Influence of physicochemical characteristics of calcium phosphate-based biomaterials in cranio-maxillofacial bone regeneration. A systematic literature review and meta-analysis of preclinical models.

Objectives: Calcium phosphate-based biomaterials (CaP) are the most widely used biomaterials to enhance bone regeneration in the treatment of alveolar bone deficiencies, cranio-maxillofacial and periodontal infrabony defects, with positive preclinical and clinical results reported. This systematic review aimed to assess the influence of the physicochemical properties of CaP biomaterials on the performance of bone regeneration in preclinical animal models. Methods: The PubMed, EMBASE and Web of Science databases were searched to retrieve the preclinical studies investigating physicochemical characteristics of CaP biomaterials. The studies were screened for inclusion based on intervention (physicochemical characterization and in vivo evaluation) and reported measurable outcomes. Results: A total of 1532 articles were retrieved and 58 studies were ultimately included in the systematic review. A wide range of physicochemical characteristics of CaP biomaterials was found to be assessed in the included studies. Despite a high degree of heterogeneity, the meta-analysis was performed on 39 studies and evidenced significant effects of biomaterial characteristics on their bone regeneration outcomes. The study specifically showed that macropore size, Ca/P ratio, and compressive strength exerted significant influence on the formation of newly regenerated bone. Moreover, factors such as particle size, Ca/P ratio, and surface area were found to impact bone-to-material contact during the regeneration process. In terms of biodegradability, the amount of residual graft was determined by macropore size, particle size, and compressive strength. Conclusion: The systematic review showed that the physicochemical characteristics of CaP biomaterials are highly determining for scaffold's performance, emphasizing its usefulness in designing the next generation of bone scaffolds to target higher rates of regeneration.

Intraoral wear of PICN CAD-CAM composite restorations used in severe tooth wear treatment: 5-year results of a prospective clinical study using 3D profilometry.

OBJECTIVES: To evaluate, in a prospective clinical study over 5 years with ex vivo 3D profilometry analyses, the intraoral wear of Polymer-Infiltrated Ceramic Network (PICN) CAD-CAM composite restorations used in severe tooth wear treatment with the One-Step No-Prep technique. METHODS: 192 PICN (Vita Enamic) restorations on molars and premolars were included in a prospective clinical study involving patients treated according to the One-step No-prep protocol (n = 7). All patients showed clinical signs of bruxism. Replicas of restorations on molars and premolars were realized at each evaluation time (baseline and then every year up to 5 years) and scanned to perform 3D profilometry. Baseline and recall scans were superimposed with Geomagic Control software. The mean material wear was calculated for the full occlusal area (FOA) and for the occlusal contact area (OCA), respectively. Clinical evaluation of restorations was performed at recall. RESULTS: At 5 years, the estimated mean material wear for FOA was inferior to the accuracy threshold of the profilometry measurement chain. For OCA, the estimated mean wear of the material was - 27.97 µm. This material wear was shown to be significantly influenced by time (p < 0.0001) and patient (p = 0.026), while the type of tooth (molar or premolar) had no influence. At 5 years, the survival and the success rates of restorations were 99.48% and 90.62%, respectively. SIGNIFICANCE: The PICN material exhibits a low wear process in the treatment of severe tooth wear despite the presence of clinical signs of bruxism, and it constitutes a suitable material for the One-step No-prep technique.

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.

Evaluation of a psychoneurological symptom cluster in patients with breast or digestive cancer: a longitudinal observational study.

BACKGROUND: A psychoneurological symptom cluster composed of cancer-related fatigue, emotional distress, sleep difficulties, and pain is very common among patients with cancer. Cognitive difficulties are also frequently associated with this cluster. Network analyses allow for an in-depth understanding of the relationships between symptoms in a cluster. This paper details the study protocol of a longitudinal assessment of the psychoneurological symptom cluster in two distinct cohorts: breast cancer and digestive cancer survivors, using network analyses. METHODS: Over two years, the symptoms involved in the psychoneurological symptom cluster, along with other common symptoms (e.g., digestive symptoms, financial difficulties) and variables (i.e., self-compassion, coping strategies) will be assessed in two cohorts: breast cancer survivors (N = 240) and digestive cancer survivors (N = 240). Online questionnaires will be completed at baseline, then 6, 12 and 24 months later. Network analyses will be used to assess the configuration of the symptom cluster at each measurement time and in each cohort. Comparison of networks between two measurement times or between the two cohorts will also be done with network comparison tests. DISCUSSION: This study will enable a better understanding of the relationships between common symptoms endured by patients with cancer. The results will be employed to develop more cost-effective interventions which, ultimately, will significantly improve the quality of life of patients with breast or digestive cancer. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05867966). Registered on the 27th of April 2023. url: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05867966 .

Alterations of erythropoiesis in Covid-19 patients: prevalence of positive Coombs tests and iron metabolism.

Background: For more than 2 years medical practice has been dealing with the Covid-19 pandemic. Atypical symptoms, such as frostbites and acrosyndromes, have appeared, and autoimmune anemias (some of which with cold agglutinins) have been described. Objectives: We planned to study the prevalence of positive direct Coombs tests (DCTs) and hemolytic autoimmune anemia in patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its correlation with complications, and then investigate the impact of the infection on iron metabolism. Design: This is an observational, cross-sectional, single-center, exploratory study. Methods: We obtained Coombs tests in a population of 179 infected patients at the CHU of Liège. We then studied iron metabolism in some of these patients, by measuring serum ferritin, erythropoietin (EPO), erythroferrone and hepcidin. Results: We did not identify any case of autoimmune hemolysis. However, there was a 20.3% prevalence of positive DCT, mainly with IgG (91.7%). These patients, compared to DCT-negative patients, were not only more anemic and transfused, but also required more transfers to intensive care units and had longer hospital stays and mechanical ventilation. The pattern of anemia was consistent with the anemia of inflammation, showing elevated hepcidin and ferritin levels, while EPO and erythroferrone values were lower than expected at this degree of anemia. Erythroferrone was higher and Hb was lower in DCT-positive patients. Finally, we identified a correlation between iron parameters and complicated forms of infection. Conclusion: Covid-19 patients suffered from inflammatory anemia with more severe forms of infection correlated to positive DCT status. This could potentially be of interest for future clinical practice.

Clinical Outcomes of Third-Generation Cephalosporin Definitive Therapy for Bloodstream Infections Due to Enterobacterales with Potential AmpC Induction: A Single-Center Retrospective Study.

The recommended therapy for severe infections caused by AmpC-inducible Enterobacterales (AmpC-E) typically involves cefepime or carbapenems. In an era of emerging resistance to these antimicrobials, we aim to assess the impact of third-generation cephalosporins (3GCs) vs. alternative antibiotics on clinical outcomes in bloodstream infections (BSIs) due to AmpC-E. We retrospectively included hospitalized adult patients with BSIs caused by 3GC-susceptible AmpC-E between 2012 and 2022, comparing the outcomes of 3GC and non-3GC definitive therapies. The primary outcome was overall treatment failure (OTF), encompassing 90-day all-cause mortality, 90-day reinfection, and 90-day readmission. Secondary outcomes comprised components of the OTF, in-hospital all-cause mortality, and length-of-stay. Within a total cohort of 353 patients, OTF occurred in 46.5% and 41.5% in the 3GC- and non-3GC-therapy groups, respectively (p = 0.36). The 3GC-therapy group exhibited a longer length-of-stay (38 vs. 21 days, p = 0.0003) and higher in-hospital mortality (23.3% vs. 13.4%, p = 0.019). However, the 90-day mortality, 90-day reinfection, and 90-day readmission were comparable between the therapy groups. Subgroup analyses involving high-risk AmpC-E and 3GC vs. standard-of-care yielded similar conclusions. Overall, our findings suggest that 3GC definitive therapy may not result in poorer clinical outcomes for the treatment of BSIs caused by AmpC-E.

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.

Progressive fibrosing interstitial lung disease in rheumatoid arthritis: A retrospective study.

Background and objective: Rheumatoid arthritis associated-interstitial lung disease (RA-ILD) is the most common pulmonary manifestation of rheumatoid arthritis (RA) and an important cause of mortality. In patients suffering from interstitial lung diseases (ILD) from different etiologies (including RA-ILD), a significant proportion is exhibiting a fibrotic progression despite immunosuppressive therapies, defined as progressive fibrosing interstitial lung disease (PF-ILD). Here, we report the frequency of RA-ILD and PF-ILD in all RA patients' cohort at University Hospital of Liège and compare their characteristics and outcomes. Methods: Patients were retrospectively recruited from 2010 to 2020. PF-ILD was defined based on functional, clinical and/or iconographic progression criteria within 24 months despite specific anti-RA treatment. Results: Out of 1,500 RA patients, about one third had high-resolution computed tomography (HRCT) performed, 89 showed RA-ILD and 48 PF-ILD. RA-ILD patients were significantly older than other RA patients (71 old of median age vs. 65, p < 0.0001), with a greater proportion of men (46.1 vs. 27.7%, p < 0.0001) and of smoking history. Non-specific interstitial pneumonia pattern was more frequent than usual interstitial pneumonia among RA-ILD (60.7 vs. 27.0%) and PF-ILD groups (60.4 vs. 31.2%). The risk of death was 2 times higher in RA-ILD patients [hazard ratio 2.03 (95% confidence interval 1.15-3.57), p < 0.01] compared to RA. Conclusion: We identified a prevalence of PF-ILD of 3% in a general RA population. The PF-ILD cohort did not seem to be different in terms of demographic characteristics and mortality compared to RA-ILD patients who did not exhibit the progressive phenotype yet.

One-Year Functional Decline in COVID-19 and Non-COVID-19 Critically Ill Survivors: A Prospective Study Incorporating a Pre-ICU Status Assessment.

We aimed to describe the one-year (1-y) functional status of survivors of COVID-19 critical illness, compared to non-COVID-19 survivors, and compared to their pre-ICU status. Adults who survived a COVID-19 critical illness (COVID group) during the first two waves in 2 hospitals were contacted by phone 1-y after discharge. They were compared to non-COVID-19 ICU survivors. A standardized assessment focused on quality of life (EQ-5D-3L), autonomy for activities of daily living (Barthel Index), and physical activity quantification (IPAQ-SF). Patients rated their 1-y and pre-ICU status. We included 220 survivors (132 COVID and 88 NC). Their age and severity scores were similar. ICU stay was shorter in NC group (3 [3−6] d) than in COVID group (8 [4.2−16.7] d) (p = 0.001). Proportions of organ supports were similar in the two groups. At 1-y, a significant reduction in EQ-5D-3L total score, in Barthel Index and in physical activity was observed in both groups, compared to the respective baseline values. Dependency (Barthel < 100) was observed in at least 35% of survivors at 1-y. Independently of the critical illness, HRQoL, autonomy and physical activities at 1-y were still significantly inferior to the pre-ICU values.

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.

In-Depth Longitudinal Comparison of Clinical Specimens to Detect SARS-CoV-2.

The testing and isolation of patients with coronavirus disease 2019 (COVID-19) are indispensable tools to control the ongoing COVID-19 pandemic. PCR tests are considered the "gold standard" of COVID-19 testing and mostly involve testing nasopharyngeal swab specimens. Our study aimed to compare the sensitivity of tests for various sample specimens. Seventy-five participants with confirmed COVID-19 were included in the study. Nasopharyngeal swabs, oropharyngeal swabs, Oracol-collected saliva, throat washes and rectal specimens were collected along with pooled swabs. Participants were asked to complete a questionnaire to correlate specific clinical symptoms and the symptom duration with the sensitivity of detecting COVID-19 in various sample specimens. Sampling was repeated after 7 to 10 days (T2), then after 14 to 20 days (T3) to perform a longitudinal analysis of sample specimen sensitivity. At the first time point, the highest percentages of SARS-CoV-2-positive samples were observed for nasopharyngeal samples (84.3%), while 74%, 68.2%, 58.8% and 3.5% of throat washing, Oracol-collected saliva, oropharyngeal and rectal samples tested positive, respectively. The sensitivity of all sampling methods except throat wash samples decreased rapidly at later time points compared to the first collection. The throat washing method exhibited better performance than the gold standard nasopharyngeal swab at the second and third time points after the first positive test date. Nasopharyngeal swabs were the most sensitive specimens for early detection after symptom onset. Throat washing is a sensitive alternative method. It was found that SARS-CoV-2 persists longer in the throat and saliva than in the nasopharynx.

Incidence and Risk Factors of COVID-19-Associated Pulmonary Aspergillosis in Intensive Care Unit-A Monocentric Retrospective Observational Study.

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is an increasingly recognized complication of COVID-19 and is associated with significant over-mortality. We performed a retrospective monocentric study in patients admitted to the intensive care unit (ICU) for respiratory insufficiency due to COVID-19 from March to December 2020, in order to evaluate the incidence of CAPA and the associated risk factors. We also analysed the diagnostic approach used in our medical centre for CAPA diagnosis. We defined CAPA using recently proposed consensus definitions based on clinical, radiological and microbiological criteria. Probable cases of CAPA occurred in 9 out of 141 patients included in the analysis (6.4%). All cases were diagnosed during the second wave of the pandemic. We observed a significantly higher realization rate of bronchoalveolar lavage (BAL) (51.1% vs. 28.6%, p = 0.01) and Aspergillus testing (through galactomannan, culture, PCR) on BAL samples during the second wave (p < 0.0001). The testing for Aspergillus in patients meeting the clinical and radiological criteria of CAPA increased between the two waves (p < 0.0001). In conclusion, we reported a low but likely underestimated incidence of CAPA in our population. A greater awareness and more systematic testing for Aspergillus are necessary to assess the real incidence and characteristics of CAPA.

Predictors of Mortality and Effect of Drug Therapies in Mechanically Ventilated Patients With Coronavirus Disease 2019: A Multicenter Cohort Study.

We conducted a multicenter cohort study to determine the effect of drug therapies on survival in mechanically ventilated patients with coronavirus disease 2019. All consecutive adult patients admitted to ICU for coronavirus disease 2019 from March 1, 2020, to April 25, 2020, and under invasive mechanical ventilation for more than 24 hours were included. Out of 2,003 patients hospitalized for coronavirus disease 2019, 361 were admitted to ICU, 257 were ventilated for more than 24 hours, and 247 were included in the study. Simple and multiple time-dependent Cox regression models were used to assess the effects of factors on survival. Methylprednisolone administration during the first week of mechanical ventilation was associated with a decrease in mortality rate from 48% to 34% (p = 0.01). Mortality was significantly associated with older age, higher creatinine, lower lymphocyte count, and mean arterial pressure lower than 70 mm Hg on the day of admission.

Evaluation of the new Id-Fungi plates from Conidia for MALDI-TOF MS identification of filamentous fungi and comparison with conventional methods as identification tool for dermatophytes from nails, hair and skin samples.

OBJECTIVES: We first compare the efficiency of mould/dermatophyte identification by MALDI-TOF MS using a new medium called Id-Fungi plates (IDFP) from Conidia® and two different databases. For the second purpose, we evaluated a new version of the medium supplemented with cycloheximide, Id-Fungi plates Plus (IDFPC) for the direct inoculation of nails, hair and skin samples and compared the efficiency of MALDI-TOF MS identification of dermatophytes to classical methods based on culture and microscopy. METHODS: A total of 71 strains have been cultured IDFP and Sabouraud gentamicin plates (SGC2) and were identified by MALDI-TOF MS. For the evaluation of the combination IDFPC/ MALDI-TOF MS as a method of identification for dermatophytes, 428 samples of hair nails and skin were cultivated in parallel on IDFPC and Sabouraud + cycloheximide medium (SAB-ACTI). RESULTS: For Aspergillus sp and non-Aspergillus moulds, the best performances were obtained on IDFP after maximum 48-h growth, following protein extraction. For dermatophytes, the best condition was using the IDFP at 72 hours, after extended direct deposit. Regarding the direct inoculation of nails, hair skin on IDFPC, 129/428 (30.1%) showed a positive culture against 150/428 (35%) on SAB-ACTI medium. Among the 129 positive strains, the identification by MALDI-TOF MS was correct for 92/129 (71.4%). CONCLUSION: The IDFP allows the generation of better spectra by MALDI-TOF MS compared to SGC2. It facilitates sampling and deposit. Regarding the use of IDFPC, this medium seems less sensitive than SAB-ACTI but among positive strains, the rate of correct identification by MALDI-TOF MS is satisfactory.