Clinical care pathways of patients with biliary tract cancer: A French nationwide longitudinal cohort study.

BACKGROUND: Although the incidence of BTC is raising, national healthcare strategies to improve care lack. We aimed to explore patient clinical care pathways and strategies to improve biliary tract cancer (BTC) care. METHODS: We analysed the French National Healthcare database of all BTC inpatients between January 1, 2017 and December 31, 2021. Multinomial logistic regression adjusted odds ratios (aOR) were used to identify healthcare organisation factors that influenced access to curative care both overall and in a longitudinal sensibility analysis using optimal matching and hierarchical ascending classification to detect a subgroup of curative-care patients with a high survival over a two-year period. RESULTS: A total of 19,825 new BTC patients and three clinical care pathways (CCP) were identified: 'Palliative care' (PC-CCP), 'Non-curative Care' (NCC-CCP) and 'Curative Care' (CC-CCP) involving 7669 (38.7%), 7721 (38.9%) and 4435 (22.4%) patients respectively. Out of 1200 centers involved in BTC treatment, 84%, 11% and 5% were of low- (<15 patients/year), medium- (15-30 patients/year) and high-volume (>30 patients/year) respectively. Among patient, tumor and hospital factors, BTC management in academic (aOR: 2.32; 95%CI: 1.98-2.71), private (2.51; 2.22-2.83), semi-private (2.25; 1.91-2.65) and in high- (2.09; 1.81-2.42) or medium-volume (1.49; 1.33-1.68) centers increased probability to CC-CCP. These results were maintained in a longitudinal cluster of 2363 (53%) CC-CCP patients presenting a higher two-year survival compared with the rest [96.4% (95.1; 97.6) vs. 38.8% (36.3; 41.4), log-rank p < 0.001]. CONCLUSIONS: Among factors subject to healthcare policy improvement, the volume and type of centers managing BTC strongly influenced access to curative care.

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.

Pharmacovigilance studies without a priori hypothesis: systematic review highlights inappropriate multiple testing correction procedures.

OBJECTIVES: The purpose of this study was to systematically review the statistical methods used in pharmacovigilance studies without a priori hypotheses. STUDY DESIGN AND SETTING: A systematic review was performed on studies published in the MEDLINE database between 2012 and 2021. The included studies were analyzed for database name and type, statistical methods, anatomical therapeutic chemical class for the studied drug(s), and SOC MedDRA classification for the studied adverse drug reaction. RESULTS: Ninety-two studies were included, with pharmacovigilance databases being the most used type. Disproportionality analysis using frequentist or Bayesian methods was the most common statistical method employed. The most studied drug classes were anti-infectives, nervous system drugs, and antineoplastics and immunomodulators. However, no common procedure was implemented to correct for multiple testing. CONCLUSION: This review highlights the limited number of statistical methods employed for pharmacovigilance studies without a priori hypotheses, with no established consensus-based method and a lack of interest in multiple testing correction. The establishment of guidelines is recommended to improve the performance of such studies.

Development and Validation of a Multi-institutional Nomogram of Outcomes for PSMA-PET-Based Salvage Radiotherapy for Recurrent Prostate Cancer.

Importance: Prostate-specific antigen membrane positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) after radical prostatectomy for patients with recurrent or persistent prostate cancer. Objective: To develop and validate a nomogram for prediction of freedom from biochemical failure (FFBF) after PSMA-PET-based sRT. Design, Setting, and Participants: This retrospective cohort study included 1029 patients with prostate cancer treated between July 1, 2013, and June 30, 2020, at 11 centers from 5 countries. The initial database consisted of 1221 patients. All patients had a PSMA-PET scan prior to sRT. Data were analyzed in November 2022. Exposures: Patients with a detectable post-radical prostatectomy prostate-specific antigen (PSA) level treated with sRT to the prostatic fossa with or without additional sRT to pelvic lymphatics or concurrent androgen deprivation therapy (ADT) were eligible. Main Outcomes and Measures: The FFBF rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse was defined as a PSA nadir of 0.2 ng/mL after sRT. Results: In the nomogram creation and validation process, 1029 patients (median age at sRT, 70 years [IQR, 64-74 years]) were included and further divided into a training set (n = 708), internal validation set (n = 271), and external outlier validation set (n = 50). The median follow-up was 32 months (IQR, 21-45 months). Based on the PSMA-PET scan prior to sRT, 437 patients (42.5%) had local recurrences and 313 patients (30.4%) had nodal recurrences. Pelvic lymphatics were electively irradiated for 395 patients (38.4%). All patients received sRT to the prostatic fossa: 103 (10.0%) received a dose of less than 66 Gy, 551 (53.5%) received a dose of 66 to 70 Gy, and 375 (36.5%) received a dose of more than 70 Gy. Androgen deprivation therapy was given to 325 (31.6%) patients. On multivariable Cox proportional hazards regression analysis, pre-sRT PSA level (hazard ratio [HR], 1.80 [95% CI, 1.41-2.31]), International Society of Urological Pathology grade in surgery specimen (grade 5 vs 1+2: HR, 2.39 [95% CI, 1.63-3.50], pT stage (pT3b+pT4 vs pT2: HR, 1.91 [95% CI, 1.39-2.67]), surgical margins (R0 vs R1+R2+Rx: HR, 0.60 [95% CI, 0.48-0.78]), ADT use (HR, 0.49 [95% CI, 0.37-0.65]), sRT dose (>70 vs ≤66 Gy: HR, 0.44 [95% CI, 0.29-0.67]), and nodal recurrence detected on PSMA-PET scans (HR, 1.42 [95% CI, 1.09-1.85]) were associated with FFBF. The mean (SD) nomogram concordance index for FFBF was 0.72 (0.06) for the internal validation cohort and 0.67 (0.11) in the external outlier validation cohort. Conclusions and Relevance: This cohort study of patients with prostate cancer presents an internally and externally validated nomogram that estimated individual patient outcomes after PSMA-PET-guided sRT.

Regulatory T cells infiltrate the tumor-induced tertiary lymphoïd structures and are associated with poor clinical outcome in NSCLC.

On one hand, regulatory T cells (Tregs) play an immunosuppressive activity in most solid tumors but not all. On the other hand, the organization of tumor-infiltrating immune cells into tertiary lymphoid structures (TLS) is associated with long-term survival in most cancers. Here, we investigated the role of Tregs in the context of Non-Small Cell Lung Cancer (NSCLC)-associated TLS. We observed that Tregs show a similar immune profile in TLS and non-TLS areas. Autologous tumor-infiltrating Tregs inhibit the proliferation and cytokine secretion of CD4+ conventional T cells, a capacity which is recovered by antibodies against Cytotoxic T-Lymphocyte-Associated protein-4 (CTLA-4) and Glucocorticoid-Induced TNFR-Related protein (GITR) but not against other immune checkpoint (ICP) molecules. Tregs in the whole tumor, including in TLS, are associated with a poor outcome of NSCLC patients, and combination with TLS-dendritic cells (DCs) and CD8+ T cells allows higher overall survival discrimination. Thus, Targeting Tregs especially in TLS may represent a major challenge in order to boost anti-tumor immune responses initiated in TLS.

Plasma CD27, a Surrogate of the Intratumoral CD27-CD70 Interaction, Correlates with Immunotherapy Resistance in Renal Cell Carcinoma.

PURPOSE: CD70 is a costimulatory molecule known to activate CD27-expressing T cells. CD27-CD70 interaction leads to the release of soluble CD27 (sCD27). Clear-cell renal cell carcinoma (ccRCC) expresses the highest levels of CD70 among all solid tumors; however, the clinical consequences of CD70 expression remain unclear. EXPERIMENTAL DESIGN: Tumor tissue from 25 patients with ccRCC was assessed for the expression of CD27 and CD70 in situ using multiplex immunofluorescence. CD27+ T-cell phenotypes in tumors were analyzed by flow cytometry and their gene expression profile were analyzed by single-cell RNA sequencing then confirmed with public data. Baseline sCD27 was measured in 81 patients with renal cell carcinoma (RCC) treated with immunotherapy (35 for training cohort and 46 for validation cohort). RESULTS: In the tumor microenvironment, CD27+ T cells interacted with CD70-expressing tumor cells. Compared with CD27- T cells, CD27+ T cells exhibited an apoptotic and dysfunctional signature. In patients with RCC, the intratumoral CD27-CD70 interaction was significantly correlated with the plasma sCD27 concentration. High sCD27 levels predicted poor overall survival in patients with RCC treated with anti-programmed cell death protein 1 in both the training and validation cohorts but not in patients treated with antiangiogenic therapy. CONCLUSIONS: In conclusion, we demonstrated that sCD27, a surrogate marker of T-cell dysfunction, is a predictive biomarker of resistance to immunotherapy in RCC. Given the frequent expression of CD70 and CD27 in solid tumors, our findings may be extended to other tumors.

Identifying homogeneous healthcare use profiles and treatment sequences by combining sequence pattern mining with care trajectory clustering in kidney cancer patients on oral anticancer drugs: A case study.

OBJECTIVE: We evaluated the ability of a coupled pattern-mining and clustering method to identify homogeneous groups of subjects in terms of healthcare resource use, prognosis and treatment sequences, in renal cancer patients beginning oral anticancer treatment. METHODS: Data were retrieved from the permanent sample of the French medico-administrative database. We applied the CP-SPAM algorithm for pattern mining to healthcare use sequences, followed by hierarchical clustering on principal components (HCPC). RESULTS AND CONCLUSION: We identified 127 individuals with renal cancer with a first reimbursement of an oral anticancer drug between 2010 and 2017. Clustering identified three groups of subjects, and discrimination between these groups was good. These clusters differed significantly in terms of mortality at six and 12 months, and medical follow-up profile (predominantly outpatient or inpatient care, biological monitoring, reimbursement of supportive care drugs). This case study highlights the potential utility of applying sequence-mining algorithms to a large range of healthcare reimbursement data, to identify groups of subjects homogeneous in terms of their care pathways and medical behaviors.

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.

Overall Survival and Prognostic Factors among Older Patients with Metastatic Pancreatic Cancer: A Retrospective Analysis Using a Hospital Database.

Pre-therapeutic factors associated with overall survival (OS) among older patients ≥70 years with metastatic pancreatic cancer (mPC) are not known. This was a retrospective single-centre cohort study in Paris including 159 consecutive older patients with mPC between 2000 and 2018. Alongside geriatric parameters, specific comorbidities, cancer-related data and chemotherapy regimens were retrieved. Cox multivariate models were run to assess predictors for OS. The median age was 80 years, 52% were women, 21.5% had diabetes, and 48% had pancreatic head cancer and 72% liver metastases. 62% of the patients (n = 99) received chemotherapy, among which the gemcitabine + nab-paclitaxel (GnP) regimen was the most frequent (72%). Median OS [95%CI] was 7.40 [5.60-10.0] and 1.40 [0.90-2.20] months respectively for patients with and without chemotherapy. The GnP regimen (aHR [95%CI] = 0.47 [0.25-0.89], p = 0.02) and diabetes (aHR = 0.44 [0.24-0.77], p = 0.004) (or anti-diabetic therapy) were multivariate protective factors for death, while ECOG-PS, liver metastases, and the neutrophil cell count were multivariate risk factors for death. In the chemotherapy group, ECOG-PS, number of metastatic sites and the GnP remained significantly associated with OS. Our study confirms the feasibility and efficacy of chemotherapy and the protective effects of diabetes among older patients with mPC.

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.

Outcomes Associated With Caustic Ingestion Among Adults in a National Prospective Database in France.

Importance: Caustic ingestion in adults may result in death or severe digestive sequelae. The scarcity of nationwide epidemiological data leads to difficulties regarding the applicability of their analysis to less specialized centers, which are nevertheless largely involved in the emergency management of adverse outcomes following caustic ingestion. Objective: To assess outcomes associated with caustic ingestion in adults across a nationwide prospective database. Design, Settings, and Participants: Adult patients aged 16 to 96 admitted to the emergency department for caustic ingestion between January 2010 and December 2019 were identified from the French Medical Information System Database, which includes all patients admitted in an emergency setting in hospitals in France during this period. Exposure: Esophageal caustic ingestion. Main Outcomes and Measures: The primary end point was in-hospital patient outcomes following caustic ingestion. Multivariate analysis was performed to assess independent predictors of in-hospital morbidity and mortality. Results: Among 22 657 226 patients admitted on an emergency outpatient basis, 3544 (0.016%) had ingested caustic agents and were included in this study. The median (IQR) age in this population was 49 (34-63) years, and 1685 patients (48%) were women. Digestive necrosis requiring resection was present during the primary hospital stay in 388 patients with caustic ingestion (11%). Nonsurgical management was undertaken in 3156 (89%). A total of 1198 (34%) experienced complications, and 294 (8%) died. Pulmonary complications were the most frequent adverse event, occurring in 869 patients (24%). On multivariate analysis, predictors of mortality included old age, high comorbidity score, suicidal ingestion, intensive care unit admission during management, emergency surgery for digestive necrosis, and treatment in low-volume centers. On multivariate analysis, predictors of morbidity included old age, higher comorbidity score, intensive care unit admission during management, and emergency surgery for digestive necrosis. Conclusions and Relevance: In this study, referral to expert centers was associated with improved early survival after caustic ingestion. If feasible, low-volume hospitals should consider transferring patients to larger centers instead of attempting on-site management.

Postoperative outcomes after laparoscopic or open gastrectomy. A national cohort study of 10,343 patients.

BACKGROUND: Laparoscopy for gastric cancer has not been as popular compared with other digestive surgeries, with conflicting reports on outcomes. The aim of this study focuses on the surgical techniques comparing open and laparoscopy by assessing the morbi-mortality and long-term complications after gastrectomy. METHODS: A retrospective study (2013-2018) was performed on a prospective national cohort (PMSI). All patients undergoing resection for gastric cancer with a partial gastrectomy (PG) or total gastrectomy (TG) were included. Overall morbidity at 90 post-operative days and long-term results were the main outcomes. The groups (open and laparoscopy) were compared using a propensity score and volume activity matching after stratification on resection type (TG or PG). RESULTS: A total of 10,343 patients were included. The overall 90-day mortality and morbidity were 7% and 45%, with reintervention required in 9.1%. High centre volume was associated with improved outcomes. There was no difference in population characteristics between groups after matching. An overall benefit for a laparoscopic approach after PG was found for morbidity (Open = 39.4% vs. Laparoscopy = 32.6%, p = 0.01), length of stay (Open = 14[10-21] vs. Laparoscopy = 11[8-17] days, p<0.0001). For TG, increased reintervention rate (Open = 10.8% vs. Laparoscopy = 14.5%, p = 0.04) and increased oesophageal stricture rate (HR = 2.54[1.67-3.85], p<0.001) were encountered after a laparoscopic approach. No benefit on mortality was found for laparoscopic approach in both type of resections after adjusted analysis. CONCLUSIONS: Laparoscopy is feasible for PG with a substantial benefit on morbidity and length of stay, however, laparoscopic TG should be performed with caution, with of higher rates of reintervention and oesophageal stricture.

Relevance of treatment-free remission recommendations in chronic phase chronic leukemia patients treated with frontline tyrosine kinase inhibitors.

BACKGROUND: Tyrosine kinase inhibitors (TKI) can be safely discontinued in chronic phase chronic myeloid leukemia (CP-CML) patients who had achieved a sustained deep molecular response. Based on the results of discontinuation trials, recommendations regarding patient selection for a treatment-free remission (TFR) attempt had been proposed. The aims of this study were to evaluate the rate of patients eligible for TKI discontinuation and molecular recurrence-free survival (MRFS) after stop according to recommendations. METHODS: Over a 10-year period, newly diagnosed CP-CML patients and treated with first-line TKI in the nine French participating centers were included. Eligibility to treatment discontinuation and MRFS were analyzed and compared according to selection criteria defined by recommendations and first-line treatments. RESULTS: From January 2006 to December 2015, 398 patients were considered. Among them, 73% and 27% of patients received imatinib or either second or third generation tyrosine kinase inhibitors as frontline treatment, respectively. Considering the selection criteria defined by recommendations, up to 55% of the patients were selected as optimal candidates for treatment discontinuation. Overall 95/398 (24%) discontinued treatment. MRFS was 51.8% [95% CI 41.41-62.19] at 2 years and 43.8% [31.45-56.15] at 5 years. Patients receiving frontline second-generation TKI and fulfilling the eligibility criteria suggested by recommendations had the lowest probability of molecular relapse after TKI stop when compare to others. CONCLUSION: One third of CP-CML patients treated with TKI frontline fulfilled the selection criteria suggested by European LeukemiaNet TFR recommendations. Meeting selection criteria and second-generation TKI frontline were associated with the highest MRFS.

Postoperative care fragmentation in bariatric surgery and risk of mortality: a nationwide study.

BACKGROUND: Readmission after bariatric surgery may to lead to fragmentation of care if readmission occurs at a facility other than the index hospital. The effect of readmission to a nonindex hospital on postoperative mortality remains unclear for bariatric surgery. OBJECTIVES: To determine postoperative mortality rates according to readmission destinations. SETTING: Nationwide analysis of all surgical facilities in France. METHODS: Multicenter, nationwide study of adult patients undergoing bariatric surgery from January 1, 2013, through December 31, 2018. Data from all surgical facilities in France were extracted from a national hospital discharge database. RESULTS: In a cohort of 278,600 patients who received bariatric surgery, 12,760 (4.6%) were readmitted within 30 days. In cases of readmission, 23% of patients were admitted to a nonindex hospital. Patients readmitted to a nonindex facility had different characteristics regarding sex (men, 23.6% versus 18.2%, respectively; P < .001), co-morbidities (Charlson Co-morbidity Index, .74 versus .53, respectively; P < .001), and travel distance (38.3 km versus 26.9 km, respectively; P < .001) than patients readmitted to the index facility. The main reasons for readmission were leak/peritonitis and abdominal pain. The overall mortality rate after readmission was .56%. The adjusted odds ratio (OR) of mortality for the nonindex group was 4.96 (95% confidence interval [CI], 3.1-8.1; P < .001). In the subgroups of patients with a gastric leak, the mortality rate was 1.5% and the OR was 8.26 (95% CI, 3.7-19.6; P < .001). CONCLUSION: Readmissions to a nonindex hospital are associated with a 5-fold greater mortality rate. The management of readmission for complications after bariatric surgery should be considered as a major issue to reduce potentially preventable deaths.

Impact of coronavirus disease 2019 (COVID-19) lockdown on in-hospital mortality and surgical activity in elective digestive resections: A nationwide cohort analysis.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) infection has led to the reorganization of hospital care in several countries. The objective was to report the postoperative mortality after elective digestive resections in a nationwide cohort during the lockdown period. METHODS: This analytic study was performed using a national billing database (the Programme de Médicalisation des Systèmes d'Informations). Patients who underwent elective digestive resections were divided in 2 groups: the lockdown group defined by hospital admissions between March 17 and May 11, 2020; and the control group, defined by hospital admissions during the corresponding period in 2019. Groups were matched on propensity score, geographical region, and surgical procedure. The primary outcome was the postoperative mortality. RESULTS: The overall population included 15,217 patients: 9,325 patients in the control group and 5,892 in the lockdown group. The overall surgical activity was decreased by 37% during the lockdown period. The overall in-hospital mortality during the hospital stay was 2.7%. After matching and adjustment, no difference in mortality between groups was reported (OR = 1.05; 95% CI: 0.83-1.34; P = .669). An asymptomatic COVID-19 infection was a risk factor for a 2-fold increased mortality, whereas a symptomatic COVID-19 infection was associated with a 10-fold increased mortality. CONCLUSION: Despite a considerable reduction in the surgical activity for elective digestive resections during the lockdown period, mortality remained stable on a nationwide scale in COVID-free patients. These findings support that systematic COVID-19 screening should be advocated before elective gastrointestinal surgery and that all efforts should be made to maintain elective surgical resection for cancer during the second wave in COVID-free patients.

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.

Prognostic value of high-sensitivity measurable residual disease assessment after front-line chemoimmunotherapy in chronic lymphocytic leukemia.

Measurable residual disease (MRD) status is widely adopted in clinical trials in patients with chronic lymphocytic leukemia (CLL). Findings from FILO group trials (CLL2007FMP, CLL2007SA, CLL2010FMP) enabled investigation of the prognostic value of high-sensitivity (0.7 × 10-5) MRD assessment using flow cytometry, in blood (N = 401) and bone marrow (N = 339), after fludarabine, cyclophosphamide, and rituximab (FCR)-based chemoimmunotherapy in a homogeneous population with long follow-up (median 49.5 months). Addition of low-level positive MRD < 0.01% to MRD ≥ 0.01% increased the proportion of cases with positive MRD in blood by 39% and in bone marrow by 27%. Compared to low-level positive MRD < 0.01%, undetectable MRD was associated with significantly longer progression-free survival (PFS) when using blood (72.2 versus 42.7 months; hazard ratio 0.40, p = 0.0003), but not when using bone marrow. Upon further stratification, positive blood MRD at any level, compared to undetectable blood MRD, was associated with shorter PFS irrespective of clinical complete or partial remission, and a lower 5-year PFS rate irrespective of IGHV-mutated or -unmutated status (all p < 0.05). In conclusion, high-sensitivity (0.0007%) MRD assessment in blood yielded additional prognostic information beyond the current standard sensitivity (0.01%). Our approach provides a model for future determination of the optimal MRD investigative strategy for any regimen.