The Cabrières Biota (France) provides insights into Ordovician polar ecosystems.

Early Palaeozoic sites with soft-tissue preservation are predominantly found in Cambrian rocks and tend to capture past tropical and temperate ecosystems. In this study, we describe the diversity and preservation of the Cabrières Biota, a newly discovered Early Ordovician Lagerstätte from Montagne Noire, southern France. The Cabrières Biota showcases a diverse polar assemblage of both biomineralized and soft-bodied organisms predominantly preserved in iron oxides. Echinoderms are extremely scarce, while sponges and algae are abundantly represented. Non-biomineralized arthropod fragments are also preserved, along with faunal elements reminiscent of Cambrian Burgess Shale-type ecosystems, such as armoured lobopodians. The taxonomic diversity observed in the Cabrières Biota mixes Early Ordovician Lagerstätten taxa with Cambrian forms. By potentially being the closest Lagerstätte to the South Pole, the Cabrières Biota probably served as a biotic refuge amid the high-water temperatures of the Early Ordovician, and shows comparable ecological structuring to modern polar communities.

Dismal outcome of refractory or relapsing patients with myelodysplasia-related acute myeloid leukemia partially alleviated by intensive chemotherapy.

BACKGROUND: Acute myeloid leukemia (AML) with myelodysplasia-related characteristics is a heterogeneous subset of AML that has been challenged throughout the history of myeloid malignancies classifications, considered to have similar outcomes as intermediate- or adverse-risk AML depending on the subgroup. However, little is known about the fate of these patients in refractory or relapsed situation (R/R) after first line therapy. METHODS: A large series of R/R AML patients, recorded in the French DATAML registry, have received either intensive chemotherapy (ICT), azacitidine (AZA) as single agent, or best supportive care (BSC). A cohort of 183 patients (median age 63-year-old) with what was called at the time AML-MRC has been explored, and data are reported here. RESULTS: Patient status was refractory for 93, while 90 had relapsed. Respectively, 88, 34, and 61 were included in the three treatment arms. The median OS of the whole cohort was 4.2 months (95%CI: 3.1-5.6) with a mean 1-year overall survival of 24% ± 3.2%. There was no significant survival difference between refractory and relapsed patients. The BSC group had overall a significantly worse outcome (p = 0.0001), and this remained true in both refractory (p = 0.01) and relapsed (p = 0.002) patients. Similar survivals were observed in both groups comparing ICT and AZA. CONCLUSIONS: These data, reporting about an ill-explored population, indicate the poor prognosis of this condition where both ICT and AZA can be proposed. The latter, which was demonstrated here to be a feasible option, should be added to new targeted therapies.

Artificial intelligence-based prediction models for acute myeloid leukemia using real-life data: A DATAML registry study.

We designed artificial intelligence-based prediction models (AIPM) using 52 diagnostic variables from 3687 patients included in the DATAML registry treated with intensive chemotherapy (IC, N = 3030) or azacitidine (AZA, N = 657) for an acute myeloid leukemia (AML). A neural network called multilayer perceptron (MLP) achieved a prediction accuracy for overall survival (OS) of 68.5% and 62.1% in the IC and AZA cohorts, respectively. The Boruta algorithm could select the most important variables for prediction without decreasing accuracy. Thirteen features were retained with this algorithm in the IC cohort: age, cytogenetic risk, white blood cells count, LDH, platelet count, albumin, MPO expression, mean corpuscular volume, CD117 expression, NPM1 mutation, AML status (de novo or secondary), multilineage dysplasia and ASXL1 mutation; and 7 variables in the AZA cohort: blood blasts, serum ferritin, CD56, LDH, hemoglobin, CD13 and disseminated intravascular coagulation (DIC). We believe that AIPM could help hematologists to deal with the huge amount of data available at diagnosis, enabling them to have an OS estimation and guide their treatment choice. Our registry-based AIPM could offer a large real-life dataset with original and exhaustive features and select a low number of diagnostic features with an equivalent accuracy of prediction, more appropriate to routine practice.

Does spinal anesthesia for total hip or knee arthroplasty entail longer operating room occupancy compared to general anesthesia? Case-control study of 337 spinal versus 243 general anesthesias.

BACKGROUND: Treatment protocols, including anesthesia, are constantly progressing to improve rapid early postoperative recovery in lower-limb arthroplasty. To the best of our knowledge, however, no studies compared general versus spinal anesthesia (GA vs. SA) in the surgical pathway of patients undergoing total knee or hip arthroplasty (TKA, THA). Better knowledge of the processes should improve efficacy in theater and optimize surgical planning. The present study comparing GA and SA in the operating room aimed to assess (1) theater occupancy times, and (2) times for each step in a surgery day according to type of anesthesia. HYPOTHESIS: SA leads to longer theater occupancy than GA in TKA and THA. METHODS: A single-center retrospective case-control study analyzed data for the period January 2019 to December 2020 in 303 TKAs (100 GA, 203 SA) and 277 THAs (143 GA, 134 SA), comparing times for all perioperative steps and particularly theater occupancy. RESULTS: In TKA, occupancy did not differ between GA and SA: 98±16min versus 98±14min respectively; Δ=0min (p=0.78). In THA, occupancy was shorter with SA than GA: 117±23min versus 123±26min respectively; Δ=-6min (p=0.02). In THA, time to perform SA was longer than induction of GA: 28±13min versus 23±12min respectively; Δ=+5min (p<0.001). In TKA, time to leaving the operating room was shorter with SA than GA: 8±5min versus 14±7min respectively; Δ=-6min (p<0.001). DISCUSSION/CONCLUSION: SA did not involve longer mean theater occupancy than GA for TKA, and reduced it by 6minutes for THA. LEVEL OF EVIDENCE: III; case-control study.

Outcomes of hamstring graft with preserved tibial insertion for ACL reconstruction: systematic review and meta-analysis.

PURPOSE: Evaluate the outcomes of ACL (Anterior Cruciate Ligament) reconstruction techniques that use a hamstring graft with a preserved tibial insertion and compare them to standard techniques. METHODS: A systematic literature review and meta-analysis was done of the PubMed, MEDLINE, Cochrane and Ovid databases to identify published clinical studies on ACL reconstruction in which a non-detached hamstring tendon (NDHT) was used as a graft and to compare them to studies in which a detached hamstring tendon (DHT) or other techniques were used. The eligible studies were analyzed for the knee laxity, Lachman test, pivot shift test, joint range of motion, anterior drawer, pain, re-tear, revision surgery, Lysholm score, Tegner score, ACL-RSI scale, KOOS, IKDC, SNQ and Howell scale. RESULTS: Twelve articles in which NDHT was used for ACL reconstruction were analyzed. There was no significant difference between NDHT and DHT in the Lachman > 1 (p = .07), pivot shift test > 1 (p = .40), re-tears (p = .62), pain (p = .85) and the Tegner score (p = .95). However, the outcomes were somewhat better with the NDHT technique for the Lachman (RR = 0.30; 95% CI 0.08-1.12), pivot shift test (RR = 0.50; 95% CI 0.10-2.49) and re-tears (RR = 0.66; 95% CI 0.13-3.42). The other criteria were not included in the meta-analysis because of lack of data or because specific outcome scores were used in each article. CONCLUSION: NDHT techniques provide similar results to DHT for ACL reconstruction and tend to produce better stability and a lower re-tear rate.

Lateral femoral chondral lesions are more frequent when an anterior cruciate ligament tear is concomitant with a lateral femoral notch sign, but do not progress over time.

BACKGROUND: The lateral femoral notch sign (LFNS) is caused by an impact to the lateral femoral condyle during a pivot shift injury and affects 25% to 33% of patients with an anterior cruciate ligament (ACL) rupture. The primary aim of this study was to compare the incidence of chondral lesions 1year after ACL reconstruction, while taking into consideration preoperative chondral damage, in patients with and without a preoperative LFNS. The primary outcome measure was the presence of chondral lesions involving the lateral femoral condyle, confirmed on magnetic resonance imaging (MRI) using the Outerbridge classification, at 1year postoperative. The secondary outcome measures were bone bruise of the lateral femoral condyle confirmed on MRI, the International Knee Documentation Committee (IKDC), Lysholm and Tegner functional scores taken 1year after surgery. METHODS: Sixty patients were included-30 with preoperative LFNS and 30 without-in a retrospective, comparative study of prospectively collected data on patients operated between August 2018 and December 2020. RESULTS: A lateral femoral chondral lesion 1year after surgery was significantly more common in the group with a preoperative LFNS (37% [n=11] versus 13% [n=4] in the group without a preoperative LFNS, p=0.036). Adjusting the statistical analysis for preoperative body mass index (BMI) did not impact these results (adjusted odds ratio [OR]=3.83 [95%CI: 1.03-14.24]; p=0.045). Adjusting for a preoperative lateral femoral chondral lesion had an impact on these results (adjusted OR=0.78 [95%CI: 0.12-5.08]; p=0.793). This indicates that a preoperative LFNS is not significantly and independently associated with a lateral femoral chondral lesion at 1year postoperative when the analysis is adjusted for a preoperative lateral femoral chondral lesion. However, having a preoperative lateral femoral chondral lesion is significantly correlated with the presence of a lateral femoral chondral lesion 1year after the surgery (adjusted OR=63.31 [95%CI: 5.94-674.8]; p=0.001). There were no significant differences in terms of bone bruise on MRI (p=1.0), or for the IKDC (p=0.310), Lysholm (p=0.416) and Tegner (p=0.644) functional scores. The LFNS was still present in 21 out of 30 patients (70%) at 1year postoperative. The preoperative LFNS was significantly smaller in the group without a chondral lesion compared to the group with a chondral lesion 1year after the surgery (median=2.30mm [IQR: 1.40; 3.00] versus 3.10mm [IQR: 2.50; 3.40]; p value=0.045). CONCLUSIONS: Patients with a preoperative LFNS are three times more likely to have a chondral lesion in the notch region 1year after surgery. These chondral lesions are concomitant to the injury and do not progress over time. LEVEL OF EVIDENCE: III.

Exploring Predictive Factors for Potentially Avoidable Emergency Department Transfers: Findings From the FINE Study.

OBJECTIVES: To assess the prevalence of potentially avoidable transfers (PAT) and identify factors associated with these transfers to emergency departments (EDs) among nursing home (NH) residents. DESIGN: This is a secondary outcome analysis of the FINE study, a multicenter observational study collecting data on NH residents, NH settings, and contextual factors of ED transfers. SETTINGS AND PARTICIPANTS: NHs in the former Midi-Pyrénées region of the southwest of France (n = 312); a total of 1037 NH residents who experienced ED transfers (n = 1017) between January 2016 and December 2016. METHODS: The analysis included resident baseline characteristics and NH and transfer decision-making characteristics. An expert group categorized the transfer status as either PAT or unavoidable. Multivariable analysis using a mixed logistic model, accounting for intra-NH correlation, was conducted to assess factors independently associated with PAT. RESULTS: Among 1017 included transfers, 87.02% (n = 885) were identified as PAT and 12.98% (n = 132) unavoidable transfers. Multivariable analysis revealed that the following patient-related factors were associated with a likely high rate of PAT: usual behavior disturbances before transfer, including productive trouble (OR 2.04, 95% CI 1.25-3.33; P = .0044) and unusual symptom of falling during the week preceding the transfer (OR 4.55, 95% CI 1.76-11.82; P = .0019). On the other hand, distance between ED and NH (OR 0.98, 95% CI 0.97-0.998; P = .0231), NH staff trained in palliative care in the last 3 years (OR 0.52, 95% CI 0.29-0.95; P = .0324), the impossibility of direct hospitalization to an appropriate unit (OR 0.54, 95% CI 0.34-0.87; P = .0117), and the resident Charlson Comorbidity Index (OR 0.90, 95% CI 0.82-0.99; P = .0369) were associated with a lower probability of PAT. CONCLUSION AND IMPLICATIONS: Transfers from NHs to hospital EDs were frequently potentially avoidable, meaning that there are still significant opportunities to reduce PAT. Our findings may help to specifically identify interventions that should be targeted at both NH and resident levels.

Vitamin C and D supplementation in acute myeloid leukemia.

Recent studies have highlighted the role of vitamin C and D in acute myeloid leukemia (AML). In 2018, we changed our practices to add both vitamins to the supportive care for all consecutive patients with AML undergoing intensive chemotherapy. In this study, we compared the outcomes of patients treated before and after this change in practice. From 2015 to 2020, 431 patients were included, 262 of whom received no supplementation and 169 of whom received vitamin supplementation. Vitamin C and vitamin D was administered from day 10 of chemotherapy until hematologic recovery from induction and consolidation. Most patients presented at diagnosis with low levels of vitamin C and D. Upon recovery from induction, vitamin D levels among the vitamin C/D group significantly increased compared with those at diagnosis, and pretransplant levels were significantly higher in the vitamin C/D group compared with the control group (median of 33 vs 19 ng/mL; P < .0001). During induction, the rates of bacterial or fungal infection, hemorrhage, or macrophage activation syndrome were lower in the vitamin C/D group, whereas there was no difference in response rate, relapse incidence, and overall survival (OS). However, the multivariate analysis for OS showed a significant interaction between vitamin C/D and NPM1 mutation, meaning that vitamin C/D supplementation was significantly and independently associated with better OS in patients with NPM1 mutations (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.30-0.90; P = .019) compared with patients with wild-type NPM1 (HR, 1.01; 95% CI, 0.68-1.51; P = .95). In conclusion, vitamin C/D supplementation is safe and could influence the outcomes of patients with AML undergoing intensive chemotherapy.

Evaluation of the All-Inside Technique for the Repair of Lateral Meniscus Root Tears at 1 Year After ACL Reconstruction.

Background: The presence of a lateral meniscus root tear (LMRT) in patients with an anterior cruciate ligament (ACL) tear makes the knee more unstable and increases the risk of osteoarthritis and osteonecrosis. An all-inside suture repair technique without bone tunnels has been proposed to treat LMRT. Purpose: To compare the 1-year postoperative findings between patients who underwent ACL reconstruction combined with LMRT repair (LMRT group) and patients who underwent isolated ACL reconstruction (control group). Study Design: Cohort study; Level of evidence, 3. Methods: The LMRT group consisted of 19 patients, and the control group consisted of 56 patients. In this study, the authors compared the postoperative magnetic resonance imaging (MRI) findings (meniscal extrusion, ghost sign, and hyperintensity in the tibial plateau beneath the LMRT), functional outcomes (International Knee Documentation Committee [IKDC], Lysholm, and Tegner scores), and reoperation rate between groups. The primary endpoint was analyzed by comparing, in the LMRT group, the 1-sided 97.5% confidence interval (CI) of the mean lateral meniscal extrusion at 1 year to the limit of noninferiority (fixed at 0.51). To take into account imbalanced baseline characteristics between groups, adjusted mean meniscal extrusion (with 1-sided 97.5% CI) was assessed using a linear regression model. Results: The mean follow-up was 12.2 months (range, 7.7-14.7 months) in the control group and 11.5 months (range, 7.1-13.0 months) in the LMRT group (P = .06). For meniscal extrusion, the LMRT group was noninferior to the control group. The mean meniscal extrusion was 2.19 mm (97.5% CI, -infinity to 2.68 mm) in the LMRT group and 2.03 mm (97.5% CI,-infinity to 2.27 mm) in the control group, indicating that the upper boundary of the 1-sided 97.5% CI in the LMRT group was less than the noninferiority threshold of 2.78 (ie, 2.27 mm + 0.51 mm = 2.78 mm). There was a statistically significant difference in the IKDC score between the LMRT and control groups (77.2 ± 8.1 vs 80.3 ± 7.3, respectively; P = .04). There was no between-group difference in the other MRI parameters, the Lysholm and Tegner scores, or the reoperation rate. Conclusion: There was no significant difference in extrusion on MRI or clinical outcomes at 1-year follow-up in patients who underwent ACL reconstruction with all-inside LMRT repair compared with patients who did not have an LMRT.

Factors Affecting Graft Remodeling and Anterior Cruciate Ligament Reconstruction: MRI Study of 180 Knees.

BACKGROUND: Several factors affect the retear rate after anterior cruciate ligament (ACL) reconstruction, but there are few data on which factors affect graft remodeling. PURPOSE: To determine which factors are associated with the remodeling of an ACL graft. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A retrospective longitudinal study was conducted to investigate the relationship between various exposure factors and the occurrence of an "event": graft remodeling measured with the signal-to-noise quotient (SNQ). Data were collected prospectively and analyzed retrospectively for this study. The endpoint was the SNQ on magnetic resonance imaging at postoperative 1 year. The effect of the following parameters on SNQ was investigated: sex, smoking habits, age at surgery, body mass index, time to surgery, time to return to sports, type of sport (in-line, pivot, contact), type of graft (free semitendinosus [ST] or attached ST), and addition of lateral tenodesis. RESULTS: An overall 180 patients were enrolled (90 with each technique). The following factors were significantly and independently associated with the SNQ: attached ST graft (ß = -2.624668; P < .001), age at the time of surgery (ß = -0.7948476; P = .012), and time elapsed between the injury event and surgery (ß = -0.7137424; P = .046). CONCLUSION: Leaving the ST graft attached distally, being older at the time of surgery, and having more time elapse between the injury event and ACL reconstruction surgery were significantly associated with better graft remodeling.

Preserving the Semitendinosus Distal Attachment Is Associated With Improved Graft Remodeling After ACL Reconstruction.

BACKGROUND: The semitendinosus (ST) tendon can be used by itself as a graft for anterior cruciate ligament (ACL) reconstruction. An increasing number of these procedures are being done while preserving the ST's tibial attachment, but there are no data on the remodeling of an attached ST (aST) graft. PURPOSE: To compare graft remodeling on magnetic resonance imaging (MRI) scans at 1 year after ACL reconstruction between standard free ST graft and aST graft. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This prospective study enrolled 180 patients who were undergoing ACL reconstruction: 90 with the ST graft and 90 with the aST graft. The analysis was performed 1 year after the surgery. The main endpoint was the signal-to-noise quotient (SNQ) on MRI scans (T1-weighted sequence). The secondary endpoints were tibial tunnel widening (TTW), graft maturation (Howell classification), retear rate, new surgery rate, Simple Knee Value, Lysholm score, International Knee Documentation Committee (IKDC) score, postoperative Tegner score, difference between pre- and postoperative Tegner scores, ACL-Return to Sport after Injury (ACL-RSI), return-to-sports rate, and time to return to sports. RESULTS: The mean adjusted SNQ was 1.18 (95% CI, 0.72-1.65) in the aST group and 3.88 (95% CI, 3.42-4.34) in the ST group (P < .001). The new surgery rate was 2.2% in the aST group and 10% in the ST group (P = .029). The median Lysholm score was significantly higher in the aST group (99; interquartile range [IQR], 95-100) than in the ST group (95; IQR, 91-99) (P = .004). The mean time to return to sports was significantly shorter in the aST group (248.73 ± 141.62 days) than the ST group (317.23 ± 144.69 days) (P = .002). No statistically significant difference was found between groups in the TTW (P = .503), Howell graft maturity grade (P = .149), retear rate (P > .999), Simple Knee Value (P = .061), postoperative Tegner score (P = .320), pre- to postoperative difference in Tegner score (P = .317), ACL-RSI (P = .097), IKDC score (P = .621), and return-to-sports rate (P > .999). CONCLUSION: At 1 year postoperatively, remodeling of an ST graft assessed using MRI is better when its distal attachment is left intact.

TIcagrelor in Rotational Atherectomy to Reduce TROPonin Enhancement: The TIRATROP Study, A Randomized Controlled Trial.

BACKGROUND: Because rotational atherectomy (RA) is associated with arterial trauma and platelet activation, patients treated with RA may benefit from more potent antiplatelet drugs. The aim of this trial was to assess the superiority of ticagrelor over clopidogrel in reducing post procedure troponin release. METHODS: TIRATROP (TIcagrelor in Rotational Atherectomy to reduce TROPonin enhancement) is a multicenter double-blind randomized controlled trial that included 180 patients with severe calcified lesions requiring RA who received either clopidogrel (300 mg loading dose, then 75 mg/d) or ticagrelor (loading dose 180 mg then 90 mg twice daily). Blood samples were collected at the beginning (T0), and 6, 12, 18, 24 and 36 h after the procedure. Primary end point was troponin release within the first 24 h using area under the curve analysis (troponin level as a function of time). RESULTS: The mean age of patients was 76 ± 10 years, 35% had diabetes. RA was used to treat 1, 2 or 3 calcified lesions in 72%, 23% and 5% of patients, respectively. Troponin release within the first 24 h was similar in both the ticagrelor (adjusted mean ±SD of ln AUC 8.85 ± 0.33) and the clopidogrel (8.77 ± 0.34, p = 0.60) arms. Independent predictors for troponin enhancement were acute coronary syndrome presentation, renal failure, elevated C-Reactive protein and multiple lesions treated with RA. CONCLUSION: Troponin release did not differ among treatment arms. Our results suggest that greater platelet inhibition does not affect periprocedural myocardial necrosis in the setting of RA.

A quadruple peripheral nerve block outside the OR for anterior cruciate ligament reconstruction reduces the OR occupancy time.

PURPOSE: The use of regional anesthesia (RA) for anterior cruciate ligament (ACL) reconstruction reduces morphine consumption, the time spent in the post-anesthesia care unit (PACU) and the hospital readmission rate. However, RA failures due to delays in the induction of anesthesia and its unpredictable success rate (Cuvillon et al. Ann Fr Anesth 29:710-715, 2010; Jankowski et al. Anesth Analg 10.1213/01.ANE.0000081798.89853.E7) can lead to disorganization of the operating room (OR) schedule. The hypothesis is that performing RA outside the OR will significantly reduce the OR occupancy time relative to using general anesthesia (GA). The primary objective was to compare the OR occupancy time between RA and GA when performing ACL reconstruction. METHODS: This was a retrospective, single-center study of data collected prospectively from consecutive patients operated by a single surgeon between January 2019 and December 2020. The patients undergoing ACL reconstruction were divided into two groups based on the type of anesthesia they received (GA, RA). RA consisted of a quadruple peripheral nerve block (femoral, sciatic, obturator and lateral femoral cutaneous nerves). The durations of the perioperative stages of the patient's journey in the OR suite were compared between these two groups. RESULTS: The analysis involved 469 ACL reconstructions: 356 GA and 113 RA. The two groups were comparable in age, gender and ASA score (American Society of Anesthesiologists). The OR occupancy time for ACL reconstruction with RA was reduced by a mean of 13 min (70 ± 12 SD vs. 83 ± 14 SD; P < 0.0001) and the PACU time by 41 min relative to GA (P < 0.0001). The entry-incision time was reduced by an average of 8 min and the end-exit time by 3 min (P < 0.0001). The care time in the PACU was reduced from 84 ± 35 to 46 ± 26 min (P < 0.0001). However, performing anesthesia outside the OR (i.e., in a RA block room) did not reduce the turnover time (n.s). CONCLUSION: Performing RA outside the OR reduced the OR occupancy time by nearly 20% relative to using GA for ACL reconstructions. LEVEL OF EVIDENCE: Level IV.

Gilteritinib activity in refractory or relapsed FLT3-mutated acute myeloid leukemia patients previously treated by intensive chemotherapy and midostaurin: a study from the French AML Intergroup ALFA/FILO.

The real-world efficacy and safety of gilteritinib was assessed in an ambispective study that included 167 R/R FLT3-mutated AML patients. Among them, 140 received gilteritinib as single agent (cohort B), including 67 previously treated by intensive chemotherapy and midostaurin (cohort C). The main differences in patient characteristics in this study compared to the ADMIRAL trial were ECOG ≥ 2 (83.6% vs. 16.6%), FLT3-TKD mutation (21.0% vs. 8.5%), primary induction failure (15.0% vs. 40.0%) and line of treatment (beyond 2nd in 37.1% vs. 0.0%). The rates of composite complete remission, excluding those that occurred after hematopoietic stem cell transplantation (HSCT), were similar at respectively 25.4% and 27.5% in cohorts B and C. Median overall survival (OS) for these two groups was also similar at respectively 6.4 and 7.8 months. Multivariate analyses for prognostic factors associated with OS identified female gender (HR 1.61), adverse cytogenetic risk (HR 2.52), and allogenic HSCT after gilteritinib (HR 0.13). Although these patients were more heavily pretreated, these real-world data reproduce the results of ADMIRAL and provide new insights into the course of patients previously treated by intensive chemotherapy and midostaurin and beyond the 2nd line of treatment who can benefit from treatment in an outpatient setting.

A scoring system for AML patients aged 70 years or older, eligible for intensive chemotherapy: a study based on a large European data set using the DATAML, SAL, and PETHEMA registries.

In a context of therapeutic revolution in older adults with AML, it is becoming increasingly important to select patients for the various treatment options by taking account of short-term efficacy and toxicity as well as long-term survival. Here, the data from three European registries for 1,199 AML patients aged 70 years or older treated with intensive chemotherapy were used to develop a prognostic scoring system. The median follow-up was 50.8 months. In the training set of 636 patients, age, performance status, secondary AML, leukocytosis, and cytogenetics, as well as NPM1 mutations (without FLT3-ITD), were all significantly associated with overall survival, albeit not to the same degree. These factors were used to develop a score that predicts long-term overall survival. Three risk-groups were identified: a lower, intermediate and higher-risk score with predicted 5-year overall survival (OS) probabilities of ≥12% (n = 283, 51%; median OS = 18 months), 3-12% (n = 226, 41%; median OS = 9 months) and <3% (n = 47, 8%; median OS = 3 months), respectively. This scoring system was also significantly associated with complete remission, early death and relapse-free survival; performed similarly in the external validation cohort (n = 563) and showed a lower false-positive rate than previously published scores. The European Scoring System ≥70, easy for routine calculation, predicts long-term survival in older AML patients considered for intensive chemotherapy.

Endoscopic ultrasound as a reliable tool for assessment of pancreatic adenocarcinoma treatment: Example of in situ gene therapy.

Background and study aims In pancreatic cancer, the antitumor effect can only be assessed by means of a computed tomography (CT) scan using RECIST (Response Evaluation Criteria in Solid Tumours) criteria. The aim of this study was to assess the intra-observer and interobserver agreement of endoscopic ultrasound (EUS) imaging in assessing tumor volume in primary pancreatic cancer. Patients and methods During a Phase 1 gene therapy trial, 21 patients had EUS before the first and second EUS-guided in situ gene therapy injections. All anonymized EUS files were then randomly distributed to three gastroenterologists/endosonographers and three radiologists (blind status). The largest tumor diameter was measured and the intraclass correlation coefficient (ICC) was determined. Results Intra-observer and interobserver agreements were good to excellent, regardless of operator experience (junior versus senior member of staff) (ICC: 0.65 to 0.84). A comparison of pretreatment and post-treatment measurements by the investigators highlighted a significant antitumor effect (-11 %; P  = 0.0098), similar to that obtained during the generic protocol (-10 %; P  = 0.0045). Conclusions Interobserver agreement regarding primary pancreatic adenocarcinoma measurements appears good to excellent, thus paving the way for the future inclusion of EUS assessments, particularly in trials assessing local therapies for pancreatic tumors.

Azacitidine, intensive chemotherapy or best supportive care in relapsed or refractory acute myeloid leukemia, a DATAML registry study.

We analyzed 526 consecutive acute myeloid leukemia patients refractory to or relapsing after chemotherapy. 270 patients received intensive salvage chemotherapy (IC), 97 azacitidine (AZA) and 159 best supportive care (BSC). Complete response was obtained in 37/19/0% (p = .0008). Allogeneic stem-cell transplantation (alloSCT) was performed in 39.3/10.3/0%. Median overall survival (OS) and 5-year OS were 8.2/9.6/2.2 months and 16/6/2% (p < .0001). Predictive factors of worse OS were post-myelodysplastic/chronic myelomonocytic leukemia, bone marrow blasts ≥20%, adverse cytogenetics, AZA cycle ≥2 and no alloSCT at R/R for AZA and age, performance status, white blood cell count and myelodysplasia-related changes for IC. The impact of treatment was time-dependent: adjusted hazard ratio for OS was in favor of AZA up to 1 month, was not different between 1 and 7 months, then was in favor of IC after 7 months. While AZA represents a therapeutic option for the oldest patients, it does not lead to long-term survivors.

One-Year Impact of COVID-19 Lockdown-Related Factors on Cardiovascular Risk and Mental Health: A Population-Based Cohort Study.

Lockdown measures have obvious psychological impacts, which could, in turn, increase cardiovascular risk. We assessed the association between lockdown-related factors and the worsening of cardiovascular risk, incident anxiety and depression during 12 months' follow-up. During lockdown (April-May 2020), 534 subjects, aged 50-89 years, were included in the PSYCOV-CV study (NCT04397835) and followed for up to 12 months post-lockdown. We found that participants with symptoms of depression during lockdown were more likely to report increased cardiovascular drug treatment (Odds-Ratio (OR) = 5.08 (1.78-14.5), p = 0.002), decreased physical activity (OR = 1.76 (1.10-2.82), p = 0.019) and weight gain (OR = 1.85 (1.08-3.17), p = 0.024) after lockdown. Moreover, changes in sleep patterns (OR = 2.35 (1.13-4.88), p = 0.022) or living in a rural area during lockdown (OR = 1.70 (0.96-3.03, p = 0.069) were associated with higher incident depression, whereas a better relationship with one's partner during lockdown was associated with less incident depression (OR = 0.56 (0.29-1.08), p = 0.084). Finally, we found that continuing to work during lockdown in a role requiring in-person contact with the public (such as cashiers, nurses or physicians) was associated with more incident anxiety after lockdown (OR = 3.38 (1.12-10.2), p = 0.031). Interestingly, decreased consumption of alcohol during lockdown was associated with less incident anxiety (OR = 0.30 (0.10-0.90), p = 0.032). Our study, conducted in a representative sample of an age group at increased risk of both cardiovascular disease and severe COVID-19, increases the understanding of modifiable factors associated with the health impacts of lockdown measures.