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.

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.

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.

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.

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.

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.

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.

Characteristics Of Difficult-To-Treat Psoriatic Arthritis: A Comparative Analysis.

OBJECTIVE: The EULAR task force recently published the difficult-to-treat rheumatoid arthritis (D2T RA) criteria, however, a definition of D2T patients in psoriatic arthritis (PsA) is still lacking. To date, we have little data concerning D2T PsA, especially in real-world. One of the limitations of the D2T RA EULAR definition is the absence of a temporal criterion. The primary endpoint of this work was to study the characteristics of D2T PsA patients using the EULAR definition. The second objective was to study a sub-group of patients with a predefined more stringent definition including a temporal criterion. METHODS: A retrospective study was performed in a tertiary center. D2T PsA was defined as failure of ≥ 2 b/tsDMARDs with different mechanism of action. Very D2T PsA was defined as failure of ≥ 2 b/tsDMARDs in less than 2 years of follow-up. D2T and Very D2T PsA patients were compared to nD2T PsA patients using statistical tests. RESULTS: 150 PsA patients were included (from 2004 to 2015): 49 D2T PsA and 101 nD2T PsA. D2T PsA was associated with a higher prevalence of axial involvement (p=0.030), axial and/or peripheral structural damage (p=0.007) at baseline and more bDMARDs discontinuation due to poor dermatological control (p=0.005). There was no significant difference regarding comorbidities such as obesity, smoking status, fibromyalgia or depression. In multivariate analysis, peripheral structural damage at baseline was found to be a predictive factor for D2T PsA with an OR of 2.57 (1.16 to 5.69; p=0.020). 17 PsA (11.3%) patients were categorized as Very D2T PsA. When compared to nD2T group, proportion of obesity was higher (p=0.015) and axial involvement was more prevalent in the Very D2T group (p=0.020). CONCLUSION: D2T PsA patients had a higher prevalence of axial involvement, peripheral structural damage and therapeutic discontinuation due to poor dermatological control whereas Very D2T PsA patients were more likely obese with axial involvement. Very D2T PsA represent a minim proportion among patients when applying a more stringent definition. Pending the PsA D2T definition by the European and American societies, this study highlights some characteristics that may help practitioners better identify D2T patients.

Association of Organizational Pathways With the Delay of Emergency Surgery.

Importance: Delayed admission of patients with surgical emergencies to the operating room occurs frequently and is associated with poor outcomes. In France, where 3 distinct organizational pathways in hospitals exist (a dedicated emergency operating room and team [DET], a dedicated operating room in a central operating theater [DOR], and no dedicated structure or team [NOR]), neither the incidence nor the influence of delayed urgent surgery is known, and no guidelines are available to date. Objective: To examine the overall frequency of delayed admission of patients with surgical emergencies to the operating room across the 3 organizational pathways in hospitals in France. Design, Setting, and Participants: This prospective multicenter cohort study was conducted in 10 French tertiary hospitals. All consecutive adult patients admitted for emergency surgery from October 5 to 16, 2020, were included and prospectively monitored. Patients requiring pediatric surgery, obstetrics, interventional radiology, or endoscopic procedures were excluded. Exposures: Emergency surgery. Main Outcomes and Measures: The main outcome was the global incidence of delayed emergency surgery across 3 predefined organizational pathways: DET, DOR, and NOR. The ratio between the actual time to surgery (observed duration between surgical indication and incision) and the ideal time to surgery (predefined optimal duration between surgical indication and incision according to the Non-Elective Surgery Triage classification) was calculated for each patient. Surgery was considered delayed when this ratio was greater than 1. Results: A total of 1149 patients were included (mean [SD] age, 55 [21] years; 685 [59.9%] males): 649 in the DET group, 320 in the DOR group, and 171 in the NOR group (missing data: n = 5). The global frequency of surgical delay was 32.5% (95% CI, 29.8%-35.3%) and varied across the 3 organizational pathways: DET, 28.4% (95% CI, 24.8%-31.9%); DOR, 32.2% (95% CI, 27.0%-37.4%); and NOR, 49.1% (95% CI, 41.6%-56.7%) (P < .001). The adjusted odds ratio for delay was 1.80 (95% CI, 1.17-2.78) when comparing NOR with DET. Conclusions and Relevance: In this cohort study, the frequency of delayed emergency surgery in France was 32.5%. Reduced delays were found in organizational pathways that included dedicated theaters and teams. These preliminary results may pave the way for comprehensive large-scale studies, from which results may potentially inform new guidelines for quicker and safer access to emergency surgery.

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.