Evolution of minimally invasive liver surgery in France over the last decade.

BACKGROUND: Despite evidence of benefits on postoperative outcomes, minimally invasive liver surgery (MILS) had a very low diffusion up to 2014, and recent evolution is unknown. Our aim was to analyze the recent diffusion and adoption of MILS and compare the trends in indications, extent of resection, and institutional practice with open liver surgery (OLS). METHODS: We analyzed the French nationwide, exhaustive cohort of all patients undergoing a liver resection in France between January 1, 2013 and December 31, 2022. Average annual percentage changes (AAPC) in the incidence of MILS and OLS were compared using mixed-effects log-linear regression models. Time trends were analyzed in terms of extent of resection, indication, and institutional practice. RESULTS: MILS represented 25.2% of 74,671 liver resections and year incidence doubled from 16.5% in 2013 to 35.4% in 2022. The highest AAPC were observed among major liver resections [+ 22.2% (19.5; 24.9) per year], primary [+ 10.2% (8.5; 12.0) per year], and secondary malignant tumors [+ 9.9% (8.2; 11.6) per year]. The highest increase in MILS was observed in university hospitals [+ 14.7% (7.7; 22.2) per year] performing 48.8% of MILS and in very high-volume (> 150 procedures/year) hospitals [+ 12.1% (9.0; 15.3) per year] performing 19.7% of MILS. OLS AAPC decreased for all indications and institutions and accelerated over time from - 1.8% (- 3.9; - 0.3) per year in 2013-2018 to - 5.9% (- 7.9; - 3.9) per year in 2018-2022 (p = 0.013). CONCLUSIONS: This is the first reported trend reversal between MILS and OLS. MILS has considerably increased at a national scale, crossing the 20% tipping point of adoption rate as defined by the IDEAL framework.

Risk factors for thromboembolic events in patients hospitalized for COVID-19 pneumonia in a general ward and requiring treatment with oxygen.

PURPOSE: To assess risk factors for arterial and venous thromboses (AVT) in patients hospitalized in general wards for COVID-19 pneumonia and requiring oxygen therapy. METHODS: Our study was based on three randomized studies conducted as part of the CORIMUNO-19 platform in France between 27 March and 26 April 2020. Adult inpatients with COVID-19 pneumonia requiring at least 3 l/min of oxygen but not ventilation were randomized to receive standard care alone or standard care plus biologics. Patients were followed up for 3 months, and adverse events were documented. Risk factor for AVT and bleeding was identified by analyzing clinical, laboratory, and treatment data at baseline among the 315 patients with complete datasets. A Fine and Gray model was used to take account of competing events. RESULTS: During the 3-month follow-up period, 39 AVT occurred in 38 (10%) of the 388 patients: 26 deep vein thromboses and/or pulmonary embolisms in 25 (6%) patients, and 14 arterial thrombotic events in 13 (3%) patients. A history of diabetes at inclusion [sHR (95% CI) = 2.65 (1.19-5.91), P = .017] and the C-reactive protein (CRP) level (sHR = 1 [1-1.01], P = .049) were significantly associated with an elevated risk of thrombosis. Obesity was not associated with a higher risk of thrombosis (sHR = 1.01 [0.4-2.57], P = .98). The CRP level and diabetes were not risk factors for hemorrhage. CONCLUSION: Among patients hospitalized in general wards for COVID-19 pneumonia during the first wave of the epidemic, diabetes (but not obesity) and a high CRP level were risk factors for AVT. The use of higher doses of anticoagulant in these high-risk patients could be considered.

Incidence of and risk factors for local complications of peripheral venous catheters in patients older than 70 years: Empirical research quantitative.

AIMS: To assess the incidence density of local complications of peripheral venous catheters in patients aged 70 years and older, to identify risk factors for local complications of peripheral venous catheters, to describe microbiological epidemiology and to assess the impact of complications on patient outcomes. DESIGN: Prospective, observational, single-centre study. METHODS: Patients 70 years and older admitted to the geriatric department of a teaching hospital in France between December 2019 and May 2020 were considered for inclusion if they had a peripheral venous catheter during their stay. Nurses checked the catheter insertion site three times a day for local complications; physicians ensured the follow-up of complications. The STROBE checklist was used in this prospective observational study. RESULTS: A total of 322 patients were included, with 849 peripheral venous catheters; the median age was 88 years and 182 (56.5%) were women. The incidence density of local complications was 50.5/1000 peripheral venous catheter-days. Risk factors for local complications on multivariate analysis were dressing replacement (OR 1.18), furosemide (OR 1.11) and vancomycin (OR 1.60) infusion, urinary continence (OR 1.09) and hematoma at the catheter insertion site (OR 1.15). Thirteen cellulitis and three abscesses were diagnosed. Occurrence of a local complication was associated with a 3-day increased duration of hospital stay (17 vs. 14 days). CONCLUSION: Risk factors for peripheral venous catheter local complications include urinary continence, furosemide or vancomycin infusion, hematoma at the peripheral venous catheter insertion site or dressing replacement. IMPLICATION FOR THE PATIENT CARE: Closer clinical monitoring may help reduce the occurrence of local peripheral venous catheters complication in patients 70 years and older. RELEVANCE TO CLINICAL PRACTICE: Patients at greater risk of peripheral venous catheter local complications deserve closer clinical monitoring or improved preventive measures, which may be beneficial to reduce the length of hospital stay. NO PATIENT OR PUBLIC CONTRIBUTION: The study was designed to describe risk factors for local complications of peripheral venous catheters in order to reinforce surveillance in this specific population by nurses and medical staffs. Patients had their peripheral venous catheter insertion site checked thrice a day by the nurse in charge as part of usual care. They, as service users, caregivers or members of the public, were not solicited for data collection, analysis, interpretation or preparation of the manuscript.

Effect of bariatric surgery on cancer risk: results from an emulated target trial using population-based data.

BACKGROUND: The impact of weight loss induced by bariatric surgery on cancer occurrence is controversial. To study the causal effect of bariatric surgery on cancer risk from an observational database, a target-trial emulation technique was used to mimic an RCT. METHODS: Data on patients admitted between 2010 and 2019 with a diagnosis of obesity were extracted from a national hospital discharge database. Criteria for inclusion included eligibility criteria for bariatric surgery and the absence of cancer in the 2 years following inclusion. The intervention arms were bariatric surgery versus no surgery. Outcomes were the occurrence of any cancer and obesity-related cancer; cancers not related to obesity were used as negative controls. RESULTS: A total of 1 140 347 patients eligible for bariatric surgery were included in the study. Some 288 604 patients (25.3 per cent) underwent bariatric surgery. A total of 48 411 cancers were identified, including 4483 in surgical patients and 43 928 among patients who did not receive bariatric surgery. Bariatric surgery was associated with a decrease in the risk of obesity-related cancer (hazard ratio (HR) 0.89, 95 per cent c.i. 0.83 to 0.95), whereas no significant effect of surgery was identified with regard to cancers not related to obesity (HR 0.96, 0.91 to 1.01). CONCLUSION: When emulating a target trial from observational data, a reduction of 11 per cent in obesity-related cancer was found after bariatric surgery.

IDNetwork: A deep illness-death network based on multi-state event history process for disease prognostication.

Multi-state models can capture the different patterns of disease evolution. In particular, the illness-death model is used to follow disease progression from a healthy state to an intermediate state of the disease and to a death-related final state. We aim to use those models in order to adapt treatment decisions according to the evolution of the disease. In state-of-the art methods, the risks of transition between the states are modeled via (semi-) Markov processes and transition-specific Cox proportional hazard (P.H.) models. The Cox P.H. model assumes that each variable makes a linear contribution to the model, but the relationship between covariates and risks can be more complex in clinical situations. To address this challenge, we propose a neural network architecture called illness-death network (IDNetwork) that relaxes the linear Cox P.H. assumption within an illness-death process. IDNetwork employs a multi-task architecture and uses a set of fully connected subnetworks in order to learn the probabilities of transition. Through simulations, we explore different configurations of the architecture and demonstrate the added value of our model. IDNetwork significantly improves the predictive performance compared to state-of-the-art methods on a simulated data set, on two clinical trials for patients with colon cancer and on a real-world data set in breast cancer.

Impact of Oral Immunonutrition on Postoperative Morbidity in Digestive Oncologic Surgery: A Nation-wide Cohort Study.

OBJECTIVE: The objective of the present study was to assess the effect of preoperative immunonutrition on a nationwide scale. BACKGROUND: According to international guidelines, immunonutrition should be prescribed before major oncologic digestive surgery to decrease postoperative morbidity. Nevertheless, this practice remains controversial. METHODS: We used a prospective national health database named "Echantillon généraliste des Bénéficiaires." Patients were selected with ICD10 codes of cancer and digestive surgery procedures from 2012 to 2016. Two groups were identified: with reimbursement of immunonutrition 45 days before surgery (IN-group) or not (no-IN-group). Primary outcome was 90-day severe morbidity. Secondary outcomes were postoperative length of stay (LOS) and overall survival. Logistic regression and survival analysis adjusted with IPW method were performed. RESULTS: One thousand seven hundred seventy-one patients were included. The proportion of different cancers was as follows: 72% patients were included in the colorectal group, 14% in the hepato-pancreato-biliary group, and 12% in the upper gastrointestinal group. Patients from the IN-group (n = 606, 34%) were younger (67.1 ±â€Š11.8 vs 69.2 ±â€Š12.2 years, P < 0.001), with increased use of other oral nutritional supplements (49.5% vs 31.8%, P < 0.001) and had more digestive anastomoses (89.4% vs 83.0%, P < 0.001). There was no significant difference between the 2 groups for 90-day severe morbidity [odds ratio (OR): 0.91, 95% confidence interval (95% CI): 0.73-1.14] or in survival (hazard ratio: 0.89, 95% CI: 0.73-1.08). LOS were shorter in the IN-group [-1.26 days, 95% CI: -2.40 to -0.10)]. CONCLUSION: The preoperative use of immunonutrition before major oncologic digestive surgery was not associated with any significant difference in morbidity or mortality. However, the LOS was significantly shorter in the IN-group.

How to analyze and interpret recurrent events data in the presence of a terminal event: An application on readmission after colorectal cancer surgery.

Recurrent events arise when an event occurs many times for a subject. Many models have been developed to analyze these kind of data: the Andersen-Gill's model is one of them as well as the Prentice-William and the Peterson's model, the Wei Lee and Weissfeld's model, or even frailty models, all assuming an independent and noninformative censoring. However, in practice, these assumptions may be violated by the existence of a terminal event that permanently stops the recurrent process (eg, death). Indeed, a patient who experiences an early terminal event is more likely to have a lower number of recurrent events than a patient who experiences a terminal event later. Thus, ignoring terminal events in the analysis may lead to biased results. Many methods have been developed to handle terminal events. In this paper, we describe the existing methods classifying into conditional or marginal methods and compare them in a simulation study to highlight bias in results if an inappropriate method is used, when recurrent events and terminal event are correlated. In addition, we apply the different models on a real dataset to show how results should be interpreted. Finally, we provide recommendations for choosing the appropriate method for analyzing recurrent events in the presence of a terminal event.

Validation of the AFP model as a predictor of HCC recurrence in patients with viral hepatitis-related cirrhosis who had received a liver transplant for HCC.

BACKGROUND & AIMS: The AFP model was shown to be superior to the Milan criteria for predicting hepatocellular carcinoma (HCC) recurrence after liver transplantation in a French population. Our aim was to test the AFP model in a non-French, post-hepatitic cirrhosis-based population of HCC candidates. METHODS: 574 patients transplanted for HCC in four Italian centers were studied. AFP score was assessed at the last evaluation before liver transplantation (LT). Probabilities of recurrence and survival were estimated by the log-rank test or competing risk analysis and compared according to the AFP model. RESULTS: 24.7% patients were beyond Milan criteria. HCC complicated hepatitis C virus (HCV) and hepatitis B virus (HBV) cirrhosis in 58.7% and 24% of the cases, respectively. Five-year probabilities of recurrence differed according to AFP score ⩽2 vs. >2 in the whole population (13.2±1.8% vs. 49.8±8.7%, p<0.001, HR=4.98), in patients within Milan criteria (12.8±2.0% vs. 32.4±12.1%, p=0.009, HR=3.51), beyond Milan criteria (14.9±4.2% vs. 58.9±11.5%, p<0.001, HR=4.26), HCV patients (14.9±2.5% vs. 67.6±14.7%, p<0.001, HR=6.56) and HBV patients (11.6±3.4% vs. 34.3±12.5%, p=0.012, HR=3.49). By net reclassification improvement analysis AFP score significantly improved prediction of non-recurrence compared to Milan criteria. Overall five-year survival rates according to AFP score ⩽2 or >2 were 71.7±2.2% vs. 42.2±8.3% (p<0.001, HR=2.14). CONCLUSIONS: The AFP model identifies HCC candidates at low risk of recurrence, otherwise excluded by Milan criteria in a population with a predominance of post-hepatitic-related HCC. The AFP score can be proposed for selection of HCC candidates in programs with a high proportion of viral/HCV-related cirrhosis. LAY SUMMARY: Selection criteria for liver transplantation of patients affected with hepatocellular carcinoma (HCC) are based on the Milan criteria, which have been shown to be too restrictive, precluding access to liver transplantation for some patients who might be cured by this operation. Recently, a French group of researchers developed a new selection model called the AFP model, or AFP score, allowing some patients with HCC not meeting Milan criteria to be transplanted with excellent results. In the present work, the AFP score was tested in a population of non-French patients transplanted for HCC occurring mainly on post-hepatitic (HCV or HBV) cirrhosis. The results confirm that in this specific population, as in the original French population of patients, the AFP model better selects patients with HCC eligible for transplantation, compared to Milan criteria. We conclude that the AFP score, which has been officially adopted by the French organization for Organ Sharing for HCC patients, can also be implemented in countries with an important burden of HCC occurring on post-hepatitic cirrhosis.

Natural History of Adjustable Gastric Banding: Lifespan and Revisional Rate: A Nationwide Study on Administrative Data on 53,000 Patients.

OBJECTIVE: The aim of this study was to analyze the adjustable gastric banding (AGB) natural history on a national basis. BACKGROUND: Adjustable gastric banding represented the most common bariatric procedure in France until 2010. Since then, the number of AGBs has decreased and the rate of band removal and revisional surgeries has progressively increased. METHODS: For analysis, we included all adult patients operated on with AGB in France between 2007 and 2013. Data were extracted from a national administrative database ("Programme De Médicalisation des Systèmes d'Information," PMSI), which is an exhaustive source of all surgical procedures performed in France. The Cox proportional hazard model was used to test univariate and multivariate associations with band survival and revisional rate. To control for center-specific effects, we performed a frailty analysis, in which each center was assumed to have a random effect indicating the possibility of different baseline risks for patients at different centers. RESULTS: During the study period, 52,868 patients underwent AGB, and 10,815 bands were removed. The removal rate at 5, 6, and 7 years was 28%, 34%, and 40%, respectively. Female sex, body mass index >50 kg/m, type 2 diabetes, hypertension, dyslipidemia, and sleep apnea were found to be significantly associated with band removal by multivariate analysis. A significant center effect was also found, but this did not change the impact of the highly significant factors already identified. After band removal, the median time to revisional surgery was 1 year (95% confidence interval 1.0-1.1) and the conversion rate at 7 years was 71%. CONCLUSIONS: With a removal rate of about 6% annually and the need for revisional surgery for more than two-thirds of patients after removal, AGB does not appear to provide a long-term solution for obesity.

ICU Patients Requiring Renal Replacement Therapy Initiation: Fewer Survivors and More Dialysis Dependents From 80 Years Old.

OBJECTIVES: To assess the role of advanced age on survival and dialysis dependency after initiation of renal replacement therapy for acute kidney injury. DESIGN: Retrospective pooled analysis of prospectively collected data. SETTING: ICUs of two teaching hospitals in Paris area, France. SUBJECTS: One thousand five hundred thirty adult patients who required renal replacement therapy initiation in the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Survival and post acute kidney injury chronic dialysis dependency were assessed at hospital discharge according to the quintile (Q) of age. The oldest quintile included 289 patients 80 years old and over. Seventy-three percent of included patients had respiratory and hemodynamic supports at renal replacement therapy initiation, similarly distributed across quintiles. Mortality increased with age strata from 63% in Q1 (≤ 52 yr) to 76% in Q5 (≥ 80 yr) (p < 0.001). After adjustment, age did not increase the risk of death up to 80 years. The oldest patients (≥ 80 yr) had a significant higher risk of dying (adjusted odds ratio, 2.59; 95% CI, 1.66-4.03). Dialysis dependency was more frequent among survivors 80 years old or older (30% vs 14%; p = 0.001). Age 80 years old or older was an independent risk for dialysis dependency only for patients with prior advanced chronic kidney disease (p = 0.04). Baseline estimated glomerular filtration rate was the only one predictor of dialysis dependency identified. CONCLUSIONS: Patients with advanced age represent a substantial subgroup of patients requiring renal replacement therapy in the ICU. From 80 years, age should be considered as an additional risk of dying over the severity of organ failures. Patients 80 years old or older are likely to recover sufficient renal function allowing renal replacement therapy discontinuation when baseline estimated glomerular filtration rate is above 44 mL/min/1.73 m. At 3 months, only 6% were living at home, dialysis independent.

Predictive Factors of "Forgotten Knee" Acquisition After Total Knee Arthroplasty: Long-Term Follow-Up of a Large Prospective Cohort.

BACKGROUND: In a large prospective cohort, we recently showed that only 66.1% of total knee arthroplasty (TKA) with a perfect outcome according to Knee Society Knee Score was completely forgotten in all everyday activities. The main objective of this study was to identify clinical and orthopedic factors associated with the acquisition of "forgotten knee" (FK). METHODS: Patients undergoing TKA were enrolled between January 2001 and January 2008. Preoperative medical history, anthropometric data, and clinical data were recorded, and composite scores (Knee Society Score, Lequesne) were assessed. Radiography was performed before and after surgery. At each follow-up, FK acquisition was assessed by a closed question "Does the operated knee feel always normal in all everyday activities?" RESULTS: We included 510 TKAs performed in 423 patients followed up for a mean of 76.6 ± 28.5 months. On multivariate analysis, depression at baseline and presence of patellar subluxation after surgery were negatively associated with FK acquisition (odds ratio [OR] = 0.28 [95% confidence interval {CI}, 0.13-0.61], P = .001; and OR = 0.31 [0.12-0.79], P = .01, respectively), whereas increased active flexion at last follow-up was positively associated (OR = 1.07 [1.03-1.10], P < .0001). In patients with a perfect outcome (Knee Society Knee Score = 100), preoperative patellar pain, and postoperative patellar subluxation were negatively associated with FK acquisition (OR = 0.41 [0.18-0.93], P = .03 and OR = 0.21 [0.05-0.90], P = .04, respectively). Gender, age, body mass index, preoperative pain and functional limitation, and patellar resurfacing were not significantly related to FK. CONCLUSION: Depression and patella maltracking may be associated with lack of FK acquisition after TKA, while postoperative increase in flexion may have a positive impact.

Effect of Acetazolamide vs Placebo on Duration of Invasive Mechanical Ventilation Among Patients With Chronic Obstructive Pulmonary Disease: A Randomized Clinical Trial.

IMPORTANCE: Acetazolamide has been used for decades as a respiratory stimulant for patients with chronic obstructive pulmonary disease (COPD) and metabolic alkalosis, but no large randomized placebo-controlled trial is available to confirm this approach. OBJECTIVE: To determine whether acetazolamide reduces mechanical ventilation duration in critically ill patients with COPD and metabolic alkalosis. DESIGN, SETTING, AND PARTICIPANTS: The DIABOLO study, a randomized, double-blind, multicenter trial, was conducted from October 2011 through July 2014 in 15 intensive care units (ICUs) in France. A total of 382 patients with COPD who were expected to receive mechanical ventilation for more 24 hours were randomized to the acetazolamide or placebo group and 380 were included in an intention-to treat analysis. INTERVENTIONS: Acetazolamide (500-1000 mg, twice daily) vs placebo administered intravenously in cases of pure or mixed metabolic alkalosis, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days. MAIN OUTCOMES AND MEASURES: The primary outcome was the duration of invasive mechanical ventilation via endotracheal intubation or tracheotomy. Secondary outcomes included changes in arterial blood gas and respiratory parameters, weaning duration, adverse events, use of noninvasive ventilation after extubation, successful weaning, the duration of ICU stay, and in-ICU mortality. RESULTS: Among 382 randomized patients, 380 (mean age, 69 years; 272 men [71.6%]; 379 [99.7%] with endotracheal intubation) completed the study. For the acetazolamide group (n = 187), compared with the placebo group (n = 193), no significant between-group differences were found for median duration of mechanical ventilation (-16.0 hours; 95% CI, -36.5 to 4.0 hours; P = .17), duration of weaning off mechanical ventilation (-0.9 hours; 95% CI, -4.3 to 1.3 hours; P = .36), daily changes of minute-ventilation (-0.0 L/min; 95% CI, -0.2 to 0.2 L/min; P = .72), or partial carbon-dioxide pressure in arterial blood (-0.3 mm Hg; 95% CI, -0.8 to 0.2 mm Hg; P = .25), although daily changes of serum bicarbonate (between-group difference, -0.8 mEq/L; 95% CI, -1.2 to -0.5 mEq/L; P < .001) and number of days with metabolic alkalosis (between-group difference, -1; 95% CI, -2 to -1 days; P < .001) decreased significantly more in the acetazolamide group. Other secondary outcomes also did not differ significantly between groups. CONCLUSIONS AND RELEVANCE: Among patients with COPD receiving invasive mechanical ventilation, the use of acetazolamide, compared with placebo, did not result in a statistically significant reduction in the duration of invasive mechanical ventilation. However, the magnitude of the difference was clinically important, and it is possible that the study was underpowered to establish statistical significance. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01627639.

Presence of B cells in tertiary lymphoid structures is associated with a protective immunity in patients with lung cancer.

RATIONALE: It is now well established that immune responses can take place outside of primary and secondary lymphoid organs. We previously described the presence of tertiary lymphoid structures (TLS) in patients with non-small cell lung cancer (NSCLC) characterized by clusters of mature dendritic cells (DCs) and T cells surrounded by B-cell follicles. We demonstrated that the density of these mature DCs was associated with favorable clinical outcome. OBJECTIVES: To study the role of follicular B cells in TLS and the potential link with a local humoral immune response in patients with NSCLC. METHODS: The cellular composition of TLS was investigated by immunohistochemistry. Characterization of B-cell subsets was performed by flow cytometry. A retrospective study was conducted in two independent cohorts of patients. Antibody specificity was analyzed by ELISA. MEASUREMENTS AND MAIN RESULTS: Consistent with TLS organization, all stages of B-cell differentiation were detectable in most tumors. Germinal center somatic hypermutation and class switch recombination machineries were activated, associated with the generation of plasma cells. Approximately half of the patients showed antibody reactivity against up to 7 out of the 33 tumor antigens tested. A high density of follicular B cells correlated with long-term survival, both in patients with early-stage NSCLC and with advanced-stage NSCLC treated with chemotherapy. The combination of follicular B cell and mature DC densities allowed the identification of patients with the best clinical outcome. CONCLUSIONS: B-cell density represents a new prognostic biomarker for NSCLC patient survival, and makes the link between TLS and a protective B cell-mediated immunity.

Predictors of flexion using the rotating concave-convex total knee arthroplasty: preoperative range of motion is not the only determinant.

PURPOSE: The range of motion achieved after a total knee arthroplasty (TKA) affects many daily activities and overall patients' satisfaction. This study aims to define the determinants affecting post-operative midterm active flexion according to a specific cruciate-sacrificing prosthesis, the rotating concave-convex (ROCC(®)) TKA. METHOD: Four hundred and eighty-four consecutive patients (584 TKAs) were prospectively followed. After baseline patient demographics and anatomical characteristics, clinical and radiological post-operative assessments were periodically recorded. The rotational alignment of the femoral component was additionally reported for 120 patients. Eligibility for final inclusion was a minimum of 5-year follow-up. Univariate analyses followed by a multivariate model were fitted to determine the independent predictors of midterm active knee flexion. RESULTS: Thirty-four TKA (5.8%) were excluded for a secondary surgery before their 50 years, 69 patients died (11.8%), and 21 (3.6%) were lost to follow-up. Overall, 460 TKAs were included. The post-operative mean knee flexion angle was measured at 127.7° ± 9.3°. Significant factors affecting final flexion under univariate analyses were the patient height and body mass index, the absence of previous surgery, a depressive state, the preoperative flexion angle, a preoperative flexion contracture, a patellar residual subluxation, the reconstructed patellar height, and the rotation of the femoral component. The multivariate model confirmed the patient's height, a depression, the preoperative flexion angle, a patellar residual subluxation, and the patellar height as statistically significant determinants. CONCLUSION: Aside from the preoperative flexion angle, numerous predictors of flexion, both patient- and procedure-related were identified. Surgeons should take these into account both when adequately informing their patient before surgery and when performing the arthroplasty itself. LEVEL OF EVIDENCE: Prognostic, Level II.

Intravoxel incoherent motion (IVIM) MR imaging of colorectal liver metastases: are we only looking at tumor necrosis?

PURPOSE: To determine if intra-voxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters, including free molecular-based (D) and perfusion-related (D*, f) diffusion parameters, correlate with the degree of tumor necrosis and viable tumor in colo-rectal cancer (CRC) metastasis. MATERIALS AND METHODS: Fifteen patients referred for resection of liver metastases from CRC were retrospectively included in this Institutional Review Board approved study. An IVIM-DWI sequence was performed on a 1.5 Tesla MR imaging system, with 10 b factors (0, 10, 20, 30, 50, 80, 100, 200, 400 and 800 s/mm(2) ). Mean D, D*, f and apparent diffusion coefficient (ADC) values were determined in metastases with a longest diameter above 10 mm. Correlations between the diffusion parameters and the degree of liver tumor necrosis and viable tissue were determined (Spearman). RESULTS: Correlation between diffusion parameters and histopathological findings was performed in 35 hepatic metastases with a diameter of more than 10 mm (mean size of 17.9 mm; range, 1-68 mm). Both D (r = 0.36; P = 0.035) and ADC (r = 0.4; P = 0.02) correlated with the degree of tumor necrosis but not with viable tumor. CONCLUSION: ADC variation observed in CRC metastases following systemic chemotherapy reflects a specific increase in free-molecular diffusion (D), in itself correlated to the degree of metastasis necrosis.

Sleep continuity: a new metric to quantify disrupted hypnograms in non-sedated intensive care unit patients.

INTRODUCTION: Sleep in intensive care unit (ICU) patients is severely altered. In a large proportion of critically ill patients, conventional sleep electroencephalogram (EEG) patterns are replaced by atypical sleep. On the other hand, some non-sedated patients can display usual sleep EEG patterns. In the latter, sleep is highly fragmented and disrupted and conventional rules may not be optimal. We sought to determine whether sleep continuity could be a useful metric to quantify the amount of sleep with recuperative function in critically ill patients with usual sleep EEG features. METHODS: We retrospectively reanalyzed polysomnographies recorded in non-sedated critically ill patients requiring non-invasive ventilation (NIV) for acute hypercapnic respiratory failure. Using conventional rules, we built two-state hypnograms (sleep and wake) and identified all sleep episodes. The percentage of time spent in sleep bouts (<10 minutes), short naps (>10 and <30 minutes) and long naps (>30 minutes) was used to describe sleep continuity. In a first study, we compared these measures regarding good (NIV success) or poor outcome (NIV failure). In a second study performed on a different patient group, we compared these measurements during NIV and during spontaneous breathing. RESULTS: While fragmentation indices were similar in the two groups, the percentage of total sleep time spent in short naps was higher and the percentage of sleep time spent in sleep bouts was lower in patients with successful NIV. The percentage of total sleep time spent in long naps was higher and the percentage of sleep time spent in sleep bouts was lower during NIV than during spontaneous breathing; the level of reproducibility of sleep continuity measures between scorers was high. CONCLUSIONS: Sleep continuity measurements could constitute a clinically relevant and reproducible assessment of sleep disruption in non-sedated ICU patients with usual sleep EEG.

MS-CPFI: A model-agnostic Counterfactual Perturbation Feature Importance algorithm for interpreting black-box Multi-State models.

Multi-state processes (Webster, 2019) are commonly used to model the complex clinical evolution of diseases where patients progress through different states. In recent years, machine learning and deep learning algorithms have been proposed to improve the accuracy of these models' predictions (Wang et al., 2019). However, acceptability by patients and clinicians, as well as for regulatory compliance, require interpretability of these algorithms's predictions. Existing methods, such as the Permutation Feature Importance algorithm, have been adapted for interpreting predictions in black-box models for 2-state processes (corresponding to survival analysis). For generalizing these methods to multi-state models, we introduce a novel model-agnostic interpretability algorithm called Multi-State Counterfactual Perturbation Feature Importance (MS-CPFI) that computes feature importance scores for each transition of a general multi-state model, including survival, competing-risks, and illness-death models. MS-CPFI uses a new counterfactual perturbation method that allows interpreting feature effects while capturing the non-linear effects and potentially capturing time-dependent effects. Experimental results on simulations show that MS-CPFI increases model interpretability in the case of non-linear effects. Additionally, results on a real-world dataset for patients with breast cancer confirm that MS-CPFI can detect clinically important features and provide information on the disease progression by displaying features that are protective factors versus features that are risk factors for each stage of the disease. Overall, MS-CPFI is a promising model-agnostic interpretability algorithm for multi-state models, which can improve the interpretability of machine learning and deep learning algorithms in healthcare.

A systematic review and meta-analysis of the incidence of post-thrombotic syndrome, recurrent thromboembolism, and bleeding after upper extremity vein thrombosis.

BACKGROUND: Data on complications after upper extremity vein thrombosis (UEVT) are limited and heterogeneous. METHODS: The aim of the present study was to evaluate the pooled proportions of venous thromboembolism (VTE) recurrence, bleeding, and post-thrombotic syndrome (PTS) in patients with UEVT. A systematic literature review was conducted of PubMed, Embase, and the Cochrane Library databases from January 2000 to April 2023 in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. All studies included patients with UEVT and were published in English. Meta-analyses of VTE recurrence, bleeding, and of PTS after UEVT were performed to compute pooled estimates and associated 95% confidence intervals (CIs). Subgroup analyses of cancer-associated UEVT and catheter-associated venous thrombosis were conducted. Patients with Paget-Schroetter syndrome or effort thrombosis were excluded. RESULTS: A total of 55 studies with 15,694 patients were included. The pooled proportions for VTE recurrence, major bleeding, and PTS were 4.8% (95% CI, 3.8%-6.2%), 3.0% (95% CI, 2.2%-4.0%), and 23.8% (95% CI, 17.0%-32.3%), respectively. The pooled proportion of VTE recurrence was 2.7% (95% CI, 1.6%-4.6%) for patients treated with direct oral anticoagulants (DOACs), 1.7% (95% CI, 0.8%-3.7%) for patients treated with low-molecular-weight heparin (LMWH), and 4.4% (95% CI, 1.5%-11.8%) for vitamin K antagonists (VKAs; P = .36). The pooled proportion was 6.3% (95% CI, 4.3%-9.1%) for cancer patients compared with 3.1% (95% CI, 2.1%-4.6%) for patients without cancer (P = .01). The pooled proportion of major bleeding for patients treated with DOACs, LMWH, and VKAs, was 2.1% (95% CI, 0.9%-5.1%), 3.2% (95% CI, 1.4%-7.2%), and 3.4% (95% CI, 1.4%-8.4%), respectively (P = .72). The pooled proportion of PTS for patients treated with DOACs, LMWH, and VKAs was 11.8% (95% CI, 6.5%-20.6%), 27.9% (95% CI, 20.9%-36.2%), and 24.5% (95% CI, 17.6%-33.1%), respectively (P = .02). CONCLUSIONS: The results from this study suggest that UEVT is associated with significant rates of PTS and VTE recurrence. Treatment with DOACs might be associated with lower PTS rates than treatment with other anticoagulants.

Cardiovascular disease healthcare trajectories: descriptions, similarities, mortality rates of heart failure in France.

AIMS: The primary objectives of this study were to analyse the nationwide healthcare trajectories of heart failure (HF) patients in France, 2 years after their first hospitalization, and to measure sequence similarities. Secondary objectives were to identify the association between trajectories and the risk of mortality. METHODS AND RESULTS: A retrospective, observational study was conducted using data extracted from the Echantillon Généraliste des Bénéficiaires database, covering the period from 1 January 2008 to 31 December 2018. Follow-up concluded upon death or at the end of the study. We developed a methodology specific to healthcare data by extracting frequent healthcare trajectories and measuring their similarity for use in a survival machine learning analysis. In total, 11 488 HF patients were included and followed up for an average of 2.9 ± 1.3 years. The mean age of the patients was 78.0 ± 13.2 years. The first-year mortality rate was 31.7% and increased to 78.8% at 5 years. Fifty per cent of patients experienced re-hospitalization for reasons related to cardiovascular diseases. We identified 1707 hospitalization sequences, and 21 sequences were associated with survival, while 15 sequences were linked to mortality. In all our models, age and gender emerged as the most significant predictors of mortality (permutation feature importance: 0.099 ± 0.00078 and 0.0087 ± 0.00018, respectively; weights could be interpreted in relative terms). Specifically, the age at initial hospitalization for HF was positively associated with mortality. Gender (male: 49.5%) was associated with poorer prognoses. Healthcare trajectories, including non-surgical device treatments, valve replacements, and atrial fibrillation ablation, were associated with a better prognosis (permutation feature importance: 0.0047 ± 0.00011, 0.0014 ± 0.000073, and 0.00095 ± 0.000097, respectively), except in cases where these invasive treatments preceded or followed hospitalization for cardiac decompensation. The predominant negative prognosis sequences were mostly those that included HF-related hospitalizations before or after other-related hospitalizations (permutation feature importance: 0.0007 ± 0.000091 and 0.00011 ± 0.000045, respectively). CONCLUSIONS: We highlight the value of healthcare trajectories on frequent hospitalization sequences, mortality, and prognosis and indicate the necessary prognostic value of HF re-hospitalization. Our work may be an essential tool for better identification of at-risk patients in order to increase and improve personalized care in the future.