Tag: pubmed

Int J Periodontics Restorative Dent. 2023 Nov 8;0(0):1-21. doi: 10.11607/prd.6598. Online ahead of print.

ABSTRACT

PURPOSE: This in vivo study in a canine model assessed the effect of recombinant human platelet-derived growth factor (rhPDGF) on healing of periapical tissues following apical surgery.

MATERIALS AND METHODS: Sixty-four premolar teeth of six 2-year-old beagle dogs were randomly assigned to 4 experimental groups; 16 teeth each. In each tooth, coronal access was done, and the pulp extirpated. The teeth were then left open to the oral cavity for one week and then sealed with IRM for 8 weeks. Nonsurgical endodontic treatment (NSRCT) was then performed. A split-mouth design was used, and intra-animal side randomization was applied to the 4 groups as follows: Group 1) Apical curettage +1.5 mm root-end resection; Group 2) Apicoectomy + mineral trioxide aggregate (MTA) root-end filling; Group 3) Apicoectomy + MTA root-end filling + rhPDGF; and Group 4) Apical curettage + rhPDGF. The animals were sacrificed 24 months following apical surgery and histological and μCT analyses were performed for bone volume loss (BVL).

RESULTS: Group 1 showed partial resolution of the periapical lesions but without signs of tissue regeneration. The BVL was 49.09 ± 10.97 mm3. Group 2 showed reformation of cementum in 9 out of 16 teeth. No direct attachment between the newly formed cementum and the MTA were observed. Bone regeneration was minimal and the BVL was 35.34 ± 10.97 mm3. Group 3 showed regeneration of all damaged apical tissues but without direct contact between the cementum and MTA. The BLV was 4.51± 1.55 mm3. Group 4 showed regeneration of PDL, bone, cementum, and attachment of functional cementum fibers was observed. The BVL for this group was 2.82 ± 2.3 mm3. The difference in BVL was statistically significant only for Group 1 and Group 2 (P<0.05). There was no significance difference in the BVL between Group 3 and Group 4.

CONCLUSIONS: Recombinant human platelet-derived growth factor may play a role in regeneration of apical tissue structures following apical surgery.

CLINICAL RELEVANCE: Oral healthcare providers should be aware that addition of recombinant human platelet-derived growth factor may positively impact the regeneration of periapical tissues following apical surgery.

PMID:37939277 | DOI:10.11607/prd.6598

J Pharm Pract. 2023 Nov 8:8971900231213701. doi: 10.1177/08971900231213701. Online ahead of print.

ABSTRACT

Background: Azithromycin is a commonly prescribed antibiotic included in many first-line regimens for pneumonia. Azithromycin also carries an FDA warning for increased risk for abnormal cardiac electrical activity, including QTc prolongation. Objective: To examine the effect of intravenous azithromycin on the QT interval in a cohort of patients receiving antibiotic therapy for community acquired pneumonia. Methods: A single-center, retrospective chart review of patients admitted to the Intensive Care Unit (ICU). The primary endpoint was change in QTc 48-72 hours after antibiotic initiation. The primary outcome was analyzed using ANOVA matched comparison. Results: Between 6/1/2019 and 3/31/2020, 241 total ICU patients received doses of either antibiotic. After application of exclusion criteria, the total number of patients included in analysis was 93, including 75 azithromycin patient and 18 doxycycline patients. The baseline QTc in the azithromycin group was 449 (95% CI 438-461) and the 72-hour QTc was 442 (95% CI 427-453) with an average change in QTc of -4 ms (P = .14). No statistically significant difference was found in QTc interval change between azithromycin and doxycycline. Conclusion: In this study, azithromycin use was not associated with a statistically significant increase in QTc interval. Based on these results, for the majority of patients receiving azithromycin, QTc prolongation is not likely a major concern. However, caution may still be warranted in patients considered high risk.

PMID:37939272 | DOI:10.1177/08971900231213701

Ann Med. 2023;55(2):2279235. doi: 10.1080/07853890.2023.2279235. Epub 2023 Nov 8.

ABSTRACT

Tumour classifications play a pivotal role in prostate cancer (PCa) management. It can predict the clinical outcomes of PCa as early as the disease is diagnosed and then guide therapeutic schemes, such as active monitoring, standalone surgical intervention, or surgery supplemented with postoperative adjunctive therapy, thereby circumventing disease exacerbation and excessive treatment. Classifications based on clinicopathological features, such as prostate cancer-specific antigen, Gleason score, and TNM stage, are still the main risk stratification strategies and have played an essential role in standardized clinical decision-making. However, mounting evidence indicates that clinicopathological parameters in isolation fail to adequately capture the heterogeneity exhibited among distinct PCa patients, such as those sharing identical Gleason scores yet experiencing divergent prognoses. As a remedy, molecular classifications have been introduced. Currently, molecular studies have revealed the characteristic genomic alterations, epigenetic modulations, and tumour microenvironment associated with different types of PCa, which provide a chance for urologists to refine the PCa classification. In this context, numerous invaluable molecular classifications have been devised, employing disparate statistical methodologies and algorithmic approaches, encompassing self-organizing map clustering, unsupervised cluster analysis, and multifarious algorithms. Interestingly, the classifier PAM50 was used in a phase-2 multicentre open-label trial, NRG-GU-006, for further validation, which hints at the promise of molecular classification for clinical use. Consequently, this review examines the extant molecular classifications, delineates the prevailing panorama of clinically pertinent molecular signatures, and delves into eight emblematic molecular classifications, dissecting their methodological underpinnings and clinical utility.

PMID:37939258 | DOI:10.1080/07853890.2023.2279235

Int J Oral Maxillofac Implants. 2023 Nov 8;0(0):1-25. doi: 10.11607/jomi.10560. Online ahead of print.

ABSTRACT

AIM: This report stems from a homogeneous patient cohort from two similarly designed prospective controlled studies in the same center on surgical reconstructive treatment of peri-implantitis. The aim of this re-analysis study was exploring prognostic factors associated with surgical outcomes.

MATERIALS AND METHODS: Individual patient data of both studies were gathered. The initial study employed a submerged healing approach via primary wound closure with implant supra-structure removal and complete coverage of grafted sites. The second study employed a non-submerged healing protocol in which healing abutments were kept in place and the implant was not fully submerged. Both studies measured all outcomes at similar timepoints throughout 1 year, to include clinical and radiographic defect fill (DF and RDF), reduction of pocket depth (PDR) and bleeding on probing (BOP). Multi-level regression was used for statistical assessment of outcomes, relative to the impact of site-/local-, surgical- and patient-related variables.

RESULTS: Overall, 59 implants (30 in submerged and 29 in the non-submerged group) were treated. A statistically significant higher DF (on average 0.9 mm higher), RDF (1.7 mm) and PDR (1.3 mm) were observed when a submerged reconstructive approach was performed, whereas BOP reduction was similar. After controlling for treatment (submerged/non-submerged), there were no other significant associations with patient- (age, gender, smoking, prior periodontitis etc.), or implant-related (previous prosthesis type, arch, KTW, etc.) factors.

CONCLUSION: Within its limitations, we conclude that a submerged reconstructive approach for surgical management of peri-implantitis leads to significantly enhanced clinical and radiographic outcomes when compared to a non-submerged approach.

PMID:37939242 | DOI:10.11607/jomi.10560

Int J Oral Maxillofac Implants. 2023 Nov 8;0(0):1-23. doi: 10.11607/jomi.10468. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this clinical study was to determine the accuracy of dental implant placement by using haptic robotic guidance in a large clinical series.

MATERIAL AND METHODS: In a prospective single-arm clinical study, 108 patients received 273 individual endosteal implants. A virtual preoperative restorative and surgical plan was created from a cone beam computed tomography (CBCT) scan and matched to the surgical workspace on the day of surgery via either a tooth-based or a bone-based fiducial splint. Intraoperatively, the surgeon manipulated a handpiece attached to haptic robotic guidance arm. A variety of drills and implants were used in this series. Both the osteotomy and the implant placement were guided by 3D haptic constraints according to the virtual plan. A postoperative CBCT scans permitted the calculation of the deviations of the actual implant placement compared to the plan for accuracy. Precision was calculated by comparing standard deviations from published literature.

RESULTS: The implants were evenly distributed by jaw with 47% placed in the maxilla and 53% in the mandible. The mean ± standard deviation signed depth deviation was 0.14 ± 0.87 mm proud. The global angular deviation averaged 1.42 ± 1.53 degrees with 95% confidence limits of 1.24 degrees and 1.60 degrees. The crown of the actual placed implant showed an average deviation from the plan of 1.10 ± 0.69 mm and the apex a deviation of 1.12 ± 0.69 mm. Haptic robotic-guidance showed greater precision than freehand, static computer-guided and dynamic computer-guided implant placement.

CONCLUSION: This large clinical series of 273 implants shows a high accuracy of implant placement in comparison to published accuracy for angular deviations for any technology as well as demonstrating statistically greater precision. Long-term clinical studies are necessary to establish the true effect of increased accuracy on clinical outcomes. Using haptic robotic guidance provides accurate implant placement while allowing additional benefits compared to computer-guided surgery, namely full visualization of the surgical field and the ability to change the plan intra-operatively.

PMID:37939239 | DOI:10.11607/jomi.10468

Int J Oral Maxillofac Implants. 2023 Nov 8;0(0):1-22. doi: 10.11607/jomi.10449. Online ahead of print.

ABSTRACT

PURPOSE: Clopidogrel is a P2Y12 purinergic receptor inhibitor and a widely prescribed antiplatelet drug for the prevention of atherosclerotic events. Accumulated evidence suggests that purinergic receptors regulate important functions in bone healing and homeostasis. The purpose of the present study was to evaluate the effect of continuous perioperative clopidogrel treatment on osseointegration of titanium implants.

MATERIALS AND METHODS: Thirty two white New Zealand rabbits were randomly assigned in two groups: a clopidogrel group and a control group. Rabbits of the clopidogrel group received daily 3mg/kg of clopidogrel and the control group received vehicle for one week prior to the surgical placement of a titanium implant in their medial femoral condyle; treatment was continued for another six weeks postoperative. At this time, postmortem histologic and histomorphometric evaluation of the implants was performed.

RESULTS: Surgical procedures and postoperative period were uneventful and well tolerated by all animals without any surgical wound dehiscence, signs of infection or other complication. No implant failure was observed in any of the groups. Histomorphometric analysis showed that BIC (%) was 48.77% for the clopidogrel group and 34.65% for the control group with statistically significant difference between them (P < 0.001). Moreover, clopidogrel group had significantly greater bone tissue density (40.52 % vs 28.74 %, p<0.001) and mean trabecular thickness (284.7 μm vs 180.7 μm, p<0.001) in proximity to the implant surface, while mean trabecular number had no difference between groups (1.56 vs 1.60, p=0.961).

CONCLUSIONS: The present study showed that continuous clopidogrel treatment does not negatively affect osseointegration, but rather promotes it in terms of BIC and bone density around the titanium implants. Further studies on the effect of the P2Y12 receptor and its antagonists on peri-implant bone homeostasis may provide useful information or applications for long-term success of dental implant therapy.

PMID:37939235 | DOI:10.11607/jomi.10449

J Nurs Adm. 2023 Nov 8. doi: 10.1097/NNA.0000000000001360. Online ahead of print.

ABSTRACT

AIM: The aim of this study was to investigate the relationship between nurses’ job crafting, organizational identification, and work attachment.

BACKGROUND: Job crafting is a proactive activity in which nurses adapt the physical, cognitive, or social aspects of their jobs to make them more meaningful. Nurses are considered fundamental healthcare stakeholders who are able to transform initiatives implemented by the healthcare organization into valuable work outcomes. Nurses’ perceptions of their jobs shape the community’s opinion toward an organization.

METHODS: This is a descriptive correlational study. Two hundred seventy nurses were recruited from 1 governmental hospital in Egypt. Respondents completed the self-administered, printed questionnaires. Measures included job crafting, organizational identification, and work attachment questionnaires. Findings were investigated via descriptive and inferential statistics.

RESULTS: Over half of the nurses reported a moderate level of job crafting, whereas none of the nurses reported a high level of organizational identification. More than half of the nurses reported low levels of work attachment.

CONCLUSION: Job crafting is significantly related to nurses’ organizational identification and work attachment.

PMID:37939170 | DOI:10.1097/NNA.0000000000001360

Clin Cancer Res. 2023 Nov 8. doi: 10.1158/1078-0432.CCR-23-0561. Online ahead of print.

ABSTRACT

BACKGROUND: The MONALEESA-2, -3, -7 trials demonstrated statistically significant and clinically meaningful progression-free survival (PFS) and overall survival (OS) benefits with ribociclib + endocrine therapy (ET) vs ET alone in hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). Understanding the association of intrinsic subtypes with survival outcomes could potentially guide treatment decisions. Here, we evaluated the association of intrinsic subtypes with OS in MONALEESA-2, -3, -7.

PATIENTS AND METHODS: Tumor samples from MONALEESA-2, -3, -7 underwent PAM50-based subtyping. The relationship between subtypes and OS was assessed using univariable and multivariable Cox proportional hazards models. Multivariable models were adjusted for clinical prognostic factors.

RESULTS: Overall, 990 tumors (among 2066 patients) from ribociclib (n=580) and placebo (n=410) arms were profiled. Subtype distribution was luminal A, 54.5%; luminal B, 28.0%; HER2E, 14.6%; basal-like, 2.8%; and was consistent across treatment arms. The luminal A subtype had the best OS outcomes in both arms, while basal-like had the worst. Patients with HER2E (HR, 0.60; P=.018), luminal B (HR, 0.69; P=.023), and luminal A (HR, 0.75; P=.021) subtypes derived OS benefit with ribociclib. Patients with basal-like subtype did not derive benefit from ribociclib (HR, 1.92; P=.137); however, patient numbers were small (n=28).

CONCLUSION: The prognostic value of intrinsic subtypes for OS was confirmed in this pooled analysis of the MONALEESA trials (largest data set in HR+/HER2- ABC). While basal-like subtype did not benefit, a consistent OS benefit was observed with ribociclib added to ET across luminal and HER2E subtypes.

PMID:37939142 | DOI:10.1158/1078-0432.CCR-23-0561

PLoS Comput Biol. 2023 Nov 8;19(11):e1011607. doi: 10.1371/journal.pcbi.1011607. Online ahead of print.

ABSTRACT

Ecological interactions are fundamental at the cellular scale, addressing the possibility of a description of cellular systems that uses language and principles of ecology. In this work, we use a minimal ecological approach that encompasses growth, adaptation and survival of cell populations to model cell metabolisms and competition under energetic constraints. As a proof-of-concept, we apply this general formulation to study the dynamics of the onset of a specific blood cancer-called Multiple Myeloma. We show that a minimal model describing antagonist cell populations competing for limited resources, as regulated by microenvironmental factors and internal cellular structures, reproduces patterns of Multiple Myeloma evolution, due to the uncontrolled proliferation of cancerous plasma cells within the bone marrow. The model is characterized by a class of regime shifts to more dissipative states for selectively advantaged malignant plasma cells, reflecting a breakdown of self-regulation in the bone marrow. The transition times obtained from the simulations range from years to decades consistently with clinical observations of survival times of patients. This irreversible dynamical behavior represents a possible description of the incurable nature of myelomas based on the ecological interactions between plasma cells and the microenvironment, embedded in a larger complex system. The use of ATP equivalent energy units in defining stocks and flows is a key to constructing an ecological model which reproduces the onset of myelomas as transitions between states of a system which reflects the energetics of plasma cells. This work provides a basis to construct more complex models representing myelomas, which can be compared with model ecosystems.

PMID:37939139 | DOI:10.1371/journal.pcbi.1011607

Clin Cancer Res. 2023 Nov 8. doi: 10.1158/1078-0432.CCR-23-1889. Online ahead of print.

ABSTRACT

PURPOSE: Evidence suggests that MAPK pathway activation, as measured by ERK1/2 phosphorylation (p-ERK), predicts overall survival (OS) in recurrent glioblastoma patients receiving anti-PD-1 therapy. We aimed to validate these findings in independent cohorts.

EXPERIMENTAL DESIGN: In a 24-patient clinical trial on recurrent glioblastoma and high-grade gliomas, we examined the link between p-ERK levels and overall survival (OS). Patients received intravenous nivolumab, followed by maximal safe resection and an intracerebral injection of either ipilimumab alone or combined with nivolumab. Bi-weekly adjuvant nivolumab was then administered up to five times (NCT03233152). Using REMARK criteria, we conducted independent analyses for p-ERK quantification and statistical evaluations. Additional comparative analysis included prior cohorts, totaling 65 patients. Cox proportional hazards models and meta-analysis were employed to assess p-ERK as a predictive biomarker post-immunotherapy.

RESULTS: Lower median p-ERK+ cell density was observed compared to prior studies, likely due to tissue handling variances. Nonetheless, high p-ERK was associated with prolonged OS, particularly in IDH wild-type glioblastomas (P=0.036). Median OS for high and low p-ERK patients were 55.6 and 30 weeks, respectively. Multivariable analysis reinforced p-ERK’s significance in survival prediction (P=0.011). Meta-analysis across three cohorts (n=65) supported the survival benefit of elevated tumor p-ERK levels (P=0.0424).

CONCLUSIONS: This study strengthens the role of p-ERK as a predictive biomarker for OS in glioblastoma patients on immune checkpoint blockade. Future research should focus on further validation in prospective trials and the standardization of preanalytical variables influencing p-ERK quantification.

PMID:37939133 | DOI:10.1158/1078-0432.CCR-23-1889