Psychological intervention improves quality of life in patients with early-stage cancer: a systematic review and meta-analysis of randomized clinical trials.

The effectiveness of psychological interventions (PI) for malignant diseases is controversial. We aimed to investigate the effect of PI on survival and quality of life (QoL) in patients with cancer. We performed a systematic search of MEDLINE, Cochrane, and Embase databases to identify randomized controlled trials comparing PI to standard care (PROSPERO registration number CRD42021282327). Outcomes were overall survival (OS), recurrence-free survival (RFS), and different domains of QoL. Subgroup analysis was performed based on the provider-, type-, environment-, duration of intervention; cancer stage, and type. Pooled hazard ratios (HR) and standardized mean difference (SMD) with 95% confidence intervals (CI) were calculated using a random-effects model. The OS and RFS did not differ significantly between the two groups (OS:HR = 0.97; CI 0.87-1.08; RFS:HR = 0.99; CI 0.84-1.16). However, there was significant improvement in the intervention group in all the analyzed domains of QoL; in the global (SMD = 0.65; CI 0.35-0.94), emotional (SMD = 0.64; CI 0.33-0.95), social (SMD = 0.32; CI 0.13-0.51) and physical (SMD = 0.33; CI 0.05-0.60) domains. The effect of PI on QoL was generally positive immediately, 12 and 24 weeks after intervention, but the effect decreased over time and was no longer found significant at 48 weeks. The results were better in the breast cancer group and early stages of cancer. PIs do not prolong survival, but they significantly improve the QoL of cancer patients. PI should be added as standard of care 3-4 times a year, at least for patients with early-stage cancer.

Prediabetes and poorly controlled type-2 diabetes as risk indicators for peri-implant diseases:A systematic review and meta-analysis.

OBJECTIVE: The study answers the PECO question: "In adults with dental implants (P), do subjects suffering from type-2 diabetes or prediabetes (E) have worse peri-implant conditions (O) than subjects without type-2 diabetes and prediabetes (C)?". Prediabetes (5.7-6.4 % HbA1c), and the different qualities of glycemic control in type-2 diabetes; well-controlled (>8 % HbA1c), and poorly controlled (>8 % HbA1c) individuals; were classified according to the recommendations of the American Diabetes Association. DATA: Predefined search keys were used with search terms including: Dental implant, diabetes mellitus, glycemic control and HbA1c. SOURCES: An electronic search in the MEDLINE, Embase, and Cochrane libraries were conducted without any filters or language restrictions. Additionally, manual search of the reference lists were carried out to identify all relevant articles. STUDY SELECTION: Eligibility criteria were cohort, case-control and cross-sectional studies that answerd our PECO question with at least 1 year of follow-up. From a total of 2660 records, 35 articles (1761 individuals) were included in the analysis. Meta-analytic difference in means for crestal bone loss was 1.2 mm [95 % CI=0.4; 2.1] in patients with prediabetes, 1.8 mm [CI=1.0; 2.7] in poorly controlled patients, whereas 0.4 mm [CI=-0.3; 1.1] in well-controlled individuals. Meta-regression showed that 1 % increase in HbA1c increased crestal bone loss by 0.24 mm. CONCLUSIONS: Within the limitations of the study, patients with poorly controlled type-2 diabetes or prediabetes may have worse peri-implant conditions compared to patients without diabetes and well-controlled type-2 diabetes. Well-controlled type-2 diabetes is not a risk indicator for peri-implant diseases. CLINICAL SIGNIFICANCE: Clinicians should measure blood HbA1c levels when planning implant-supported restorations, thus patients with undiagnosed or poorly controlled type-2 diabetes can be identified, that allows for glycemic level adjustment prior to dental implant surgery, ensuring peri-implant health. PROTOCOL REGISTRATION NUMBER: (CRD42022375263).

Are Artificial Intelligence-Assisted Three-Dimensional Histological Reconstructions Reliable for the Assessment of Trabecular Microarchitecture?

Objectives: This study aimed to create a three-dimensional histological reconstruction through the AI-assisted classification of tissues and the alignment of serial sections. The secondary aim was to evaluate if the novel technique for histological reconstruction accurately replicated the trabecular microarchitecture of bone. This was performed by conducting micromorphometric measurements on the reconstruction and comparing the results obtained with those of microCT reconstructions. Methods: A bone biopsy sample was harvested upon re-entry following sinus floor augmentation. Following microCT scanning and histological processing, a modified version of the U-Net architecture was trained to categorize tissues on the sections. Detector-free local feature matching with transformers was used to create the histological reconstruction. The micromorphometric parameters were calculated using Bruker's CTAn software (version 1.18.8.0, Bruker, Kontich, Belgium) for both histological and microCT datasets. Results: Correlation coefficients calculated between the micromorphometric parameters measured on the microCT and histological reconstruction suggest a strong linear relationship between the two with p-values of 0.777, 0.717, 0.705, 0.666, and 0.687 for BV/TV, BS/TV, Tb.Pf Tb.Th, and Tb.Sp, respectively. Bland-Altman and mountain plots suggest good agreement between BV/TV measurements on the two reconstruction methods. Conclusions: This novel method for three-dimensional histological reconstruction provides researchers with a tool that enables the assessment of accurate trabecular microarchitecture and histological information simultaneously.

Comparative analysis of surgical and prosthetic rehabilitation in maxillectomy: A systematic review and meta-analysis on quality-of-life scores and objective speech and masticatory measurements.

STATEMENT OF PROBLEM: Patients with oro-antral communication, whether from trauma, disease, or congenital anomalies, have options for surgical reconstruction or prosthetic obturation, but guiding interdisciplinary protocols are lacking. PURPOSE: The purpose of this systematic review and meta-analysis was to compare surgical reconstruction and prosthetic obturation, identifying correlations with baseline characteristics to determine the most effective approach for specific patients. MATERIAL AND METHODS: A systematic search was conducted in 4 databases. Searching, screening, data extraction, and risk of bias assessment were performed by 2 reviewers. Eligible studies focused on patients with palatomaxillary defects from cancer-related maxilla surgeries. Traumatic or congenital defects were excluded. The study compared prosthetic restoration (either with surgical or definitive obturators) to surgical reconstruction using flaps or grafts. Patients with surgical restoration after tooth extraction were excluded. Both subjective and objective outcomes were used for comparison. RESULTS: Thirteen articles were included in the qualitative synthesis and 9 in the meta-analysis. Patient scores on quality-of-life questionnaires, objective speech, and masticatory ability evaluations were compared. The number of patients who underwent surgical reconstruction was 206, whereas 260 patients received prosthetic obturators. Results showed no significant differences. In the "activity" domain of the University of Washington QoL questionnaire, however, the 1.92 (0.45, 3.40) score difference was not clinically relevant. However, the heterogeneity of trials, the transient nature of subjective evaluations, the low number of participants, and major confounding biases did not allow a solid conclusion to be drawn. CONCLUSIONS: The growing number of maxillectomy patients demands firm evidence on which rehabilitation to choose and when it should be done. The result suggests that obturator devices and surgical reconstruction have similar effects on quality of life and health outcomes. A multicentric registry in which patient strata could be analyzed separately by age, adjuvant therapies, defect sizes, and remaining dentition is advocated.

Advancing accuracy in guided implant placement: A comprehensive meta-analysis: Meta-Analysis evaluation of the accuracy of available implant placement Methods.

OBJECTIVES: This meta-analysis aimed to determine the accuracy of currently available computer-assisted implant surgery (CAIS) modalities under in vitro conditions and investigate whether these novel techniques can achieve clinically acceptable accuracy. DATA: In vitro studies comparing the postoperative implant position with the preoperative plan were included. Risk of bias was assessed using the Quality Assessment Tool For In Vitro Studies (QUIN Tool) and a sensitivity analysis was conducted using funnel plots. SOURCES: A systematic search was performed on April 18, 2023, using the following three databases: MEDLINE (via PubMed), EMBASE, and Cochrane Central Register of Controlled Trials. No filters or restrictions were applied during the search. RESULTS: A total of 5,894 studies were included following study selection. Robotic- and static CAIS (sCAIS) had the most accurate and clinically acceptable outcomes. sCAIS was further divided according to the guidance level. Among the sCAIS groups, fully guided implant placement had the greatest accuracy. Augmented reality-based CAIS (AR-based CAIS) had clinically acceptable results for all the outcomes except for apical global deviation. Dynamic CAIS (dCAIS) demonstrated clinically safe results, except for horizontal apical deviation. Freehand implant placement was associated with the greatest number of errors. CONCLUSIONS: Fully guided sCAIS demonstrated the most predictable outcomes, whereas freehand sCAIS demonstrated the lowest accuracy. AR-based and robotic CAIS may be promising alternatives. CLINICAL SIGNIFICANCE: To our knowledge, this is the first meta-analysis to evaluate the accuracy of robotic CAIS and investigate the accuracy of various CAIS modalities.

The use of autogenous tooth bone graft is an efficient method of alveolar ridge preservation - meta-analysis and systematic review.

BACKGROUND: Ridge resorption following tooth extraction may be reduced by alveolar ridge preservation (ARP). Previous randomized clinical trials and systematic reviews have suggested that autogenous tooth bone graft (ATB) can be an effective alternative material for ARP. However, the results are heterogeneous. Therefore, our research aimed to evaluate the efficacy of ATB in ARP. METHODS: A systematic search was conducted in Cochrane Library, Embase, MEDLINE and Scopus for studies published from inception to 31 November 2021. We searched searched for randomized, non-randomized controlled trials and case series reporting on ATB use for ARP. The primary outcome was the ridge width difference pre- and post-surgery, measured in millimetres (mm) measured on CBCT (cone beam computed tomography). The secondary outcomes were the histological results. We followed the PRISMA2020 recommendations for reporting our systematic review and meta-analysis. RESULTS: The analysis included eight studies for the primary and six for the secondary outcomes. The meta-analysis revealed a positive ridge preservation effect with a pooled mean difference ridge width change of -0.72 mm. The pooled mean residual graft proportion was 11.61%, and the newly formed bone proportion was 40.23%. The pooled mean of newly formed bone proportion was higher in the group where ATB originated from both the root and crown of the tooth. CONCLUSIONS: ATB is an effective particulate graft material in ARP. Complete demineralization of the ATB tends to decrease the proportion of newly formed bone. ATB can be an attractive option for ARP. TRIAL REGISTRATION: The study protocol was registered on PROSPERO (CRD42021287890).

Evaluation of the Histomorphometric and Micromorphometric Performance of a Serum Albumin-Coated Bone Allograft Combined with A-PRF for Early and Conventional Healing Protocols after Maxillary Sinus Augmentation: A Randomized Clinical Trial.

The aim of this study was to compare the microarchitecture of augmented bone following maxillary sinus augmentation (MSA) after healing periods of 3 (test) and 6 (control) months using the combination of advanced platelet-rich fibrin (A-PRF) and a serum albumin-coated bone allograft (SACBA). Twenty-six patients with 30 surgical sites who required two-stage MSA were enrolled and grafted with the combination of A-PRF and SACBAs. The surgical sites were randomly allocated to the test or control group. During implant site preparation, 17 bone core biopsy samples were collected from each study group for histological, histomorphometric and micromorphometric analysis. Resonance frequency analysis was performed at the time of implant placement and 6, 8, 10, and 12 weeks postoperatively. The percentage of newly formed bone was 44.89 ± 9.49% in the test group and 39.75 ± 8.15% in the control group (p = 0.100). The results of the µCT analysis showed no significant differences in morphometric parameters between the study groups. The implant stability quotient was not significantly different between the two groups at 10 and 12 weeks postoperatively. Based on these findings, the total treatment time may be reduced by 3 months with the use of A-PRF and SACBAs for two-stage MSA.

Comparison between Micro-Computed Tomography and Cone-Beam Computed Tomography in the Assessment of Bone Quality and a Long-Term Volumetric Study of the Augmented Sinus Grafted with an Albumin Impregnated Allograft.

The purpose of our study was to compare micromorphometric data obtained by cone-beam computed-tomography (CBCT) and microcomputed-tomography (micro-CT) of the augmented sinus and to evaluate the long-term stability of the bone gain achieved using BoneAlbumin. Sinus lifts, and after 6-months, healing bone-biopsy and implant placement were carried out. Specimens were analyzed by micro-CT. A total of 16 samples were collected from nine patients (mean age 54.7 ± 6.5 years). Pre-, postoperative, and 3-year control CBCT-data were registered to determine from where the biopsy samples were harvested. Micromorphometric variables were calculated from the micro-CT- and CBCT-data, and their correlation was determined by Spearman's test. The volume of augmented bone was calculated at the time of implant placement and after 3 years. A positive correlation was found between bone-volume fraction, trabecular-separation, open-, and total-porosity, while a negative correlation was found between trabecular-thickness obtained from CBCT- and micro-CT-data (p < 0.05). Mean volumetric reduction of 39.28% (11.88-60.02%) was observed. Correlation of CBCT- and micro-CT-data suggested that micromorphometric analysis of CBCT reconstructions of the augmented sinuses provided reliable information on the microarchitecture of augmented bone. CBCT as a modality might be adequate in the analysis of bone quality in the augmented sinus. At the 3-year, control sinus grafts showed volumetric stability.

Serum albumin-coated bone allograft (BoneAlbumin) results in faster bone formation and mechanically stronger bone in aging rats.

Serum albumin-coated bone allografts (BoneAlbumin) have successfully supported bone regeneration in various experimental models by activating endogenous progenitors. However, the effect of tissue aging, linked to declining stem cell function, has yet to be explicitly examined within the context of BoneAlbumin's regenerative capacity. Stem cell function was tested with an in vitro attachment assay, which showed that albumin coating increases stem cell attachment on demineralized bone surfaces in an aging cell population. Bone regeneration was investigated in vivo by creating critical size bone defects on the parietal bones of aging female rats. Demineralized bone matrices with and without serum albumin coating were used to fill the defects. Bone regeneration was determined by measuring the density and the size of the remaining bone defect with computed tomography (CT). Microcomputed tomography (MicroCT) and mechanical testing were performed on the parietal bone explants. In vivo CT and ex vivo microCT measurements showed better regeneration with albumin-coated grafts. Additionally, the albumin-coated group showed a twofold increase in peak fracture force compared with uncoated allografts. In the present study, serum albumin-coated demineralized bone matrices successfully supported faster and functionally superior bone regeneration in aging rats. Because stem cell function, a key contributor of bone remodelling, decreases with age and serum albumin is an effective activator of endogenous progenitor cells, this method could be an effective and safe adjuvant in bone regeneration of aging adult and osteo-compromised populations.

Development of a quantitative preclinical screening model for implant osseointegration in rat tail vertebra.

OBJECTIVES: Functional tooth replacement and bone regeneration are parts of the daily practice in modern dentistry, but well-reproducible and relatively inexpensive experimental models are still missing. We aimed to develop a new small animal model to monitor osseointegration utilizing the combination of multiple evaluation protocols. MATERIAL AND METHODS: After cutting the tail between the C4 and C5 vertebrae in Wistar rats, costume made, parallel walled, non-threaded implants were placed into the center of the tail parallel with its longitudinal axis using a surgical guide. Osseointegration of the titanium implants was followed between 4 and 16 weeks after surgery applying axial extraction force, and resonance frequency analysis as functional tests, and histomorphometry and micro-CT as structural evaluations. RESULTS: In functional tests, we observed that both methods are suitable for the detection of the time-dependent increase in osseointegration, but the sensitivity of the pull-out technique (an approximately five times increase with rather low standard error) was much higher than that of the resonance frequency analysis. In structural evaluations, changes in the detected bone implant contact values measured by histomorphometry (yielding 1.5 times increase, with low variations of data) were more reliable than micro-CT based evaluations to screen the developments of contact between bone and implant. CONCLUSION: Our results provide evidence that the caudal vertebrae osseointegration model is useful for the preclinical evaluation of implant integration into the bone. CLINICAL RELEVANCE: The combination of the biomechanical and structural tests offers a well-reproducible small animal system that can be suitable for studying the integration of various implant materials and surface treatments.

Microarchitecture of the Augmented Bone Following Sinus Elevation with an Albumin Impregnated Demineralized Freeze-Dried Bone Allograft (BoneAlbumin) versus Anorganic Bovine Bone Mineral: A Randomized Prospective Clinical, Histomorphometric, and Micro-Computed Tomography Study.

Serum albumin has been identified as an endogenous protein that is integral to early bone regeneration. We hypothesized that albumin addition to allografts may result in better bone remodeling than what can be achieved with anorganic xenografts. Sinus elevations were performed at 32 sites of 18 patients with the lateral window technique. Sites either received filling with an anorganic bovine bone mineral (ABBM, BioOss, Geistlich, CH) or albumin impregnated allograft (BoneAlbumin, OrthoSera, AT). After 6-months patients received dental implants and 16 bone core biopsy samples were obtained from the ABBM filled, and 16 from the BoneAlbumin augmented sites. The biopsies were examined by histomorphometry and µCT. Percentage of the residual graft in the BoneAlbumin group was 0-12.7%, median 5.4% vs. ABBM 6.3-35.9%, median 16.9%, p < 0.05. Results of the µCT analysis showed that the microarchitecture of the augmented bone in the BoneAlbumin group resembles that of the native maxilla in morphometric parameters Trabecular Pattern Factor and Connectivity. Our data show that while ABBM successfully integrates into the newly formed bone tissue as persisting particles, BoneAlbumin is underway towards complete remodeling with new bone closely resembling that of the intact maxilla.

Pituitary Adenylate Cyclase-Activating Peptide (PACAP), a Novel Secretagogue, Regulates Secreted Morphogens in Newborn Rat Retina.

Purpose: Pituitary adenylate cyclase-activating peptide (PACAP)1-38 has been reported to be responsible for regulation of a disparate array of developmental processes in the central nervous system, and its antiapoptotic effect has been revealed in numerous models, pointing to its relevance in the etiology of neurodegenerative disorders. However, its function in retinal development remains unclear. Here, we aimed to point out that versatility can be achieved through interaction with other regulators, in which PACAP can act indirectly on the retinal microenvironment. Methods: Wistar rats at age postnatal day 1 were injected intravitreally with PACAP or PAC1 receptor antagonist (PACAP6-38, M65) or VPAC1 antagonist (PG97-269) alone or in combination. Retinas were removed at 3, 6, 12, or 24 hours after injection. Changes in mRNA level were assessed using quantitative PCR, whereas changes in protein levels were measured by Western blot. Results: Intravitreal injection of PACAP or PAC1 receptor antagonists or the VPAC1 antagonist showed that PACAP receptors regulate the expression of five key secreted molecules (i.e., Fgf1, Bmp4, Wnt1, Gdf3, and Ihh), wherease other crucial morphogens (i.e., Fgf2, Fgf4, Fgf8, Fgf9, Shh, and Bmp9) were not affected. Pharmacologic dissection revealed that both PAC1 and VPAC1 induced downstream signaling and could cause upregulation of Fgf1, Bmp4, and Wnt1, whereas expression of Gdf3 might be mediated through the VPAC2 receptor. Conclusions: Our data are the first to shed light on PACAP as a secretagogue regulating a sustained production of morphogens, which in turn could enable PACAP to serve as a mitogen for retinal cells, to induce ganglion cell differentiation, and to contribute to RPE development.

Development-related splicing regulates pituitary adenylate cyclase-activating polypeptide (PACAP) receptors in the retina.

PURPOSE: The ubiquitous pituitary adenylate cyclase-activating peptide (PACAP) has a disparate array of functions in development (e.g., proliferation and apoptosis). Among three types of PACAP receptor (VPAC1, VPAC2, and PAC1), PAC1 is subject to alternative splicing that generates isoforms. Although the literature documenting the presence of PACAP receptors in the central nervous system is vast, their expression during development has not been established yet. Here, we performed quantitative analyses on the expression of PACAP receptors during the postnatal development of the rat retina. METHODS: Retinas were harvested from postnatal days 0 to 20 (P0-P20). Using a comprehensive primer system, expression changes were followed employing quantitative real-time PCR. Changes at the protein level were detected by immunoblotting using anti-VPAC1, -VPAC2, and -PAC1 receptor antibodies. RESULTS: The expression of VPAC1 showed increases at P10 and P15. Peaks in VPAC2 expression were observed at P5 and P15. Using splicing variant-specific primers for PAC1 receptor, splicing regulation of Null, Hip, Hop1, and Hiphop1 variants was revealed in correlation with postnatal development. Transcript levels of the Null and Hip variants showed a decline, while Hop1 became the major PACAP receptor by P20. Hiphop1 transcript levels did not display remarkable changes except for a transient increase at P10. Immunoblotting confirmed the presence and expression level changes of the receptors. CONCLUSIONS: We conclude that both VPAC1 and VPAC2 could have roles at all stages of retinal development, that PACAP acts through a specific set of PAC1 isoforms, and that Hip and Hop1 are predominantly involved in the postnatal development of rat retina.

Comparing the folding and misfolding energy landscapes of phosphoglycerate kinase.

Partitioning of polypeptides between protein folding and amyloid formation is of outstanding pathophysiological importance. Using yeast phosphoglycerate kinase as model, here we identify the features of the energy landscape that decide the fate of the protein: folding or amyloidogenesis. Structure formation was initiated from the acid-unfolded state, and monitored by fluorescence from 10 ms to 20 days. Solvent conditions were gradually shifted between folding and amyloidogenesis, and the properties of the energy landscape governing structure formation were reconstructed. A gradual transition of the energy landscape between folding and amyloid formation was observed. In the early steps of both folding and misfolding, the protein searches through a hierarchically structured energy landscape to form a molten globule in a few seconds. Depending on the conditions, this intermediate either folds to the native state in a few minutes, or forms amyloid fibers in several days. As conditions are changed from folding to misfolding, the barrier separating the molten globule and native states increases, although the barrier to the amyloid does not change. In the meantime, the native state also becomes more unstable and the amyloid more stable. We conclude that the lower region of the energy landscape determines the final protein structure.