The natural history of splenic artery aneurysms: factors that predict aneurysmal growth.

PURPOSE: This study examines the natural history of splenic artery aneurysms at a single institution and assesses the effect of patient factors and aneurysm characteristics on aneurysm growth. MATERIALS AND METHODS: This single-center retrospective study included patients with splenic artery aneurysms that underwent serial imaging over 30 years (1990-2020). Patient demographics and aneurysm characteristics were collected. The variables contributing to aneurysm growth were assessed using non-parametric tests for continuous variables and Chi-square for categorical variables. Multivariable linear regression was performed using aneurysm growth rate as a continuous dependent variable. RESULTS: A total of 132 patients were included in this study. The median maximum diameter of the splenic artery aneurysms was 15.8 mm (range 4.0 - 50.0 mm). 39% of the aneurysms demonstrated interval growth over time, while the remaining 61% were stable in size. Of aneurysms that increased in size, the median aneurysm growth rate was 0.60 mm/year (range 0.03 - 5.00 mm/year). Maximum aneurysm diameter of >2 cm and the presence of >50% mural thrombus were significant positive predictors for aneurysm growth rate (p=0.020 and p=0.022, respectively). Greater than 50% rim calcification was a significant negative predictor for aneurysm growth rate (p=.009) in multivariate analysis. CONCLUSION: A larger baseline splenic artery aneurysm size, presence of mural thrombus, and lack of rim calcification are associated with increased aneurysm growth rate.

Risk of postoperative bleeding after dental extraction in patients on antiplatelet therapy: systematic review and meta-analysis.

OBJECTIVE: To determine the risk of bleeding after minor extraction in patients on different antiplatelet therapy (APT) regimens. STUDY DESIGN: A search was conducted using PubMed and Google Scholar. Thirty-five papers were included in the systematic review, of which 23 papers provided the requisite information for meta-analysis. Subgroups were created based on the controls, as follows: (1) no control, (2) healthy control, and (3) interrupted APT control. In a meta-analysis, the studies were further subdivided into immediate and delayed bleeding. RESULTS: No immediate or delayed bleeding risk was found in patients treated with aspirin vs healthy controls (relative risk [RR] = 1.26; P = .5 and RR = 2.17; P = .09, respectively). A higher immediate bleeding was recorded for patients on single nonaspirin APT vs those in the healthy population (RR = 3.72; P = .0009). A high risk of bleeding was recorded in patients receiving dual APT compared with healthy controls for immediate (RR = 10.3; P < .0001) and delayed (RR = 7.72; P = .001) bleeding. Dual APT continuation showed a higher risk of immediate bleeding (RR = 2.13) than interrupted APT, but the difference was insignificant (P = .07). CONCLUSIONS: Dental extraction can be performed safely in patients on aspirin monotherapy. In contrast, patients receiving dual APT should be considered at risk for immediate and continued bleeding.

Rendezvous intervention using combined surgical carotid endarterectomy followed by endovascular thrombectomy in patients with acute tandem occlusions: a proof-of-concept experience at a tertiary care center.

BACKGROUND: Endovascular thrombectomy (EVT) is highly effective in acute stroke patients with intracranial large vessel occlusion (LVO), however, presence of concomitant cervical occlusion of the internal carotid artery (ICA) may limit the endovascular access. This study describes feasibility and efficacy of a surgical carotid access (cutdown) to perform interdisciplinary recanalization therapy including carotid endarterectomy (CEA) followed by EVT for recanalization of intracranial LVO in stroke patients with tandem occlusions. METHODS: We identified stroke patients with tandem occlusions who underwent a combined surgical-endovascular approach over a 5-year period. Surgical cutdown was provided by a cardiovascular surgery team at the angio-suite followed by EVT performed by the neuroradiological team. Demographics, stroke characteristics, treatments including antithrombotic management, procedure times, and clinical follow-up were assessed. RESULTS: Four patients with acute stroke because of tandem occlusions received CEA followed by EVT (two patients after frustrating femoral catheterization, two as first-line approach). Successful recanalization (TICI ≥ 2b) via endovascular thrombectomy was achieved in all patients at a median of 28 min after successful surgical CEA. Intraprocedural complication was observed in one case (25%; i.e. ICA dissection). CONCLUSIONS: This small study provides evidence that a combined interdisciplinary approach of CEA followed by EVT in the angio-suite in acute stroke patients with tandem occlusions is a feasible procedure in patients otherwise not accessible to endovascular recanalizing therapy and, therefore, high likelihood of developing large hemispheric infarction. Prospective data are warranted to identify patients who benefit from this combined approach as first-line therapy.

Angiotensin(1-7) attenuates tooth movement and regulates alveolar bone response during orthodontic force application in experimental animal model.

BACKGROUND: Renin-angiotensin system and its ACE2/Ang(1-7)/Mas receptor axis regulates skeletal response to multiple physiological and pathological conditions. Recent research suggested a vital role of Ang(1-7) in regulating alveolar bone metabolism and remodeling. In this context, this study evaluated the effects of the Ang(1-7)/Mas receptor axis on orthodontic tooth movement (OTM) and the alveolar bone response to mechanical load. METHODS: A coil spring was placed between the right maxillary first molar and the anterior tooth of Wistar rats to apply bidirectional mechanical force. Ang(1-7) with or without a specific Mas receptor antagonist (A779) was infused using subcutaneous osmotic pumps (200 and 400 ng/kg/min: respectively). Animals were killed after 5 and 14 days from the OTM procedure after the clinical evaluation of tooth movement and mobility. Morphometric analysis of alveolar bone structure was conducted using micro-CT and the histological picture was evaluated after H&E staining. Moreover, collagen fiber distribution was assessed using Picro-Sirius red stain. In addition, bone samples were collected from the pressure and tension sites around the anterior tooth for gene expression analysis. RESULTS: Ang(1-7) infusion suppressed the tooth movement and mobility after 14 days of the orthodontic force application. Additionally, Ang(1-7) infusion preserved the morphometric and histological structure of the alveolar bone at pressure and tension sides. These effects were abolished by adding A779 infusion. Collagen fiber distribution was dysregulated mainly by the A779 Mas receptor blockage. Ang(1-7) affected the bone formation, remodeling- and vascularity-related genes in the pressure and tension sides, suggesting a prominent suppression of osteoclastogenesis. Ang(1-7) also improved osteoblasts-related genes on the tension side, whereas the osteoclasts-related genes were augmented by A779 on the pressure side. CONCLUSION: Collectively, the activation of Ang(1-7)/Mas receptor axis appears to hinder tooth movement and regulates alveolar bone remodeling in response to mechanical force.

Usage of Inhalative Sedative for Sedation and Treatment of Patient with Severe Brain Injury in Germany, a Nationwide Survey.

Brain injured patients often need deep sedation to prevent or treat increased intracranial pressure. The mainly used IV sedatives have side effects and/or high context-sensitive half-lives, limiting their use. Inhalative sedatives have comparatively minor side effects and a brief context-sensitive half-life. Despite the theoretical advantages, evidence in this patient group is lacking. A Germany-wide survey with 21 questions was conducted to find out how widespread the use of inhaled sedation is. An invitation for the survey was sent to 226 leaders of intensive care units (ICU) treating patients with brain injury as listed by the German Society for Neurointensive Care. Eighty-nine participants answered the questionnaire, but not all items were responded to, which resulted in different absolute counts. Most of them (88%) were university or high-level hospital ICU leaders and (67%) were leaders of specialized neuro-ICUs. Of these, 53/81 (65%) use inhalative sedation, and of the remaining 28, 17 reported interest in using this kind of sedation. Isoflurane is used by 43/53 (81%), sevoflurane by 15/53 (28%), and desflurane by 2. Hypotension and mydriasis are the most common reported side effects (25%). The presented survey showed that inhalative sedatives were used in a significant number of intensive care units in Germany to treat severely brain-injured patients.

A Prospective, Observational Cost Comparison of Laparoscopic and Open Appendicectomy in Three Tertiary Hospitals in Nigeria.

BACKGROUND: The clinical benefits of laparoscopic appendicectomy are well recognized over open appendicectomy. However, laparoscopic procedures are not frequently conducted in many low-and middle-income countries (LMICs) for several reasons, including perceived higher costs. The aim of this study was to assess the feasibility and cost of laparoscopic appendicectomy compared to open appendicectomy in Nigeria. METHODS: A multicenter, prospective, cohort study among patients undergoing appendicectomy was conducted at three tertiary hospitals in Nigeria. Data were collected from October 2020 to February 2022 and analyses compared the average healthcare costs at 30 days after surgery. Quantile regression was conducted to identify variables that had an impact on the costs, reported in Nigerian Naira (Naira) and US dollars ($), with standard deviations (SD). FINDINGS: This study included 105 patients, of which 39 had laparoscopic appendicectomy and 66 had open appendicectomy. The average healthcare cost of laparoscopic appendicectomy (147,562 Naira (SD: 97,130) or $355 (SD: 234)) was higher than open appendicectomy (113,556 Naira (SD: 88,559) or $273 (SD: 213)). The average time for return to work was shorter with laparoscopic than open appendicectomy (mean: 8 days vs. 14 days). At the average daily income of $5.06, laparoscopic appendicectomy was associated with 9778 Naira or $24 cost savings in return to work. Further, 5.1% of laparoscopic appendicectomy patients had surgical site infections compared to 22.7% for open appendicectomy. Regression analysis results showed that laparoscopic appendicectomy was associated with $14 higher costs than open appendicectomy, albeit non-significant (p = 0.53). INTERPRETATION: Despite selection bias in this real-world study, laparoscopic appendicectomy was associated with a slightly higher overall cost, a lower societal cost, a lower infection rate, and a faster return to work, compared to open appendicectomy. It is technically and financially feasible, and its provision in Nigeria should be expanded.

The importance of community health workers as frontline responders during the COVID-19 pandemic, Somalia, 2020-2021.

Introduction: We examined the contribution of community health workers as frontline responders for the community-based surveillance in Somalia during the first year of the COVID-19 pandemic for detection of COVID-19 cases and identification of contacts. Methods: We retrieved COVID-19 surveillance data from 16 March 2020 to 31 March 2021 from the health ministry's central database. These data were collected through community health workers, health facilities or at the points of entry. We compared the number of suspected COVID-19 cases detected by the three surveillance systems and the proportion that tested positive using the chi-squared test. We used logistic regression analysis to assess association between COVID-19 infection and selected variables. Results: During the study period, 154,004 suspected cases of COVID-19 were detected and tested, of which 10,182 (6.6%) were positive. Of the notified cases, 32.7% were identified through the community-based surveillance system, 54.0% through the facility-based surveillance system, and 13.2% at points of entry. The positivity rate of cases detected by the community health workers was higher than that among those detected at health facilities (8.6% versus 6.4%; p < 0.001). The community health workers also identified more contacts than those identified through the facility-based surveillance (13,279 versus 1,937; p < 0.001). The odds of COVID-19 detection generally increased by age. Community-based surveillance and health facility-based surveillance had similar odds of detecting COVID-19 cases compared with the points-of-entry surveillance (aOR: 7.0 (95% CI: 6.4, 7.8) and aOR: 7.5 (95% CI: 6.8, 8.3), respectively). Conclusion: The community health workers proved their value as first responders to COVID-19. They can be effective in countries with weak health systems for targeted community surveillance in rural and remote areas which are not covered by the facility-based surveillance system.

Targeting Pseudomonas aeruginosa quorum sensing with sodium salicylate modulates immune responses in vitro and in vivo.

Introduction: Chronic infections are a major clinical challenge in hard-to-heal wounds and implanted devices. Pseudomonas aeruginosa is a common causative pathogen that produces numerous virulence factors. Due to the increasing problem of antibiotic resistance, new alternative treatment strategies are needed. Quorum sensing (QS) is a bacterial communication system that regulates virulence and dampens inflammation, promoting bacterial survival. QS inhibition is a potent strategy to reduce bacterial virulence and alleviate the negative impact on host immune response. Aim: This study investigates how secreted factors from P. aeruginosa PAO1, cultured in the presence or absence of the QS inhibitor sodium salicylate (NaSa), influence host immune response. Material and methods: In vitro, THP-1 macrophages and neutrophil-like HL-60 cells were used. In vivo, discs of titanium were implanted in a subcutaneous rat model with local administration of P. aeruginosa culture supernatants. The host immune response to virulence factors contained in culture supernatants (+/-NaSa) was characterized through cell viability, migration, phagocytosis, gene expression, cytokine secretion, and histology. Results: In vitro, P. aeruginosa supernatants from NaSa-containing cultures significantly increased THP-1 phagocytosis and HL-60 cell migration compared with untreated supernatants (-NaSa). Stimulation with NaSa-treated supernatants in vivo resulted in: (i) significantly increased immune cell infiltration and cell attachment to titanium discs; (ii) increased gene expression of IL-8, IL-10, ARG1, and iNOS, and (iii) increased GRO-α protein secretion and decreased IL-1ß, IL-6, and IL-1α secretion, as compared with untreated supernatants. Conclusion: In conclusion, treating P. aeruginosa with NaSa reduces the production of virulence factors and modulates major immune events, such as promoting phagocytosis and cell migration, and decreasing the secretion of several pro-inflammatory cytokines.

Exploring the Roles and Responsibilities of an Educational Supervisor in Medical Training Within the United Kingdom.

Medical trainees or junior doctors within the United Kingdom, regardless of their level of training or specialty, are assigned an educational supervisor (ES). The General Medical Council within the United Kingdom defines an ES as "a trainer who is selected and appropriately trained to be responsible for the overall supervision and management of a specified trainee's educational progress during a clinical placement or series of placements." This article critically evaluates the current literature to explore the roles of the ES in supporting and monitoring a trainee's progress while discussing challenges associated with the role. Through clearer delineation of the role of an ES, barriers to improving training can be identified and overcome, thus improving overall satisfaction with training.

COVID-19 and severe pulmonary alveolar proteinosis (PAP): A case report.

Background: Pulmonary alveolar proteinosis (PAP) is a rare lung disease that mainly presents with dyspnea. PAP diagnosis can be easily missed in the background of a coronavirus disease 2019 (COVID-19) infection, due to the similarity of their presentation and radiological findings. We present a case report of a post-COVID-19 patient, who later developed severe PAP. Case presentation: A 55-year-old male patient presented to the emergency department with progressive exertional dyspnea and hypoxia following a COVID-19 infection. Chest X-ray showed severe bilateral infiltrates. Patient received multiple courses of broad-spectrum antibiotics and prolonged course of corticosteroids without improvement. "Crazy paving" appearance in a follow up chest computed tomography raised the suspicion of PAP of what was initially thought to be a post-COVID-19 syndrome presentation. A diagnostic segmental bronchioalveolar lavage with a lung biopsy revealed a proteinaceous material filling the alveoli, with a positive periodic acid-Schiff (PAS) stain. Due to severe hypoxia, therapeutic segmental followed by whole lung lavage was performed with significant improvement. Conclusion: Diagnosing PAP is challenging due to the rarity of the disease. An accurate diagnosis of PAP requires a combination of medical history, imaging, and bronchoalveolar lavage staining positive for PAS. Decision whether to treat with a segmental or whole lung lavage is individualized to each patient. Further studies are needed to confirm whether COVID-19 or long-term use of steroids might be contributing to PAP.

Exploring the Role of Urocortin in Osteoporosis.

Osteoporosis is a debilitating disease that affects over 200 million people worldwide. Overactive osteoclast activity leads to micro-architectural defects and low bone mass. This culminates in fragility fractures, such as femoral neck fractures. Treatments currently available either are not completely effective or have considerable side effects; thus, there is a need for more effective treatments. The urocortin (Ucn) family, composed of urocortin 1 (Ucn1), urocortin 2 (Ucn2), urocortin 3 (Ucn3), corticotropin-releasing factor (CRF) and corticotropin-releasing factor-binding protein (CRF-BP), exerts a wide range of effects throughout the body. Ucn1 has been shown to inhibit murine osteoclast activity. This review article will aim to bridge the gap between existing knowledge of Ucn and whether it can affect human osteoclasts.

Modulation of gene expression and bone formation by expanded and dense polytetrafluoroethylene membranes during guided bone regeneration: An experimental study.

BACKGROUND: Nonresorbable membranes promote bone formation during guided bone regeneration (GBR), yet the relationships between membrane properties and molecular changes in the surrounding tissue are largely unknown. AIM: To compare the molecular events in the overlying soft tissue, the membrane, and the underlying bone defect during GBR using dual-layered expanded membranes versus dense polytetrafluoroethylene (PTFE) membranes. MATERIALS AND METHODS: Rat femur defects were treated with either dense PTFE (d-PTFE) or dual-layered expanded PTFE (dual e-PTFE) or left untreated as a sham. Samples were collected after 6 and 28 days for gene expression, histology, and histomorphometry analyses. RESULTS: The two membranes promoted the overall bone formation compared to sham. Defects treated with dual e-PTFE exhibited a significantly higher proportion of new bone in the top central region after 28 days. Compared to that in the sham, the soft tissue in the dual e-PTFE group showed 2-fold higher expression of genes related to regeneration (FGF-2 and FOXO1) and vascularization (VEGF). Furthermore, compared to cells in the d-PTFE group, cells in the dual e-PTFE showed 2.5-fold higher expression of genes related to osteogenic differentiation (BMP-2), regeneration (FGF-2 and COL1A1), and vascularization (VEGF), in parallel with lower expression of proinflammatory cytokines (IL-6 and TNF-α). Multiple correlations were found between the molecular activities in membrane-adherent cells and those in the soft tissue. CONCLUSION: Selective surface modification of the two sides of the e-PTFE membrane constitutes a novel means of modulating the tissue response and promoting bone regeneration.

Assessment of health-related behaviors among medical students: A cross-sectional study.

Background and Aim: Students sometimes participate in harmful activities that adversely influence their behaviors and well-being throughout college, which is one of the sensitive phases in an individual's life. Aim: To assess the health-related behaviors of university students. Methods: A cross-sectional study that includes systematic randomly selected 383 students from various colleges of Ras Al Khaimah Medical and Health Sciences University (RAKMHSU), Ras Al Khaimah Emirate, United Arab Emirates. A self-reported questionnaire included students' demographic traits and behaviors, including safety, medication intake, cigarette smoking, nutrition, physical activity, and health-related topics. Results: Most participants were females (69.7%), 13.3% were obese while 28.2% were overweight. The data revealed a significant difference between male and female students regarding medication intake without prescription, nutrition, physical activity, and health-related topics. The data also revealed that the majority of the students were attempting to lose weight, and the former male smokers had fewer trials to quit the use of all tobacco products than females. Conclusion: More than a quarter of participants were overweight, and the majority of students did not adhere to the guidelines for safety and nutritious eating. This study recognized significant health promotion opportunities for university students that can be carried out to establish a healthier youth for society.

Bevacizumab, a vascular endothelial growth factor inhibitor, promotes orthodontic tooth movement in an experimental rat model.

Objective: This study aimed to evaluate the impact of bevacizumab on orthodontic tooth movement (OTM) in Wistar rats. Materials and methods: The OTM model was constructed by placing an orthodontic coil spring between the maxillary first molar and anterior tooth. Bevacizumab (Avastin®; 10 mg/kg twice per week) was started one week before the OTM and continued for 3 weeks. After 1 and 2 weeks, OTM distance and anterior tooth mobility were measured. Thereafter, the maxilla was dissected for micro-CT microarchitectural analysis, followed by histological analysis, and tartrate-resistant acid phosphatase (TRAP) staining. Moreover, the distributions of collagen fibers type-I and -III (Col-I and Col-III) were evaluated using Picro-Sirius red staining. Results: Orthodontic force prompted bone resorption and formation on the pressure and tension sides, respectively. Bevacizumab therapy resulted in a 42% increase of OTM, particularly after 2 weeks. Furthermore, bevacizumab disturbed the morphometric structure at both pressure and tension sites. The histological evaluation indicated about 35-44% fewer osteoblasts in the bevacizumab group, especially at the tension side, whereas the proportion of TRAP-positive osteoclasts at the pressure side was 34-37% higher than the control. The mature Col-I was reduced at the tension site by 33%, whereas the Col-III/Col-I ratio was enhanced by 20-44% at pressure and tension sites, after 2 weeks, in the bevacizumab group. Conclusion: Anti-vascular bevacizumab therapy accentuates OTM in rat model, possibly through the enhancement of bone resorption, at the pressure side, and the reduction of bone formation, at the tension side as well as dysregulation of collagen fibers distribution.

Magnesium implant degradation provides immunomodulatory and proangiogenic effects and attenuates peri-implant fibrosis in soft tissues.

Implants made of magnesium (Mg) are increasingly employed in patients to achieve osteosynthesis while degrading in situ. Since Mg implants and Mg2+ have been suggested to possess anti-inflammatory properties, the clinically observed soft tissue inflammation around Mg implants is enigmatic. Here, using a rat soft tissue model and a 1-28 d observation period, we determined the temporo-spatial cell distribution and behavior in relation to sequential changes of pure Mg implant surface properties and Mg2+ release. Compared to nondegradable titanium (Ti) implants, Mg degradation exacerbated initial inflammation. Release of Mg degradation products at the tissue-implant interface, culminating at 3 d, actively initiated chemotaxis and upregulated mRNA and protein immunomodulatory markers, particularly inducible nitric oxide synthase and toll-like receptor-4 up to 6 d, yet without a cytotoxic effect. Increased vascularization was demonstrated morphologically, preceded by high expression of vascular endothelial growth factor. The transition to appropriate tissue repair coincided with implant surface enrichment of Ca and P and reduced peri-implant Mg2+ concentration. Mg implants revealed a thinner fibrous encapsulation compared with Ti. The detailed understanding of the relationship between Mg material properties and the spatial and time-resolved cellular processes provides a basis for the interpretation of clinical observations and future tailoring of Mg implants.

Inflammatory response to epoxy resin and calcium silicate sealers preheated with different temperatures: an in vivo study.

OBJECTIVE: To determine the impact of heat exposure of different sealers on inflammatory cytokine secretions and tissue response in vivo. MATERIALS AND METHODS: Silicone tubes were prefilled with epoxy resin (ER) or calcium silicate (CS) sealers, preheated at 37, 60, or 120 °C, and implanted in rat subcutaneous site. Peri-implant exudate and tissue were analyzed after 1 and 4 weeks for cytokine secretions and tissue organization. RESULTS: At 1 week, 120 °C-preheated CS and ER induced higher secretions of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), respectively, as compared to sham/empty tube groups. At 4 weeks, whereas TNF-α secretion was reduced in CS, it increased in ER group, particularly for 120 °C. Both sealers revealed high IL-6 after 4 weeks as compared to sham/empty tube, and generally, higher IL-6 secretions were associated with ER. Histology at 1 week revealed lower degree of inflammatory infiltrate in the groups of the highest preheating temperature (120 °C). Nonetheless, at 4 weeks, whereas fibrous capsule area and inflammatory infiltrate remained low in the CS120 group, they were high in ER120. CONCLUSION: Preheating ER sealer to 120 °C induced high and prolonged secretion of proinflammatory cytokines (TNF-α and IL-6), whereas this effect was transient for the CS sealer. This was associated with increased fibrous capsule and inflammatory infiltrate in response to 120 °C-preheated ER. CLINICAL RELEVANCE: Heat-induced changes in sealer properties alter the inflammatory response in vivo, which may affect the clinical outcome. This will not only help appropriate selection of obturation technique for different sealers, but also for optimizing the properties of new generation of sealers.

Inflammatory and differentiation cellular response to calcium silicate cements: An in vitro study.

AIM: Inflammatory-regenerative cell interaction is believed to mediate hard tissue formation. This study aimed to investigate the interaction between human inflammatory monocytes with human regenerative fibroblasts after exposure to different calcium silicate materials. METHODOLOGY: Human monocytes were cultured on three materials, polystyrene (PS), mineral trioxide aggregates (MTA) and biodentine (BD), in the presence or absence of lipopolysaccharide (LPS). Half of the monocyte-conditioned media (MoCM) of each group was used to analyse inflammatory cytokine secretion, namely TNF-α, IL-1ß, IL-1RA and IL-6. The remaining MoCM was used to culture recipient fibroblasts, measuring the cell number (proliferation) and levels of alkaline phosphatase (differentiation) and lactic acid dehydrogenase (cytotoxicity). RESULTS: In absence of LPS, MTA was associated with higher secretion of TNF-α and lower secretion of IL-1ß, while BD triggered higher secretions of both cytokines when both materials were compared to control (PS). When LPS was added, higher levels of all analysed cytokines were observed in the PS and BD groups, whereas for the MTA group, only TNF-α and IL-6 were increased. Fibroblasts responded differently to the MoCM from the different groups, revealing significant increases in proliferation and differentiation capacities, particularly when cultured in CM from monocytes exposed to MTA. The morphological evaluation revealed different patterns of fibroblast shape and spread in the different MoCM groups. CONCLUSION: Calcium silicate materials modulate the monocyte inflammatory response, which subsequently induce differential effects on the recipient fibroblasts. MTA appears to promote the secretion of prodifferentiation signals from the monocytes, which are received by fibroblasts, promoting their proliferation and differentiation. The model represents a promising tool to evaluate the interaction of different cells in response to different materials.

Bone without borders - Monetite-based calcium phosphate guides bone formation beyond the skeletal envelope.

Calcium phosphates (CaP) represent an important class of osteoconductive and osteoinductive biomaterials. As proof-of-concept, we show how a multi-component CaP formulation (monetite, beta-tricalcium phosphate, and calcium pyrophosphate) guides osteogenesis beyond the physiological envelope. In a sheep model, hollow dome-shaped constructs were placed directly over the occipital bone. At 12 months, large amounts of bone (∼75%) occupy the hollow space with strong evidence of ongoing remodelling. Features of both compact bone (osteonal/osteon-like arrangements) and spongy bone (trabeculae separated by marrow cavities) reveal insights into function/need-driven microstructural adaptation. Pores within the CaP also contain both woven bone and vascularised lamellar bone. Osteoclasts actively contribute to CaP degradation/removal. Of the constituent phases, only calcium pyrophosphate persists within osseous (cutting cones) and non-osseous (macrophages) sites. From a translational perspective, this multi-component CaP opens up exciting new avenues for osteotomy-free and minimally-invasive repair of large bone defects and augmentation of the dental alveolar ridge.

Osseointegrated prostheses for the rehabilitation of patients with transfemoral amputations: A prospective ten-year cohort study of patient-reported outcomes and complications.

Background: Osseointegrated implants for patients with transfemoral amputations (TFAs) are a novel treatment under development, and prospective long-term evidence is lacking. The objectives were to determine patient-reported outcomes (PROs) and complications after ten years compared to before treatment and to compare the first five-year period with the later five-year period with regard to the outcomes. Methods: In a nonrandomized, prospective cohort study, patients with TFAs treated between 1999 and 2007 with the Osseointegrated Prosthesis for the Rehabilitation of Amputees (OPRA) system (n â€‹= â€‹51) (28 men/23 women; mean age at amputation: 32 years old; mean age at treatment: 44 years old in a single university hospital were followed for ten years. PROs included the Questionnaire for Persons with a Transfemoral Amputation (Q-TFA, four scores 0-100) and the Short Form 36 Health Survey (SF-36, ten scores 0-100) and were answered before treatment and until the ten-year follow-up after treatment. Analyses of differences in PRO scores were conducted using Wilcoxon's signed rank test. The implant survival and revision-free rates with respect to adverse events (implant revision, mechanical complications, and deep infections) were presented as Kaplan-Meier graphs with 95% confidence intervals (CIs). The incidences of events per ten and five person-years were calculated. Spearman's correlation analysis was used for analyses of associations between adverse events. Results: PROs showed statistically significant mean improvements between baseline and the ten-year follow-up with regard to all Q-TFA scores: the prosthetic use score (+36), prosthetic mobility score (+18), problem score (-28) and global score (+38) (all p â€‹< â€‹0.001), and the SF-36 physical functioning score (+26, p â€‹< â€‹0.001) and physical component score (+6, p â€‹< â€‹0.01). No PROs showed a statistically significant deterioration. Over the ten years, 12 patients were lost (one lost to follow-up, one dropped out of the study, two died, and eight had implants removed (four before five years and four between five and ten years). At ten years, the revision-free survival rates were 83% (CI: 69%-91%), 65% (CI: 49%-77%) and 17% (CI: 7%-29%) for implant revision, deep infection and mechanical complications, respectively. Mechanical complications, 3.9 per 10 person-years (CI: 2.2-5.1) constituted the most common serious adverse event and were more common during the last five years than during the first five years (p â€‹< â€‹0.001). No significant difference in the incidence of deep infections was observed between the earlier and the later five-year periods: 0.3 per 5 person-years (CI: 0.1-0.5) vs. 0.3 per person-years (CI: 0.1-0.5) (p â€‹= â€‹0.740). Correlation analyses between the earlier and later five years revealed a positive association between deep infections and implant removal (0.57, p â€‹< â€‹0.001) and between mechanical complications and adverse events (0.65, p â€‹< â€‹0.001). Conclusion: Improved PROs were demonstrated ten years after the introduction of a novel principle for bone anchorage of amputation prostheses. Nevertheless, an increasing rate of mechanical complications is of concern.

Effectiveness of pharmacogenomic tests including CYP2D6 and CYP2C19 genomic variants for guiding the treatment of depressive disorders: Systematic review and meta-analysis of randomised controlled trials.

Major depressive disorders are prevalent conditions with limited treatment response and remission. Pharmacogenomics tests including CYP2D6 and CYP2C19 genomic variants provide the most reliable actionable approach to guide choice and dosing of antidepressants in major depression to improve outcomes. We carried out a meta-analysis and meta-regression analyses of randomised controlled trials evaluating pharmacogenomic tests with CYP2D6 and CYP2C19 polymorphisms in major depression. A systematic review was conducted according to PRISMA and Cochrane guidelines to search several electronic databases. Logarithmically transformed odds ratios (OR) and confidence intervals (CI) for improvement, response and remission were calculated. A random-effects meta-analysis and meta-regression analyses were subsequently carried out. Twelve randomised controlled trials were included. Pharmacogenomic tests in the treatment of depression were more effective than treatment as usual for improvement (OR:1.63, CI: 1.19-2.24), response (OR: 1.46; CI: 1.16-1.85) and remission (OR: 1.85; CI: 1.23-2.76) with no evidence of publication bias. Remission was less favourable in recent studies. The results are promising but cautious use of pharmacogenomics in major depression is advisable. PROSPERO registration ID: CRD42021261143.