnormalities are at an increased risk of adverse neonatal outcomes. The aim of this study was to investigate if placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), or the sFlt-1/PlGF ratio were efficient predictive factors of adverse neonatal outcomes in small-for-gestational-age (SGA) newborns. A prospective observational multicenter cohort study was performed between 2020 and 2023. At the time of the SGA fetus diagnosis, serum angiogenic biomarker measurements were performed. The primary outcome was an adverse neonatal outcome, diagnosed in the case of any of the following: <34 weeks of gestation: mechanical ventilation, sepsis, necrotizing enterocolitis, intraventricular hemorrhage grade III or IV, and neonatal death before discharge; ≥34 weeks of gestation: Neonatal Intensive Care Unit hospitalization, mechanical ventilation, continuous positive airway pressure, sepsis, necrotizing enterocolitis, intraventricular hemorrhage grade III or IV, and neonatal death before discharge. In total, 192 women who delivered SGA newborns were included in the study. The serum concentrations of PlGF were lower, leading to a higher sFlt-1/PlGF ratio in the adverse outcome group. No significant differences in sFlt-1 levels were observed between the groups. Both PlGF and sFlt-1 had a moderate correlation with adverse neonatal outcomes (PlGF: R - 0.5, p < 0.001; sFlt-1: 0.5, p < 0.001). The sFlt-1/PlGF ratio showed a correlation of 0.6 (p < 0.001) with adverse outcomes. The uterine artery pulsatility index (PI) and the sFlt-1/PlGF ratio were identified as the only independent risk factors for adverse outcomes. An sFlt-1/PlGF ratio of 19.1 exhibited high sensitivity (85.1%) but low specificity (35.9%) in predicting adverse outcomes and had the strongest correlation with them. This ratio allowed the risk of adverse outcomes to be assessed as low with approximately 80% certainty. The sFlt-1/PlGF ratio seems to be an efficient predictive tool in adverse outcome risk assessment. More studies on large cohorts of SGA-complicated pregnancies with and without preeclampsia are needed to develop an optimal and detailed formula for the risk assessment of adverse outcomes in SGA newborns.

Association between Height and Functional Outcomes of Patients 6 Months after a Stroke: A Multicenter Prospective Observational Cohort Study.

Many physical factors influence post-stroke functional outcomes. However, few studies have examined the influence of height on these outcomes. Here, data from the Korean Stroke Cohort for Functioning and Rehabilitation were used and patients' height was categorized into three groups: short (lower 25%), middle (middle 50%), and tall (upper 25%). Differences in the modified Rankin scale (mRS), functional ambulatory category (FAC), and Korean-translated version of the Modified Barthel Index (K-MBI) scores were analyzed for each group at 6 months post-stroke. A subgroup analysis was conducted based on the initial Fugl-Meyer Assessment (FMA) score. We analyzed functional outcomes in 5296 patients at 6 months post-stroke, adjusting for age and body mass index. The short-height group exhibited higher mRS scores (1.88 ± 0.043), lower FAC scores (3.74 ± 0.045), and lower K-MBI scores (82.83 ± 0.748) than the other height groups (p < 0.05). In the subgroup analysis, except for the very severe FMA group, the short-height group also exhibited worse outcomes in terms of mRS, FAC, and K-MBI scores (p < 0.05). Taken together, the short-height group exhibited worse outcomes related to disability, gait function, and ADLs at 6 months post-stroke.

An MRI-based multi-parameter clinical decision support system (NeoMDSS) for early prediction of pathological complete response after the first cycle of neoadjuvant therapy in breast cancer: A multi-center prospective observational cohort study.

592 Background: Currently, there is no reliable and convenient way to predict response rates in early stages of neoadjuvant therapy (NAT) for breast cancer, which can affect the prognosis of non-responsive patients. Methods: In this prospective multi-center observational study, eligible participants who underwent NAT followed by radical surgery were recruited. All patients underwent magnetic resonance imaging (MRI) examination before and after the first cycle of NAT (1st-NAT). We analyzed the effects of clinicopathological features, such as histological grade, hormone receptor (HR) and HER2 status, Ki-67 expression, blood cell analysis, and MRI parameters including the reduction ratio of tumor diameter (ΔD%), apparent diffusion coefficient (ADC), and early enhancement ratio (EER) on NAT. By incorporating independent influencing factors, we developed a multiparametric clinical decision support system (NeoMDSS) model based on a retrospective cohort and validated its accuracy in both a prospective single-center internal cohort and a prospective multi-center external cohort. Relevant clinical trial details can be found under the identifier NCT04909554. Results: A total of 301 breast cancer patients were enrolled between January 2019 and December 2023, including 140 patients in the training cohort, 120 patients in the internal validation cohort, and 41 patients in the external validation cohort. The NeoMDSS model demonstrated excellent performance in predicting pathological complete response (pCR) at 1st-NAT, with an AUC of 0.874 (95% CI 0.813-0.935) in the training cohort, 0.845 (95% CI 0.771-0.919) in the internal validation cohort, and 0.867 (95% CI 0.742-0.992) in the external validation cohort. The NeoMDSS model exhibited a sensitivity, specificity, and accuracy of 80.0%, 81.3%, and 80.5%, respectively, in the internal validation cohort, and 87.0%, 83.3%, and 85.4%, respectively, in the external validation cohort. Calibration curves and decision curve analysis (DCA) further supported the clinical value of the NeoMDSS model. To facilitate the clinical application of the NeoMDSS model, a nomogram and an online website ( www.gdphneomdss.com ) were developed to calculate the probability of pCR, which the sensitivity, specificity, and accuracy of the NeoMDSS model were all 80.0% in the internal validation cohort and 80.0%, 81.3%, and 80.5% in the external validation cohort. Conclusions: The NeoMDSS model serves as a convenient tool in clinical practice at 1st-NAT to calculate and accurately predict the probability of pCR after NAT. This assists clinicians in determining whether to modify the treatment plan and improving personalized treatment for patients with poor response to NAT. Clinical trial information: NCT04909554 .

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.

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

Doppler ultrasound surveillance of recently formed haemodialysis arteriovenous fistula: the SONAR observational cohort study.

Arteriovenous fistulas are considered the best option for haemodialysis provision, but as many as 30% fail to mature or suffer early failure. To assess the feasibility of performing a randomised controlled trial that examines whether, by informing early and effective salvage intervention of fistulas that would otherwise fail, Doppler ultrasound surveillance of developing arteriovenous fistulas improves longer-term arteriovenous fistula patency. A prospective multicentre observational cohort study (the 'SONAR' study). Seventeen haemodialysis centres in the UK. Consenting adults with end-stage renal disease who were scheduled to have an arteriovenous fistula created. Participants underwent Doppler ultrasound surveillance of their arteriovenous fistulas at 2, 4, 6 and 10 weeks after creation, with clinical teams blinded to the ultrasound surveillance findings. Fistula maturation at week 10 defined according to ultrasound surveillance parameters of representative venous diameter and blood flow (wrist arteriovenous fistulas: ≥ 4 mm and > 400 ml/minute; elbow arteriovenous fistulas: ≥ 5 mm and > 500 ml/minute). Mixed multivariable logistic regression modelling of the early ultrasound scan data was used to predict arteriovenous fistula non-maturation by 10 weeks and fistula failure at 6 months. A total of 333 arteriovenous fistulas were created during the study window (47.7% wrist, 52.3% elbow). By 2 weeks, 37 (11.1%) arteriovenous fistulas had failed (thrombosed), but by 10 weeks, 219 of 333 (65.8%) of created arteriovenous fistulas had reached maturity (60.4% wrist, 67.2% elbow). Persistently lower flow rates and venous diameters were observed in those fistulas that did not mature. Models for arteriovenous fistulas' non-maturation could be optimally constructed using the week 4 scan data, with fistula venous diameter and flow rate the most significant variables in explaining wrist fistula maturity failure (positive predictive value 60.6%, 95% confidence interval 43.9% to 77.3%), whereas resistance index and flow rate were most significant for elbow arteriovenous fistulas (positive predictive value 66.7%, 95% confidence interval 48.9% to 84.4%). In contrast to non-maturation, both models predicted fistula maturation much more reliably [negative predictive values of 95.4% (95% confidence interval 91.0% to 99.8%) and 95.6% (95% confidence interval 91.8% to 99.4%) for wrist and elbow, respectively]. Additional follow-up and modelling on a subset (n = 192) of the original SONAR cohort (the SONAR-12M study) revealed the rates of primary, assisted primary and secondary patency arteriovenous fistulas at 6 months were 76.5, 80.7 and 83.3, respectively. Fistula vein size, flow rate and resistance index could identify primary patency failure at 6 months, with similar predictive power as for 10-week arteriovenous fistula maturity failure, but with wide confidence intervals for wrist (positive predictive value 72.7%, 95% confidence interval 46.4% to 99.0%) and elbow (positive predictive value 57.1%, 95% confidence interval 20.5% to 93.8%). These models, moreover, performed poorly at identifying assisted primary and secondary patency failure, likely because a subset of those arteriovenous fistulas identified on ultrasound surveillance as at risk underwent subsequent successful salvage intervention without recourse to early ultrasound data. Although early ultrasound can predict fistula maturation and longer-term patency very effectively, it was only moderately good at identifying those fistulas likely to remain immature or to fail within 6 months. Allied to the better- than-expected fistula patency rates achieved (that are further improved by successful salvage), we estimate that a randomised controlled trial comparing early ultrasound-guided intervention against standard care would require at least 1300 fistulas and would achieve only minimal patient benefit. This trial is registered as ISRCTN36033877 and ISRCTN17399438. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135572) and is published in full in Health Technology Assessment; Vol. 28, No. 24. See the NIHR Funding and Awards website for further award information.

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,...

Aerosol drug therapy in critically ill patients (Aero-in-ICU study): A multicentre prospective observational cohort study.

In recent years, a significant understanding of delivering optimal aerosol therapy and the availability of various drugs and devices have led to an increase in its use in clinical practice. There are only a few studies available regarding their use in critically ill patients from a few parts of the world. We aimed to study the practice pattern of aerosol therapy in critically ill patients from Indian intensive care units (ICUs). After ethical approval, this multi-centric prospective observational study was performed over a study period of four weeks. Newly admitted adult patients considered who had an artificial airway and/or ventilation (including non-invasive). Patients were followed up for the next 14 days or until ICU discharge/death (whichever came first) for details of each aerosol therapy, including ongoing respiratory support, drug type, and aerosol-generating device. From the nine participating centers across India, 218 patients were enrolled. Of 218 enrolled patients, 72.48% received 4884 aerosols with 30.91 ± 27.15 (95%CI: 26.6-35.1) aerosols per patient over 1108 patient days. Approximately 62.7% during IMV, 30.2% during NIV, 2.3% in spontaneously breathing patients with an artificial airway during weaning, and 4.7% were given without an artificial airway after weaning or decannulation. In 59%, a single drug was used, and bronchodilators were the most frequent. The jet nebulizer was the most common, followed by the ultrasonic and vibrating mesh aerosol generator. The ventilator setting was changed in only 6.6% of the aerosol sessions with IMV and none with NIV. Aerosol therapy is frequently used with a wide variation in practices; bronchodilators are the most commonly used drugs, and jet nebulizers are the most widely used.

COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants

BackgroundDuring the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11–28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants.MethodsThis is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria.Results566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4–7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay.ConclusionThis study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.

Short-term outcomes of a multicentre prospective study using a "visible" polyvinylidene fluoride onlay mesh for the prevention of midline incisional hernia.

Prophylactic meshes in high-risk patients prevent incisional hernias, although there are still some concerns about the best layer to place them in, the type of fixation, the mesh material, the significance of the level of contamination, and surgical complications. We aimed to provide answers to these questions and information about how the implanted material behaves based on its visibility under magnetic resonance imaging (MRI). This is a prospective multicentre observational cohort study. Preliminary results from the first 3months are presented. We included general surgical patients who had at least two risk factors for developing an incisional hernia. Multivariate logistic regression was used. A polyvinylidene fluoride (PVDF) mesh loaded with iron particles was used in an onlay position. MRIs were performed 6weeks after treatment. Between July 2016 and June 2022, 185 patients were enrolled in the study. Surgery was emergent in 30.3% of cases, contaminated in 10.7% and dirty in 11.8%. A total of 5.6% of cases had postoperative wound infections, with the requirement of stoma being the only significant risk factor (OR = 7.59, p = 0.03). The formation of a seroma at 6weeks detected by MRI, was associated with body mass index (OR = 1.13, p = 0.02). The prophylactic use of onlay PVDF mesh in midline laparotomies in high-risk patients was safe and effective in the short term, regardless of the type of surgery or the level of contamination. MRI allowed us to detect asymptomatic seromas during the early process of integration. This protocol was registered at ClinicalTrials.gov (NCT03105895).