Caffeine consumption outcomes on amyotrophic lateral sclerosis disease progression and cognition.

Caffeine consumption outcomes on Amyotrophic Lateral Sclerosis (ALS) including progression, survival and cognition remain poorly defined and may depend on its metabolization influenced by genetic variants. 378 ALS patients with a precise evaluation of their regular caffeine consumption were monitored as part of a prospective multicenter study. Demographic, clinical characteristics, functional disability as measured with revised ALS Functional Rating Scale (ALSFRS-R), cognitive deficits measured using Edinburgh Cognitive and Behavioural ALS Screen (ECAS), survival and riluzole treatment were recorded. 282 patients were genotyped for six single nucleotide polymorphisms tagging different genes involved in caffeine intake and/or metabolism: CYP1A1 (rs2472297), CYP1A2 (rs762551), AHR (rs4410790), POR (rs17685), XDH (rs206860) and ADORA2A (rs5751876) genes. Association between caffeine consumption and ALSFRS-R, ALSFRS-R rate, ECAS and survival were statistically analyzed to determine the outcome of regular caffeine consumption on ALS disease progression and cognition. No association was observed between caffeine consumption and survival (p = 0.25), functional disability (ALSFRS-R; p = 0.27) or progression of ALS (p = 0.076). However, a significant association was found with higher caffeine consumption and better cognitive performance on ECAS scores in patients carrying the C/T and T/T genotypes at rs2472297 (p-het = 0.004). Our results support the safety of regular caffeine consumption on ALS disease progression and survival and also show its beneficial impact on cognitive performance in patients carrying the minor allele T of rs2472297, considered as fast metabolizers, that would set the ground for a new pharmacogenetic therapeutic strategy.

Muscle involvement in systemic sclerosis: high mortality not associated with nature of histological lesions.

OBJECTIVES: The aim of this study was to determine the association between different histological patterns and prognosis in patients with SSc and histologically proven muscle involvement. METHODS: A multicentre retrospective study was conducted of a cohort of scleroderma patients who had undergone muscle biopsy. The biopsies were reviewed in a coordinated manner to classify patients based on histological findings. Three different patterns were observed: fibrosing myopathy (FM), inflammatory myopathy (IM) and necrotizing myopathy (NM). Rates of survival, muscle relapse, and cardiac and pulmonary events were compared between these three groups. RESULTS: Among 71 scleroderma patients with muscle biopsy specimens available for review, 33 (46.5%) were classified in the FM group, 18 (25.5%) in the IM group, and 20 (28%) in the NM group. The median follow-up time was 6.4 years (interquartile range, 2.2-10.9 years) and 21 patients died during follow-up, primarily from heart disease and infections. The 10-year survival rate after the first non-Raynaud's disease symptom was 80% and the cumulative incidence of muscle relapse was 25%. Neither factor differed significantly between the three groups. The risk of pulmonary events was lowest in the OM group, significantly lower than in the FM group (hazard ratio, 0.17; 95% CI, 0.04-0.67) and non-significantly lower than in the IMNM group (hazard ratio, 0.28; 95% CI, 0.06-1.24). The risk of cardiac events did not differ significantly between the three groups. CONCLUSION: The mortality rate of scleroderma patients with muscle involvement was not associated with their histological patterns.

Long-Term Follow-up After Ovariectomy Reveals Correlations Between Bone Marrow Adiposity and Trabecular Bone Quality in the Proximal Metaphysis of Tibiae in Rats.

This study aimed to evaluate the correlation between BMAT and bone quality, describe the long-term effects of ovariectomy on bone, and investigate BMAT's spatial distribution. Fifteen-months-old female Sprague‒Dawley rats were studied, comparing ovariectomized (OVX, n = 22) and sham-operated (SHAM, n = 11) groups at 6 months. Tibias were analyzed for bone microarchitecture, BMAT (microcomputed tomography), mineral parameters (quantitative backscattered electron imaging), and bone composition (Raman microspectroscopy). The OVX tibias showed severe trabecular bone loss (lower bone volume/total volume, p < 0.001) with increased BMAT (higher adipose volume per marrow volume, p < 0.001), decreased mineral content (lower calcium concentration, p < 0.001), and altered organic components (lower mineral/matrix ratio in new bone, p = 0.03 trabecular surface, p < 0.001 trabecular core). When the data are pooled over both groups (SHAM and OVX), the adipose volume/marrow volume ratio was negatively correlated with bone volume/total volume (r = - 0.79, p < 0.001) and mineral/matrix ratio (r = - 0.37, p = 0.04 trabecular surface; r = - 0.65, p < 0.001 trabecular core) and positively correlated with crystallinity (r = 0.55, p = 0.001 trabecular surface; r = 0.49, p = 0.006 trabecular core). The mineral/matrix ratio of trabecular surface new bone was strongly negatively correlated with the adipose compartment nearest to the bone surface. These findings suggest mechanisms underlying BMAT's role in bone resorption.

Intraoperative Mechanical Power and Postoperative Pulmonary Complications in Noncardiothoracic Elective Surgery Patients: A 10-Year Retrospective Cohort Study.

BACKGROUND: Postoperative pulmonary complications is a major issue that affects outcomes of surgical patients. The hypothesis was that the intraoperative ventilation parameters are associated with occurrence of postoperative pulmonary complications. METHODS: A single-center retrospective cohort study was conducted at the Lille University Hospital, France. The study included 33,701 adults undergoing noncardiac, nonthoracic elective surgery requiring general anesthesia with tracheal intubation between January 2010 and December 2019. Intraoperative ventilation parameters were compared between patients with and without one or more postoperative pulmonary complications (respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, and aspiration pneumonitis) within 7 days of surgery. RESULTS: Among 33,701 patients, 2,033 (6.0%) had one or more postoperative pulmonary complications. The lower tidal volume to predicted body weight ratio (odds ratio per -1 ml·kgPBW-1, 1.08; 95% CI, 1.02 to 1.14; P < 0.001), higher mechanical power (odds ratio per 4 J·min-1, 1.37; 95% CI, 1.26 to 1.49; P < 0.001), dynamic respiratory system compliance less than 30 ml·cm H2O (1.30; 95% CI, 1.15 to 1.46; P < 0.001), oxygen saturation measured by pulse oximetry less than 96% (odds ratio, 2.42; 95% CI, 1.97 to 2.96; P < 0.001), and lower end-tidal carbon dioxide (odds ratio per -3 mmHg, 1.06; 95% CI, 1.00 to 1.13; P = 0.023) were independently associated with postoperative pulmonary complications. Patients with postoperative pulmonary complications were more likely to be admitted to the intensive care unit (odds ratio, 12.5; 95% CI, 6.6 to 10.1; P < 0.001), had longer hospital length of stay (subhazard ratio, 0.43; 95% CI, 0.40 to 0.45), and higher in-hospital (subhazard ratio, 6.0; 95% CI, 4.1 to 9.0; P < 0.001) and 1-yr mortality (subhazard ratio, 2.65; 95% CI, 2.33 to 3.02; P < 0.001). CONCLUSIONS: In the study's population, decreased rather than increased tidal volume, decreased compliance, increased mechanical power, and decreased end-tidal carbon dioxide were independently associated with postoperative pulmonary complications.

Impact of primary endoscopic resection on oncological outcomes after esophagectomy for cancer: a retrospective propensity score-based cohort study.

BACKGROUND: Esophageal cancer posed significant global health challenges, particularly due to poor survival rates, especially in advanced stages. Primary endoscopic resection had emerged as an alternative treatment for early esophageal cancer, aiming to preserve organ function and reduce surgical morbidity. METHODS: This retrospective multicenter cohort study included 334 patients with early esophageal cancer (T1a-b, N0) from 30 French-speaking European centers between 2000 and 2010. Patients underwent either primary endoscopic resection followed by esophagectomy (E group, n = 36) or esophagectomy alone (S group, n = 298). Cox proportional hazards models adjusted for TNM stage and propensity score weighting were used to assess the impact of primary endoscopic resection on recurrence-free survival (RFS), overall survival (OS), and postoperative complications. RESULTS: Primary endoscopic resection did not significantly influence RFS (adjusted HR 0.92, 95% CI 0.31 to 2.68, p = 0.88) or OS (adjusted HR 1.06, 95% CI 0.35 to 3.13, p = 0.92) compared to esophagectomy alone. Initial higher thromboembolic complications in the endoscopic resection group were not significant after adjustment (adjusted OR 4.73, 95% CI 0.34 to 64.27, p = 0.24). CONCLUSIONS: Primary endoscopic resection followed by esophagectomy for early esophageal cancer did not alter oncological outcomes or overall survival in this retrospective cohort. These findings supported the role of primary endoscopic resection as a safe initial treatment strategy, warranting validation in larger prospective studies. REGISTRATION: Our study was registered retrospectively on the Clinicaltrials.com website under the identifier NCT01927016. We acknowledge the importance of prospective registration and regret that this was not done before the commencement of the study.

Can we predict the risk of esophageal stricture after caustic injury?

Nonoperative management of severe caustic injuries has demonstrated its feasibility, avoiding the need for emergency esogastric resection and resulting in low mortality rates. However, leaving superficial necrosis in place could increase the risk of esophageal stricture development. Data on the risk factors of esophageal stricture secondary to caustic ingestion are scarce. The aim of our study was to identify the risk factors for esophageal strictures after caustic ingestion at admission. From February 2015 to March 2021, all consecutive patients with esophageal or gastric caustic injury score ≥ II according to the Zargar classification were retrospectively analyzed. For each patient, we collected over 50 criteria at admission to the emergency room and then selected among them 20 criteria with the best clinical relevance and limited missing data for risk factor analyses. Among the 184 patients included in this study, 37 developed esophageal strictures (cumulative rate 29.4%). All esophageal strictures occurred within 3 months. In multivariate analyses, the risk factors for esophageal strictures were voluntary ingestion (cause-specific hazard ratio 5.92; 95% confidence interval 1.76-19.95, P = 0.004), Zargar's esophageal score ≥ III (cause-specific hazard ratio 14.30; 95% confidence interval 6.07-33.67, P < 0.001), and severe ear, nose, and throat lesions (cause-specific hazard ratio 2.15; 95% confidence interval 1.09-4.22, P = 0.027). Intentional ingestion, severe endoscopic grade, and severe ENT lesions were identified as risk factors for esophageal stricture following caustic ingestion. Preventive measures for this population require further evaluation.

Association of caffeine consumption with cerebrospinal fluid biomarkers in mild cognitive impairment and Alzheimer's disease: A BALTAZAR cohort study.

INTRODUCTION: We investigated the link between habitual caffeine intake with memory impairments and cerebrospinal fluid (CSF) biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. METHODS: MCI (N = 147) and AD (N = 116) patients of the Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk (BALTAZAR) cohort reported their caffeine intake at inclusion using a dedicated survey. Associations of caffeine consumption with memory impairments and CSF biomarkers (tau, p-tau181, amyloid beta 1-42 [Aß1-42], Aß1-40) were analyzed using logistic and analysis of covariance models. RESULTS: Adjusted on Apolipoprotein E (APOE ε4), age, sex, education level, and tobacco, lower caffeine consumption was associated with higher risk to be amnestic (OR: 2.49 [95% CI: 1.13 to 5.46]; p = 0.023) and lower CSF Aß1-42 (p = 0.047), Aß1-42/Aß1-40 (p = 0.040), and Aß1-42/p-tau181 (p = 0.020) in the whole cohort. DISCUSSION: Data support the beneficial effect of caffeine consumption to memory impairments and CSF amyloid markers in MCI and AD patients. HIGHLIGHTS: We studied the impact of caffeine consumption in the BALTAZAR cohort. Low caffeine intake is associated with higher risk of being amnestic in MCI/AD patients. Caffeine intake is associated with CSF biomarkers in AD patients.

Efficacy and management of tocilizumab in polymyalgia rheumatica: results of a multicenter retrospective observational study.

OBJECTIVES: The efficacy of anti-IL6 receptors such as Tocilizumab (TCZ) was demonstrated in patients with Polymyalgia Rheumatica (PMR) in two recent randomized controlled trials. The objective of this multicentre retrospective study was to assess the efficacy of TCZ in PMR patients requiring GC-sparing treatment, as well as different strategies for TCZ withdrawal. METHODS: We conducted a multicentre study in French tertiary health care departments for patients with PMR. PMR patients receiving off-label TCZ between 2015 and 2022 were included. The primary end point was the proportion of patients tapering to glucocorticoids (GCs) ≤5mg/day 6 months after the first TCZ infusion. The secondary endpoints were the proportion in whom GC was discontinued during follow-up, and the proportion of patients in whom TCZ was discontinued. RESULTS: Fifty-three PMR patients were included. Thirty-one (31) patients suffered from active PMR despite csDMARDs. GCs were ≤5mg/day in 77% of the patients (95% confidence interval [CI95%]: 36-89) at 6 months, and in 97% of the patients at 12 months. Six and 12 months after the first TCZ infusion, the proportions of GC-free patients were 22.5% (CI95%: 12.7-37.8) and 58.3% (CI95%: 43.2-74.1), respectively. Among TCZ withdrawal strategies, TCZ infusion spacing and TCZ dose reduction were more successful (success in 87% and 79% of attempts, respectively) than TCZ discontinuation (success in 52% of attempts; p= 0.012 and p= 0.039, respectively). CONCLUSION: In GC-dependent PMR patients, treatment with TCZ led to a drastic decrease in GC dose and remission of PMR. TCZ dose reduction or TCZ infusion spacing are good options to consider in TCZ withdrawal.

Complications of one-step button percutaneous endoscopic gastrostomy in children.

To assess the complications of one-step button percutaneous endoscopic gastrostomy (B-PEG) and determine risk factors for developing stomal infections or gastropexy complications. A retrospective study of 679 children who underwent a B-PEG procedure in a single tertiary care center over a 10-year period to December 2020 was conducted. Patient characteristics, early complications (occurring ≤ 7 days after the procedure), late complications (> 7 days after the procedure), and outcomes were collected from medical records. A list of potential risk factors, including age at procedure, prematurity, underlying neurological disease, and undernutrition, was determined a priori. At least 1 year of follow-up was available for 513 patients. Median follow-up duration was 2.8 years (interquartile range 1.0-4.9 years). Major complications were rare (< 2%), and no death was related to B-PEG. Early complications affected 15.9% of the study population, and 78.0% of children presented late complications. Development of granulation tissue was the most common complication followed in frequency by tube dislodgment and T-fastener complications. Only 24 patients (3.5%) presented stomal infections. Young age at the time of PEG placement (odds ratio (OR) 2.34 [1.03-5.30], p = .042) was a risk factor for developing peristomal infection. T-fastener migration occurred in 17.3% of children, and we found underlying neurological disease was a protective factor (OR 0.59 [0.37-0.92], p = .019).  Conclusion: B-PEG is a safe method and associated with a low rate of local infection. However, T-fasteners are associated with significant morbidity and require particular attention in young and premature infants. What is Known: • Percutaneous endoscopic gastrostomy (PEG) is the preferred method to provide long-term enteral nutrition in children to prevent malnutrition. The Pull-PEG method is still the most commonly used with complications , such as stomal infection. Since its description, only a few studies have reported postoperative complications of one-step button PEG (B-PEG). What is New: • T-fastener complications were not rare, and underlying neurologic disease was a protective factor. A very low rate of stomal infection was described, and young age at the time of PEG placement was a risk factor. The B-PEG is a safe method with fewer major complications than P-PEG in children.

Is the presence of antiphospholipid antibodies a poor prognostic factor for patients with hemolysis, elevated liver enzymes, and low platelet count syndrome?

BACKGROUND: The characteristics of antiphospholipid syndrome-associated hemolysis, elevated liver enzymes, and low platelet count syndrome are poorly described, likely because of the low frequency of this combination of syndromes. OBJECTIVE: This study aimed to compare the characteristics and prognosis of hemolysis, elevated liver enzymes, and low platelet count syndrome in patients with and without antiphospholipid syndrome. STUDY DESIGN: In this multicenter, case-control study, adult women diagnosed with hemolysis, elevated liver enzymes, and low platelet count syndrome before 34 weeks' gestation and who were also tested for antiphospholipid antibodies according to international diagnostic recommendations were included. Cases labeled "HELLP-APS+" were defined as patients who fulfilled the international classification criteria for antiphospholipid syndrome; they were retrospectively recruited by screening the 672 patients with antiphospholipid syndrome in our antiphospholipid syndrome database. Control cases labeled "HELLP-APS-" were defined as patients who did not fulfill the criteria for antiphospholipid syndrome; they were retrospectively recruited from our hospital admission database. RESULTS: Overall, 71 patients were included (mean age, 30±5 years), with 23 patients in the hemolysis, elevated liver enzymes, and low platelet count syndrome with antiphospholipid syndrome group and 48 patients in the hemolysis, elevated liver enzymes, and low platelet count syndrome without antiphospholipid syndrome group. The live birth rate was significantly lower for patients with hemolysis, elevated liver enzymes, and low platelet count with antiphospholipid syndrome than for those with hemolysis, elevated liver enzymes, and low platelet count syndrome without antiphospholipid syndrome (43.5% vs 89.4%; P<.001). The patients with hemolysis, elevated liver enzymes, and low platelet count syndrome with antiphospholipid syndrome gave birth prematurely more often than the patients without antiphospholipid syndrome (24 weeks' gestation; 22.0-28.0 weeks vs 30 weeks' gestation; 27.0-33.0 weeks; P<.001). Among the patients with hemolysis, elevated liver enzymes, and low platelet count syndrome with antiphospholipid syndrome, 39% required an induced abortion owing to hemolysis, elevated liver enzymes, and low platelet count syndrome severity vs 8.5% of the patients with hemolysis, elevated liver enzymes, and low platelet count syndrome without antiphospholipid syndrome (P=.006). The intensive care unit admission rate was 61.9% in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome with antiphospholipid syndrome, which was significantly higher than the rate of 27.7% in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome without antiphospholipid syndrome (P=.007). None of the mothers died. CONCLUSION: Our results suggest that the presence of antiphospholipid syndrome is a poor prognostic factor for both the mother and fetus in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome.

Randomized controlled open-label trial to evaluate prioritization software for the secondary triage of patients in the pediatric emergency department.

BACKGROUND: The continual increase in patient attendance at the emergency department (ED) is a worldwide health issue. The aim of this study was to determine whether the use of a secondary prioritization software reduces the patients' median length of stay (LOS) in the pediatric ED. METHODS: A randomized, controlled, open-label trial was conducted over a 30-day period between March 15th and April 23rd 2021 at Lille University Hospital. Work days were randomized to use the patient prioritization software or the pediatric ED's standard dashboard. All time intervals between admission and discharge were recorded prospectively by a physician not involved in patient care during the study period. The study's primary endpoint was the LOS in the pediatric ED, which was expected to be 15 min shorter in the intervention group than in the control group. The secondary endpoints were specific time intervals during the stay in the pediatric ED and levels of staff satisfaction. RESULTS: 1599 patients were included: 798 in the intervention group and 801 in the control group. The median [interquartile range] LOS was 172 min [113-255] in the intervention group and 167 min [108-254) in the control group (p = 0.46). In the intervention group, the time interval between admission to the first medical evaluation for high-priority patients and the time interval between the senior physician's final evaluation and patient discharge were shorter (p < 0.01). The median satisfaction score was 68 [55-80] (average). CONCLUSION: The patients' total LOS was not significantly shorter on days of intervention. However, use of the electronic patient prioritization tool was associated with significant decreases in some important time intervals during care in the pediatric ED. CLINICALTRIALS: gov: NCT05994196 Trial registration number: NCT05994196. Date of registration: August 16th, 2023.

Characteristics of difficult-to-treat axial spondyloarthritis: Results of a real-world multicentric study.

OBJECTIVE: The EULAR task force recently published the difficult-to-treat RA (D2T RA) definition, however, a definition of D2T axSpA is still lacking and limitations in this definition exist. The objectives were to study the characteristics of D2T axSpA patients using the EULAR definition and to study a subgroup of patients with a predefined more stringent definition including a temporal criterion. METHODS: A multicentric retrospective study was performed. D2T axSpA was defined as failure of≥2 b/tsDMARDs with different mechanism of action. Very D2T axSpA was defined as failure of≥2 b/tsDMARDs in less than 2 years of follow-up. D2T and Very D2T axSpA patients were compared to non-D2T (nD2T) axSpA patients. RESULTS: Three hundred and eleven axSpA patients were included: 88 D2T axSpA (28.3%) and 223 non-D2T (nD2T) axSpA (71.7%). Peripheral involvement was more prevalent in the D2T group (34.9 vs. 21.4%; P=0.015). BASDAI level at baseline was higher in the D2T group (63.7±16.5 vs. 58.8±14.7; P=0.015). Fibromyalgia was found to be more frequent in the D2T group vs nD2T group (P<0.001). Twelve patients (3.8%) were categorized as very D2T axSpA. Compared to nD2T, Very D2T patients had a higher CRP level at baseline (42.0±31.3 vs. 17.8±23.1; P=0.010). IBD prevalence at baseline was higher in the very D2T group (41.7 vs. 3.1%; P<0.001). None of the very D2T patients presented a fibromyalgia. CONCLUSION: D2T axSpA was associated with higher disease activity, peripheral involvement, extra-musculoskeletal manifestations and fibromyalgia. Very D2T patients represented a minim proportion of patients after applying a more stringent definition including a temporal criterion of 2 years and might be independent from fibromyalgia.

Nutritional and physical fitness parameters in adolescence impact cardiovascular health in adulthood.

BACKGROUND & AIMS: Cardiovascular diseases are the leading cause of mortality worldwide, originating in the first decades of life. A better understanding of their early determinants would allow for better prevention. This study aimed to evaluate the impact of nutritional and activity-related characteristics during adolescence on young adult cardiovascular risk factors. METHODS: The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study included adolescents (aged 12.5-17.5 years) in 10 European centres. Four centres designed a nested cohort including 236 participants who were reassessed as young adults (21-32 years). Food consumption was evaluated by dietary recalls, physical activity by accelerometers, physical fitness using physical tests and nutritional knowledge by questionnaires. Cardiovascular health was assessed by Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study risk scores and its components. Factors associated with cardiovascular risk were identified using a multivariable regression model. RESULTS: Higher Diet Quality Index (DQI, P = 0.012) and nutritional knowledge (P = 0.015) were significantly associated with lower modified PDAY risk scores. Ultra-processed foods were associated with a lower non-high-density lipoprotein (non-HDL) cholesterol (P = 0.003), whereas DQI (P = 0.014) and Planetary Health Diet Index (P = 0.016) were associated with a higher HDL cholesterol. Higher DQI was also related to a lower body mass index (BMI, P = 0.006). In addition, cardiorespiratory fitness was related to a lower BMI (P = 0.004). CONCLUSIONS: Nutritional knowledge, diet quality and adherence to a sustainable diet in adolescence decrease cardiovascular risk in adulthood, whereas ultra-processed food consumption increases risk. These factors appear as targeted prevention tools for promoting a healthier adolescent lifestyle to decrease long-term cardiovascular risk. CLINICAL TRIAL REGISTRY NUMBER: Clinicaltrials.gov NCT02899416.

The impact of cirrhosis on short and long postoperative outcomes after distal pancreatectomy.

BACKGROUND: The impact of cirrhosis on the postoperative outcomes of distal pancreatectomy is yet to be reported. We aimed to evaluate the outcomes of distal pancreatectomy in patients with cirrhosis. METHODS: We conducted a retrospective, multicentric study patients with cirrhosis who underwent planned distal pancreatectomy between 2008 and 2020 in French high volume centers. Patients with cirrhosis were matched 1:4 for demographic, surgical, and histologic criteria with patients without cirrhosis. The primary endpoint was severe morbidity (Clavien-Dindo grade ≥III). The secondary endpoints were postoperative complications, specifically related to cirrhosis and pancreatic surgery, and survival for patients with pancreatic adenocarcinoma. RESULTS: Overall, 32 patients with cirrhosis were matched with 128 patients without cirrhosis. Most patients (93.5%) had Child-Pugh A cirrhosis. The severe morbidity rate after distal pancreatectomy was higher in patients with cirrhosis than in those without cirrhosis (28.13% vs 25.75%, P = .11. The operative time was significantly longer in the cirrhotic group compared with controls (P = .01). However, patients with and without cirrhosis had comparable blood loss and conversion rates. Postoperatively, the two groups had similar rates of pancreatic fistula, hemorrhage, reoperation, postoperative mortality, and survival rates at 1, 3, and 5 years. CONCLUSION: The current study suggests that distal pancreatectomy in high-volume centers is feasible for patients with compensated cirrhosis.

Genomic profiling of mycosis fungoides identifies patients at high risk of disease progression.

ABSTRACT: Mycosis fungoides (MF) is the most prevalent primary cutaneous T-cell lymphoma, with an indolent or aggressive course and poor survival. The pathogenesis of MF remains unclear, and prognostic factors in the early stages are not well established. Here, we characterized the most recurrent genomic alterations using whole-exome sequencing of 67 samples from 48 patients from Lille University Hospital (France), including 18 sequential samples drawn across stages of the malignancy. Genomic data were analyzed on the Broad Institute's Terra bioinformatics platform. We found that gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), or mutations in JUNB and TET2 are associated with high-risk disease stages. Furthermore, gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), and del6q16.3 (TNFAIP3) are coupled with shorter survival. Del6q16.3 (TNFAIP3) was a risk factor for progression in patients at low risk. By analyzing the clonal heterogeneity and the clonal evolution of the cohort, we defined different phylogenetic pathways of the disease with acquisition of JUNB, gain10p15.1 (IL2RA and IL15RA), or del12p13.1 (CDKN1B) at progression. These results establish the genomics and clonality of MF and identify potential patients at risk of progression, independent of their clinical stage.

Nociception level response to calibrated stimulations in children: First assessment of the nociception level index in pediatric anesthesia.

INTRODUCTION: Intraoperative monitoring of nociception has made great progress in adult anesthesia. However, pediatric data are scarce. The Nociception Level (NOL) is one of the most recent indexes of nociception. Its originality is that it provides a multiparametric assessment of nociception. In adults, NOL monitoring allowed lower perioperative opioid requirements, hemodynamic stability, and qualitative postoperative analgesia. So far, the NOL has never been used in children. Our objective was to validate the ability of NOL to provide a quantitative assessment of nociception in anesthetized children. METHODS: In 5-12 years old children anesthetized with sevoflurane and alfentanil (10 µg kg-1), before surgical incision, we performed three standardized tetanic stimulations (5 s, 100 Hz) of different intensities (10-30-60 mA) in a randomized order. NOL, heart rate, blood pressure and Analgesia-Nociception Index variations were assessed after each stimulation. RESULTS: Thirty children were included. Data were analyzed with a covariance pattern linear mixed regression model. NOL increased after the stimulations (p < 0.05 at each intensity). NOL response was influenced by stimulation intensity (p < 0.001). Heart rate and blood pressure were barely modified by the stimulations. Analgesia-Nociception Index decreased after the stimulations (p < 0.001 at each intensity). Analgesia-Nociception index response was not influenced by stimulation intensity (p = 0.064). NOL and Analgesia-Nociception Index responses were significantly correlated (Pearson r = 0.47; p < 0.001). CONCLUSIONS: NOL allows a quantitative assessment of nociception under anesthesia in 5-12 years-old children. This study provides a solid basis for all future investigations on NOL monitoring in pediatric anesthesia. REGISTRATION: NCT05233449.

Breech presentation induction compared to cephalic presentation: Effectiveness and characteristics.

INTRODUCTION: The objective of our study was to compare the effectiveness of induction in cephalic presentations to that of breech presentations as well as the characteristics of the latter and the maternal-fetal morbidity and mortality. MATERIAL AND METHODS: This was a single-center retrospective study carried out at the Lille University Hospital in the Jeanne de Flandre Maternity Hospital including all patients with a breech fetus for whom an induction was indicated beyond 37 weeks of gestation between January 2014 and December 2020. A matching was performed to include 2 cephalic presentations for one breech presentation. The primary outcome was successful induction defined by two things: passage into the active phase (cervical dilatation > 5 cm) and vaginal delivery. RESULTS: 101 inductions of breech presentations were included and matched to 202 cephalic presentations. After adjustment by BISHOP score, there was no significant difference in the caesarean section rate between the two groups (25.7% in cephalic vs 33.7% in breech, OR 0.67 [CI95% 0.38-1.18]) or in the rate of transition to active phase (80.7% in cephalic vs 82.2% in breech, OR 1.26 [CI95% 0.65-2.44]). Post-partum blood loss was not significantly different between the two groups (14.4% in cephalic vs 12.9% in breech, OR 1.22 [CI95% 0.57-2.57]). Moderate neonatal acidosis was more frequent in the breech group (6,4% in cephalic vs 15,8% in breech, OR 3.04 [CI95% 1.38-6.71]). CONCLUSION: Induction of breech births beyond 37 weeks of gestation appeared to be as effective as induction of cephalic presentations. There was no difference in the rate of caesarean section and transition to active labor. Maternal morbidity was not increased.

Hip resurfacing for small-sized osteonecrosis: 73 cases at a median 8years' follow-up.

INTRODUCTION: Total hip resurfacing arthroplasty (THRA) is an alternative to conventional total hip replacement (THR) in young patients with osteonecrosis of the femoral head. Series have been small, without criteria regarding extent of necrosis, thus vitiating results. We therefore conducted a retrospective assessment of THRA for small necrosis, to determine (1) implant survival, (2) functional scores, and (3) systemic chromium, cobalt and titanium ion concentrations. HYPOTHESIS: The study hypothesis was that the revision rate is low, meeting the National Institute for Health and Care Excellence (NICE) criterion of<0.5% revision per year. MATERIAL AND METHOD: A single-center single-surgeon retrospective study included 62 patients, for 73 RTHAs, with a mean age of 45.6years (range: 23-68years) presenting Ficat stage 3 or 4 osteonecrosis of the femoral head with<330° total Kerboul angle (frontal+lateral angles) on simple preoperative X-ray. Study data comprised implant survival and preoperative and last follow-up functional scores (Postel-Merle-d'Aubigné, Oxford-12, Harris, and Devane) and titanium, chromium and cobalt blood concentrations. Necrosis size was assessed on preoperative Kerboul angle. RESULTS: At a median 8years' follow-up (IQR: 5.9-9.3years), implant survival was 98.6% (95% CI: 97.22-99.98%). Only 1 implant was exchanged, for femoral loosening. Three other patients underwent revision surgery: 2 cases of lavage for infection, and 1 muscle hernia repair. Postel-Merle-d'Aubigné, Oxford-12 and Harris functional scores and Devane activity scores were significantly improved at follow-up, by a median +5 (IQR: 5 to 7), -26 (IQR: -29 to -23), +55 (IQR: 49 to 61) and +1 (IQR: 1 to 2), respectively (all p<0.001). Ion concentrations at last follow-up for titanium, chromium and cobalt were respectively 4.0µg/L (range: 3.6-4.1), 1.1µg/L (range: 0.8-1.9) and 1.1µg/L (range: 0.6-1.8). CONCLUSION: THRA is a useful option in the long-term for young patients with osteonecrosis with Kerboul angle<330°. LEVEL OF EVIDENCE: IV, retrospective study.