PDGFR‐β and kidney fibrosis Ortiz, Alberto
EMBO molecular medicine,
06 March 2020, Volume:
12, Issue:
3
Journal Article
Peer reviewed
Open access
Chronic kidney disease (CKD) is one of the fastest growing global causes of death, estimated to rank among the top five by 2040 (Foreman et al, 2018). This illustrates current pitfalls in diagnosis ...and management of CKD. Advanced CKD requires renal function replacement by dialysis or transplantation. However, earlier CKD stages, even when renal function is still normal, are already associated with an increased risk of premature death (Perez‐Gomez et al, 2019). Thus, novel approaches to diagnose and treat CKD are needed. The histopathological hallmark of CKD is kidney fibrosis, which is closely associated with local inflammation and loss of kidney parenchymal cells. Thus, kidney fibrosis is an attractive process to develop tests allowing an earlier diagnosis of CKD and represents a potential therapeutic target to slow CKD progression or promote regression.
A. Ortiz shares his views on the new model of primary renal fibrosis, based on transgenic mice with specific PDGFR‐β activation in renal mesenchymal cells, developed by P. Boor and collaborators (in this issue of EMBO Molecular Medicine).
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objectives
The present systematic review aimed at evaluating the efficacy of reconstructive surgical therapy at peri‐implantitis‐related bone defects.
Methods
Studies reporting on outcomes of ...reconstructive surgery at peri‐implantitis‐related bone defects at 12 months were identified through an electronic search. Following data extraction, two different sets of meta‐analyses were performed. Primarily, controlled studies were used to evaluate the potential benefit of reconstructive surgical therapy over controls. Secondly, overall outcome of reconstructive surgical therapy was assessed by comparing baseline values with outcomes at 12 months. Results were expressed as weighted mean differences (WMD) or risk ratios (RR). Heterogeneity was described by I2 and prediction intervals.
Results
The potential benefit of reconstructive techniques over control procedures was evaluated in three studies, representing a total of 116 implants. Altogether, 16 studies reported on the outcome of reconstructive measures at 12 months after surgery. The meta‐analyses identified a larger improvement in marginal bone levels (MBL, WMD = 1.7 mm) and in defect fill (WMD = 57%) for test procedures, but found no differences for clinical measures (reduction of probing depth (PD) and bleeding on probing (BOP). Changes of clinical attachment and soft tissue levels were not considered. In terms of overall outcome, therapy resulted in improved MBL (WMD = 2.0 mm) and CAL (WMD = 1.8 mm), in recession (WMD = 0.7 mm), in reduced PD (WMD = 2.8 mm) and in reduced BOP (Implants: RR = 0.4/Sites: RR = 0.2). None of the included studies addressed patient‐reported outcome measures.
Conclusions
The available evidence on reconstructive therapy at peri‐implantitis‐related defects is limited by (a) the low number of controlled studies, (b) the lack of controlled studies for commonly used procedures, (c) the heterogeneity between studies and (d) the choice of outcome measures. A high variability for predicted outcomes at 12 months was noted. The interpretation of the demonstrated larger MBL gain for test procedures is difficult as graft material may not be distinguishable from newly formed bone. Potential aesthetic and patient‐reported advantages remain to be demonstrated.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
With the continual improvement of computing hardware and algorithms, simulations have become a powerful tool for understanding all sorts of (bio)molecular processes. To handle the large simulation ...data sets and to accelerate slow, activated transitions, a condensed set of descriptors, or collective variables (CVs), is needed to discern the relevant dynamics that describes the molecular process of interest. However, proposing an adequate set of CVs that can capture the intrinsic reaction coordinate of the molecular transition is often extremely difficult. Here, we present a framework to find an optimal set of CVs from a pool of candidates using a combination of artificial neural networks and genetic algorithms. The approach effectively replaces the encoder of an autoencoder network with genes to represent the latent space, i.e., the CVs. Given a selection of CVs as input, the network is trained to recover the atom coordinates underlying the CV values at points along the transition. The network performance is used as an estimator of the fitness of the input CVs. Two genetic algorithms optimize the CV selection and the neural network architecture. The successful retrieval of optimal CVs by this framework is illustrated at the hand of two case studies: the well-known conformational change in the alanine dipeptide molecule and the more intricate transition of a base pair in B-DNA from the classic Watson–Crick pairing to the alternative Hoogsteen pairing. Key advantages of our framework include the following: optimal interpretable CVs, avoiding costly calculation of committor or time-correlation functions, and automatic hyperparameter optimization. In addition, we show that applying a time-delay between the network input and output allows for enhanced selection of slow variables. Moreover, the network can also be used to generate molecular configurations of unexplored microstates, for example, for augmentation of the simulation data.
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IJS, KILJ, NUK, PNG, UL, UM
Bone‐regenerative interventions aiming to restore deficient alveolar ridges, such as the use of block grafts or through the application of guided bone‐regeneration principles, have reported positive ...outcomes in the published scientific literature. These interventions, however, are invasive, and hence, intraoperative and/or postoperative complications may occur. The types of complications and their severity may vary from the exposure of the biomaterial (membrane or graft) to postsurgical infections, neurosensorial disturbances, occurrence of hemorrhage, and pain, etc. The aim of the present narrative review was to search the available scientific evidence concerning the incidence of these complications, their effect on treatment outcomes, their clinical management and, finally, strategies aimed at prevention. Exposure of the barrier membrane or the block graft is the most common complication associated with oral regenerative interventions. To manage these complications, depending on the extent of the exposure and the presence or absence of concomitant infections, therapeutic measures may vary, from the topical application of antiseptics to the removal of the barrier membrane or the block graft. Regardless of their treatment, the occurrence of these complications has been associated with patient selection, with compliant patients (eg, nonsmokers) having a lower reported incidence of complications. Similarly, surgical factors such as correct flap elevation and a tensionless closure are of obvious importance. Finally, to prevent the incidence of complications, it appears prudent to utilize whenever possible less invasive surgical interventions.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aim
The aim of this study was to evaluate the efficacy of a xenogeneic collagen matrix to augment the width of keratinized mucosa (KM), concomitantly to the surgical treatment of peri‐implantitis, ...when compared to the use of an autologous soft tissue graft.
Material and methods
In this 12‐month parallel‐arm randomized controlled clinical trial, patients with peri‐implantitis were randomly assigned, one month after non‐surgical therapy, to surgical resective treatment of peri‐implantitis consisting on an apically positioned flap (APF) in combination with a KM augmentation procedure, either with an autologous free gingival graft (FGG) or a collagen matrix (CM). Primary outcomes were the increase in the width of KM and probing pocket depth (PPD) reduction at 12 months. As secondary outcomes, peri‐implant radiographic and patient‐reported outcomes were assessed.
Results
The intention‐to‐treat population consisted of 49 subjects, assigned to either the APF + FGG (n = 23) or APF + CM (n = 26) group. PPDs were reduced by 1.6 mm (SD 1.0) and 1.7 mm (SD 1.2), respectively, being these differences non statistically significant (p = .782). However, the increase in KM was significantly higher in the APF + FGG compared with APF + CM (2.5 mm SD 1.6 vs. 1.6 mm SD 1.2, respectively (p = .033).
Conclusion
The tested surgical modalities resulted in similar improvements of the clinical parameters. Both free gingival graft and collagen matrix significantly increased the peri‐implant keratinized mucosa, but this KM gain was significantly higher with the free gingival graft. Use of CM, however, was better appreciated by the patients, in terms of pain perception and analgesic consumption, although the surgical time was similar.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In this letter, we introduce iBoW-LCD, a novel appearance-based loop-closure detection method. The presented approach makes use of an incremental bag-of-words (BoW) scheme based on binary descriptors ...to retrieve previously seen similar images, avoiding any vocabulary training stage usually required by classic BoW models. In addition, to detect loop closures, iBoW-LCD builds on the concept of dynamic islands, a simple but effective mechanism to group similar images close in time, which reduces the computational times typically associated with Bayesian frameworks. Our approach is validated using several indoor and outdoor public datasets, taken under different environmental conditions, achieving a high accuracy and outperforming other state-of-the-art solutions.
Chronic kidney disease (CKD) is a devastating condition that is reaching epidemic levels owing to the increasing prevalence of diabetes mellitus, hypertension and obesity, as well as ageing of the ...population. Regardless of the underlying aetiology, CKD is slowly progressive and leads to irreversible nephron loss, end-stage renal disease and/or premature death. Factors that contribute to CKD progression include parenchymal cell loss, chronic inflammation, fibrosis and reduced regenerative capacity of the kidney. Current therapies have limited effectiveness and only delay disease progression, underscoring the need to develop novel therapeutic approaches to either stop or reverse progression. Preclinical studies have identified several approaches that reduce fibrosis in experimental models, including targeting cytokines, transcription factors, developmental and signalling pathways and epigenetic modulators, particularly microRNAs. Some of these nephroprotective strategies are now being tested in clinical trials. Lessons learned from the failure of clinical studies of transforming growth factor β1 (TGFβ1) blockade underscore the need for alternative approaches to CKD therapy, as strategies that target a single pathogenic process may result in unexpected negative effects on simultaneously occurring processes. Additional promising avenues include preventing tubular cell injury and anti-fibrotic therapies that target activated myofibroblasts, the main collagen-producing cells.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aim
To evaluate the potential adjunctive effect of a resorbable collagen membrane covering a xenogeneic bone replacement graft in the reconstructive surgical therapy of peri‐implantitis.
Materials ...and Methods
Forty‐three patients (43 implants) diagnosed with peri‐implantitis associated with intra‐bony defects were treated with a surgical reconstructive approach that included a xenogeneic bone substitute material. Additionally, resorbable collagen membranes were placed over the grafting material at sites randomly allocated to the test group; conversely, no membranes were placed in the control group. Clinical outcomes, namely probing pocket depth (PPD), bleeding and suppuration on probing (BoP and SoP), marginal mucosal level (REC) and keratinized mucosa width (KMW), were recorded at baseline and 6 and 12 months after surgery. Radiographic marginal bone levels (MBLs) and patient‐reported outcomes (PROs) were assessed at baseline and 12 months. A composite outcome (success) was evaluated at 12 months, which included the absence of BoP/SoP, PPD ≤5 mm and reduction of buccal marginal mucosal level (buccal REC) of ≤1 mm.
Results
At 12 months, no implants were lost and treatment success was observed at 36.8% and 45.0% of implants in the test and control groups, respectively (p = .61). Similarly, there were no significant differences between groups in terms of changes of PPD, BoP/SoP, KMW, MBL or buccal REC. Post‐surgical complications were observed in the test group only (e.g., soft tissue dehiscence, exposure of particulate bone graft and/or resorbable membrane). Longer surgical times (~10 min; p < .05) and higher levels of self‐reported pain at 2 weeks (p < .01) were observed in the test group.
Conclusions
This study failed to demonstrate the presence of added clinical or radiographic benefits of the use of a resorbable membrane to cover a bone substitute material within the reconstructive surgical therapy of peri‐implantitis associated with intra‐bony defects.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
To evaluate the potential benefit of the use of a bone substitute material in the reconstructive surgical therapy of peri‐implantitis.
Methods
In this multicenter randomized clinical trial, ...138 patients (147 implants) with peri‐implantitis were treated surgically, randomized by coin toss to either a control (access flap surgery) or a test group (reconstructive surgery using bone substitute material). Clinical assessments, including probing pocket depth (PPD), bleeding and suppuration on probing (BOP & SOP) as well as soft tissue recession (REC), were recorded at baseline, 6 and 12 months. Marginal bone levels (MBL), measured on intra‐oral radiographs, and patient‐reported outcomes (PROs) were recorded at baseline and 12 months. No blinding to group allocation was performed. The primary outcome at 12 months was a composite measure including (i) implant not lost, (ii) absence of BOP/SOP at all aspects, (iii) PPD ≤5 mm at all aspects and (iv) ≤1 mm recession of mucosal margin on the buccal aspect of the implant. Secondary outcomes included (i) changes of MBL, (ii) changes of PPD, BOP%, and buccal KM, (iii) buccal REC and (iv) patient‐reported outcomes.
Results
During follow‐up, four implants (one in the test group, three in the control group) in four patients were removed due to disease progression. At 12 months, a total of 69 implants in the test and 68 implants in the control group were examined. Thus, 16.4% and 13.5% of implants in the test and control group, respectively, met all predefined criteria of the composite outcome. PPD reduction and MBL gain were 3.7 mm and about 1.0 mm in both groups. Reduction in mean BOP% varied between 45% (test) and 50% (control), without significant differences between groups. Buccal REC was less pronounced in the test group (M = 0.7, SD = 0.9 mm) when compared to controls (M = 1.1, SD = 1.5 mm). PROs were favorable in both groups without significant differences. One case of allergic reaction to the antibiotic therapy was recorded. No other adverse events were noted.
Conclusions
Surgical therapy of peri‐implantitis effectively improved the clinical and radiographic status at 12 months. While the use of a bone substitute material did not improve reductions of PPD and BOP, buccal REC was less pronounced in the test group. Patient satisfaction was high in both groups.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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