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 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.

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.

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.

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.

Interval From Simulation Imaging to Treatment Delivery in SABR of Lung Lesions: How Long is Too Long for the Lung?

Purpose: The purpose of this study was to evaluate the effect of delay between planning computed tomography (CT) used as a basis for treatment planning and the start of treatment (delay planning treatment [DPT]), on local control (LC) for lung lesions treated by SABR. Methods and Materials: We pooled 2 databases from 2 monocentric retrospective analysis previously published and added planning CT and positron emission tomography (PET)-CT dates. We analyzed LC outcomes based on DPT and reviewed all available cofounding factors among demographic data and treatment parameters. Results: A total of 210 patients with 257 lung lesions treated with SABR were evaluated. The median DPT was 14 days. Initial analysis revealed a discrepancy in LC as a function of DPT and a cutoff delay of 24 days (21 days for PET-CT almost systematically done 3 days after planning CT) was determined according to the Youden method. Cox model was applied to several predictors of local recurrence-free survival (LRFS). Univariate analysis showed LRFS decreasing significantly related to DPT ≥24 days (P = .0063), gross tumor volume, and clinical target volume (P = .0001 and P = .0022), but also with the presence of >1 lesion treated with the same planning CT (P = .024). LRFS increased significantly with higher biological effective dose (P < .0001). On multivariate analysis, LRFS remained significantly lower for lesions with DPT ≥24 days (hazard ratio, 2.113; 95% confidence interval, 1.097-4.795; P = .027). Conclusions: DPT to SABR treatment delivery for lung lesions appears to reduce local control. Timing from imaging acquisition to treatment delivery should be systematically reported and tested in future studies. Our experience suggests that the time from planning imaging to treatment should be <21 days.

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.

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.

Factors associated with the efficacy and safety of endoscopic dilatation of symptomatic strictures in Crohn's disease: a retrospective cohort study.

OBJECTIVE: Endoscopic balloon dilatation (EBD) is a standard treatment for intestinal strictures in Crohn's disease (CD). No evidence-based guidelines exist regarding the balloon diameter or the balloon pressure to be used, with recent studies suggesting the use of a smaller diameter than classically used. We sought to analyze the factors associated with safety and efficacy of EBD in CD strictures, particularly looking at balloon diameter and dilatation pressure. METHODS: We conducted a monocentric retrospective study of patients who underwent EBD between 2005 and 2020. RESULTS: Our endoscopy department performed EBD in 94 CD patients during the considered period. The mean size of balloon dilatation was 16 mm (±2.5; including 21 patients with balloon <14 mm) and the mean dilatation pressure was 5.3 atm (±1.5). No perforation was observed. Over a median follow-up of 5.6 years, the probability of being operated was 5.4% at 1 year and 10.4% at 3 years. Smaller height (HR = 0.90, p = 0.022) and a higher BMI (HR = 1.23, p = 0.014) were associated with the risk of operation. The probability of being operated or redilated was 30.1% at 1 year and 52.5% at 3 years. No factor was significantly associated with this risk. The size of the balloon had no impact on outcomes. CONCLUSION: In this retrospective cohort, including a significant proportion of CD patients dilated with balloon <14 mm, no perforation was observed and the size of the balloon or the dilatation pressure had no impact on the risk of surgery or redilatation.

Early Post-Operative Endoscopy Is Associated with Lower Surgical Recurrence of Crohn's Disease: A Retrospective Study of Three Successive Cohorts.

Background: The severity of endoscopic recurrence during the first year after intestinal resection for Crohn's disease is predictive of clinical recurrence. The aim of our study was to assess the impact of the implementation of an ileocolonoscopy during the first year after surgery on surgical recurrence. Methods: All patients who underwent a first intestinal resection for Crohn's disease between 1992 and 2018 at the University Hospital of Liège were retrospectively included. The time to surgical recurrence was compared in three successive groups of patients operated on in the period 1992-2001 (group A), 2002-2011 (group B), and 2012-2020 (group C) using the Kaplan-Meier method and the Log-Rank test. To identify independent prognostic factors, a multivariate analysis was used via the Cox model. Results: 223 patients (group A = 69, group B = 94, group C = 60) were included. Probabilities of surgical recurrence were significantly lower in group C (2.2% and 4.7% at 3 and 5 years, respectively) compared with group B (4.2% and 7.6% at 3 and 5 years, respectively) and with group A (9% and 18.2% at 3 and 5 years, respectively) (p = 0.0089). Ileocolonoscopy during the year after surgery was associated with a significantly reduced surgical recurrence rate in univariate and multivariate analysis (HR = 0.31, p = 0.0049). Conclusion: The implementation of an early ileocolonoscopy after surgery for Crohn's disease since early 2000 has been associated with a reduced surgical recurrence over the last 30 years.

Overall Survival Rate in Allogeneic Stem Cell Transplanted Patients Requiring Intensive Care Can Be Predicted by the Prognostic Index for Critically Ill Allogeneic Transplantation Patients (PICAT) and the Sequential Organ Failure Assessment (SOFA) Scores.

Background. Allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients requiring intensive care unit (ICU) have high mortality rates. Methods. In the current study, we retrospectively assessed whether the Prognostic Index for Critically Ill Allogeneic Transplantation patients (PICAT) score predicted overall survival in a cohort of 111 consecutive allo-HCT recipients requiring ICU. Results. Survival rates at 30 days and 1 year after ICU admission were 57.7% and 31.5%, respectively, and were significantly associated with PICAT scores (p = 0.036). Specifically, survival at 30-day for low, intermediate, and high PICAT scores was 64.1%, 58.1%, and 31.3%, respectively. At one-year, the figures were 37.5%, 29%, and 12.5%, respectively. In multivariate analyses, high PICAT score (HR = 2.23, p = 0.008) and relapse prior to ICU admission (HR = 2.98, p = 0.0001) predicted higher mortality. We next compared the ability of the PICAT and the Sequential Organ Failure Assessment (SOFA) scores to predict mortality in our patients using c-statistics. C statistics for the PICAT and the SOFA scores were 0.5687 and 0.6777, respectively. Conclusions. This study shows that while the PICAT score is associated with early and late mortality in allo-HCT recipients requiring ICU, it is outperformed by the SOFA score to predict their risk of mortality.

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.

Predictive factors for the presence and long-term persistence of SARS-CoV-2 antibodies in healthcare and university workers.

While patient groups at risk for severe COVID-19 infections are now well identified, the risk factors associated with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) transmission and immunization are still poorly understood. In a cohort of staff members of a Belgian tertiary academic hospital tested for SARS-CoV-2 antibodies during the early phase of the pandemic and followed-up after 6 weeks, 3 months and 10 months, we collected personal, occupational and medical data, as well as symptoms based on which we constructed a COVID-19 score. Seroprevalence was higher among participants in contact with patients or with COVID-19 confirmed subjects or, to a lesser extent, among those handling respiratory specimens, as well as among participants reporting an immunodeficiency or a previous or active hematological malignancy, and correlated with several symptoms. In multivariate analysis, variables associated with seropositivity were: contact with COVID-19 patients, immunodeficiency, previous or active hematological malignancy, anosmia, cough, nasal symptoms, myalgia, and fever. At 10 months, participants in contact with patients and those with higher initial COVID-19 scores were more likely to have sustained antibodies, whereas those with solid tumors or taking chronic medications were at higher risk to become seronegative.

Kinetics of Cardiac Remodeling and Fibrosis Biomarkers During an Extreme Mountain Ultramarathon.

Objectives: The effects of ultra-distance on cardiac remodeling and fibrosis are unclear. Moreover, there are no data reporting the kinetics of cardiac alterations throughout the event and during recovery. Our aim was to investigate the kinetics of biological markers including new cardiac fibrosis biomarkers suppression of tumorigenicity 2 (ST2) and galectin-3 (Gal-3) during and after an extreme mountain ultramarathon. Methods: Fifty experienced runners participating in one of the most challenging mountain ultramarathons (330 km, D+ 25,000 m) were enrolled in our study. Blood samples were collected at four time points: before (Pre-), at 148 km (Mid-), at the finish line (Post-), and 3 days after the recovery period (Recov-). Results: The cardiac fibrosis biomarkers (ST2 and Gal-3) increased from Pre- to Mid-. During the second half, ST2 remained higher than pre-values as opposed to Gal-3. Necrosis, ischemia, and myocyte injury biomarkers increased until Mid- then decreased but remained higher at Recov- than Pre-values. Oxidative stress appeared at Mid-. Lipid peroxides remained higher at Recov- compared to Pre-. The maximal value in most of these biomarkers was observed at Mid- and not at Post-. Conclusions: The present study supports biphasic kinetics of cardiac fibrosis biomarkers, with a relative recovery during the second half of the event that seems specific to this extreme event. Overall, performing at such an extreme ultramarathon seems less deleterious for the heart than shorter events.

The Effects of Abutment Materials on Peri-Implant Soft Tissue Integration: A Study in Minipigs.

PURPOSE: To evaluate, in a minipig model, the soft tissue integration of four different transmucosal materials, as well as the peri-implant bone remodeling. MATERIALS AND METHODS: A total of 40 implants were placed in five minipigs in a single stage surgery, and two of each of the following abutment materials were used in each animal: (1) titanium (Ti; control), (2) polymethylmethacrylate (PMMA), (3) zirconia (Zi), and (4) veneering ceramic (VC). After a healing period of 3 months, 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 and the distance from the implant margin to first bone-to-implant contact (BIC) was measured. RESULTS: The mean biological width-characterized by the sum of junctional epithelium and connective tissue measurements-was 3.8 (0.6) mm and no statistically significant difference was found between the four groups (p = 0.41). However, a long junctional epithelium (3.3-3.8 mm) and a very short connective tissue attachment (0.1-0.2 mm) were observed with all abutments. The measured peri-implant bone remodeling was similar in all four groups (p = 0.88). CONCLUSIONS: Within its limitations, this study showed that all tested materials allowed soft tissue integration, consisting of a long junctional epithelium, extending close to the bone level, and a rather short portion of connective tissue.

Predictors of neutralizing antibody response to BNT162b2 vaccination in allogeneic hematopoietic stem cell transplant recipients.

BACKGROUND: Factors affecting response to SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients remain to be elucidated. METHODS: Forty allo-HCT recipients were included in a study of immunization with BNT162b2 mRNA vaccine at days 0 and 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD) were assessed at days 0, 21, 28, and 49 while neutralizing Ab against SARS-CoV-2 wild type (NT50) were assessed at days 0 and 49. Results observed in allo-HCT patients were compared to those obtained in 40 healthy adults naive of SARS-CoV-2 infection. Flow cytometry analysis of peripheral blood cells was performed before vaccination to identify potential predictors of Ab responses. RESULTS: Three patients had detectable anti-RBD Ab before vaccination. Among the 37 SARS-CoV-2 naive patients, 20 (54%) and 32 (86%) patients had detectable anti-RBD Ab 21 days and 49 days postvaccination. Comparing anti-RBD Ab levels in allo-HCT recipients and healthy adults, we observed significantly lower anti-RBD Ab levels in allo-HCT recipients at days 21, 28 and 49. Further, 49% of allo-HCT patients versus 88% of healthy adults had detectable NT50 Ab at day 49 while allo-HCT recipients had significantly lower NT50 Ab titers than healthy adults (P = 0.0004). Ongoing moderate/severe chronic GVHD (P < 0.01) as well as rituximab administration in the year prior to vaccination (P < 0.05) correlated with low anti-RBD and NT50 Ab titers at 49 days after the first vaccination in multivariate analyses. Compared to healthy adults, allo-HCT patients without chronic GVHD or rituximab therapy had comparable anti-RBD Ab levels and NT50 Ab titers at day 49. Flow cytometry analyses before vaccination indicated that Ab responses in allo-HCT patients were strongly correlated with the number of memory B cells and of naive CD4+ T cells (r > 0.5, P < 0.01) and more weakly with the number of follicular helper T cells (r = 0.4, P = 0.01). CONCLUSIONS: Chronic GVHD and rituximab administration in allo-HCT recipients are associated with reduced Ab responses to BNT162b2 vaccination. Immunological markers could help identify allo-HCT patients at risk of poor Ab response to mRNA vaccination. TRIAL REGISTRATION: The study was registered at clinicaltrialsregister.eu on 11 March 2021 (EudractCT # 2021-000673-83).