Multicenter Evaluation Research Articles

Determining the Association of Hyperoxia While on Extracorporeal Life Support with Mortality in Neonates Following Norwood Operation

Background: Patients requiring extracorporeal life support (ECLS) support post-Norwood operation constitute an extremely high-risk group. Materials & Methods: We retrospectively aimed to evaluate the relationship of hyperoxia with mortality and other clinical outcomes in patients who required ECLS following Norwood operation between January/2010 – December/2020 in a large volume center. Results: During the study period 65 patients required ECLS post-Norwood. Using receiver operating characteristic (ROC) curve analysis, mean PaO2 of 182 mmHg in the first 48-hours on ECLS was determined to have the optimal discriminatory ability for mortality (sensitivity 68%, specificity 70%). Of the 65 patients, 52% had PaO2>182 mmHg and were designated as hyperoxia-group. Patients in the hyperoxia-group had longer cardiopulmonary bypass time (187 vs 165 minutes, p=0.023), shorter duration from CICU arrival to ECLS-cannulation (13.28 vs 132.58 hours, p=0.003), higher serum lactate within 2-hours from ECLS-canulation (14.55 vs 5.80, p=0.01), higher ECLS flows in the 1st 4-hours (152.68 vs 124.14, p=0.006), and higher mortality (77% vs 39%, p=0.005). In the unadjusted-analysis, using a derived cut-point, patients in the hyperoxia-group had 5.15-higher odds of mortality (p=0.003). However, this association was insignificant when adjusting for confounding variables (p=0.104). Using functional status scale, new morbidity (38% vs 21%), and unfavorable outcomes (13% vs 5%) were higher in the hyperoxia-group. Despite being higher in the hyperoxia group, this did not reach statistical significance. Conclusion: Neonates with hyperoxia (PaO2 >182 torr) during the first 48-hours of ECLS post-Norwood operation had 5-times higher odds of mortality in the unadjusted analysis, however, this was insignificant when adjusting for confounding variables. Patients in the hyperoxia-group had shorter duration from CICU arrival to ECLS-cannulation, higher serum lactate prior to ECLS-canulation, and higher ECLS flows in the 1st 4-hours, (p<0.05). Multicenter evaluation of this modifiable risk-factor is imperative to improve the care of this high-risk cohort.

Intention-to-treat outcomes of patients with hepatocellular carcinoma receiving immunotherapy before liver transplant: the multicenter VITALITY study

The use of immune checkpoint inhibitors (ICI) in patients with advanced hepatocellular carcinoma (HCC) has become widespread with encouraging outcomes in the neoadjuvant setting. Safety and intention to treat (ITT) outcomes in the peri transplant setting are currently based on small and heterogenous single center reports. This first multiregional US study (2016-2023) included 117 consecutive HCC patients assessed for LT and treated preoperatively with ICIs. Intention to treat ITT and survival analyses were conducted with evaluation of post LT rejection rates. In total, 86 (73.5%) patients exceeded MC and 65 (75.6%) were successfully downstaged (DS) within a median of 5.6 months. 43 (36.7%) underwent transplantation, including 18 (15.4%) within MC and 23 (19.7%) initially beyond and DS. Overall, 94% of the cohort received concurrent ICIs and locoregional therapies. No grade 4-5 adverse events occurred on the waiting list. The 3-year cumulative probability of dropout was 28% for those within MC and 48% for those beyond. Independent predictors of dropout included: being beyond MC (p<0.001), AFP doubling from baseline (p=0.014) and radiographic responses (p<0.001). The 3-year ITT survival was 71.1% (73.5% within MC vs 69.7% beyond MC, p=0.329), with 3-year post LT survival rate of 85%. Post-LT rejection occurred in 7 patients, six received their last dose of ICI less than 3 months prior to LT, resulting in one graft loss. The first multicenter evaluation of HCC patients receiving ICI pre-LT demonstrates favorable survival and safety outcomes, justifying continued utilization and further evaluation of this strategy in clinical practice. High tumor burden, doubling of AFP levels, and radiographic response were identified as predictors of unfavorable oncologic outcomes. The first multicenter evaluation of pre-transplant immune-checkpoint-inhibitors in hepatocellular carcinoma to show promising intention-to-treat survival, safety and rejection rates. Immune-checkpoint-inhibitors, either alone or combined with LRT, demonstrate reliable efficacy. This preoperative strategy could be particularly beneficial for high-risk patients, including those requiring downstaging or with elevated AFP levels despite locoregional treatment. These findings fill current knowledge gaps and offer reassuring evidence for the feasibility of pre-transplant use of immune-checkpoint-inhibitors, pending results from ongoing trials.

Prognostic value of electroanatomic-guided endomyocardial biopsy in patients with myocarditis, arrhythmogenic cardiomyopathy and non dilated left ventricular cardiomyopathy

A wide variety of non-invasive and invasive techniques for SCD risk stratification in non ischemic cardiomyopathy (NICM) have been proposed, including left ventricular (LV) ejection fraction, QRS duration, late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) and invasive electrophysiologic study with or without three-dimensional electroanatomic mapping (3D-EAM), to identify and characterize the arrhythmogenic substrate. There is still no clear consensus on the risk stratification in this clinical setting.The aim of our study is to characterize the 3D-EAM substrate in patients with the same clinical presentation of unexplained complex VAs and NICM using CMR, three-dimensional electranatomic mapping (3D-EAM) in association with endomyocardial biopsy (EMB) and genetic screening, as a more precise and early diagnostic assessment may provide important subsequent prognostic impact. The study was designed as a prospective multi-center observational evaluation and the patient follow-up was scheduled at 6 months interval. We enrolled 125 patients distinct into four different group by complete diagnostic work-up: myocarditis, non-dilated left ventricular cardiomyopathy, arrhythmogenic cardiomyopathy and control group. The four groups were compared in terms of clinical, imaging and 3D-EAM data. At multivariate analysis sustained VT/VF on admission [HR: 3.64 (1.79–7.4), p < 0.001], total bipolar scar area of left and right ventricle detected by 3D-EAM [HR: 2.24 (1.13–4.49), p = 0.02], histological diagnosis of myocarditis by 3D-EAM guided endomyocardial biopsy (EBM) [HR: 2.79 (1.04–7.44), p = 0.01] were independent predictors of complex VAs or death at follow-up. 3D-EAM guided EMB represent not only a valid diagnostic tool to identify the arrhythmogenic substrate in patients with NICM and ventricular arrhythmic phenotype but also an important predictor of complex Vas at long term follow-up.

An international, multicenter post hoc analysis comparing in-person and virtual medication management strategies in post-ICU recovery clinics.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. To compare the incidence of ICU pharmacist interventions in intensive care unit recovery center (ICU-RC) in-person and virtual clinic visits. This was a post hoc analysis of interventions implemented by ICU pharmacists among adult patients who were referred to 12 ICU-RCs across the United States and the United Kingdom between September 2019 and July 2021, as reported in a previously published study "An International, Multicenter Evaluation of Comprehensive Medication Management by Pharmacists in ICU Recovery Centers." That study included patients who received a comprehensive medication review by an ICU pharmacist. Medication-related interventions performed by an ICU pharmacist during ICU-RC in-person clinic visits were compared to those performed during virtual clinic visits. There were 507 patients referred to an ICU-RC, of whom 474 patients attended a clinic visit. Of those, 472 received a comprehensive medication review, with 313 patients attending in-person visits and 159 patients attending virtual visits. The incidence of medication-related interventions implemented was higher in the ICU-RC in-person clinic group compared to the virtual clinic group (86.5% vs 79.2%, P = 0.04). There was no difference in the median number of ICU pharmacist interventions per patient between the in-person and virtual clinic groups (2 vs 2, P = 0.13). An ICU admission diagnosis was an independent predictor of medication-related interventions among all patients. The incidence of ICU pharmacist interventions was higher at ICU-RC in-person clinic visits compared to virtual clinic visits. Pharmacists aid in meeting the complex pharmacologic challenges of post-intensive care syndrome in both settings.

Artificial intelligence-driven volumetric CT outcome score in cystic fibrosis: longitudinal and multicenter validation with/without modulators treatment.

Holistic segmentation of CT structural alterations with 3D deep learning has recently been described in cystic fibrosis (CF), allowing the measurement of normalized volumes of airway abnormalities (NOVAA-CT) as an automated quantitative outcome. Clinical validations are needed, including longitudinal and multicenter evaluations. The validation study was retrospective between 2010 and 2023. CF patients undergoing Elexacaftor/Tezacaftor/Ivacaftor (ETI) or corticosteroids for allergic broncho-pulmonary aspergillosis (ABPA) composed the monocenter ETI and ABPA groups, respectively. Patients from six geographically distinct institutions composed a multicenter external group. All patients had completed CT and pulmonary function test (PFT), with a second assessment at 1 year in case of ETI or ABPA treatment. NOVAA-CT quantified bronchiectasis, peribronchial thickening, bronchial mucus, bronchiolar mucus, collapse/consolidation, and their overall total abnormal volume (TAV). Two observers evaluated the visual Bhalla score. A total of 139 CF patients (median age, 15 years [interquartile range: 13-25]) were evaluated. All correlations between NOVAA-CT to both PFT and Bhalla score were significant in the ETI (n = 60), ABPA (n = 20), and External groups (n = 59), such as the normalized TAV (ρ ≥ 0.76; p < 0.001). In both ETI and ABPA groups, there were significant longitudinal improvements in peribronchial thickening, bronchial mucus, bronchiolar mucus and collapse/consolidation (p ≤ 0.001). An additional reversibility in bronchiectasis volume was quantified with ETI (p < 0.001). Intraclass correlation coefficient of reproducibility was > 0.99. NOVAA-CT automated scoring demonstrates validity, reliability and responsiveness for monitoring CF severity over an entire lung and quantifies therapeutic effects on lung structure at CT, such as the volumetric reversibility of airway abnormalities with ETI. Normalized volume of airway abnormalities at CT automated 3D outcome enables objective, reproducible, and holistic monitoring of cystic fibrosis severity over an entire lung for management and endpoints during therapeutic trials. Visual scoring methods lack sensitivity and reproducibility to assess longitudinal bronchial changes in cystic fibrosis (CF). AI-driven volumetric CT scoring correlates longitudinally to disease severity and reliably improves with Elexacaftor/Tezacaftor/Ivacaftor or corticosteroid treatments. AI-driven volumetric CT scoring enables reproducible monitoring of lung disease severity in CF and quantifies longitudinal structural therapeutic effects.

A multi-center evaluation of a novel IVF cryostorage device in an active clinical setting

The objective of this study was to evaluate the function, and usability of a novel automated software-guided cryostorage system in an active IVF laboratory setting. The investigational device (ID) was installed at 3 IVF laboratories (sites: α, β, and γ). A total of 15 embryologists were trained to use the ID. Mock patient specimens containing mirrored live patient data were handled using the ID. Temperature readings were recorded every minute. Successful identification, storage, and retrieval of mock patient specimens by the ID were evaluated. To assess an LN2 pressure builder, the frequency of use and events of workflow interruption were logged. Student’s t-test was used to determine statistical significance. The ID was in active use for 164 days total. During this time, 329 mock patient egg and embryo cohorts were handled by the ID. The mean ± SD temperatures during active use were: α, − 176.57 ± 1.83 °C; β, − 178.21 ± 2.75 °C; γ, − 178.98 ± 1.74 and did not differ significantly. The highest recorded temperatures were: α, − 165.14 °C; β, − 157.41 °C; γ, − 164.45 °C. A total of 1064 automation transactions on 409 specimen vessels were performed. Data was managed on 1501 eggs and embryos. The ID did not lose or misplace any specimen data or vessels, and no mock specimen was exposed to a detrimental (> − 150 °C) temperature excursion. Over the 25 LN2 pressure builder usages during 99 total days, there was 1 occurrence where usage interrupted workflow due to a lack of LN2 pressure. The ID has advantages over the current manual-based cryostorage systems, including radio frequency identification (RFID) tracking, automation of manual tasks, and software guidance to ensure accurate specimen storage and retrieval. The results of this study indicate that the ID can be integrated into active IVF laboratories.

Operational feasibility and multi-centric evaluation of ‘TBDetect sputum microscopy kit’ for the direct detection of Mycobacterium tuberculosis in field settings

Background India relies primarily on direct smear microscopy for tuberculosis (TB) diagnosis. However, the low sensitivity of smear microscopy emphasizes the need to improve its performance. We recently described the development of ‘TBDetect’ kit which showed improved performance over direct smear microscopy at National Reference Laboratories (NRLs) in India. Methods The present study was aimed to assess the operational feasibility of ‘TBDetect’ microscopy in field settings. This was evaluated by (i) assessing the performance of ‘TBDetect’ microscopy vs. LED-fluorescence microscopy (LED-FM) on consecutive presumptive pulmonary TB patients (n = 5300) who attended Designated Microscopy Centres (DMCs, n = 13) under 4 NRLs at Bhubaneswar, Bhopal, Chennai, and New Delhi, and (ii) obtaining feedback from Scientists (n = 10) and laboratory technicians (n = 42) using semi-structured questionnaires under the following parameters: feasibility of initiation of ‘TBDetect’ microscopy in DMCs, sample preparation and testing, training, time-to-result, logistics, and troubleshooting. A scoring questionnaire was also used to assess ‘TBDetect’ microscopy vs. LED-FM and statistical significance of the scores was calculated using paired t-test. Results The overall positivity of ‘TBDetect’ microscopy was 10.32% (547/5300) vs. 8.96% (475/5300) of LED-FM at all sites and the increment in positivity was significant (p = 0.019). In addition, ‘TBDetect’ microscopy yielded an increment in smear grade status over LED-FM (p = 0.043). The feedback from the study-in-charge and kit users indicated that ‘TBDetect’ microscopy was easily adapted in point-of-care settings. An analysis of scoring feedback suggested that it was easy to perform and observe in comparison to LED-FM (p < 0.005). Conclusions This study established the feasibility of ‘TBDetect’ microscopy in field settings.

Multicenter and inter-software evaluation of ablative margins after thermal ablation of colorectal liver metastases.

To assess the association between minimal ablative margin (MAM) and local tumor progression (LTP) following CT-guided thermal ablation of colorectal liver metastases (CRLM) in a multicenter cohort and across two confirmation software. This multicenter retrospective study included patients who underwent CT-guided radiofrequency or microwave ablation for CRLM between 2009 and 2021 in three institutions. Three-dimensional (3D) MAM was retrospectively assessed using dedicated ablation confirmation software by automatic non-rigid (Ablation-fit) or semi-automatic rigid co-registration (SAFIR) of intraprocedural pre- and post-ablation contrast-enhanced CT scans by two independent reader teams blinded to patient outcomes. LTP was assessed on a per-tumor basis. Factors associated with LTP-free survival were assessed using multivariable Cox regression analysis. Overall, 113 patients (mean age: 67 ± 10 years; 78 men) who underwent thermal ablation for 189 CRLM (mean diameter: 1.9 ± 1.1 cm) met the inclusion criteria. 173/189 (92%) CRLM could be successfully analyzed using both software. Over a median follow-up of 31 months (IQR: 22-47), 21 of 173 CRLM (12.1%) developed LTP. On multivariable analysis, 3D MAM was independently associated with LTP in both software (Ablation-fit: HR 0.47, 95% CI: 0.36-0.61, p < 0.001; SAFIR: HR 0.42, 95% CI: 0.32-0.55, p < 0.001). No LTP was observed in CRLM ablated with MAM ≥ 4 mm (Ablation-fit) and ≥ 5 mm (SAFIR). The per-tumor median absolute difference in MAM quantification between both software was 2 mm (IQR: 1-3). MAM was independently associated with LTP after thermal ablation of CRLM across multicenter data and two confirmation software. Ablations achieving a MAM ≥ 5 mm were associated with local control in both software. MAMs from intraprocedural contrast-enhanced CT were independently associated with LTP after thermal ablation of CRLM across multicenter data and two confirmation software, with a margin ≥ 5 mm associated with local control in both software. Sufficient ablative margins are critical for local control following thermal ablation of CRLM. Intraprocedural CT-derived MAM was the only independent factor associated with LTP across two confirmation software. No LTP was observed in CRLM ablated with a MAM ≥ 5 mm.

317 Multicenter evaluation of deep-learning based deliverable automated radiotherapy planning

317 Multicenter evaluation of deep-learning based deliverable automated radiotherapy planning

Prospective multi-center evaluation of the incidence of unplanned extubation and its outcomes in French intensive care units. The Safe-ICU study

BackgroundWe aimed to determine the epidemiology and outcomes of unplanned extubation (UE), both accidental and self-extubation, in ICU. MethodsA multicentre prospective cohort study was conducted in 47 French ICUs. The number of mechanical ventilation (MV) days, and planned and unplanned extubation were recorded in each center over a minimum period of three consecutive months to evaluate UE incidence. Patient characteristics, UE environmental factors, and outcomes were compared based on the UE mechanism (accidental or self-extubation). Self-extubation outcomes were compared with planned extubation using a propensity-matched population. Finally, risk factors for extubation failure (re-intubation before day 7) were determined following self-extubation. ResultsDuring the 12-month inclusion period, we found a pooled UE incidence of 1.0 per 100 MV days. UE accounted for 9% of all endotracheal removals. Of the 605 UE, 88% were self-extubation and 12% were accidental-extubations. The latter had a worse prognosis than self-extubation (34% vs. 8% ICU-mortality, p < 0.001). Self-extubation did not increase mortality compared with planned extubation (8% vs. 11%, p = 0.075). Regardless of the type of extubation, planned or unplanned, extubation failure was independently associated with a poor outcome. Cancer, higher respiratory rate, lower PaO2/FiO2 at the time of extubation, weaning process not-ongoing, and immediate post-extubation respiratory failure were independent predictors of failed self-extubation. ConclusionUnplanned extubation, mostly represented by self-extubation, is common in ICU and accounts for 9% of all endotracheal extubations. While accidental extubations are a serious and infrequent adverse event, self-extubation does not increase mortality compared to planned extubation.

Successful and sustained implementation of a behaviour-change informed strategy for emergency nurses: a multicentre implementation evaluation

BackgroundImplementing evidence that changes practice in emergency departments (EDs) is notoriously difficult due to well-established barriers including high levels of uncertainty arising from undifferentiated nature of ED patients, resource shortages, workload unpredictability, high staff turnover, and a constantly changing environment. We developed and implemented a behaviour-change informed strategy to mitigate these barriers for a clinical trial to implement the evidence-based emergency nursing framework HIRAID® (History including Infection risk, Red flags, Assessment, Interventions, Diagnostics, communication, and reassessment) to reduce clinical variation, and increase safety and quality of emergency nursing care.AimTo evaluate the behaviour-change-informed HIRAID® implementation strategy on reach, effectiveness, adoption, quality (dose, fidelity) and maintenance (sustainability).MethodsAn effectiveness-implementation hybrid design including a step–wedge cluster randomised control trial (SW-cRCT) was used to implement HIRAID® with 1300 + emergency nurses across 29 Australian rural, regional, and metropolitan EDs. Evaluation of our behaviour-change informed strategy was informed by the RE-AIM Scoring Instrument and measured using data from (i) a post HIRAID® implementation emergency nurse survey, (ii) HIRAID® Instructor surveys, and (iii) twelve-week and 6-month documentation audits. Quantitative data were analysed using descriptive statistics to determine the level of each component of RE-AIM achieved. Qualitative data were analysed using content analysis and used to understand the ‘how’ and ‘why’ of quantitative results.ResultsHIRAID® was implemented in all 29 EDs, with 145 nurses undertaking instructor training and 1123 (82%) completing all four components of provider training at 12 weeks post-implementation. Modifications to the behaviour-change informed strategy were minimal. The strategy was largely used as intended with 100% dose and very high fidelity. We achieved extremely high individual sustainability (95% use of HIRAID® documentation templates) at 6 months and 100% setting sustainability at 3 years.ConclusionThe behaviour-change informed strategy for the emergency nursing framework HIRAID® in rural, regional, and metropolitan Australia was highly successful with extremely high reach and adoption, dose, fidelity, individual and setting sustainability across substantially variable clinical contexts.Trial registrationANZCTR, ACTRN12621001456842. Registered 25 October 2021.

Cochlear Implantation in Single-Sided Deafness and Asymmetric Hearing Loss: 12 Months Follow-up Results of a European Multicenter Evaluation.

People with single-sided deafness (SSD) or asymmetric hearing loss (AHL) have particular difficulty understanding speech in noisy listening situations and in sound localization. The objective of this multicenter study is to evaluate the effect of a cochlear implant (CI) in adults with single-sided deafness (SSD) or asymmetric hearing loss (AHL), particularly regarding sound localization and speech intelligibility with additional interest in electric-acoustic pitch matching. A prospective longitudinal study at 7 European tertiary referral centers was conducted including 19 SSD and 16 AHL subjects undergoing cochlear implantation. Sound localization accuracy was investigated in terms of root mean square error and signed bias before and after implantation. Speech recognition in quiet and speech reception thresholds in noise for several spatial configurations were assessed preoperatively and at several post-activation time points. Pitch perception with CI was tracked using pitch matching. Data up to 12 months post activation were collected. In both SSD and AHL subjects, CI significantly improved sound localization for sound sources on the implant side, and thus overall sound localization. Speech recognition in quiet with the implant ear improved significantly. In noise, a significant head shadow effect was found for SSD subjects only. However, the evaluation of AHL subjects was limited by the small sample size. No uniform development of pitch perception with the implant ear was observed. The benefits shown in this study confirm and expand the existing body of evidence for the effectiveness of CI in SSD and AHL. Particularly, improved localization was shown to result from increased localization accuracy on the implant side.

Outcomes, mortality risk factors, and functional status post-Norwood: A single-center study

BackgroundThe Norwood operation (NO) for infants with univentricular physiology has high interstage mortality. This study evaluated outcomes and risk factors for mortality following NO. MethodsRetrospective single-center study of patients undergoing NO from 2010 to 2020. Analysis used appropriate statistics. ResultsOf 269 patients undergoing NO, 213 (79.2 %) survived to discharge. Non-survivors had longer bypass times, delayed sternal closure, required nitric oxide, higher vasoactive scores, required post-operative catheterization, Extracorporeal Life Support (ECLS), and longer ventilation (p < 0.05). Logistic regression showed moderate-severe atrioventricular valve regurgitation on intraoperative TEE (OR 2.6), requiring nitric oxide (OR 2.63), delayed sternal closure (OR 2.94), post-operative catheterization (OR 10.48), and ECLS (OR 14.54) increased mortality odds (p < 0.05). Multivariable analysis confirmed catheterization (aOR 10.48) and ECLS (aOR 14.54) as significant predictors. Of survivors, 26 (12.3 %) developed new morbidity, 9 (4.2 %) had unfavorable outcomes. Functional status improved from 6.0 to 8.04, mainly in feeding and respiratory domains (p < 0.0001). ConclusionsNorwood survival was 79.2 %. Requiring post-operative catheterization and ECLS significantly increased mortality risk. Multicenter evaluation of these modifiable risk factors is needed to improve outcomes in this high-risk population.

Clinical utility of investigations in triple-negative thrombocytosis: A real-world, multicentre evaluation of UK practice.

Diagnosis of essential thrombocythaemia (ET) is challenging in patients lacking JAK2/CALR/MPL mutations. In a retrospective evaluation of 320 patients with 'triple-negative thrombocytosis', we assessed utility of bone marrow histology (90.9% of patients) and myeloid gene panel (MGP, 55.6%). Supportive histology ('myeloproliferative neoplasm-definite/probable', 36.8%) was associated with higher platelet counts and varied between centres. 14.6% MGP revealed significant variants: 3.4% JAK2/CALR/MPL and 11.2% other myeloid genes. Final clinical diagnosis was strongly predicted by histology, not MGP. 23.7% received cytoreduction (17.6% under 60 years). Real-world 'triple-negative' ET diagnosis currently depends heavily on histology; we advocate caution in MGP-negative cases and that specific guidelines are needed.

Multi-centric evaluation of Truenat MTB and MTB-RIF Dx assays for diagnosis of extrapulmonary tuberculosis

Extra-pulmonary TB (EPTB) is difficult to diagnose due to paucibacillary nature of disease. Current study evaluated accuracy of Truenat MTB and MTB-Rif Dx (TN), for detection of Mycobacterium tuberculosis and resistance to rifampicin. Samples were collected from 2103 treatment naive adults with presumptive EPTB, and tested by smear microscopy, liquid culture (LC) (MGIT-960) and GeneXpert MTB/RIF (GX) (Microbiological Reference Standards, MRS). TN results were compared to MRS and Composite Reference Standards (CRS, Microbiology, histopathology, radiology, clinical features prompting decision to treat, response to treatment). CRS grouped patients into 551 confirmed, 1096 unconfirmed, and 409 as unlikely TB. TN sensitivity and specificity was 73.7% and 90.4% against GX. Against LC, Overall sensitivity of GX was 67.6%, while that of TN was 62.3%. Highest sensitivity by TN was observed in pus samples (89%) and highest specificity (92%) in CSF samples, similar to GX. TN sensitivity was better in fluid and biopsy samples and slightly inferior for lymph node aspirates compared to GX. TN sensitivity for RIF resistance detection was slightly superior to GX. TN and GX results were further compared to Clinical Reference Standards. TN detected 170 TB patients initiated on treatment missed by GX, while GX detected 113 such patients missed by TN. Of 124 samples with RIF resistance discordance between GX and TN, GX reported 103/124 as sensitive, 3/124 as indeterminate and 18 as resistant (13/18 samples had low/very low DNA load) while TN reported RIF resistance indeterminate in 103/111 low/very low DNA load samples. Due to paucibacillary nature of EPTB samples, culture yield was poor and phenotypic drug susceptibility testing failed to resolve the discordance. The study establishes TN at par with GX and can be utilized for quick and accurate diagnosis of EPTB.

A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC)

BackgroundTherapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking.MethodsTrans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses.DiscussionThe SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research.Trial registrationanzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

Multicenter evaluation of mechanical thrombectomy for distal medium vessel occlusions with National Institute of Health Stroke Scale Scores ≥ 6 and ≤ 6.

While mechanical thrombectomy is considered standard of care for large vessel occlusions, scientific evidence to support treatment for distal and medium vessel occlusions remains scarce. To evaluate feasibility, safety, and outcomes in patients with low National Institute of Health Stroke Scale scores undergoing mechanical thrombectomy for treatment of distal medium vessel occlusions. Retrospective data review and analysis of prospectively maintained databases at 41 academic centers in North America, Asia, and Europe between January 2017 and January 2022. Characteristics and outcomes were compared between groups with low stroke scale score (≤ 6) versus and higher stroke scale scores (> 6). Propensity score matching using the optimal pair matching method and 1:1 ratio was performed. Data were collected on a total of 1068 patients. After propensity score matching, there were a total of 676 patients included in the final analysis, with 338 patients in each group. High successful reperfusion rates were seen in both groups, 90.2% in ≤ 6 and 88.7% in the > 6 stroke scale groups. The frequency of excellent and good functional outcome was seen more common in low versus higher stroke scale score patients (64.5% and 81.1% versus 39.3% and 58.6%, respectively). The 90-day mortality rate observed in the ≤ 6 stroke scale group was 5.3% versus 13.3% in the > 6 stroke scale group. Mechanical thrombectomy in distal and medium vessel occlusions, specifically in patients with low stroke scale scores is feasible, though it may not necessarily improve outcomes over IVT.

O-250 Never a lost cause: can artificial intelligence (AI)-powered ranking help decrease time to pregnancy when only poor-quality embryos are available?

Abstract Study question Can an objectively trained AI system complement embryologists in their ranking of embryos and minimize time to pregnancy, when only poor-quality embryos are available? Summary answer An objective AI algorithm could have decreased cycle to pregnancy by 18% in cohorts of embryos where only poor-quality embryos were available. What is known already Morphokinetics is a key criterion for embryologists to rank embryos as good, fair, or poor quality, with the latter frequently being discarded. Although poor-quality embryos can still lead to a pregnancy, selection of a viable embryo remains challenging to embryologists due to their depleted morphological characteristics. Unlike embryologists, an AI can be trained to see beyond embryo morphological quality, on data that includes many poor-quality embryos that resulted in a pregnancy. As such, AI has the potential to recognize viable poor-quality embryos, which becomes especially crucial in cases where good or fair embryos are unavailable from the embryo pool. Study design, size, duration Data from a French center was acquired through a MIRI® (ESCO) time-lapse system and uploaded on EMBRYOLY, between January 2022 and March 2023. For a total of 204 patients (women’s average age 35 y.o.), embryologists were faced with having to choose an embryo to transfer among 4.3 ± 1.7 poor-quality embryos either because the cohort was composed of only poor-quality embryos or because higher quality embryos had already been transferred. Participants/materials, setting, methods A previously described deep learning algorithm trained on videos of developing embryos with known pregnancy outcome was used to score embryos according to their chances of leading to a clinical pregnancy (fetal heartbeat between 6-9 weeks). A 2D ResNet model was trained, validated and tested on 8138 images of day 5 embryos annotated by senior embryologists to identify those of poor-quality (Gardner grade ICM and/or TE = C, corresponding to 44.7% of the dataset). Main results and the role of chance The association between video predictions and pregnancy was assessed with a logistic regression. A McNemar test was used to compare cycle to pregnancy (CTP) with and without EMBRYOLY’s hypothetical impact. EMBRYOLY’s AI was able to rank poor-quality embryos, as illustrated by a 2-7% relative increase in likelihood of clinical pregnancy observed with an increase in the video score (logistic regression with unit level +0.02, OR = 1.04, 95CI = [1.02-1.07], N = 261 transferred embryos, p &amp;lt; 0.05). EMBRYOLY’s first choice was concordant with the embryologists’ first choice in 74% of the cases that led to a pregnancy (N = 42 embryos). For patients who had two poor-quality embryos transferred with at least one pregnancy (N = 14 cycles), the results show that if the embryologist had first transferred the highest EMBRYOLY-ranked embryo, the number of cycles to pregnancy would have been reduced by 18% (from 1.7 to 1.4, McNemar, p &amp;lt; 0.05), corresponding to a median of 2.3 months. Limitations, reasons for caution The endpoint used was clinical pregnancy as measured by fetal heartbeat, and does not indicate the probability of live birth. The current investigation was performed with retrospective data from a single center. In the future, a multi-centre evaluation should be performed to generalize our findings. Wider implications of the findings Our findings support that an objectively trained AI can help embryologists not miss out on poor-quality embryos that can lead to a pregnancy, which is all the more important to target when good or fair embryos are unavailable from the embryo pool. Trial registration number not applicable

Internal urethral sphincter reconstruction with anterior bladder neck tube for robotic and laparoscopic radical prostatectomy: improving early return of continence.

In recent years, despite several surgical techniques having been applied, the early incontinence rate after radical prostatectomy (RP) remains high. In this study, we reconstructed an internal urethral sphincter (IUS) with anterior bladder neck tube (ABNT) to improve early return of continence and find a more effective technique for early urinary incontinence after RP. In this study, 96 previous patients who did not receive an ABNT between October 2018 and May 2020 were compared as historical controls (the control group). A total of 210 consecutive patients underwent robotic or laparoscopic RP with ABNT between May 2020 and February 2023 (the ABNT group). The inclusion criteria included Eastern Cooperative Oncology Group (ECOG) score 0-1 and localized prostate cancer (clinical stages cT1-3, cN0, cM0). The exclusion criteria included patients with diabetes, neurologic diseases, previous pelvic operations, symptoms of urinary incontinence, prior radiation, focal therapy, or androgen deprivation therapy for prostate cancer. ABNT was reconducted with a U-shaped flap from the anterior wall of the bladder neck, and was then anastomosed with the urethra. In the control group, the bladder outlet was directly anastomosed with the urethra. Continence, as defined if 0 pads were used per day and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score ≤6, was assessed at 1, 4, 8, 12, and 24 weeks after catheter removal. At 2 weeks after catheter removal, urethral pressure profilometry (UPP) and upright urethrography were performed to evaluate the function of ABNT in the ABNT group. More patients in the ABNT group were continent than those in the control group at 1 week (85.2% vs. 22.9%, P<0.001), 4 weeks (91.4% vs. 27.1%, P<0.001), 8 weeks (95.2% vs. 40.6%, P<0.001), 12 weeks (100% vs. 71.9%, P<0.001), and at 24 weeks (100% vs. 87.5%, P<0.001) after catheter removal. Stricture was presented in 5.2% and 2.1% (P=0.34) in the ABNT group and control group, respectively. UPP showed that a functional IUS was reconstructed with ABNT. Upright urethrography showed that the ABNT was filled with contrast medium in the urination period and with no contrast medium during the storage period and interruption of urination. The ABNT technique significantly improved early return of continence in comparison with the no ABNT technique, especially the immediate continence. The ABNT technique reconstructed the functional IUS with acceptable urethral stricture. The limitations of the present study include that the comparison was conducted retrospectively with a historical cohort and lack of randomization, and the single center setting. A prospective, randomized, and multicenter evaluation is expected.

Endoscopic Versus Traditional Thoracic Discectomy: A Multicenter Retrospective Case Series and Meta-Analysis.

Surgical treatment for symptomatic thoracic disc herniations (TDH) involves invasive open surgical approaches with relatively high complication rates and prolonged hospital stays. Although advantages of full endoscopic spine surgery (FESS) are well-established in lumbar disc herniations, data are limited for the endoscopic treatment of TDH despite potential benefits regarding surgical invasiveness. The aim of this study was to provide a comprehensive evaluation of potential benefits of FESS for the treatment of TDH. PubMed, MEDLINE, EMBASE, and Scopus were systematically searched for the term "thoracic disc herniation" up to March 2023 and study quality appraised with a subsequent meta-analysis. Primary outcomes were perioperative complications, need for instrumentation, and reoperations. Simultaneously, we performed a multicenter retrospective evaluation of outcomes in patients undergoing full endoscopic thoracic discectomy. We identified 3190 patients from 108 studies for the traditional thoracic discectomy meta-analysis. Pooled incidence rates of complications were 25% (95% CI 0.22-0.29) for perioperative complications and 7% (95% CI 0.05-0.09) for reoperation. In this cohort, 37% (95% CI 0.26-0.49) of patients underwent instrumentation. The pooled mean for estimated blood loss for traditional approaches was 570 mL (95% CI 477.3-664.1) and 7.0 days (95% CI 5.91-8.14) for length of stay. For FESS, 41 patients from multiple institutions were retrospectively reviewed, perioperative complications were reported in 4 patients (9.7%), 4 (9.7%) required revision surgery, and 6 (14.6%) required instrumentation. Median blood loss was 5 mL (IQR 5-10), and length of stay was 0.43 days (IQR 0-1.23). The results suggest that full endoscopic thoracic discectomy is a safe and effective treatment option for patients with symptomatic TDH. When compared with open surgical approaches, FESS dramatically diminishes invasiveness, the rate of complications, and need for prolonged hospitalizations. Full endoscopic spine surgery has the capacity to alter the standard of care for TDH treatment toward an elective outpatient surgery.