Introduction: Many recent studies have investigated the hospital volume-outcome relationship in surgery. In some cases, the results have prompted the centralization of surgical activity. However, the methodologies and interpretations differ markedly from one study to another. The objective of the present scoping review was to describe the various features used to assess the volume-outcome relationship: the analyzed datasets, study population, outcome, covariates, confounders, volume modalities, and statistical methods. Methods and analysis: The review was conducted according to a study protocol published in BMJ Open in 2020. Two authors (both of whom had helped to design the study protocol) screened publications independently according to the title, the abstract and then the full text. To ensure exhaustivity, all the papers included by each reviewer went through to the next step. Interpretation: The 403 included studies covered 90 types of surgery, 61 types of outcome, and 72 covariates or potential confounders. 191 (47.5%) studies focussed on oncological surgery and 37.8% focussed visceral or digestive tract surgery. Overall, 86.6% of the studies found a statistically significant volume-outcome relationship, although the findings differed from one type of surgery to another. Furthermore, the types of outcome and the covariates were highly diverse. The majority of studies were performed in Western countries, and oncological and visceral surgical procedures were over-represented; this might limit the generalizability and comparability of the studies’ results.

Gene expression studies have consistently identified a HOXA-overexpressing cluster of T-cell acute lymphoblastic leukemia, but it is unclear if this constitutes a homogeneous clinical entity, and the biological consequences of HOXA overexpression have not been systematically examined. We characterized the biology and outcome of 55 HOXA positive cases among 209 adult T-cell acute lymphoblastic leukemia patients uniformly treated during the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003 and -2005 studies. HOXA positive patients had markedly higher rates of an early thymic precursor-like immunophenotype (40.8% v 14.5%, p = 0.0004), chemoresistance (59.3% v 40.8%, p = 0.026) and positive minimal residual disease (48.5% v 23.5%, p = 0.01) than the HOXA negative group. These differences were due to particularly high frequencies of chemoresistant early thymic precursor-like acute lymphoblastic leukemia in HOXA positive cases harboring fusion onco-proteins that trans-activate HOXA. Strikingly, the presence of an early thymic precursor-like immunophenotype was associated with marked outcome differences within the HOXA positive group (5 year overall survival 31.2% in HOXA positive early thymic precursor v 66.7% in HOXA positive non-early thymic precursor, p = 0.03), but not in HOXA negative cases (5 year overall survival 74.2% in HOXA negative early thymic precursor v 57.2% in HOXA negative non-early thymic precursor, p = 0.44). Multivariate analysis further revealed that HOXA positivity independently affected event-free survival (p = 0.053) and relapse risk (p = 0.039) of chemoresistant T-cell acute lymphoblastic leukemia. These results show that the underlying mechanism of HOXA deregulation dictates clinico-biological phenotype, and that the negative prognosis of early thymic precursor acute lymphoblastic leukemia is exclusive to HOXA positive patients, suggesting that early treatment intensification is currently suboptimal for therapeutic rescue of HOXA positive chemoresistant adult early thymic precursor acute lymphoblastic leukemia.

Introduction: Prevalence of iron deficiency (ID) at intensive care (ICU) admission is around 25 to 40%. Blood losses are important during ICU stay, leading to iron losses, but prevalence of ID at ICU discharge is unknown. ID has been associated with fatigue and muscular weakness, and may thus impair post-ICU rehabilitation. This study assessed ID prevalence at ICU discharge, day 28 (D28) and six months (M6) after and its relation with fatigue. Methods: We conducted this prospective, multicenter observational study at four University hospitals ICUs. Anemic (hemoglobin (Hb) less than 13 g/dL in male and less than 12 g/dL in female) critically ill adult patients hospitalized for at least five days had an iron profile taken at discharge, D28 and M6. ID was defined as ferritin less than 100 ng/L or less than 300 ng/L together with a transferrin saturation less than 20%. Fatigue was assessed by numerical scale and the Multidimensional Fatigue Inventory-20 questionnaire at D28 and M6 and muscular weakness by a hand grip test at ICU discharge. Results: Among 107 patients (men 77%, median (IQR) age 63 (48 to 73) years) who had a complete iron profile at ICU discharge, 9 (8.4%) had ID. At ICU discharge, their hemoglobin concentration (9.5 (87.7 to 10.3) versus 10.2 (92.2 to 11.7) g/dL, P =0.09), hand grip strength (52.5 (30 to 65) versus 49.5 (15.5 to 67.7)% of normal value, P =0.61) and visual analog scale fatigue scale (57 (40 to 80) versus 60 (47.5 to 80)/100, P =0.82) were not different from non-ID patients. At D28 (n =80 patients) and M6 (n =78 patients), ID prevalence increased (to 25 and 35% respectively) while anemia prevalence decreased (from 100% to 80 and 25% respectively, P <0.0001). ID was associated with increased fatigue at D28, after adjustment for main confounding factors, including anemia (regression coefficient (95%CI), 3.19 (0.74 to 5.64), P =0.012). At M6, this association disappeared. Conclusions: The prevalence of ID increases from 8% at discharge to 35% six months after prolonged ICU stay (more than five days). ID was associated with increased fatigue, independently of anemia, at D28.

The association between elevated plasma vitamin B12 (B12) level and solid cancers has been documented by two national registries. However, their design did not allow for the adjustment for other conditions associated with elevated B12. The objectives of this study were to confirm this association after the adjustment for all causes of elevated B12, and to study the variations according to the increasing B12 level, the type of cancers, and the presence of metastases. We compared 785 patients with B12 ≥ 1000 ng/L with 785 controls matched for sex and age with B12 < 1000 ng/L. Analyses were adjusted for the causes of elevated B12: myeloid blood malignancies, acute or chronic liver diseases, chronic kidney failure, autoimmune or inflammatory diseases, and excessive B12 supplementation. A B12 ≥ 1000 ng/L was associated with the presence of solid cancer without metastases (OR 1.96 [95%CI: 1.18 to 3.25]) and with metastases (OR 4.21 [95%CI: 2.67 to 6.64]) after adjustment for all elevated B12-related causes. The strength of the association rose with the increasing B12 level, in particular in cases of metastases. No association between liver cancers and elevated B12 level was found after adjustment for chronic liver diseases. In conclusion, unexplained elevated B12 levels should be examined as a possible marker of solid cancer.