Artificial intelligence software standardizes electrogram-based ablation outcome for persistent atrial fibrillation.

INTRODUCTION: Multiple groups have reported on the usefulness of ablating in atrial regions exhibiting abnormal electrograms during atrial fibrillation (AF). Still, previous studies have suggested that ablation outcomes are highly operator- and center-dependent. This study sought to evaluate a novel machine learning software algorithm named VX1 (Volta Medical), trained to adjudicate multipolar electrogram dispersion. METHODS: This study was a prospective, multicentric, nonrandomized study conducted to assess the feasibility of generating VX1 dispersion maps. In 85 patients, 8 centers, and 17 operators, we compared the acute and long-term outcomes after ablation in regions exhibiting dispersion between primary and satellite centers. We also compared outcomes to a control group in which dispersion-guided ablation was performed visually by trained operators. RESULTS: The study population included 29% of long-standing persistent AF. AF termination occurred in 92% and 83% of the patients in primary and satellite centers, respectively, p = 0.31. The average rate of freedom from documented AF, with or without antiarrhythmic drugs (AADs), was 86% after a single procedure, and 89% after an average of 1.3 procedures per patient (p = 0.4). The rate of freedom from any documented atrial arrhythmia, with or without AADs, was 54% and 73% after a single or an average of 1.3 procedures per patient, respectively (p < 0.001). No statistically significant differences between outcomes of the primary versus satellite centers were observed for one (p = 0.8) or multiple procedures (p = 0.4), or between outcomes of the entire study population versus the control group (p > 0.2). Interestingly, intraprocedural AF termination and type of recurrent arrhythmia (i.e., AF vs. AT) appear to be predictors of the subsequent clinical course. CONCLUSION: VX1, an expertise-based artificial intelligence software solution, allowed for robust center-to-center standardization of acute and long-term ablation outcomes after electrogram-based ablation.

Intraoperative Mapping Angiograms of the Parathyroid Glands Using Indocyanine Green During Thyroid Surgery: Results of the Fluogreen Study.

BACKGROUND: During thyroid surgery, preservation of parathyroid gland (PG) feeding vessels is often impossible. The aim of the Fluogreen study was to determine the feasibility of using indocyanine green (ICG)-based intraoperative mapping angiograms of the PG (iMAP) to improve vascular preservation. STUDY DESIGN: This prospective study enrolled all patients undergoing thyroid lobectomy or total thyroidectomy at the Hôpital Européen Marseille between September and December 2018. After exploring the thyroid lobe by autofluorescence to locate the PGs, ICG solution was injected intravenously to locate the PG feeding vessels and guide dissection. A second ICG injection was administered at the end of the lobectomy to assess perfusion of the PGs. The primary outcome was the quality of the angiogram, scaled as iMAP 0 (not informative), iMAP 1 (general vascular pattern visible but no clear vascular pedicle flowing into the PG), or iMAP 2 (clear vascular pedicle flowing into the PG). The secondary outcome was the PG perfusion score at the end of surgery, scaled from ICG 0 (no perfusion) to ICG 2 (intense uptake). RESULTS: A total of 47 adult patients were analyzed, including 34 total thyroidectomies and 13 lobectomies. ICG angiography assessed 76 PGs, which were scored as iMAP 2 in 24 cases (31.6%), iMAP 1 in 46 (60.5%) and iMAP 0 in six (7.9%). At the end of dissection, the ICG perfusion score was significantly better for the PGs with informative angiography (iMAP 1 or 2), than for the PGs with uninformative angiography (iMAP 0), or the PGs not evaluated by vascular angiography (p < 0.05). CONCLUSION: iMAP is feasible and provides direct vascular information in one-third of the cases. Further improvements to this technology are necessary, and the influence of this technique on patient outcomes during thyroidectomy will need to be further evaluated.

Performance of digital single-operator cholangiopancreatoscope for biliopancreatic diseases in real life: results from a prospective multicenter study.

OBJECTIVES: Peroralcholangio-pancreatoscopy (POCP) is used for diagnosis and treatment of biliopancreatic disease when standard endoscopy (ERCP) or pre-operative imaging workup failed. We aimed to evaluate the diagnostic and therapeutic performance of POCP in complex biliary and pancreatic diseases. MATERIALS AND METHODS: Patients with indeterminate biliary or pancreatic duct (PD) strictures, and patients with failure of complex biliary or pancreatic stones removal, were enrolled (six centers). The primary endpoint evaluated malignancy diagnostic performances (accuracy, sensitivity, specificity) and therapeutic performances (biliary or pancreatic stones extraction). Secondary endpoints evaluated: technical success in lesion visualization, ease of maneuvering, image quality and 30-days complications. RESULTS: From November 2016 to March 2018, 66 patients were included: 29/37 women/men, median age (IQR): 73 (64-82). Fifty-three patients had diagnostic POCP and 13 patients therapeutic POCP. One endoscopist with one or two endoscopy nurses performed 94% of the POCP. The 'POCP visual impression' of malignancy showed 92.0% sensitivity, 92.9 % specificity and 92.5 % overall accuracy compared with the final diagnosis. 'POCP-guided samples histological analysis' showed 75.0 % sensitivity and 91.6% specificity. The technical success for lesion visualization was 98.5%. The median VAS scores for insertions in bile and PD were respectively 9.0 (8.1-9.6) and 9.0 (8.8-10.0). Median VAS score for access to the lesion and image quality were respectively 9.0 (7.7-9.6) and 9.0 (7.9-9.7). Only three 30-day minor complications occurred without any major complications. CONCLUSIONS: POCP was an effective, safe and easy-to-use tool in routine clinical practice for the management of complex diagnostic and therapeutic biliary and pancreatic diseases (NCT03190343).

19 G nitinol needle versus 22 G needle for transduodenal endoscopic ultrasound-guided sampling of pancreatic solid masses: a randomized study.

BACKGROUND: The aim of this prospective multicenter study was to compare a flexible 19 G needle with nitinol shaft (19 G Flex) with a standard 22 G needle for transduodenal endoscopic ultrasound (EUS)-guided sampling of pancreatic head tumors. METHODS: Patients with pancreatic head tumors requiring tissue diagnosis were randomized into two arms: puncture with either a 19 G Flex needle or a 22 G needle. The primary end point was diagnostic accuracy for malignancy. The secondary end points were ergonomic scores, sample cytohistological quality, and complications. A 6-month follow-up was performed. RESULTS: 125 patients were randomized and 122 were analyzed: 59 patients in the 19 G Flex arm and 63 patients in the 22 G arm. The final diagnosis was malignancy in 111 patients and benign condition in 11. In intention-to-treat analysis, the diagnostic accuracy for malignancy of the 19 G Flex and 22 G needles was 69.5 % (95 % confidence interval [CI] 56.1 % - 80.8 %) vs. 87.3 % (95 %CI 76.5 % - 94.4 %), respectively (P = 0.02). In per-protocol analysis excluding eight technical failures in the 19 G Flex group, the diagnostic accuracy of the 19 G Flex and 22 G needles was not statistically different: 80.4 % (95 %CI 66.9 % - 90.2 %) vs. 87.3 % (95 %CI 76.5 % - 94.4 %; P = 0.12). Technical success was higher in the 22 G arm than in the 19 G Flex arm: 100 % (95 %CI 94.3 % - 100 %) vs. 86.4 % (95 %CI 75.0 % - 94.0 %), respectively (P = 0.003). Transduodenal EUS-guided sampling was more difficult with the 19 G Flex (odds ratio 0.68, 95 %CI 0.47 - 0.97). CONCLUSION : The 19 G Flex needle was inferior to a standard 22 G needle in diagnosing pancreatic head cancer and more difficult to use in the transduodenal approach.

Double guidewire endoscopic technique, a major evolution in endoscopic retrograde cholangiopancreatography: Results of a retrospective study with historical controls comparing two therapeutic sequential strategies.

BACKGROUND AND AIM: Endoscopic access to the common bile duct (CBD) remains difficult in 10% of cases, requiring alternative techniques .CBD access was difficult after either five unsuccessful attempts, five unintentional insertions into the pancreatic duct or >10-min-long unsuccessful attempts. This retrospective study with historical controls aimed to evaluate the benefit of the double guidewire (DGW) technique after failure of standard CBD cannulation. METHODS: From January 2012 to December 2014, all patients requiring therapeutic endoscopic retrograde cholangiopancreatography (ERCP) with difficult access to CBD were included in a Studied group. This group was compared to a historical ERCP control group from January 2009 to December 2011. In the Studied group, a sequential strategy including DGW technique was done when the guidewire was unintentionally passed into the pancreatic duct. In the control group, only pre-cut technique was used. RESULTS: Among the 538 patients with naive papilla eligible for ERCP, 73 had difficult CBD access. Successful CBD access rate was higher in the Studied group: 91% (50/55) versus 67% (12/18) P = 0.0215. Complication rates were similar in both groups: 28% versus 20%, P = 0.5207. LOS was shorter in the Studied group (9.2 ± 8.5 vs 14.4 ± 7.4 days, P = 0.0028). Post-ERCP cholangitis were lower in the Studied group: 2% (1/55) versus 22% (4/18), P = 0.0118. CONCLUSION: After standard cannulation failure, DGW technique increased successful CBD access rate and decreased LOS without increasing complications.

HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir.

BACKGROUND & AIMS: Recent clinical trials of direct-acting-antiviral agents (DAAs) against hepatitis C virus (HCV) achieved >90% sustained virological response (SVR) rates, suggesting that cure often took place before the end of treatment (EOT). We sought to evaluate retrospectively whether early response kinetics can provide the basis to individualize therapy to achieve optimal results while reducing duration and cost. METHODS: 58 chronic HCV patients were treated with 12-week sofosbuvir+simeprevir (n=19), sofosbuvir+daclatasvir (n=19), or sofosbuvir+ledipasvir in three French referral centers. HCV was measured at baseline, day 2, every other week, EOT and 12weeks post EOT. Mathematical modeling was used to predict the time to cure, i.e., <1 virus copy in the entire extracellular body fluid. RESULTS: All but one patient who relapsed achieved SVR. Mean age was 60±11years, 53% were male, 86% HCV genotype-1, 9% HIV coinfected, 43% advanced fibrosis (F3), and 57% had cirrhosis. At weeks 2, 4 and 6, 48%, 88% and 100% of patients had HCV<15IU/ml, with 27%, 74% and 91% of observations having target not detected, respectively. Modeling results predicted that 23 (43%), 16 (30%), 7 (13%), 5 (9%) and 3 (5%) subjects were predicted to reach cure within 6, 8, 10, 12 and 13weeks of therapy, respectively. The modeling suggested that the patient who relapsed would have benefitted from an additional week of sofosbuvir+ledipasvir. Adjusting duration of treatment according to the modeling predicts reduced medication costs of 43-45% and 17-30% in subjects who had HCV<15IU/ml at weeks 2 and 4, respectively. CONCLUSIONS: The use of early viral kinetic analysis has the potential to individualize duration of DAA therapy with a projected average cost saving of 16-20% per 100-treated persons.

Retreatment with TACE: the ABCR SCORE, an aid to the decision-making process.

BACKGROUND & AIMS: Transarterial chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC) and it is the most commonly used treatment for HCC worldwide. However, no prognostic indices, designed to select appropriate candidates for repeat conventional TACE, have been incorporated in the guidelines. METHODS: From January 2007 to April 2012, 139 consecutive HCC patients, mainly with an alcohol- or viral-induced disease, were treated with TACE. Using a regression model on the prognostic variables of our population, we determined a score designed to help for repeat TACE and we validated it in two cohorts. We also compared it to the ART score. RESULTS: In the multivariate analysis, four prognostic factors were associated with overall survival: BCLC and AFP (>200 ng/ml) at baseline, increase in Child-Pugh score by ⩾2 from baseline, and absence of radiological response. These factors were included in a score (ABCR, ranging from -3 to +6), which correlates with survival and identifies three groups. The ABCR score was validated in two different cohorts of 178 patients and proofed to perform better than the ART score in distinguishing between patients' prognosis. CONCLUSIONS: The ABCR score is a simple and clinically relevant index, summing four prognostic variables endorsed in HCC. An ABCR score ⩾4 prior to the second TACE identifies patients with dismal prognosis who may not benefit from further TACE sessions.

Laboratory tests for investigating anemia: From an expert system to artificial intelligence.

Objective: To compare the laboratory tests conducted in real-life settings for patients with anemia with the expected prescriptions derived from an optimal checkup. Methods: A panel of experts formulated an "optimal laboratory test assessment" specific to each anemia profile. A retrospective analysis was done of the laboratory tests conducted according to the type of anemia (microcytic, normocytic or macrocytic). Using an algorithmic system, the laboratory tests performed in real-life practice were compared with the recommendations suggested in the "optimal laboratory test assessment" and with seemingly "unnecessary" laboratory tests. Results: In the analysis of the "optimal laboratory test assessment", of the 1179 patients with microcytic anemia, 269 (22.8%) had had one of the three tests recommended by the expert system, and only 33 (2.8%) had all three tests. For normocytic anemia, 1054 of 2313 patients (45.6%) had one of the eleven recommended tests, and none had all eleven. Of the 384 patients with macrocytic anemia, 196 (51%) had one of the four recommended tests, and none had all four. In the analysis of "unnecessary laboratory tests", one lab test was unnecessarily done in 727/3876 patients (18.8%), i.e. 339 of 1179 (28.8%) microcytic, 171 of 2313 (7.4%) normocytic, and 217 of 384 (56.5 %) macrocytic anemias. Conclusion: Laboratory investigations of anemia remain imperfect as more than half of the cases did not receive the expected tests. Analyzing other diagnostic domains, the authors are currently developing an artificial intelligence system to assist physicians in enhancing the efficiency of their laboratory test prescriptions.

Outcomes and safety of atezolizumab plus bevacizumab in the treatment of hepatocellular carcinoma: treatment prognosis and comparison with tyrosine kinase inhibitors in a French multicenter matched real-life study.

BACKGROUND AND AIMS: The combination of atezolizumab plus bevacizumab (Atz/Bev) has radically changed the treatment strategy for advanced hepatocellular carcinoma (HCC) but raises questions. Our objectives were to determine survival outcomes and safety in a real-life multicenter French cohort, to investigate the on-treatment prognostic value of the bioinflammatory RECA score, and to perform a matched comparison with patients who previously received tyrosine kinase inhibitors (TKIs). METHODOLOGY: A retrospective analysis of 109 consecutive patients enrolled from September 2020 to January 2023 and a post matched comparison with a TKI cohort (n = 79) by the propensity score matching method. RESULTS: The Atz/Bev population was mainly nonviral disease patients (69%) with Child-Pugh grade A (90%), performance status 0/1 (90%), and Barcelona Clinic Liver Cancer stage B (38%) or stage C (62%) classification. After a median follow-up of 6.5 months (3.6-11.7), overall survival (OS) was 13.0 (5.1-28.7) months. OS was independently associated with metastasis, increased alkaline phosphatase, and serum bilirubin levels. Treatment-related adverse events were reported in 78% of patients, mostly grade 1 or 2. The RECA score clearly revealed two different prognosis groups after three cycles. No difference in OS was observed after matching between sequential treatment with TKIs and Atz/Bev. CONCLUSION: This real-life study highlights the importance of liver function when using Atz/Bev combination and the necessity of identifying predictive markers of response to HCC therapies. Our findings suggest a change in practices, with a marked proportion of intermediate stages, and support the on-treatment prognostic value of an inflammatory score.

HPV genotype distribution according to severity of cervical neoplasia using the Digene HPV genotyping LQ test.

A new genotyping-based DNA assay (Digene LQ(®)) was developed recently. The primary aim was to assess the distribution of HPV types using this new assay in atypical squamous cells of undeterminate significance (ASCUS). The secondary aim was to correlate the HPV types with the severity of the disease. The study population comprised 376 ASCUS women. The women were all Hybrid Capture II (HCII) positive and were admitted in three European referral gynecology clinics between 2007 and 2010. A colposcopy with histological examination was performed in all these patients. HPV 16 was typed in 40 % of patients, HPV 18 in 7 %, and HPV 31 in 17 %, and 18 % of patients had mixed genotypes. Patients aged over 30 more often had the HPV 16 genotype than patients aged under 30 (29 % vs. 11 %, chi-square test p < 0.001). The risk of cervical intra-epithelial neoplasia of grade 2 or more (CIN2 +) when HPV 18 positive is lower than the probability associated with HPV 16 or HPV 31: 28 % vs. 58 % and 52 %, respectively (chi-square test, p = 0.005 and p = 0.05, respectively). The Digene LQ(®), a new sequence-specific hybrid capture sample preparation, is fast and efficient and allows high-throughput genotyping of 18 HR HPV types by PCR compared to traditional non-sequence-specific sample preparation methods.

Comparison of the performance of carcinogenic HPV typing of the Roche Linear Array and Qiagen LiquiChip® HPV assays.

BACKGROUND: Cervical cancer is caused by high-risk types of human papillomavirus (HPV). DNA testing of such high-risk types of HPV could improve cervical screening.The aim of the study was to compare the sensitivities and positive predictive values of two commercially available typing assays (Qiagen LQ and Roche LA) and to comparatively assess the distribution of HPV types with these two assays. METHODS: The study population comprised 311 ASCUS + women with abnormal pap tests who were HCII positive and who were admitted to three European referral gynecology clinics between 2007 and 2010 (Madrid, Marseille and Milan). All patients underwent LQ and LA tests. RESULTS: The sensitivity of the two assays for HPV typing was 94% for LQ and 99% for LA (compared with HCII). The overall concordance between LQ and LA was 93%. The three prevalent genotypes, HPV16, HPV18, and HPV31, were identified with a high concordance using the two assays: kappa 0.93, 0.83, and 0.91, respectively. Mixed genotypes were more frequently detected by LA than by LQ: 52% vs. 18%, respectively (p < .0001). CONCLUSIONS: These assays have a good clinical sensitivity for detecting HPV types in CIN2+ patients and allow the virus type to be detected in the same experiment. Our study revealed no significant difference between LQ and LA for CIN2+ or CIN3+ diagnosis, indicating similar distributions of HPV types and a mixed genotype detection that is higher for LA than for LQ.

Small Intestinal Bacterial Overgrowths and Intestinal Methanogen Overgrowths Breath Testing in a Real-Life French Cohort.

INTRODUCTION: Breath testing has become a widely used tool to diagnose small intestinal bacterial overgrowths (SIBOs) and intestinal methanogen overgrowths (IMOs) in clinical settings. Owing to the heterogeneity in clinical manifestations and lack of standardization among centers performing breath testing, SIBO and IMO can be easily overlooked by the clinician. We studied the prevalence and symptoms of SIBO/IMO in French patients referred for breath testing after seeking medical advice. METHODS: Breath test data and symptoms of 331 patients were assessed for SIBO/IMO using the H 2 /CH 4 lactulose breath test (LBT). Wilcoxon test or χ 2 test were used to compare patients with SIBO/IMO with patients without SIBO/IMO. LBT positive patients (H 2 +, CH 4 +, and CH 4 +/H 2 +) were compared using Kruskal-Wallis test for continuous data or χ 2 test for categorical data. RESULTS: Among the 186 (68.1%) patients tested positive for an overgrowth with 40.3%, 47.3%, and 12.4% for H 2 +, CH 4 + and CH 4 +/H 2 +, respectively, the presence of diarrhea was significantly increased in hydrogen type overgrowths ( P < 0.001). No significant difference according to age, gender, and symptoms was associated with a positive test except for joint pain that was less prevalent among LBT positive patients ( P = 0.038). In 86.5% of IMOs, positivity with CH 4 values ≥10 ppm could be identified at baseline. DISCUSSION: There are little discriminating symptoms that can help the clinician to identify patients likely to have a SIBO/IMO. However, SIBO/IMOs remain a common disorder widely underdiagnosed that need further studies to better apprehend functional bowel disorders.

Anti-spike protein to determine SARS-CoV-2 antibody levels: Is there a specific threshold conferring protection in immunocompromised patients?

BACKGROUND: Identifying a specific threshold level of SARS-CoV-2 antibodies that confers protection in immunocompromised patients has been very challenging. The aim was to assess the threshold of 264 binding antibody units (BAU)/ml using four different SARS-CoV-2 antibody assays (Abbott, Beckman, Roche, and Siemens) and to establish a new optimal threshold of protection for each of the four antibody assays. METHODS: This study was performed on data retrieved from 69 individuals, who received at least one dose of the Pfizer/BioNTech BNT162b2 or Moderna COVID-19 vaccine (Spikevax) at the Alphabio Laboratory in Marseille, France (European Hospital, Alphabio-Biogroup). The results were compared to the percent inhibition calculated using a functional surrogate of a standardized virus neutralization test (Genscript). RESULTS: Samples from 69 patients were analyzed. For a reference cutoff of 264 BAU/ml, assays showed moderate to good overall concordance with Genscript: 87% concordance for Abbott, 78% for Beckman, 75% for Roche, and 88% for Siemens. Overall concordance increased consistently after applying new thresholds, i.e., 148 BAU/ml (Abbott), 48 (Beckman), 559 (Roche), and 270 (Siemens). CONCLUSION: We suggest specific adjusted thresholds (BAU/ml) for the four commercial antibody assays that are used to assess pre-exposure prophylaxis in immunocompromised patients.

Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma: Real-life Data on Liver Disease, Treatment and Prognosis.

Background and Aims: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) have common features and differences. This real-life study investigated their characteristics, treatment modalities, and prognoses. Methods: This retrospective comparative study was performed in 1,075 patients seen at one tertiary center between January 2008 and December 2020. Overall survival (OS) was estimated by the Kaplan-Meier method. Subclassification of iCCAs after histological and radiological review, and molecular profiling was performed. Results: HCCs patients were more likely to have early-stage disease than iCCA patients. iCCA patients were more likely to be female, especially those patients without cirrhosis (43% vs. 17%). Cirrhosis was prominent among HCC patients (89% vs. 34%), but no difference in underlying liver disease among cirrhotic patients was found. OS of HCC patients was 18.4 (95% CI: 6.4, 48.3) months, that of iCCA patients was 7.0 (95% CI: 3.4, 20.1) months. OS of Barcelona Clinic Liver Cancer C HCC patients was 7.8 (95% CI: 4.3, 14.2) months, that of advanced/metastatic iCCA patients was 8.5 (95% CI: 5.7, 12.3) months. In patients treated with sorafenib, OS was longer in HCC patients who received subsequent tyrosine kinase inhibitor therapies. No significant OS difference was found between iCCA patients with and without cirrhosis or according to histological subtype. A targetable molecular alteration was detected in 50% of the iCCA patients. Conclusions: In this French series, cirrhosis was common in iCCA, which showed etiological factors comparable to those of HCC, implying a distinct oncogenic pathway. Both entities had a dismal prognosis at advanced stages. However, systemic therapies sequencing in HCC and molecular profiling in iCCA offer new insights.