Prospective Multicenter Study Research Articles

#636 A phase 4, open label, multicenter prospective study of the safety and efficacy of agalsidase beta in Chinese patients with Fabry disease

Abstract Background and Aims Fabry disease (FD) is a rare inherited lysosomal storage disease caused by pathogenic GLA gene variants which result in a deficiency of the enzymatic activity of α-galactosidase A. Enzyme replacement therapy (ERT) is the mainstay of FD-specific treatment, but there are currently no reported clinical trials of ERT for FD in the Chinese population. This is the first phase 4 study to evaluate the safety and efficacy of ERT for FD in China since the approval of agalsidase beta in China in 2019. Method A 54-week, phase 4, open label, single arm, prospective, post-marketing surveillance (PMS) study of agalsidase beta (NCT05054387) was performed at 6 sites in China. Twenty-two Chinese ERT-naïve FD participants (≥8 years) with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 were enrolled and received infusions of agalsidase beta (Fabrazyme®, Sanofi) at a dose of 1.0 mg/kg every 2 weeks for up to 48 weeks. The primary endpoint was safety and tolerability of agalsidase beta. The endpoints of clinical efficacy included the changes of plasma globotriaosylceramide (GL-3), globotriaosylsphingosine (Lyso-GL-3), FD symptoms (including angiokeratoma, hypohidrosis, anhidrosis, abdominal pain, headache, tinnitus, heat tolerance, and activity tolerance), and eGFR from baseline to week 48. A post-hoc subgroup analysis was conducted to explore the differences in ERT efficacy between two subgroups of different ages (<30 years and ≥30 years). Results All 22 patients completed the study intervention. There were 18 males (81.8%) and the mean age of ERT initiation was 29.0 ± 13.5 years. Treatment-related adverse events (AEs) and infusion-associated reactions (IARs) were reported in 8 participants (36.4%), which was less than ∼60% as previously reported for IARs. Most AEs were mild or moderate and no AE caused permanent treatment discontinuation or death. The mean plasma GL-3 and Lyso-GL-3 levels decreased remarkably at week 6 and remained stable throughout the trial, with the mean percentage reduction from baseline to week 6 through week 48 ranged from −34.6% ± 27.4% to ­41.9% ± 14.9% and −58.8% ± 20.2% to ­64.9% ± 12.7%, respectively (Fig. 1a and b). The reduction was more remarkable for the classic male patients (n = 18; GL-3: 7.99 ± 2.19 ug/mL at baseline and 4.31 ± 1.71 ug/mL at week 48, −46.0% ± 18.4%; Lyso-GL-3: 83.11 ± 25.69 ng/mL at baseline and 25.89 ± 13.43 ng/mL at week 48, −67.8% ± 17.6%). Thirteen (59.1%) participants experienced improved FD symptoms at week 48, with no cases of worsening symptoms. The mean eGFR was 115.6 ± 37.3 mL/min/1.73 m2 at baseline and 118.4 ± 42.9 mL/min/1.73 m2 at week 48, with a change of 0.0 ± 12.4 mL/min/1.73 m2 from baseline to week 48 (Fig. 1c). In the subgroup analysis, participants were divided into the younger group with age <30 years (n = 11) and the older group with age ≥30 years (n = 11) according to their age of ERT initiation. At week 48, the reduction of mean plasma GL-3 (−47.1% ± 23.6% vs −22.0% ± 26.0%) and Lyso-GL-3 levels (−72.4 ± 17.3% vs −48.2% ± 19.8%), the stabilization of renal function (the mean change of eGFR from baseline to week 48: 5.2 ± 7.9 mL/min/1.73 m2 vs −5.2 ± 14.1 mL/min/1.73 m2) and the percentage of symptom improvement (81.8% vs. 36.4%) were generally more remarkable in the younger group than in the older group (Table 1). Conclusion This first phase 4 study of ERT for Fabry disease in China demonstrates that agalsidase beta is safe and well tolerated with a relatively low IAR rate, and effective in reducing plasma GL-3 and Lyso-GL-3, improving symptoms, and stabilizing renal function in Chinese patients with FD. Furthermore, the present study implies that patients who initiate ERT at a younger age benefit more from the therapy. Funding: Commercial support - Sanofi Pharmaceuticals.

#1340 Validation of artificial intelligence algorithm classifying arteriovenous access aneurysms in hemodialysis: a blinded multicenter prospective study

Abstract Background and Aims In hemodialysis (HD) patients, arteriovenous (AV) access aneurysms may lead to severe and potentially life-threatening consequences, such as rupture. To address this issue, we developed an artificial intelligence-based application that utilizes images of the AV access to classify AV aneurysms [1]. We conducted a blinded, multicenter, prospective pilot study to assess the correlation between the classification results generated by the aneurysm classification application and the independent clinical examination conducted by physicians specializing in vascular access care. Method AV accesses were photographed using tablets. These images were then uploaded to the cloud, where they were classified as either "Advanced" or "Not Advanced" by a convolutional neural network algorithm [1] (Fig. 1A). The study compared AV aneurysm classifications generated by our application to those made by vascular access physicians blinded to the app results. The physicians’ classifications served as the ground truth for our analysis. Results The study was conducted at two vascular access care centers in New York, NY, USA. A total of 121 patients were included in the analysis (Table 1). The physicians’ assessment identified a 21% prevalence of advanced aneurysms. The application accurately classified 84 out of 95 aneurysm images as “Not Advanced” and 20 out of 26 as “Advanced,” resulting in an accuracy of 86.0% (95% CI: 78.5% to 91.6%), a sensitivity of 76.9% (95% CI: 56.4% to 91.0%), a specificity of 88.4% (95% CI: 80.2% to 94.1%), and an area under the receiver operating characteristics curve (AUROC) of 0.87 (95% CI: 0.78 to 0.94) (Fig. 1B). Conclusion Our results demonstrate that an AI-powered application exhibits actionable accuracy in classifying AV aneurysms within a demographically diverse HD population. These findings align with Zhang et al., where a team of vascular access experts classified 1,093 out of 1,341 (81.5%) images as “Not Advanced” aneurysms and 248 (18.5%) as “Advanced,” resulting in an AUROC of 0.96 in the validation set (n = 402) [1]. The difference in AUROCs can be attributed to the fact that, in Zhang et al., vascular access experts evaluated only AV access images, whereas in the present study, they performed a physical examination of the patient. Our tool may have the potential to support aneurysm monitoring processes, enabling timely detection, decision-making, and interventions.

#1043 Metabolomics and proteomics study on kidney function post-liver transplantation

Abstract Background and Aims Hepatorenal syndrome (HRS) is a serious complication characterized by kidney dysfunction in patients with advanced liver disease. The pathophysiology of HRS is poorly understood and involves a combination of hemodynamic, circulatory, inflammatory, and hormonal factors. While some patients with HRS restore kidney function after liver transplantation (LT), others continue to have impaired kidney function. Understanding the mechanisms associated with persistent kidney dysfunction is essential for developing effective treatments and stratifying patients for combined liver-kidney transplantation versus LT only. Method We analyzed serum samples from 10 patients of the multicenter prospective study (INAID CTOT14). Five of them had no HRS and maintained an eGFR > 50 ml/min post-LT. One patient with HRS recovered kidney function post-LT. Four patients with HRS failed to regain kidney function at one- and two-months post-LT (eGFR < 30 ml/min). We categorized the five patients without HRS and one patient with recovered eGFR as Normal Kidney Function (NKF) group and the other four patients as Impaired Kidney Function (IKF) group. Serum samples were collected at one (visit 1) and two months (visit 2) post-LT and stored at −80°C until analysis. Both untargeted metabolomics and proteomics analysis were conducted using quantitative liquid chromatography tandem mass spectroscopy (LC-MS/MS) on Agilent® Q-TOF 6546. Data was analyzed by Agilent® Qualitative Workflow 10, Agilent® Profinder 10, MetaboAnalyst (V6.0), and Spectrum Mill MS software. Results A total of 150 metabolites were identified by LC-MS/MS based metabolomics. Principal component analysis (PCA) did not show significant differences between visit 1 and visit 2 samples (Fig. 1A). Therefore, visit 1 and visit 2 samples were analyzed together. With 12 samples in NKF and 8 samples in IKF group, the PCA score plot showed distinct clustering of the two groups (Fig. 1B). Volcano plot analysis was conducted to analyze metabolite differences between NKF and IKF. P-values were calculated using a Student's t-test, and differential metabolites were identified with a P-value cut-off of < .05 and a fold change > 2.0. The result revealed 37 downregulated and 13 upregulated metabolites when comparing NKF and IKF (Fig. 1C). Notably, creatinine was among the downregulated metabolites in the NKF group, validating the accuracy of our analysis. Untargeted proteomics analysis was also performed on all 20 samples. Using a P-value cut-off of .05 and a fold change >1.25, 43 proteins were found to be upregulated, and four proteins to be downregulated when comparing NKF to IKF. Fig. 2A lists the top 10 regulated proteins, with beta-2-microglobulin as the most significantly changed. Reactome® pathway analysis of these 47 proteins highlighted potential impacts on various biological pathways (Fig. 2B), providing potential valuable insights into the molecular alterations associated with kidney function post-LT. Conclusion Our comprehensive metabolomics and proteomics study characterized the molecular alterations associated with kidney function post-LT. The identified metabolites and proteins may provide valuable insights for understanding persistent kidney damage. Future research is warranted to confirm and correlate these findings with clinical outcomes, enhancing the applicability and significance of our results in the broader context of HRS and LT.

Resurgence of common respiratory viruses in patients with community-acquired pneumonia (CAP)—A prospective multicenter study

BackgroundCommunity-acquired pneumonia (CAP) is a major global cause of death and hospitalization. Bacteria or community-acquired viruses (CARVs) cause CAP. COVID-19 associated restrictions effectively reduced the circulation of CARVs. ObjectivesThe aim of this study was to analyze the proportion of CARVs in adult patients with CAP from mid-2020 to mid-2023. Specifically, we aimed to compare the rate of influenza virus, SARS-CoV-2, and RSV detections in patients aged 18–59 years and ≥60 years. Study designWe analyze the proportion of 21 community-acquired respiratory viruses (CARVs) and three atypical bacteria (Bordetella pertussis, Legionella pneumophila, and Mycoplasma pneumoniae) in nasopharyngeal swab samples using molecular multiplex methods within the prospective, multicentre, multinational study of the German study Group CAPNETZ. We used stringent inclusion criteria throughout the study. ResultsWe identified CARVs in 364/1,388 (26.2 %) patients. In detail, we detected SARS-CoV-2 in 210/1,388 (15.1 %), rhino-/enterovirus in 64/1,388 (4.6 %), influenza virus in 23/1,388 (1.6 %) and RSV in 17/1,388 (1.2 %) of all patients. We detected RSV and influenza more frequently in patients ≥60 years, especially in 22/23 compared to the previous season. None of the atypical bacteria were detected. ConclusionsBeginning in 2023, we demonstrate a re-emergence of CARVs in CAP patients. Effective vaccines or specific antiviral therapies for more than two thirds of the detected viral infections are currently available. High detection rates of vaccine-preventable viruses in older age groups support targeted vaccination campaigns.

Endoscopic hand suturing using a modified through-the-scope needle holder for mucosal closure after colorectal endoscopic submucosal dissection: Prospective multicenter study (with video).

Endoscopic hand suturing (EHS) is a novel technique for closing a mucosal defect after endoscopic submucosal dissection (ESD). We investigated the technical feasibility of colorectal EHS using a modified flexible through-the-scope needle holder. This was a prospective multicenter study conducted at two referral centers between June 2022 and April 2023. This study included colorectal neoplasms 20-50 mm in size located in the sigmoid colon or rectum. A modified flexible through-the-scope needle holder, with an increased jaw width to facilitate needle grasping, was used for colorectal EHS. The primary end-points were sustained closure rate on second-look endoscopy (SLE) performed on postoperative days 3-4 and suturing time for colorectal EHS. Secondary end-points included complete closure rate and delayed adverse events. We enrolled 20 colorectal neoplasms in 20 patients, including four patients receiving antithrombotic agents. The tumor location was as follows: lower rectum (n = 8), upper rectum (n = 2), rectosigmoid colon (n = 4), and sigmoid colon (n = 6), and the median mucosal defect size was 37 mm (range, 21-65 mm). The complete closure rate was 90% (18/20 [95% confidence interval (CI) 68.3-98.8%]), and the median suturing time was 49 min (range, 23-92 min [95% CI 35-68 min]). Sustained closure rate on SLE was 85% (17/20 [95% CI 62.1-96.8%]). No delayed adverse events were observed. EHS demonstrated a high sustained closure rate. Given the long suturing time and technical difficulty, EHS should be reserved for cases with a high risk of delayed adverse events.

Elevated serum levels of anti-collagen type I antibodies in patients with spontaneous cervical artery dissection and ischemic stroke: a prospective multicenter study

Elevated serum levels of anti-collagen type I antibodies in patients with spontaneous cervical artery dissection and ischemic stroke: a prospective multicenter study

Communicating the diagnosis of a hematological neoplastic disease to patients' minor children: a multicenter prospective study.

When a hematological malignancy is diagnosed, the whole family carries the burden of the disease; parents often try to protect minor children from suffering by avoiding communication about their disease. Since 2009, patients with minors at the Adult Hematology Division at San Gerardo Hospital (Monza) can take part in the "Emanuela Project": children can visit parents and talk with psychologists and hematologists, who explain the disease through simple metaphors. The EMY STUDY aimed to evaluate the impact of illness-related communication on children's behavior, comparing Monza's experience with other Hematology Units, where the communication is delegated to parents or psychological support. Questionnaires exploring the children's main behaviors (school performance, appetite, sleeping patterns, attachment to family figures, and family dialogue) were administered to both sick (SP) and healthy (HP) parents. From 2017 to 2021, 32 patients were enrolled, 20 from Monza and 12 from other hospitals; 84 questionnaires were globally collected. In Monza's group, no major changes in children's behavior were observed and an open dialogue about the disease was often possible. Disease communication is considered crucial and perceived as a responsibility of parents together with a professional figure, mainly the hematologist. Patients were satisfied with "Emanuela Project," reporting positive effects on doctor-patient relationship. Difficulties in separation were significantly higher at other hospitals (P=.019) than in Monza. While at other centers communication is considered parents' responsibility, Monza's patients emphasize the role of professional figures (P=.007). Differently from other hospitals, the role of the hematologist is crucial to Monza's patients (P = .001). Disease communication to patients' offspring is a crucial moment in the process of care, and the hematologist can play a major role in this difficult task, with potential positive effects both on children's well-being and on doctor-patient relationship.

Health Care Personnel Workdays Lost and Direct Health Care Salary Costs Incurred due to COVID-19 Infection in the Age of Widespread Vaccine Availability.

Vaccination against coronavirus disease 2019 (COVID-19) can mitigate the burden of health care worker (HCW) infection. We investigate the burden of HCW illness and its associated direct health care personnel costs in the setting of widespread vaccine availability and explore factors influencing these outcomes. This multicenter prospective study followed HCWs over an 8-month period from January to August 2023. Data recorded included incident COVID-19 infection, symptom burden, workdays missed, and vaccine history. Workdays lost due to illness were used to calculate direct health care personnel costs due to COVID-19 infection. Univariate analysis and multivariable regression investigated the factors associated with workdays lost and direct health care personnel. In total, 1218 participants were enrolled and followed for 8 months, with 266 incidents of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, 1191 workdays lost, and health care personnel costs of €397 974. Multivariable regression revealed that workdays lost were associated with incomplete primary COVID-19 vaccination course. Being unvaccinated, older age, and male were associated with increased health care personnel costs. Health care workdays lost remain a significant issue and are associated with health care system burden despite vaccine availability. These can be mitigated via targeted implementation of vaccine programs. Seasonal variation in health care workdays lost should inform workforce planning to accommodate surge periods.

Highly comparative time series analysis of oxygen saturation and heart rate to predict respiratory outcomes in extremely preterm infants.

Highly comparative time series analysis (HCTSA) is a novel approach involving massive feature extraction using publicly available code from many disciplines. The Prematurity-Related Ventilatory Control (Pre-Vent) observational multicenter prospective study collected bedside monitor data from >700 extremely preterm infants to identify physiologic features that predict respiratory outcomes. We calculated a subset of 33 HCTSA features on >7M 10-minute windows of oxygen saturation (SPO2) and heart rate (HR) from the PreVent cohort to quantify predictive performance. This subset included representatives previously identified using unsupervised clustering on >3500 HCTSA algorithms. Performance of each feature was measured by individual area under the receiver operating curve (AUC) at various days of life and binary respiratory outcomes. We hypothesized that the best HCTSA algorithms would compare favorably to optimal PreVent physiologic predictor IH90_DPE (duration per event of intermittent hypoxemia events below 90%).

Main Results: The top HCTSA features were from a cluster of algorithms associated with the autocorrelation of SPO2 time series and identified low frequency patterns of desaturation as high risk. These features had comparable performance to and were highly correlated with IH90_DPE but perhaps measure the physiologic status of an infant in a more robust way that warrants further investigation. The top HR HCTSA features were symbolic transformation measures that had previously been identified as strong predictors of neonatal mortality. HR metrics were only important predictors at early days of life which was likely due to the larger proportion of infants whose outcome was death by any cause. A simple HCTSA model using 3 top features outperformed IH90_DPE at day of life 7 (.778 versus .729) but was essentially equivalent at day of life 28 (.849 versus .850). These results validated the utility of a representative HCTSA approach but also provides additional evidence supporting IH90\_DPE as an optimal predictor of respiratory outcomes.

Effectiveness and safety of bridging therapy and endovascular therapy in patients with large cerebral infarctions: from ANGEL-ASPECT

Background and purposeThe benefits of thrombolytic therapy before endovascular thrombectomy in cases of acute ischaemic stroke, with a large infarction volume, remain unclear. This analysis aims to evaluate the effectiveness...

Intraoperative left-sided colorectal anastomotic testing in clinical practice: a multi-treatment machine-learning analysis of the iCral3 prospective cohort.

Current evidence about intraoperative anastomotic testing after left-sided colorectal resections is still controversial. The aim of this study was to analyze the impact of Indocyanine Green fluorescent angiography (ICG-FA) and air-leak test (ALT) over standard assessment on anastomotic leakage (AL) rates according to surgeon's perception of anastomosis perfusion and/or integrity in clinical practice. A database of 2061 patients who underwent left-sided colorectal resections was selected from patients enrolled in a prospective multicenter study. It was retrospectively analyzed through a multi-treatment machine-learning model considering standard visual assessment (NW; No. = 899; 43.6%) as the reference treatment arm, compared to ICG-FA alone (WP; No. = 409; 19.8%), ALT alone (WI; No. = 420; 20.4%) or both (WPI; No. = 333; 16.2%). Twenty-four covariates potentially affecting the outcomes were included and balanced into the model within the subgroups. The primary endpoint was AL, the secondary endpoints were overall morbidity (OM), major morbidity (MM), reoperation for AL, and mortality. All the results were reported as odds ratio (OR) with 95% confidence intervals (95%CI). The WPI subgroup showed significantly higher AL risk (OR 1.91; 95% CI 1.02-3.59; p 0.043), MM risk (OR 2.35; 95% CI 1.39-3.97; p 0.001), and reoperation for AL risk (OR 2.44; 95% CI 1.12-5.31; p 0.025). No other significant differences were recorded. This study showed that the surgeons' perception of both anastomotic perfusion and integrity (WPI subgroup) was associated to a significantly higher risk of AL and related morbidity, notwithstanding the extensive use of both ICG-FA and ALT testing.

Mechanism Matters: Differential benefits of cold-stored whole blood for trauma resuscitation from a prospective multicenter study.

Resuscitation with cold-stored low-titre whole blood (LTOWB) has increased despite the paucity of robust civilian data. Most studies are in predominately blunt trauma and lack analysis of specific subgroups or mechanism of injury. We sought to compare outcomes between patients receiving LTOWB vs. balanced component therapy (BCT) after blunt (BL) and penetrating (PN) trauma. Secondary analysis of a prospective multicenter study of patients receiving either LTWOB-containing or BCT resuscitation was performed. Patients were grouped by mechanism of injury (BL vs PN). A generalized estimated equations model using inverse probability of treatment weighting was employed. Primary outcome was mortality and secondary outcomes were acute kidney injury, venous thromboembolism, pulmonary complications, and bleeding complications. Additional analyses were performed on non-traumatic brain injury (TBI), severe torso injury, and LTOWB-only resuscitation patients. 1617 patients (BL 47% vs PN 54%) were identified; 1175 (73%) of which received LTOWB. PN trauma patients receiving LTOWB demonstrated improved survival compared to BCT (77% vs. 56%; p<0.01). Interval survival was higher at 6 hrs (95% vs. 88%), 12 hrs (93% vs. 80%) and 24 hrs (88% vs. 57%) (all p<0.05). The survival benefit following LTOWB was also seen across PN non-TBI (83% vs. 52%), and severe torso injuries (75% vs. 43%) (all p <0.05). After controlling for age, sex, injury severity, and trauma center, LTWOB was associated with decreased odds of death (OR .31, p<.05) in PN trauma. However, no difference in overall mortality was seen across the BL groups. Both PN and BL patients receiving LTOWB had more frequent AKI compared to BCT (19% vs. 7% and 12% vs 6%, respectively; p<0.05). LTOWB resuscitation was independently associated with decreased mortality following PN trauma, but not BL trauma. Further analysis in BL trauma is required to identify subgroups that may demonstrate survival benefit. Therapeutic/Care Management, III.

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

Hand, foot, and mouth disease: could EPs® 7630 be a treatment option? A prospective randomized open-label multicenter clinical study

PurposeHand, foot and mouth disease (HFMD) is a viral contagious disease of children caused by human enteroviruses (EVs) and coxsackieviruses (CVs). There is no specific treatment option for HFMD. EPs® 7630's anti-infective and immunomodulatory properties have previously been demonstrated in several in vitro and in vivo studies; however, the use of this herbal medicine in children with HFMD has not previously been investigated.MethodsThis prospective randomized multicenter clinical study included 208 children with HFMD. The diagnosis was made by pediatricians. The patients who were within the first 48 h of symptom onset (according to the first onset of fever and skin findings) were enrolled. The study participants were assigned into 2 groups as EPs® 7630 and control groups. All patients were followed up twice more, 48 h after the first admission and on the 5th–7th day. Another phone evaluation was conducted for those with continued complaints from the previous visit.ResultsThe median age was 27 (12–112) months. The male-female ratio was 0.98. One hundred thirty one (63%) of 190 patients had no history of household contact. EPs® 7630 group included 94 and control group included 96 patients. A significant difference was found between the groups in terms of complaint scores at the visits made at the 48th h of the treatment and on days 5–7 (p &amp;lt; 0.001). The mean ± SD disease duration of EPs® 7630 users was significantly shorter 6.07 ± 0.70 days (95% CI: 5.92–6.21)] than the control group [8.58 ± 0.94 days (95% CI: 8.39–8.77)] (p &amp;lt; 0.001). Besides, the hospitalization rate among the EPs® 7630 users were significantly lower (p = 0.019). No side effects were observed, except for unpleasant taste, which was reported in 5 patients (EPs® 7630 group).ConclusionConsidering its efficacy and safety profile EPs® 7630 may represent a feasible herbal-based treatment option for children with HFMD. Clinical Trial RegistrationClinicalTrials.gov, identifier (NCT06353477).

In Reply: Letter to the Editor Regarding Health-related Quality of Life in Idiopathic Toe Walkers: A Multicenter Prospective Cross-sectional Study.

In Reply: Letter to the Editor Regarding Health-related Quality of Life in Idiopathic Toe Walkers: A Multicenter Prospective Cross-sectional Study.

The lung ultrasound in children with SARS-COV-2 infection: a national multicenter prospective study.

Coronavirus disease-19 (COVID-19) caused hospitalizations, severe disease, and deaths in any age, including in the youngest children. The aim of this multicenter national study is to characterize the clinical and the prognostic role of lung ultrasound (LU) in children with COVID-19.We enrolled children between 1 month and 18 years of age with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection who underwent a LU within 6h from the first medical evaluation.A total of 213 children were enrolled, 51.6% were male, median age was 2 years and 5 months (interquartile range (IQR) 4months-11 years and 4 months). One hundred and forty-eight (69.4%) children were admitted in hospital, 9 (6.1%) in pediatric intensive care unit. We found an inverse correlation between the lung ultrasound score (LUS) and the oxygen saturation at the first clinical evaluation (r = -0.16; p = 0.019). Moreover, LUS was significantly higher in patients requiring oxygen supplementation (8 (IQR 3-19) vs 2 (IQR 0-4); p = 0.001).Among LU pathological findings, irregular pleural lines, subpleural consolidations, and pleural effusions were significantly more frequent in patients needing oxygen supplementation (p = 0.007,p = 0.006, and p = 0.001, respectively). Conclusion: This multicenter study showed that LU in children with COVID-19 can highlight pleural line irregularities, vertical artifacts, and subpleural consolidation. Notably, children with higher LUS have a higher risk of hospitalization and need for oxygen supplementation, supporting LU as a valid and safe point-of-care first level tool for the clinical evaluation of children with COVID-19. What is Known: • Few children infected with SARS-CoV-2 develop a severe disease and need oxygen therapy. • Lung ultrasound can easily detect low respiratory tract infection during SARS-CoV-2. What is New: • Children with higher lung ultrasound score have a higher risk of need for oxygen supplementation. • Irregular pleural line, sub-pleural consolidations and pleural effusions were significantly more frequent in patients needing oxygen supplementation.

Implementation of lung ultrasonography by general practitioners for lower respiratory tract infections: a feasibility study

Objective To evaluate the feasibility of lung ultrasonography (LUS) performed by novice users’ general practitioners (GPs) in diagnosing lower respiratory tract infections (LRTIs) in primary health care settings. Design A prospective interventional multicenter study (December 2019–March 2020). Settings and subjects Patients aged >3 months, suspected of having LRTI consulting in three different general practices (GPs) (rural, semirural and urban) in France. Main outcome measures Feasibility of LUS by GPs was assessed by (1) the proportion of patients where LUS was not performed, (2) technical breakdowns, (3) interpretability of images by GPs, (4) examination duration and (5) patient perception and acceptability. Results A total of 151 patients were recruited, and GPs performed LUS for 111 (73.5%) patients (LUS group). In 99.1% (n = 110) of cases, GPs indicated that they were able to interpret images. The median [IQR] exam duration was 4 [3–5] minutes. LRTI was diagnosed in 70.3% and 60% of patients in the LUS and no-LUS groups, respectively (p = .43). After LUS, GPs changed their diagnosis from ‘other’ to ‘LRTI’ in six cases (+5.4%, p < .001), prescribed antibiotics for five patients (+4.5%, p = .164) and complementary chest imaging for 10 patients (+9%, p < .001). Patient stress was reported in 1.8% of cases, 81.7% of patients declared that they better understood the diagnosis, and 82% of patients thought that the GP diagnosis was more reliable after LUS. Conclusions LUS by GPs using handheld devices is a feasible diagnostic tool in primary health care for LRTI symptoms, demonstrating both effectiveness and positive patient reception. Trial Registration Number Clinicaltrial.gov: NCT04602234, 20/10/2020.

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.

Antibiotic adherence in dermatologic surgery: a Multicenter prospective cohort study.

Understanding patient non-adherence to prescribed antibiotics can inform clinical practices, patient counseling, and antibiotic efficacy study design in dermatology. The primary objective was to determine the rate of and reasons for antibiotic non-adherence in the dermatologic surgery setting. The secondary objective was to test the applicability of previously studied survey questions for antibiotic non-adherence screening in the dermatologic surgery setting. Five academic outpatient dermatologic surgery centers across the United States conducted one multicenter prospective cohort study. Dermatologic surgery patients ≥ 18 years of age who were prescribed an antibiotic were included as part of this study. 15.2% (42/276) of patients did not adhere to their antibiotic regimen after dermatologic surgery. Most common reasons for incomplete antibiotic courses included forgotten antibiotics (42.9%,18/42) and side effects (28.6%, 12/42). Previously evaluated questions to identify and predict non-adherence had modest performance in the dermatologic surgery setting (Area under the curve of 0.669 [95% CI (0.583-0.754)]). Antibiotic non-adherence after skin surgery is prevalent and commonly due to reasons that physicians can address with patients.

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.