Endovascular Treatment of Abdominal Aortic Aneurysm: Impact of Diabetes on Endoleaks and Reintervention.

Background: Diabetes has a protective effect on abdominal aortic aneurysms (AAAs); however, there are contrasting reports on the impact of diabetes on endovascular aortic repair (EVAR) outcomes, endoleaks (ELs) being the major negative outcome. The present study characterizes ELs and their outcomes in AAA patients, diabetic or not. Methods: This single-center, retrospective, comparative study was carried out on 324 AAA patients who underwent elective EVARs between 2007 and 2016 at the University Hospital of Liège (Belgium). The primary endpoint was the incidence and effect of ELs on the evolution of the aneurysmal sac; the secondary endpoints were surgical reintervention and mortality rate. Diabetic and non-diabetic patients were compared with respect to various risk factors by logistic regression, while a Cox regression was used to analyze survival. Results: In AAA patients meeting the inclusion criteria (n = 248), 23% were diabetic. EL incidence was comparable (p = 0.74) in diabetic (38.7%) vs. non-diabetic (43.9%) patients. EL risk factors were age (HR = 1.04, p = 0.014) and fibrate intake (HR = 3.12, p = 0.043). A significant association was observed between ELs and aneurysm sac enlargement (p < 0.001), regardless of group (p = 0.46). Aneurysm sac regression per month for non-diabetic patients was -0.24 ± 0.013, while for diabetics it was -0.18 ± 0.027 (p = 0.059). Dyslipidemia (HR = 3.01, p = 0.0060) and sulfonylureas (HR = 8.43, p = 0.043) were associated with shorter EL duration, while diabetes (HR = 0.080, p = 0.038) and beta blockers (HR = 0.46, p = 0.036) were associated with longer EL duration. The likelihood of reoperation decreased with more recent surgery (OR = 0.90, p = 0.040), regardless of diabetic status. All-cause mortality was higher for the non-diabetic group (45.5% vs. 26.3%, p = 0.0096). Conclusions: Endoleak occurrence is a known risk factor for sac expansion. In diabetic patients, endoleaks lasted longer, and regression of the aneurysm sac tended to be slower. The number and type of reintervention was not related to the diabetic status of AAA patients, but overall survival was higher in patients with diabetes.

Gestational weight gain: Toward best practices in managing gestational weight gain in patients with obesity: Comparison of recommendations.

BACKGROUND AND AIMS: In 2009, the Institute of Medicine (IOM) issued recommendations for gestational weight gain (GWG) based on body mass index (BMI). Several studies have challenged those recommendations for women with obesity, considering them too liberal and advising more limited weight gain - or even weight loss - during pregnancy to improve maternal and neonatal outcomes. Our aim was to study how gestational weight gain in women with obesity impacted maternal and fetal complications in the Belgian population. We did this by comparing the results from two groups of patients with obesity: those who met the 2009 IOM standards and those who satisfied the stricter recommendations suggested by other authors. MATERIALS AND METHODS: This is a retrospective cohort study using data collected at the Centre d'Epidémiologie Périnatale (CEpiP) from obese (BMI ≥ 30 kg/m2) pregnant women with live singleton deliveries between 2010 and 2019 in Wallonia-Brussels Federation (n = 65,314). RESULTS: Compared to obese patients whose GWG satisfied the IOM standards, those with GWG meeting the stricter recommendations had lower rates of gestational hypertension (7.1 % vs. 10.1 %; p = 0.0059), cesarean section (22.1 % vs. 26.3 %; p = 0.0074), and macrosomia (12.0 % vs. 17.7 %; p < 0.0001). There was no significant difference in the rate of preterm delivery (6.9 % vs 5.8 %; p = 0.12) or small-for-gestational-age births (7.2 % vs. 6.2 %; p = 0.16). CONCLUSION: Gestational weight gain below that currently recommended by the IOM appears beneficial to the health of mothers with obesity and their children. These data, from our population, further challenge the standards proposed since 2009.

Optical imaging (HandScan) can identify ultrasound remission in rheumatoid arthritis.

BACKGROUND: Identifying remission is of high importance in rheumatoid arthritis (RA) because remission is associated with less structural progression. We investigated the efficacy of a new optical imaging device, HandScan, to identify RA remission, as defined by ultrasound (US). METHODS: 61 RA patients were included. Disease activity was evaluated by clinical assessment and US, using gray-scale (GS) and Power Doppler (PD). HandScan determined unitary optical spectral transmission (OST) values for wrists, metacarpophalangeal and proximal interphalangeal joints. At the patient level, three composite HandScan (HS) scores were calculated: total HS score; disease activity score OST (DAS-OST) and DAS-OST without patient global assessment (PtGA). Using ROC curves, we determined HS cut-offs to identify US-defined remission. RESULTS: At the joint level, unitary OST values significantly correlated with GS synovitis [odds ratio (OR) 2.43, p < 0.0001] and PD positivity (OR 3.72, p = 0.0002 ). At the patient level, total HS score and DAS-OST were significantly associated with all gray-scale US (GSUS) and power doppler US (PDUS) parameters evaluated (synovitis number and grade, synovial thickness, PD grade) (p < 0.05). The cut-off to identify US-defined remission at the joint level was of 0.92, giving an 81% sensitivity and a 96% positive predictive value (PPV). At the patient level, ROC-curves failed to identify a robust cut-off for the total HS score, but did identify a cut-off (3.68) for DAS-OST to identify US-defined remission, but with lower sensitivity (75%), specificity (56%) and PPV (67%). CONCLUSIONS: HandScan is a non-invasive optical imaging technique providing OST values that correlate with GSUS and PDUS parameters. In addition, HandScan is able to reliably identify US-defined remission in RA at the joint level, with a good sensitivity and high PPV. At the patient level, HandScan DAS-OST can also determine US remission (while total HS score failed to do so), but with lower performance.

Matrix gla protein, a potential marker of tissue remodelling and physiological ageing of the gut in crohn's disease.

BACKGROUND: The inactive dephosphorylated and uncarboxylated form of the matrix Gla protein (dp-ucMGP) has been shown to be increased in plasma of inflammatory bowel disease (IBD) patients. Our aim was to assess if the plasmatic level of dp-ucMGP could reflect disease endoscopic activity, presence of strictures and cumulative structural bowel damage in Crohn's disease (CD) patients. METHODS: The plasmatic level of dp-ucMGP was measured in a monocentric cohort of prospectively recruited patients. The analysis was done by chemiluminescent immunoassay on blood samples collected the day of a planned ileocolonoscopy. In addition to classical clinical data (gender, age, body mass index (BMI), disease duration, current treatment), endoscopic data (disease location, Crohn's Disease Endoscopic Index of Severity (CDEIS), mucosal healing (MH), presence of 9 CD lesion types) and biological markers (faecal calprotectin and C-reactive protein (CRP)) were collected. The association between dp-ucMGP level and Lémann index was also investigated. Univariate linear regression was used to investigate the relationship between dp-ucMGP level and different parameters collected. RESULTS: A total of 82 ileocolonoscopies and dp-ucMGP assays were performed in 75 CD patients (45 females; 37 ileocolonic, 19 ileal and 19 colonic diseases) between October 2012 and November 2019. A total of 24 patients (29.3%) showed MH. The dp-ucMGP levels were not associated with MH, CDEIS, faecal calprotectin or CRP levels. Plasmatic dp-ucMGP levels increased significantly with age (p = 0.0032), disease duration (p = 0.0033), corticosteroids use (p = 0.019) and tended to increase in patients with intestinal strictures (p = 0.086) but not with the Lémann index. CONCLUSION: The significant increase of plasmatic dp-ucMGP levels with age, disease duration and the trend observed in patients with non-ulcerated strictures may suggest that this extracellular matrix protein could be a marker of tissue remodelling and physiological ageing of the gut.

Histological healing induced by tofacitinib in ulcerative colitis: A multicentre study.

BACKGROUND: While the efficacy of tofacitinib to induce and maintain clinical and endoscopic remission is well established in ulcerative colitis (UC), little is known about its efficacy to induce histological remission. METHODS: We conducted a retrospective multicentric cohort study. UC patients ≥ 16 years treated by tofacitinib in whom histological activity has been evaluated before and after induction were eligible. The primary endpoint was the histological remission at the end of induction, assessed by the Nancy index and the epithelial neutrophilic infiltrate. RESULTS: A total of 42 patients with UC (93% previously exposed to an anti-TNF and 81% to vedolizumab) were included between July 2018 and April 2022 and were followed for a median duration of 84 weeks [IQR, 35-134]. At the end of induction period (whether prolonged or not), 19% and 24% of patients achieved histological remission, using the Nancy index and the epithelial neutrophilic infiltrate, respectively. Survival without tofacitinib discontinuation was significantly longer in patients without epithelial neutrophilic infiltrate at the end of induction (whether prolonged or not) compared with patients with epithelial neutrophilic infiltrate (p = 0.036). CONCLUSION: Tofacitinib induced histological remission in one fifth to one quarter of patients with UC who have previously failed anti-TNF or/and vedolizumab after induction (whether prolonged or not).

Standardized 4-point scoring scale of [18F]-FDG PET/CT imaging helps in the diagnosis of renal and hepatic cyst infections in patients with autosomal dominant polycystic kidney disease: a validation cohort.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is prone to multiple complications, including cyst infection (CyI). 2-Deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography ([18F]-FDG PET/CT) imaging has proved useful in the diagnosis of renal and hepatic CyI. A 4-point scale comparing the uptake of [18F]-FDG in the suspected infected cyst versus the hepatic physiological background has been recently proposed. We performed an independent validation of this semi-quantitative scoring system. Methods: All ADPKD patients hospitalized between January 2009 and November 2019 who underwent an [18F]-FDG PET/CT for suspected CyI were retrospectively identified using computer-based databases. Medical files were reviewed. CyI was conventionally defined by the combination of fever (≥38°C), abdominal pain, increased plasma C-reactive protein levels (≥70 mg/L), absence of any other cause of inflammation and favourable outcome after ≥21 days of antibiotics. [18F]-FDG uptake of the suspected CyI was evaluated using a 4-point scale comparing the uptake of [18F]-FDG around the infected cysts with the uptake in the hepatic parenchyma. Statistics were performed using SAS version 9.4. Results: Fifty-one [18F]-FDG PET/CT scans in 51 patients were included, of which 11 were cases of CyI. The agreement between the 4-point scale and the gold-standard criteria of CyI was significant [odds ratio of 6.03 for CyI in case of a score ≥3 (P = .014)]. The corresponding sensitivity, specificity, and positive and negative predictive values of [18F]-FDG PET/CT using the 4-point scale were 64% [Clopper-Pearson 95% confidence interval (CI) 30%-89%], 78% (95% CI 62%-89%), 44% (95% CI 20%-70%) and 89% (95% CI 73%-97%), respectively. Conclusions: Our independent validation cohort confirms the use of a semi-quantitative 4-point scoring system of [18F]-FDG PET/CT imaging in the diagnosis of CyI in patients with ADPKD. Considering its performance metrics with high specificity and negative predictive value, the scoring system is particularly useful to distinguish other causes of clinical inflammation than CyI and as such avoid unnecessarily long antibiotic treatment.

The antihyperlipidemic effect of a combined supplement of standardized dry extracts of amla (Emblica officinalis), walnut (Juglans regia), olive (Olea europaea) and red yeast rice (Monascus purpureus) powder: Reduction in circulatory low-density lipoprotein-cholesterol (LDL-C) and remnant cholesterol (RC) levels in patients with hypercholesterolemia.

Background: Hyperlipidemia is associated with a higher rate of cardiovascular, cerebrovascular, and peripheral vascular disease. Conventional drugs such as statins are effective in controlling hyperlipidemia; however, they are associated with various side effects, especially myalgia. Nutraceutical lipid-lowering interventions are becoming increasingly popular, particularly among patients who are intolerant or refractory to statins. Substantial preclinical and clinical evidence suggests that extracts of amla, walnut, and olive, and red yeast rice (RYR) powder possess significant antihyperlipidemic effects. Aims: This study aimed to evaluate the efficacy, safety, and patient satisfaction of a combined supplementation of standardized dry extracts of amla fruit (500 mg), walnut leaves (50 mg), olive fruit (25 mg), and RYR powder (33.6 mg) (Cholesfytol NG®) in hypercholesterolemic patients. Methods: This was a real-life setting, retrospective, observational, single-arm, non-randomized study in hypercholesterolemic patients (total cholesterol (TC) ≥ 200 mg/dL or low-density lipoprotein-cholesterol (LDL-C) ≥ 130 mg/dL), enrolled at 57 general practitioner (GP) surgeries in Belgium from March 2020 to January 2022. These patients received a GP-prescribed daily single dosage of two oral tablets of Cholesfytol NG® supplementation for 2 months to overcome their hypercholesterolemia in the absence of a conventional lipid-lowering drug (n = 208) or with a lipid-lowering drug (n = 13). At 2-month follow-up, the lipid profile was re-evaluated, alongside a patient's questionnaire on treatment general satisfaction and willingness to pursue supplementation. Results: After supplementation, TC decreased by 15%, LDL-C by 19%, non-high-density lipoprotein-cholesterol (non-HDL-C) by 20% (all p < 0.0001), triglycerides (TG) by 9% (p = 0.0028) (-18.4%, p = 0.0042, in patients with baseline TG > 180 mg/dL, n = 58), and remnant cholesterol (RC) by 12% (p = 0.0001). These changes were unaffected by statin intolerance status in patients who received Cholesfytol NG® alongside statin. The supplement was well tolerated by all patients, and no serious adverse events or supplement-emergent effects were reported. Most patients were satisfied with the supplementation and wanted to pursue the nutraceutical. Conclusion: According to the results of this study, a combined supplementation of amla, walnut, and olive extracts, and RYR powder exerts a significant antihyperlipidemic effect, leading to a decrease in circulatory LDL-C and RC levels in patients with hypercholesterolemia. The supplementation bears excellent safety and tolerability, and is rated as satisfactory and pursuable, even among patients with statin intolerance. Clinical Trial Registration: clinicaltrials.gov; identifier number: NCT06002893.

The Effects of Direct Polymethyl Methacrylate and Zirconia-on-Ti-Base Abutments on Peri-implant Soft Tissue Integration: A Study in Minipigs.

PURPOSE: To assess two types of abutment materials routinely used in daily practice-direct polymethyl methacrylate (PMMA) and a zirconia-on-Ti-base abutment-and their effects on peri-implant soft tissues and bone remodeling in a minipig model. MATERIALS AND METHODS: A total of 40 implants were placed in five minipigs in a single-stage surgery. Four different types of abutment materials (n = 10 per group) were used: (1) titanium (control); (2) zirconia (control); (3) PMMA (test 1); and (4) Ti-base (zirconia bonded to a titanium framework; test 2). After 3 months of healing, the samples were collected and subjected to nondecalcified histology. The soft tissue dimensions (sulcus, junctional epithelium, and connective tissue attachment) were assessed on each abutment mesially and distally, and the distance from the implant margin to the first bone-to-implant contact (BIC) was measured. RESULTS: No statistically significant differences were found among the four groups regarding soft tissue dimensions (P = .21), and a long junctional epithelium (mean: 4.1 mm) and a short connective tissue attachment (mean: 0.3 mm) were found in the majority of abutments. In some samples, the junctional epithelium extended all the way to the bone level. The measured peri-implant bone remodeling was similar in all four groups (P = .25). CONCLUSIONS: The present findings indicate that both direct PMMA and zirconia-on-Ti-base abutments seem to allow soft tissue integration similar to that of titanium and zirconia abutments. However, clinical studies are warranted to either confirm or refute the observed findings and to further investigate the influence of different materials on mucointegration.

Impact of Assisted Reproduction Techniques on Adverse Maternal Outcomes and on the Rate of Hospitalization in Maternal Intensive Care.

Background and Objective: The aim of this retrospective cohort study is to evaluate the impact of assisted reproductive treatment (ART) on adverse maternal outcomes and the rate of hospitalization in maternal intensive care (MIC) in a tertiary university center in Liege, Belgium. Materials and Methods: This is a retrospective cohort study comparing two groups, 6557 patients who achieved pregnancy spontaneously and 330 patients who achieved pregnancy after ART, between January 2020 and December 2022. These patients were followed in the academic obstetrics department of Citadelle Hospital, Liège. The database of the ART center was compared with the database of the delivery unit to determine the cohort of patients who conceived after ART. Adverse maternal outcomes and MIC hospitalization rates were compared with between spontaneous pregnancies and ART groups. ART groups were also compared with each other. Results: The rate of hospitalization in maternal intensive care for patients who achieved pregnancy spontaneously was 12.1%, compared to 17.3% after ART. Comparing the rate of pre-eclampsia, 3.5% of spontaneous pregnancies were complicated by pre-eclampsia, while after ART, 10.9% of patients developed this complication during pregnancy. This rate was higher after IVF (12%) compared to intrauterine insemination and particularly after frozen embryo transfer (FET) in artificial cycle (17.9%). The birthweight of newborns after ART was also analyzed. A significant difference was obtained when comparing fresh embryo transfer with FET. Conclusions: Our study confirmed that FET in artificial cycle is a risk factor for pre-eclampsia and that fresh embryo transfer is associated with a higher rate of newborns with a lower percentile of birthweight. Our data showed that the rate of MIC hospitalization was significantly higher after ART but did not differ between groups.

Benralizumab in severe eosinophilic asthma in real life: confirmed effectiveness and contrasted effect on sputum eosinophilia versus exhaled nitric oxide fraction - PROMISE.

Background: Randomised controlled trials have shown that benralizumab, an anti-interleukin-5 receptor monoclonal antibody, reduces exacerbations and oral corticosteroid dose and improves asthma control and lung function in severe eosinophilic asthma. The aim of this study was to confirm results of randomised controlled trials in real life in a population of 73 patients with severe eosinophilic asthma treated with benralizumab for at least 12 months. Methods: Patients underwent careful monitoring of asthma exacerbations, exhaled nitric oxide fraction, lung function, asthma control and quality of life questionnaire responses and sputum induction, and gave a blood sample at baseline, after 6 months and then every year. Results: We found significant reductions in exacerbations (by 92%, p<0.0001) and oral corticosteroid dose (by 83%, p<0.001) after 6 months that were maintained over time, with 78% of patients able to stop oral corticosteroid therapy. Patients improved their Asthma Control Test (ACT) score (from 11.7±5.1 to 16.9±5.35, p<0.0001), Asthma Control Questionnaire (ACQ) score (from 2.88±1.26 to 1.77±1.32, p<0.0001) and Asthma Quality of Life Questionnaire score (+1.04, p<0.0001) at 6 months and this was maintained during follow-up. Only 35% and 43% of patients reached asthma control according to an ACT score ≥20 and ACQ score <1.5, respectively. We observed stable post-bronchodilation lung function over time and a significant reduction in sputum eosinophil count, with 85% of patients exhibiting sputum eosinophil counts <3% after 6 months (p<0.01) with no effect on exhaled nitric oxide fraction. Conclusion: In our real-life study, we confirm the results published in randomised controlled trials showing a sharp reduction in exacerbations and oral corticosteroid therapy, an improvement in asthma control and quality of life, and a dramatic reduction in sputum eosinophil count.

The effects of direct polymethylmethacrylate and zirconia-on-Ti-base abutments on peri-implant soft tissue integration: A study in minipigs.

PURPOSE: To assess two types of abutment materials routinely used in daily prac-tice-direct polymethyl methacrylate (PMMA) and a zirconia-on-Ti-base abut-ment-and their effects on peri-implant soft tissues and bone remodeling in a mini-pig model. MATERIALS AND METHODS: A total of 40 implants were placed in five mini-pigs in a single-stage surgery. Four different types of abutment materials (n = 10 per group) were used: (1) titanium (control); (2) zirconia (control); (3) PMMA (test 1); and (4) Ti-base (zirconia bonded to a titanium framework; test 2). After 3 months of healing, the samples were collected and subjected to nondecalcified histology. The soft tissue dimensions (sulcus, junctional epithelium, and connective tissue attach-ment) were assessed on each abutment mesially and distally, and the distance from the implant margin to the first bone-to-implant contact (BIC) was measured. RESULTS: No statistically significant differences were found among the four groups regarding soft tissue dimensions (P = .21), and a long junctional epithelium (mean: 4.1 mm) and a short connective tissue attachment (mean: 0.3 mm) were found in the majority of abutments. In some samples, the junctional epithelium extended all the way to the bone level. The measured peri-implant bone remodeling was similar in all four groups (P = .25). CONCLUSION: The present findings indicate that both di-rect PMMA and zirconia-on-Ti-base abutments seem to allow soft tissue integration similar to that of titanium and zirconia abutments. However, clinical studies are war-ranted to either confirm or refute the observed findings and to further investigate the influence of different materials on mucointegration.

Clinical and radiographic assessment of circular versus triangular cross-section neck implants in the posterior maxilla: Five-year follow-up of a randomized controlled trial.

OBJECTIVES: Dental implants with a triangular neck design have been developed in order to maintain peri-implant bone. The primary aim of this randomized controlled trial (RCT) was to assess after 5 years the peri-implant bone stability and the peri-implant soft tissue conditions with this new triangular implant neck design compared to a conventional round neck implant design. MATERIAL AND METHODS: This is a secondary evaluation of a RCT including 34 patients. Patients were recalled after 1, 3, and finally 5 years to assess implant survival and peri-implant bone levels using standardized radiographs. Peri-implant soft tissue health was also evaluated by recording probing depth, plaque index and Bleeding on Probing. Patient Reported Outcome Measures (PROMs) and the Pink Esthetic Score were also assessed. RESULTS: No implant loss occurred during the 5-year follow up period. The mean ± SD proximal bone remodeling after 5 years reached 0.38 ± 0.39 mm for the circular design and 0.29 ± 0.58 mm for the triangular design (p = .49). Peri-implant soft tissue health parameters and PROMs were found to be comparable. Altogether, 80% of implants presented peri-implant mucositis whereas one implant (4%) displayed sings of peri-implantitis. CONCLUSION: The 5-year evaluation of the triangular neck implants showed similar results to the circular neck implants.

Involvement of KCa3.1 channel activity in immediate perioperative cognitive and neuroinflammatory outcomes.

BACKGROUND: Potassium channels (KCa3.1; Kv1.3; Kir2.1) are necessary for microglial activation, a pivotal requirement for the development of Perioperative Neurocognitive Disorders (PNDs). We previously reported on the role of microglial Kv1.3 for PNDs; the present study sought to determine whether inhibiting KCa3.1 channel activity affects neuroinflammation and prevents development of PND. METHODS: Mice (wild-type [WT] and KCa3.1-/-) underwent aseptic tibial fracture trauma under isoflurane anesthesia or received anesthesia alone. WT mice received either TRAM34 (a specific KCa3.1 channel inhibitor) dissolved in its vehicle (miglyol) or miglyol alone. Spatial memory was assessed in the Y-maze paradigm 6 h post-surgery/anesthesia. Circulating interleukin-6 (IL-6) and high mobility group box-1 protein (HMGB1) were assessed by ELISA, and microglial activitation Iba-1 staining. RESULTS: In WT mice surgery induced significant cognitive decline in the Y-maze test, p = 0.019), microgliosis (p = 0.001), and increases in plasma IL-6 (p = 0.002) and HMGB1 (p = 0.001) when compared to anesthesia alone. TRAM34 administration attenuated the surgery-induced changes in cognition, microglial activation, and HMGB1 but not circulating IL-6 levels. In KCa3.1-/- mice surgery neither affected cognition nor microgliosis, although circulating IL-6 levels did increase (p < 0.001). CONCLUSION: Similar to our earlier report with Kv1.3, perioperative microglial KCa3.1 blockade decreases immediate perioperative cognitive changes, microgliosis as well as the peripheral trauma marker HMGB1 although surgery-induced IL-6 elevation was unchanged. Future research should address whether a synergistic interaction exists between blockade of Kv1.3 and KCa3.1 for preventing PNDs.

Diagnostic Performance of Immunohistochemistry Compared to Molecular Techniques for Microsatellite Instability and p53 Mutation Detection in Endometrial Cancer.

Molecular algorithms may estimate the risk of recurrence and death for patients with endometrial cancer (EC) and may impact treatment decisions. To detect microsatellite instabilities (MSI) and p53 mutations, immunohistochemistry (IHC) and molecular techniques are used. To select the most appropriate method, and to have an accurate interpretation of their results, knowledge of the performance characteristics of these respective methods is essential. The objective of this study was to assess the diagnostic performance of IHC versus molecular techniques (gold standard). One hundred and thirty-two unselected EC patients were enrolled in this study. Agreement between the two diagnostic methods was assessed using Cohen's kappa coefficient. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the IHC were calculated. For MSI status, the sensitivity, specificity, PPV and NPV were 89.3%, 87.3%, 78.1% and 94.1%, respectively. Cohen's kappa coefficient was 0.74. For p53 status, the sensitivity, specificity, PPV, and NPV were 92.3%, 77.1%, 60.0% and 96.4%, respectively. Cohen's kappa coefficient was 0.59. For MSI status, IHC presented a substantial agreement with the polymerase chain reaction (PCR) approach. For the p53 status, the moderate agreement observed between IHC and next generation sequencing (NGS) methods implies that they cannot be used interchangeably.

Airflow obstruction as a marker of adverse prognosis in rheumatoid arthritis.

Objectives: In our study, we explored the specific subgroup of patients with rheumatoid arthritis (RA) suffering from obstructive lung disease (OLD) and its impact on morbi-mortality. Methods: Our retrospective study included 309 patients suffering from RA with either obstructive (O-RA) or non-obstructive patterns (non-O-RA). OLD was defined based on the Tiffeneau index at the first available pulmonary functional test (PFT). Survival was then calculated and represented by a Kaplan-Meier curve. The comparison between the populations considered was performed by the Log-Rank test. Results: Out of the 309 RA patients, 102 (33%) had airway obstruction. The overall survival time was significantly lower in the O-RA group than in the non-O-RA group (n = 207) (p < 0.001). The median survival time was 11.75 years in the O-RA group and higher than 16 years in the non-O-RA group. Multivariate analysis identified OLD as an independent risk factor for mortality (HR 2.20; 95% CI 1.21-4.00, p < 0.01). Conclusion: Airway obstruction can be an independent risk factor of mortality in RA and should be considered as an early marker of poor prognosis. Further prospective longitudinal studies are required in order to determine the best clinical management for O-RA patients.

Lung Function Impairment, Associating Hyperinflation with Impaired Diffusion Capacity and Transfer Coefficient, Is a Risk Factor for Hip Osteoporosis in Patients with Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a risk factor for osteoporosis. Our objective is to determine if functional indices associated with emphysema on pulmonary function tests (DLCO-diffusion capacity of the lung for CO-; DLCO/AV-DLCO corrected for alveolar volume- and TLC-total lung capacity), considered alone or together, can identify COPD patients with osteoporosis. METHODS: 90 COPD patients underwent dual-energy X-ray absorptiometry (DEXA) and pulmonary function tests. RESULTS: 26% of the COPD patients were osteoporotic. In univariate analysis, each functional parameter associated with emphysema, analyzed separately, was not associated with osteoporosis. In contrast, patients with hyperinflation associated with impaired diffusion capacity and transfer coefficient, defined by the association of the three functional indices (DLCO < 70%, DLCO/AV < 80% and CPT > 115%), had significantly more osteoporosis at the total hip (OR: 5.9, CI: 1.5-23.8, p = 0.013). In multivariate analysis, this phenotype was confirmed as an independent factor associated with hip osteoporosis. In contrast, COPD airway obstruction severity, based on FEV1 (%), was not associated with osteoporosis. A lower BMI, female gender and age were also identified as osteoporosis risk factors. CONCLUSIONS: COPD patients with hyperinflation associated with impaired diffusion capacity and transfer coefficient are at higher risk for osteoporosis. Pulmonary function tests associated with emphysema detection can help to identify COPD patients with osteoporosis, in addition to the classical risk factors.

Multipotent mesenchymal stromal cells as treatment for poor graft function after allogeneic hematopoietic cell transplantation: A multicenter prospective analysis.

Introduction: Poor graft function (PGF) is a rare but serious complication of allogeneic hematopoietic cell transplantation (alloHCT). Due to their hematopoietic supporting properties and immune regulatory effects, multipotent mesenchymal stromal cells (MSC) could be considered a good candidate to help to restore bone marrow (BM) niches homeostasis and facilitate hematopoiesis after alloHCT. Methods: We prospectively assessed the efficacy and safety of ex-vivo expanded BM-derived MSC from third-party donor in a series of 30 patients with prolonged severe cytopenia and PGF after alloHCT. This multicenter trial was registered at www.clinicaltrials.gov (#NTC00603330). Results: Within 90 days post-MSC infusion, 53% (95% CI, 35 - 71%) of patients improved at least one cytopenia (overall response, OR) and 37% (95% CI, 19 - 54%) achieved a complete hematological response (CR: absolute neutrophil count, ANC >0.5 x 109/L, Hb > 80g/L and platelet count > 20 x 109/L with transfusion independence). Corresponding response rates increased to 67% (95% CI, 50 - 84%) OR and 53% (95% CI, 35 - 71%) CR within 180 days after MSC infusion. A significant decrease in red blood cells and platelets transfusion requirement was observed after MSC (median of 30-days transfusion requirement of 0.5 and 0 from d90-120 post-MSC versus 5 and 6.5 before MSC, respectively, p ≤0.001). An increase in ANC was also noted by day +90 and +180, with 3/5 patients with severe neutropenia having recovered an ANC > 1 x 109/L within the 90-120 days after MSC infusion. Overall survival at 1 year post-MSC was 70% (95% CI, 55.4 - 88.5), with all but one of the patients who achieved CR being alive. A single infusion of third-party MSC appeared to be safe, with the exception of one deep vein thrombotic event possibly related to the intervention. Discussion: In conclusion, a single i.v. infusion of BM-derived MSC from third party donor seemed to improve hematological function after alloHCT, although spontaneous amelioration cannot be excluded. Comparative studies are warranted to confirm these encouraging results.