The Possible Synergistic Pharmacological Effect of an Oral Berberine (BBR) and Curcumin (CUR) Complementary Therapy Alleviates Symptoms of Irritable Bowel Syndrome (IBS): Results from a Real-Life, Routine Clinical Practice Settings-Based Study.

Irritable bowel syndrome (IBS) is a prevalent chronic functional gastrointestinal disorder, characterised by recurrent abdominal discomfort and altered bowel movements. IBS cause a significantly negative impact on quality of life (QoL). Growing pharmacological evidence suggests that berberine (BBR) and curcumin (CUR) may mitigate IBS symptoms through multiple complementary synergistic mechanisms, resulting in the attenuation of intestinal inflammation and regulation of bowel motility and gut functions. In the present observational study conducted under real-life routine clinical practice settings, 146 patients diagnosed with IBS were enrolled by general practitioner clinics and pharmacies in Belgium. For the first time, this study assessed the potential synergistic pharmacological effect of a combined oral BBR/CUR supplement (Enterofytol® PLUS, containing 200 mg BBR and 49 mg CUR) (two tablets daily for 2 months), serving as complementary therapy in the management of IBS. Following the 2-month supplementation, significant improvements were observed in the patients' IBS severity index (IBSSI) (47.5%) and all the primary IBS symptoms, such as abdominal discomfort (47.2%), distension (48.0%), intestinal transit (46.8%), and QoL (48.1%) (all p < 0.0001). The improvement in the patients' IBSSI was independent of age, sex, and IBS sub-types. The patients' weekly maximum stool passage frequency decreased significantly (p < 0.0001), and the stool status normalized (p < 0.0001). The patients' need for concomitant conventional IBS treatment decreased notably: antispasmodics by 64.0% and antidiarrhoeals by 64.6%. Minor adverse effects were reported by a small proportion (7.1%) of patients, mostly gastrointestinal. The majority (93.1%) experienced symptom improvement or resolution, with a high satisfaction rate (82.6%) and willingness to continue the supplementation (79.0%). These findings support the potential synergistic pharmacological role of BBR and CUR in IBS, and their co-supplementation may alleviate IBS symptoms and improve QoL.

Association between PET/CT Scan Findings, Treatment, and Cancer Incidence in a Cohort of AAA Patients.

Background: Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease that poses several challenges. Given the increasing evidence that AAA patients are more likely to develop cancer and the importance of its early detection, we strived to develop a non-invasive tool based on serial FDG-PET/CT scan examinations to identify, among AAA patients, those at risk of cancer. Methods: Between 2006 and 2011 we recruited 149 AAA patients, free of cancer at baseline, and followed them until the end of 2021. All patients underwent an FDG-PET/CT scan at inclusion and possibly more scans during follow-up. At each medical imaging examination, the aneurysmal FDG uptake was recorded. Patients were stratified based on their aortic wall PET status (negative/positive). Any occurrence of cancer was reported. A Cox regression analysis and competing-risk modeling were applied to the data. Results: The proportion of AAA patients who developed cancer was 31.5% (mean time to diagnosis was 5.7 ± 3.4 years) and the death rate was 59%. A difference in cancer incidence between PET+ and PET- patients was detected (46.8% vs. 27.3%; HR = 1.96, 95%CI: 1.07-3.57, p = 0.028). Moreover, AAA patients undergoing surgical treatment had a lower risk of cancer than unoperated patients (28% vs. 50%; HR = 0.41, 95%CI: 0.21-0.80, p = 0.009). Conclusions: In AAA patients, diagnostic imaging with an FDG-PET/CT scan can help identify those patients at a higher risk of developing cancer. Moreover, the higher cancer risk in non-surgically treated patients calls for further analysis of associations between aneurysm growth and malignant disease.

Influence of the scanning path on the accuracy of intraoral scanners in the implanted edentulous patient: an in vitro study.

AIM: The aim of this in vitro study was to investigate the influence of scan paths on the accuracy (trueness and precision) of intra-oral scanning of an implant impression on an edentulous patient. MATERIAL AND METHODS: An epoxy resin maxillary model was made with 6 bone level implants (NobelParallel Conical Connection RP, NobelBiocare®). The implants were placed at the spot of the first incisor, the canine and the first molar. The trans gingival component (Multi-unit, NobelBiocare®) was screwed onto the implants. The scanbodies (IO 2C-A, Elos Accurate®) were then screwed onto the multi-units. The model was run through a coordinate measurement machine to obtain a control cast. Then, five different scanning paths, respectively the zigzag technique (ZZT), the zigzag technique with palatal (ZZTP), the wrap technique (WT), the wrap technique with palatal (WTP), and the big zigzag technique (BZZT), were applied by a single operator. Finally, each scan was compared to the control model. Results were assessed by one-way ANOVA and linear mixed effects models at P<0.05. RESULTS: The study showed that scan paths ZZT and ZZTP had significantly lower absolute positioning errors and residual mean square errors than the others (P<0.0001). For distances between consecutive implant axes and for absolute vertical errors, their superiority was borderline (P<0.10). Overall, techniques ZZT and ZZTP were equally performant and proved to be the most accurate. CONCLUSIONS: This in vitro experimental study demonstrates that the scan path can have an influence on the accuracy of the optical impression for full arch rehabilitation on implants.

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.

A Pilot Study on Oxidative Stress during the Recovery Phase in Critical COVID-19 Patients in a Rehabilitation Facility: Potential Utility of the PAOT® Technology for Assessing Total Anti-Oxidative Capacity.

BACKGROUND: Oxidative stress (OS) could cause various COVID-19 complications. Recently, we have developed the Pouvoir AntiOxydant Total (PAOT®) technology for reflecting the total antioxidant capacity (TAC) of biological samples. We aimed to investigate systemic oxidative stress status (OSS) and to evaluate the utility of PAOT® for assessing TAC during the recovery phase in critical COVID-19 patients in a rehabilitation facility. MATERIALS AND METHODS: In a total of 12 critical COVID-19 patients in rehabilitation, 19 plasma OSS biomarkers were measured: antioxidants, TAC, trace elements, oxidative damage to lipids, and inflammatory biomarkers. TAC level was measured in plasma, saliva, skin, and urine, using PAOT and expressed as PAOT-Plasma, -Saliva, -Skin, and -Urine scores, respectively. Plasma OSS biomarker levels were compared with levels from previous studies on hospitalized COVID-19 patients and with the reference population. Correlations between four PAOT scores and plasma OSS biomarker levels were analyzed. RESULTS: During the recovery phase, plasma levels in antioxidants (γ-tocopherol, ß-carotene, total glutathione, vitamin C and thiol proteins) were significantly lower than reference intervals, whereas total hydroperoxides and myeloperoxidase (a marker of inflammation) were significantly higher. Copper negatively correlated with total hydroperoxides (r = 0.95, p = 0.001). A similar, deeply modified OSS was already observed in COVID-19 patients hospitalized in an intensive care unit. TAC evaluated in saliva, urine, and skin correlated negatively with copper and with plasma total hydroperoxides. To conclude, the systemic OSS, determined using a large number of biomarkers, was always significantly increased in cured COVID-19 patients during their recovery phase. The less costly evaluation of TAC using an electrochemical method could potentially represent a good alternative to the individual analysis of biomarkers linked to pro-oxidants.

Selected biomarkers of oxidative stress in healthy Beagle dogs: A preliminary study.

Introduction: While oxidative stress has been studied in pathologic conditions in dogs, data in presumably healthy dogs and standardized protocols are lacking. This work purposed to bridge the gap by presenting provisional physiological ranges for oxidative stress biomarkers in a group of Beagle dogs. Methods: Based on our long-standing clinical expertise in the field of oxidative stress, nine plasma biomarkers of oxidative stress were evaluated for their concentrations (mean ± SD) in 14 healthy adult Beagle dogs. Results: Selected biomarkers were: vitamins C (7.90 ± 1.36 µg/mL) and E (34.1 ± 6.63 µg/mL), zinc (0.80 ± 0.17 mg/L), copper (0.54 ± 0.048 mg/L), selenium (256 ± 25.7 µg/L), total and oxidized glutathione (822 ± 108 µM and 3.56 ± 1.76 µM), myeloperoxidase (67.4 ± 56.2 ng/mL), and isoprostanes (340 ± 95.3 ng/mL). Glutathione peroxidase activity and superoxide anion production in whole blood were also measured. Glutathione peroxidase activity was 473 ± 34.0 IU/g of hemoglobin and superoxide anion production in whole blood was 18,930 ± 12,742 counts per 30 min. Reduced glutathione/oxidized glutathione and copper/zinc ratios were, respectively, 280 ± 139 and 0.70 ± 0.15. Sex-related differences were recorded for zinc (p = 0.0081), copper/zinc ratio (p = 0.0036) and plasma isoprostanes (p = 0.0045). Conclusion: Provisional physiological norms covering 95% of our group were proposed for each biomarker and should be of interest for future studies of canine oxidative stress.

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.

Clinical usefulness of quantitative thermal sensory testing in the diagnosis and surgical treatment of women with pudendal neuropathy.

BACKGROUND: The aim of this study, conducted on women with pudendal neuropathy, was to evaluate the usefulness of quantitative thermal sensory testing (QTST) in the diagnosis, surgical management, and prognosis of the disease. METHODS: The study was conducted on 90 women with pudendal neuropathy. QTST in pudendal nerve sensory innervation territory was realized before and more than 24 months after operative pudendoscopy on most patients. Cold and warm thresholds were evaluated together with a search for qualitative anomalies. The diagnostic value of QTST was assessed by comparing baseline data with normative values previously derived from 41 presumably healthy women. The effect of operative pudendoscopy on thermal sensitivity was tested by comparing preoperative and postoperative measurements. Assessment of the long-term prognostic value of QTST was based on "surgical success" defined as a VAS pain level less than 4 at least 2 years after surgery. RESULTS: The existence of qualitative anomalies, like anesthesia, allodynia, dysesthesia, radiation, and dyslocalization, was clearly indicative of pudendal neuropathy. The presence of after sensation and "out of limit" values of skin temperature and cold detection threshold were also helpful for diagnosing the disease. Surgery reduced qualitative anomalies but had no positive effect on QTST thresholds. QTST measurements had no real prognostic value but other factors like constipation and abnormal perineal descent were predictive of surgical success. CONCLUSION: For women with pudendal neuropathy, QTST can be considered a useful, non-invasive tool in the diagnosis, and management of the disease, but it cannot predict satisfactorily long-term outcome of operative pudendoscopy.

Curcuma longa and Boswellia serrata extract combination for hand osteoarthritis: an open-label pre-post trial.

CONTEXT: Osteoarthritis (OA) of the hand is a common painful musculoskeletal disorder with no cure. There is a need for an efficient and safe treatment to relieve OA pain. OBJECTIVE: To investigate the effects of a Curcuma longa and Boswellia serrata food supplement in addition to standard care on hand pain. MATERIALS AND METHODS: This open-label, non-controlled, post-observational study was based on 232 patients suffering from hand pain with or without joint deformity. Patients received a medical prescription for a three-month treatment with a food supplement containing 89 mg of C. longa dry extract, 120 mg of B. serrata resin, and 1.8 µg vitamin D. Pain was evaluated on a 10-point visual analog scale (VAS). The number of painful hand joints, patient satisfaction, nonsteroidal anti-inflammatory drugs intake, and side effects were also recorded. RESULTS: Baseline pain intensity (regression coefficient ± SE: -0.19 ± 0.01, p < 0.0001) and the number of painful joints (regression coefficient ± SE: -0.022 ± 0.0029, p < 0.0001) decreased significantly throughout the 3 months treatment period. NSAIDs intake and topical drug application were significantly decreased by 64% (p < 0.0001) and 79% (p < 0.0001) after 12 weeks, respectively. Only 3/239 (1.3%) patients reported side effects probably related to the product. 80.3% were satisfied with the treatment and 75.5% wished to continue treatment. CONCLUSION: This is the first clinical trial showing that C. longa and B. serrata resin can relieve symptoms in patients with hand osteoarthritis. The study provides useful information for the design of a clinical trial including a broader population.

Predicting probing depth reduction after periodontal non-surgical treatment in smokers according to the nicotine dependence and the number of cigarette consumed.

Introduction: Smoking is considered as a risk factor for the poor outcomes after periodontitis non-surgical treatment (PNST). The aim of this short communication is to predict probing depth reduction after periodontal non-surgical treatment in smokers according to the nicotine dependence (FTND) and the number of cigarette consumed (NCC). Methods: This work is a post-hoc study of a prospective controlled study on the effect of oral hygiene instructions and PNST on periodontal outcomes. This short communication focused only on the current conventional smokers (N = 34), based on specific smoking indicators, and on probing depth (PD) parameter that were recorded at baseline (time 0), after oral hygiene instruction (time 1) and 3 months after PNST (time 2). Results: The 34 smokers had a mean age 46.5 ± 11.5 years. The NCC- and FTND-based predictions allowed to show in a specific nomogram the PD values 3 months after PNST for each NCC and FTND category. Conclusion: Two nomograms are proposed for prognostic purposes and allow patients to understand the impact of smoking on periodontitis according to the number of cigarette consumed and the level of nicotine dependence. These nomograms might be also used for supporting smoking cessation. Clinical significance: In smoker patients with periodontitis, there is a need to predict, for both patient and clinicians, the impact of the number of cigarettes consumed and the level of nicotine dependence on probing depth after oral hygiene instructions and debridement. Two nomograms are proposed for prognostic purposes.

One-stage versus two-stage piezocision-assisted orthodontic tooth movement: A preclinical study based on Nano-CT and RT-PCR analyses.

OBJECTIVE: To evaluate the effect of a second-stage piezocision on the biological response. MATERIALS AND METHODS: 60 rats were randomly allocated to 6 experimental groups of 10 rats. Rats undergoing a one-stage piezocision were sacrified on day 7, 28 and 42 (groups 1-3) while rats undergoing a two-satge piezocision were sacrified on day 42, 63 and 90 (groups 4-6), respectively. The biological response was investigated in 3D at the tissue level using Nano-computed tomography (Nano-CT) and, at the molecular level using the qRT-PCR technique. Bone Volume Fraction (BVF) loss was the primary endpoint. RESULTS: Similar loss of BVF were observed both after the first and second piezocisions. The change in BVF loss between 7 and 28 days after each piezocision were 25.1 ± 13.0 (SE)% and 11.2 ± 11.6 (SE)% respectively and did not differ from each other (p = 0.43). Changes in BVF loss from 7 to 42 days were also comparable in one-stage and two-stage piezocision (4.9 ± 12.3 (SE) vs. -19.9 ± 13.4 (SE), p = 0.19). At the molecular level, all parameters except Translating Ribosome Affinity Purification (TRAP) protein had identical patterns. CONCLUSION: Within the limits of the present study, a second piezocision allowed to re-induce the Regional Acceleratory Phenomenon (RAP) effect. Nevertheless, the relevance of the findings to the clinical effect has not been tested.

Widespread kidney anomalies in children with Down syndrome.

BACKGROUND: Rare autopsy studies have described smaller kidneys as well as urinary tract anomalies in Down syndrome. This observation has never been investigated in vivo and little is known about the possible consequences upon kidney function. Here we wish to confirm whether children with Down syndrome have smaller kidneys and to evaluate their kidney function in vivo. METHODS: This retrospective cohort study enrolled 49 children with Down syndrome, as well as 49 age- and sex-matched controls at the Queen Fabiola Children's University Hospital in Brussels, Belgium. Doppler and kidney ultrasonography, spot urine albumin to creatinine ratio, estimated glomerular filtration rate (eGFR), and anthropometric data were recorded. RESULTS: Kidney size in children with Down syndrome was smaller than age- and sex-matched controls in terms of length (p < 0.001) and volume (p < 0.001). Kidney function based on eGFR was also decreased in Down syndrome compared to historical normal. Twenty-one of the children with Down syndrome (42%) had eGFR < 90 mL/min/1.73 m2, with 5 of these (10%) having an eGFR < 75 mL/min/1.73 m2. In addition, 7 of the children with Down syndrome (14%) had anomalies of the kidney and/or urinary tract that had previously been undiagnosed. CONCLUSIONS: Children with Down syndrome have significantly smaller kidneys than age-matched controls as well as evidence of decreased kidney function. These findings, in addition to well-noted increased kidney and urologic anomalies, highlight the need for universal anatomical and functional assessment of all individuals with Down syndrome. A higher resolution version of the Graphical abstract is available as Supplementary information.

Parental Perception of Body Weight Status of Their 8-year-old Children: Findings from the European CHOP Study.

BACKGROUND: Maternal perception of child weight status in children with overweight or obesity has received a lot of attention but data on paternal perception of children from presumably healthy cohorts are lacking. OBJECTIVE: We aimed to investigate paternal and maternal perception of child weight status at the age of 8 years in a cohort of 591 children from 5 European countries. MATERIAL AND METHODS: Included were 8-year-old children and their parents participating in the European Childhood Obesity Project (EU CHOP). Weight and height of children and parents were measured and Body Mass Index (BMI, kg/m2) was calculated. Both parents were asked to assess their perception of child weight status using Eckstein scales and their concern about child overweight. The agreement between mother and father perceptions was assessed by Cohen kappa coefficient and their relationship was analyzed by linear mixed effects models based on ordinal logistic regression, accounting for country, child gender and BMI, parental BMI, level of education, concern and type of feeding during first year of life. RESULTS: Data from children and both parents were available for 432 girls and boys. Mean BMI was comparable in boys and girls (16.7 ± 2.31 vs. 16.9 ± 2.87 kg/m2, P = 0.55). In total, 172 children (29.3%) were overweight or obese. There was a high degree of agreement between mother and father perceptions of their child's weight status (Cohen kappa 0.77). Multivariate modelling showed that perception levels significantly increased with child BMI but were globally lower than assessed. They differed between countries, gender and types of feeding during first year of life, were influenced by education level of the father but were not related to parental BMI and concern about childhood overweight. CONCLUSIONS: The study showed no overall differences between mothers and fathers in rating their child's weight status but both parents had a propensity to underestimate their child's actual weight, particularly in boys. The EU CHOP trial registered at clinicaltrials.gov as NCT00338689.

Outcomes and Predictors of Mortality in a Belgian Population of Patients Admitted with Ruptured Abdominal Aortic Aneurysm and Treated by Open Repair in the Contemporary Era.

BACKGROUND: Abdominal aortic aneurysm (AAA) rupture is a serious condition that results in extremely high mortality rates. Some improvements in outcome have been reported during the last 2 decades. The objective of the present study was to determine the overall and operative (by open repair) mortality related to ruptured AAA in the contemporary era and to identify preoperative, intraoperative, and early postoperative parameters associated with poor outcomes. METHODS: We performed a retrospective review of all consecutive patients admitted to our single institution with a diagnosis of ruptured AAA between 2004 and 2013. A total of 103 parameters, including demographic characteristics, medical history, clinical and biological parameters, cardiovascular risk factors, emergency level, diagnostic modalities, time from symptoms to diagnosis and treatment, type of operative procedure and postoperative complications, were analyzed. The primary endpoint considered in this study was the cumulative incidence rate of mortality. The secondary endpoint was the identification, by logistic regression methods, of risk factors for overall mortality as well as for operative, and postoperative mortality. RESULTS: Within our study period, 104 patients were admitted for a ruptured AAA. The majority of patients (84.6%) were male, and the AAA was known in 34.6% of the patients. Rupture occurred for a maximal diameter lower than 55 mm in 25% of the female population, compared to 5.7% of the male population (P = 0.030). The proportions of admitted patients who died before (preoperative mortality), during (intraoperative mortality) or after (postoperative hospital mortality) surgery was 17.3%, 16.3%, and 18.3%, respectively, yielding a cumulative in-hospital mortality of 51.9%. In the multivariate analysis, age ≥ 80 (P = 0.001), myocardial ischemia on the admission ECG (P = 0.046), and management by the physician response unit (P = 0.002) were the only preoperative parameters associated with a higher risk of hospital mortality. Four risk factors were found to be associated with a higher risk of postoperative mortality in the multivariate analysis, and all patients presenting with 3 or more of these risk factors (n = 5) died. CONCLUSIONS: The overall mortality of ruptured AAA in a contemporary cohort of patients who underwent open repair remains high and does not seem to have decreased during recent decades. Ruptures occur at smaller diameters in women than in men, supporting a lower threshold for intervention in women with known AAA. We developed risk scores to predict the mortality of patients with rAAA at different times of their hospital course. The validity of these scores should be assessed in prospective clinical studies.

Leveraging historical data to optimize the number of covariates and their explained variance in the analysis of randomized clinical trials.

The amount of data collected from patients involved in clinical trials is continuously growing. All baseline patient characteristics are potential covariates that could be used to improve clinical trial analysis and power. However, the limited number of patients in phases I and II studies restricts the possible number of covariates included in the analyses. In this paper, we investigate the cost/benefit ratio of including covariates in the analysis of clinical trials with a continuous outcome. Within this context, we address the long-running question "What is the optimum number of covariates to include in a clinical trial?" To further improve the benefit/cost ratio of covariates, historical data can be leveraged to pre-specify the covariate weights, which can be viewed as the definition of a new composite covariate. Here we analyze the use of a composite covariate to improve the estimated treatment effect in small clinical trials. A composite covariate limits the loss of degrees of freedom and the risk of overfitting.

Dissociation between 2-[18F]fluoro-2-deoxy-D-glucose positron emission computed tomography, ultrasound and clinical assessments in patients with non-severe rheumatoid arthritis, including remission.

BACKGROUND: Inflammation of patients joints with severe disease activity of rheumatoid arthritis (RA) has already been visualized and quantified by 2-[18F]fluoro-2-deoxy-D-glucose positron emission computed tomography ([18F] FDG PET/CT), but little is known about the metabolic status and its relationship with clinical and ultrasonography (US) metrology in patients with low/moderate activity or in remission. METHODS: Clinical assessments [based on 28-joint disease activity score (DAS28-CRP) and Clinical Disease Activity Index (CDAI)], [18F] FDG PET/CT, US and X-ray were performed on 63 RA patients classified into remission or low/moderate or severe disease activity groups. PET/CT was visually and then semi-quantitatively analysed by determining the standardized uptake value (SUV) of positive joints. RESULTS: Of the 1764 joints, 21.1% were tender only, 13.7% swollen only, 27.6% tender or swollen, 7.3% tender and swollen, 20.5% PET/CT-positive and 8.6% US-positive. PET and US measurements were correlated, albeit with poor concordance. The positive predictive value of PET/CT for clinical evaluation (tender and/or swollen) was low, whereas its negative predictive value was high. Highly significant differences were found with the number of PET/CT-positive joints and with cumulative SUV between "severe" and "non-severe" patients (including those in remission and those with low/moderate activity) and not between those classified as "remission" and "non-remission" or "remission" and "low/moderate activity". Moreover, the correlation between PET/CT measurements and clinical activity was positive only in the CDAI severe disease group. In patients in remission or with low/moderate activity, only 20-30% of joints were PET/CT-negative. In remission, PET/CT and US were positive in different joints, and PET/CT-positive but US-negative joints mainly exhibited RA (38.1%) or normal (49.2%) and not osteoarthritic (12.7%) X-ray patterns. CONCLUSIONS: [18F] FDG PET/CT was effective at distinguishing patients with severely active disease from other patients. In non-severe RA patients, including those in remission, PET/CT results are discordant from US and clinical observations. A longitudinal analysis is needed to explore the clinical relevance of such infra-clinical disease.

Disentangling the effects of CAD/CAM customized appliances and piezocision in orthodontic treatment.

OBJECTIVES: To discern the effects of computer-aided design (CAD)/computer-aided manufactured (CAM) customized appliances and piezocision on orthodontic treatment (OT). MATERIALS AND METHODS: The study combined findings from two previously published randomized controlled trials: (1) standard OT vs piezocision-assisted standard OT, and (2) CAD/CAM OT vs piezocision-assisted CAD/CAM OT. Piezocision is a minimally invasive corticotomy surgical procedure used to accelerate orthodontic treatment and CAD/CAM refers to CAD/CAM customized brackets and archwires. The outcomes were the overall treatment time, and the durations of the alignment phase and fine-tuning phase. Clinical and radiological features also were evaluated. RESULTS: The combined study included 48 patients with similar baseline characteristics. Compared to the standard treatment, CAD/CAM technology alone significantly decreased the overall median OT time from 543 to 394 days (P < .001) and from 543 to 254 days (P < .0001) when combined with piezocision. Although piezocision significantly reduced the duration of the alignment phase in the mandible and maxilla, CAD/CAM technology considerably shortened the fine-tuning phase. All periodontal and radiographic parameters remained stable from the start to the end of treatment in all groups. CONCLUSIONS: CAD/CAM technology combined with piezocision accelerates the entire OT process, during the alignment phase for piezocision and during the fine-tuning phase for CAD/CAM, with a global reduction of the overall treatment time of more than 50%.

Oxidative Stress Status in COVID-19 Patients Hospitalized in Intensive Care Unit for Severe Pneumonia. A Pilot Study.

BACKGROUND: A key role of oxidative stress has been highlighted in the pathogenesis of COVID-19. However, little has been said about oxidative stress status (OSS) of COVID-19 patients hospitalized in intensive care unit (ICU). MATERIAL AND METHODS: Biomarkers of the systemic OSS included antioxidants (9 assays), trace elements (3 assays), inflammation markers (4 assays) and oxidative damage to lipids (3 assays). RESULTS: Blood samples were drawn after 9 (7-11) and 41 (39-43) days of ICU stay, respectively in 3 and 6 patients. Vitamin C, thiol proteins, reduced glutathione, γ-tocopherol, ß-carotene and PAOT® score were significantly decreased compared to laboratory reference values. Selenium concentration was at the limit of the lower reference value. By contrast, the copper/zinc ratio (as a source of oxidative stress) was higher than reference values in 55% of patients while copper was significantly correlated with lipid peroxides (r = 0.95, p < 0.001). Inflammatory biomarkers (C-reactive protein and myeloperoxidase) were significantly increased when compared to normals. CONCLUSIONS: The systemic OSS was strongly altered in critically ill COVID-19 patients as evidenced by increased lipid peroxidation but also by deficits in some antioxidants (vitamin C, glutathione, thiol proteins) and trace elements (selenium).