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OBJECTIVE: A review of network meta-analysis to assess efficacy and safety of biologics for the treatment of psoriatic arthritis (PsA). MATERIALS AND METHODS: A systematic search was conducted on electronic databases to identify Bayesian meta-analysis reporting clinical parameters of efficacy, safety and cost-effectiveness of biologics that are approved for the treatment of PsA patients. RESULTS: We identified 19 studies and included them for review. There is insufficient statistical evidence to demonstrate clear differences in effectiveness between available biologic agents for PsA due to many differences in methods and clinical parameters reported in the studies. Old biologics are reported to be safe. CONCLUSIONS: New molecules approved for the treatment of PsA appear promising treatments but further comparative studies methodologically well-conducted are necessary. It is also necessary to follow strictly international recommendations to conduct NMA to better help physicians and decision-makers in making appropriate decisions. [ABSTRACT FROM AUTHOR]

Introduction: An active straight leg raise (SLR) is a weight bearing test which assesses pain upon movement and a patient's ability to load their pelvis, lumbar, and thoracic spine. Since many stable patients undergo computed tomography (CT) scanning solely for spinal tenderness, our hypothesis is that performing active straight leg raising could effectively rule out lumbar and thoracic vertebral fractures., Methods: Blunt trauma patients ≥18 years of age with Glasgow Coma Scale 15 presenting in hemodynamically stable condition were screened. Patients remaining in the supine position were asked to perform SLR at 12, 18, and 24 inches above the bed. The patient's ability to raise the leg, baseline pain, and pain at each level were assessed. Patients also underwent standard CT scanning of the chest, abdomen and pelvis. The clinical examination results were then matched post hoc with the official radiology reports., Results: 99 patients were screened, 65 males and 34 females. Spinal fractures were present in 15/99 patients (16%). Mechanisms of injury included motor vehicle collision 51%, pedestrian struck 25%, fall1 9%, and other 4%. The median pain score of patients with and without significant spinal fractures at 12, 18, 24 inches was 7.5, 7, 6 and 5, 5, 4, respectively. At 24 inches, active SLR had sensitivity of 0.47, a specificity of 0.59, a positive predictive value of 0.17, and an negative predictive value of 0.86., Conclusions: Although SLR has been discussed as a useful adjunct to secondary survey and physical exam following blunt trauma, its positive and more importantly negative predictive value are insufficient to rule out spinal column fractures. Liberal indications for CT based upon mechanism and especially pain and tenderness are necessary to identify all thoraco-lumbar spine fractures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hepatocellular carcinoma (HCC) represents a worldwide health matter with a major care burden, high prevalence, and poor prognosis. Its pathogenesis mainly varies depending on the underlying etiological factors, although it develops from liver cirrhosis in the majority of cases. This review summarizes the role of the most interesting soluble factors as biomarkers for early diagnosis and as recommended targets for treatment in accordance with the new challenges in precision medicine. In the premalignant environment, inflammatory cells release a wide range of cytokines, chemokines, growth factors, prostaglandins, and proangiogenic factors, making the liver environment more suitable for hepatocyte tumor progression that starts from acquired genetic mutations. A complex interaction of pro-inflammatory (IL-6, TNF-α) and anti-inflammatory cytokines (TGF-α and -β), pro-angiogenic molecules (including the Angiopoietins, HGF, PECAM-1, HIF-1α, VEGF), different transcription factors (NF-kB, STAT-3), and their signaling pathways are involved in the development of HCC. Since cytokines are expressed and released during the different stages of HCC progression, their measurement, by different available methods, can provide in-depth information on the identification and management of HCC.

Background: Hepatocellular carcinoma (HCC) is a global health problem associated with chronic liver disease. Its pathogenesis varies according to the underlying etiological factors, although in most cases it develops from liver cirrhosis. The disease progression is accompanied by pathological angiogenesis, which is a prerequisite that favors the development of HCC., Aims: This study aims at contributing to our understanding of the role of angiogenic factors in the progression of liver disease. For this purpose, we evaluate the clinical significance of serum angiogenic markers (VEGF, Ang-1, Ang-2, the angiopoietin receptor Tie1/2, HGF, and PECAM-1) first in cirrhotic and HCC patients separately, and then comparing cirrhotic patients with and without HCC., Materials and Methods: We enrolled 62 patients, out of whom 33 were diagnosed with HCC and 29 with liver cirrhosis without signs of neoplasia. Patients underwent venous blood sampling before and after receiving treatments for the diagnosed disease. Serum markers were evaluated using ELISA assays for Tie1 and the Bio-Plex Multiplex system for the remaining ones. Biomarker levels were investigated as a function of clinical scores for disease staging (MELD and Fibrosis Index, FI)., Results: In cirrhotic patients, Ang-1 and Ang-2 correlate with MELD (ρ Ang-1 = -0.73, p = 2E-5) and FI (ρ Ang-1 = -0.52, p = 7E-3, ρ Ang-2 = 0.53, p = 3E-3). A reduction of Ang-2 levels ( p = 0.047) and of the Ang-2/Ang-1 ratio ( p = 0.031) is observed in cirrhotic patients diagnosed with viral hepatitis after antiviral treatments. In HCC patients, Ang-1 negatively correlates with FI (ρ = -0.63, p = 1E-4), and PECAM-1 positively correlates with MELD (ρ = 0.44, p = 0.01). A significant Ang-1 reduction was observed in deceased patients during the study compared to ones who survived ( p = 0.01). In HCC patients, VEGF levels were increased after tumor treatment ( p = 0.037). Notably, HGF levels in cirrhotic patients with HCC are significantly raised ( p = 0.017) compared to that in those without HCC., Conclusions: Our results suggest that serum angiogenic markers, with emphasis on Ang-1/2, can contribute to the development of quantitative tools for liver disease staging and therapy monitoring. The comparison between cirrhotic patients with and without HCC suggests that HGF levels are potentially useful for monitoring the insurgence of HCC after a cirrhosis diagnosis. High Ang-1 levels in HCC patients appear to have a protective role as well as prognostic significance.

Nuclear lamina components have long been regarded as scaffolding proteins, forming a dense fibrillar structure necessary for the maintenance of the nucleus shape in all the animal kingdom. More recently, mutations, aberrant localisation and deregulation of these proteins have been linked to several diseases, including cancer. Using publicly available data we found that the increased expression levels of the nuclear protein Lamin A/C correlate with a reduced overall survival in The Cancer Genome Atlas Research Network (TCGA) patients affected by glioblastoma multiforme (GBM). We show that the expression of the LMNA gene is linked to the enrichment of cancer-related pathways, particularly pathways related to cell adhesion and cell migration. Mimicking the modulation of LMNA in a GBM preclinical cancer model, we confirmed both in vitro and in vivo that the increased expression of LMNA is associated with an increased aggressiveness and tumorigenicity. In addition, delving into the possible mechanism behind LMNA -induced GBM aggressiveness and tumorigenicity, we found that the mTORC2 component, Rictor, plays a central role in mediating these effects.

Mitotane (MTT) is an adrenolytic drug used in adjuvant and advanced treatments of adrenocortical carcinoma (ACC). Ionizing radiation (IR) is also used in adrenal cancer treatment, even though its biological action remains unknown. To provide a reliable in vivo preclinical model of ACC, we used mouse xenografts bearing human ACC to test the effects of MTT and IR alone and in combination. We evaluated tumor growth inhibition by the RECIST criteria and analyzed the cell cycle by flow cytometry (FCM). In the xenograft ACC model treated with MTT/IR in combination, we observed a marked inhibition of tumor growth, with strong tumor regression ( p < 0.0001) compared to MTT and IR given alone ( p < 0.05). The MTT results confirm its antisteroidogenic activity ( p < 0.05) in the xenograft ACC model, revealing its ability to render cancer cells more prone to radiotherapy treatment. In addition, to explain the biological effect of these treatments on the Mismatch Repair System (MMR), we interfered with the MSH2 gene expression in untreated and MTT/IR-treated H295R and SW13 cell lines. Moreover, we observed that upon treatment with MTT/IR to induce DNA damage, MSH2 gene inhibition in both the H295R and SW13 cell lines did not allow DNA damage repair, thus inducing cell death. In conclusion, MTT seems to have a radiosensitizing property and, when given in combination with IR, is able to promote neoplastic growth inhibition, leading to a significant reduction in tumor size due to cell death., Competing Interests: The authors have nothing to disclose.

Introduction: Low back pain (LBP) poses a significant burden of disease worldwide, and identifying safe and effective non-pharmacologic treatment options for LBP is a research priority. The aim of this study was to pilot a clinical trial of a portable pulsed electromagnetic field (PEMF) therapy device for subjects with mixed duration non-specific LBP., Methods: This work was a randomized, double-blind, sham-controlled, parallel-group study conducted at a chiropractic school outpatient clinic. The primary end point was functional capacity measured by the Oswestry Disability Index (ODI) at baseline, 6 weeks, and 12 weeks. Analysis was conducted on the intent-to-treat population and as a trend of change in pain scores over time using the Freidman test of repeated measures., Results: Forty-two participants were randomized to receive usual care plus PEMF therapy or usual care plus sham, and 25 completed the study. Significant improvements in ODI scores from baseline to week 6 were reported in the experimental group (χ 2  = 14.68, p < 0.001, compared with patients in the sham group, χ 2  = 4.00, p = 0.135, n.s.). This difference persisted at week-12 follow-up. Adverse events were rare and mild., Conclusion: It is feasible to conduct a clinical trial of a PEMF therapy device for non-specific LBP. This work shows that the device was safe and provides preliminary evidence of effectiveness in improving function in patients with non-specific LBP., Trial Registration: ClinicalTrials.gov identifier, NCT03053375., Funding: Aerotel Ltd.

Background: Proton pump inhibitors (PPI) may decrease the availability of clopidogrel by competitive antagonism, leading to a potential increase in ischemic events., Methods: We evaluated patients from the all-comer PARIS registry treated with dual antiplatelet therapy (DAPT) with aspirin and clopidogrel following coronary stenting for outcomes stratified by PPI use. Two-year major adverse cardiovascular events (MACE), composite of cardiac death, myocardial infarction, definite or probable stent thrombosis or target lesion revascularization (TLR), and net adverse cardiac events (NACE), composite of MACE or Bleeding Academic Research consortium (BARC) type 3 or 5 bleeding were assessed. We also explored associations between PPI use and patterns of 2-year DAPT cessation., Results: The cohort comprised 4635 patients (23% PPI users) with mean age 64.4 ±11.4 years. Two year adjusted risk of MACE (HR: 1.27, 95% CI: 1.04-1.55), NACE (HR: 1.21, 95% CI: 1.01-1.44) and TLR (HR: 1.33, 95% CI: 1.04-1.71) were significantly higher in PPI users vs. non-users, without a difference in bleeding. Although the incidence of 2-year DAPT discontinuation and interruption was similar, DAPT disruption was significantly lower among PPI users vs. non-users (10.0% vs. 14.7%, P <0.0001). Compared to non-PPI users on continued DAPT, disruption was associated with higher MACE in both PPI users (HR: 2.34, 95% CI: 1.38-3.97) and non-users (HR: 1.41, 95% CI: 1.02-1.94) but greater BARC 3,5 bleeding only in non-PPI users (HR: 2.06, 95% CI: 1.21-3.51)., Conclusions: In clopidogrel treated PCI patients, the 2-year adjusted risk of MACE and NACE was significantly higher in PPI users driven by higher TLR compared to non-PPI users, without a difference in bleeding. PPI use was associated with lower incidence of DAPT disruption without an increase in disruption related bleeding compared to non-PPI users on DAPT. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objectives: The purpose of this study was to investigate the safety and efficacy of new-generation drug-eluting stents (DES) versus early-generation DES in women undergoing complex percutaneous coronary intervention (CPCI)., Background: Whether the benefits of new-generation DES are preserved in women undergoing complex percutaneous revascularization is unknown., Methods: We pooled patient-level data from women enrolled in 26 randomized trials of DES. Study population was categorized according to the presence or absence of CPCI, which was defined as the composite of total stent length >30 mm, ≥2 stents implanted, ≥2 lesions treated, or bifurcation lesion as target vessel. The primary endpoint was major adverse cardiovascular events (MACE) defined as a composite of all-cause mortality, myocardial infarction, or target lesion revascularization at 3 years of follow-up., Results: Of 10,241 women included in the pooled database, 4,629 (45%) underwent CPCI. Compared with non-CPCI, women who underwent CPCI had a higher 3-year risk of MACE (adjusted hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.45 to 1.83; p < 0.0001). In women who underwent CPCI, use of new-generation DES was associated with significantly lower 3-year risk of MACE (adjusted HR: 0.81; 95% CI: 0.68 to 0.96), target lesion revascularization (adjusted HR: 0.74; 95% CI: 0.57 to 0.95), and definite or probable stent thrombosis (ST) (adjusted HR: 0.50; 95% CI: 0.30 to 0.83). The benefit of new-generation DES on efficacy and safety outcomes was uniform between CPCI and non-CPCI groups, without evidence of interaction. By landmark analysis, new-generation DES were associated with low rates (≤0.4%) of very-late ST irrespective of procedural complexity., Conclusions: Women undergoing CPCI remain at higher risk of adverse events. The long-term ischemic benefits of new-generation DES platforms are uniform among complex and non-complex percutaneous revascularization procedures in women., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Universities now exist in an environment of increasing accountability for their academic performance, both in teaching and research. Dental schools are expected to meet the academic expectations of their parent university and, in addition, to contribute to the health-care needs of the community. Individual staff members must achieve collectively the performance targets required of their school and individually must develop skills and expertise in their academic and clinical activities to merit tenure and promotion. This discussion examines the issues which impact on current problems of recruitment and retention of academic staff in dental schools internationally. The essential issue is career development in a manner which maintains the values that will ensure the credibility of dentistry as a scientifically based discipline and profession, while balancing the achievable academic needs with the added demands of achieving specialist clinical skills. Central to this balance is recognition that scholarship, which provides the bridge between research and teaching, can be broadly defined and that different individuals can be scholarly in a range of ways. Increasingly, schools are recognizing the importance of providing structured opportunities and guidance for career development of younger staff and of the need for flexibility in their criteria for tenure and promotion, recognizing that a diversity of individual strengths and teamworking are necessary both for the collective performance of the institution and the morale and development of the individual.

Purpose: To provide a head-to-head comparison of the anticaries efficacy associated with two commercially-available and American Dental Association-accepted dentifrices: Crest Cavity Fighting Toothpaste with Fluoristat, containing 0.243% sodium fluoride in a silica base, and Colgate Great Regular Flavor Fluoride Toothpaste, containing 0.76% sodium monofluorophosphate in a dicalcium phosphate dihydrate base. The study was conducted in harmony with the published 1988 American Dental Association guidelines for studies geared toward this purpose., Materials and Methods: The study employed a double-blind, parallel-groups, multi-center two-treatment design, and involved third, fourth, and fifth grade schoolchildren from Newark, New Jersey, and from the Cidra and Lares areas of Puerto Rico. Qualifying subjects were stratified according to age and sex, and were randomly assigned to the two treatment groups, with multiple subjects in the same household all assigned to the dentifrice randomly allocated to the first among them. Caries examinations were conducted in accordance with U.S. Food and Drug Administration guidelines for the clinical evaluation of drugs to prevent dental caries. After treatment assignment, study participants were instructed to brush their teeth at home with their assigned dentifrice at least twice daily. Brushing instructions were reinforced by the presentation of educational films and lectures at school, by semi-annual mailings to parents, and through the periodic distribution of small novelty gifts along with the dentifrice deliveries, in order to enhance the interest and enthusiasm of study participants. Post-baseline examinations were performed after 1 and after 2 yrs of product use. Two thousand four hundred seventy-nine (2,479) subjects completed this 2-yr study. For these subjects, the mean (S.D.) DFS scores at baseline were 2.77 (3.35) for the Crest group, and 2.66 (3.18) for the Colgate group. For caries increment after 1 yr, the respective means were 1.68 (2.53) and 1.70 (2.57). After 2 yrs, the mean caries increments were 3.56 (4.11) for the Crest group, and 3.56 (4.05) for the Colgate group., Results: The analysis of the 2-yr caries increment scores support the conclusion that the anticaries efficacy associated with Colgate Great Regular Flavor Fluoride Toothpaste is equivalent to that associated with Crest Cavity Fighting Toothpaste with Fluoristat, in accordance with the procedures and standards provided by the published guidelines of the American Dental Association. Further, consistent with those same standards, the results of this study serve to lend additional support to the conclusion that dentifrices formulated with sodium monofluorophosphate provide an equivalent level of anticaries efficacy as to those formulated with sodium fluoride.

The dental school plans to incorporate CODE into the curriculum so that more students have community-based dental educational experiences. Future plans also include increasing standardization of reports, clinical and administrative procedures, resources, and processes across the sites in order to lower managerial overhead. This process will be aided by further enhancement of computerized information systems and electronic links. The major lesson learned is that new extramural programs can be created and sustained by pooling school resources with those from the private and public sectors. Funding sources and opportunities available to one party alone are insufficient. While one-time funding was used to build and furnish the NJDS extramural sites, the clinics were established only after business plans demonstrated the availability of funds to sustain their operations. The Statewide Network of Community Oral Health Care and CODE models are still evolving, but they are replicable not only in dental education but in other types of health services. The details of the partnerships and funding streams will vary from site to site, but through outreach and careful negotiation with potential partners and detailed contracts, the community service and educational missions of a health professions school can have a successful outcome.

No comprehensive national study has ever been completed on the oral health status of people with disabilities, their patterns of use of oral health services and access-to-care barriers. The authors describe the Special Olympics, Special Smiles program, conducted as part of the New Jersey Summer Special Olympics Games, and assess a pilot-tested model for collecting epidemiologic data. The results of this initial data collection are also compared with the goals of the U.S. Public Health Service, as outlined in the Healthy People 2000 publication.

A Patient Instructor (PI) program designed to improve students' data-gathering and interpersonal skills is evaluated. Each student in two consecutive classes of third-year students (class of 1996, n = 60; class of 1997, n = 72) interviewed four patient instructors (PIs) during a three-hour rotation. Each PI portrayed one of six scenarios. PIs assessed students using content checklists and an abbreviated Arizona Clinical Interview Rating Scale (ACIR). After the interview, each PI gave student constructive feedback regarding interpersonal behavior and ability to identify salient content items from the patient's history. Significant improvement was observed on content checklists (p < 0.01) between the first and second rounds. Significant improvement was also noted on the ACIR (p < 0.01) between rounds one, two and three. The results indicate that data-gathering and interpersonal skills can be enhanced by using patient instructors. Student evaluation of the program was positive.

Participation in a self-administered quality assessment (SAQA) program led to changes in New Jersey dentists' perceptions of practice quality. Ninety-four percent indicated they discovered practice deficiencies. This study suggests that using a self-administered quality assessment program, such as the SAQA program, can lead to a better understanding of a practice's strengths and weaknesses.

Age-related changes in renal function have been attributed to alterations in the chemical composition of the kidney tissues. Hence, the glycosaminoglycan composition of the renal cortex and medulla at varying age intervals was investigated. Glycosaminoglycans were isolated from the tissues by means of digestion with collagenase and pronase and purified by ethanol precipitation. Subsequent separation of various polyanions was accomplished by ion exchange chromatography on a Dowex 1-X2 column, using sodium chloride buffers of increasing ionic strengths. The glycosaminoglycans in each fraction were identified and quantitated by digestion with specific enzymes, including hyaluronidase, chondroitinase AC and ABC. The enzyme resistant material was separated and further digested with nitrous acid to quantitate the proportion of heparon sulfate. The results indicate that the glycosaminoglycan content of the renal medulla was much higher than the cortex at all the age intervals studied, and age-induced reduction was mainly cortical. There was a significant reduction in the heparan sulfate content of the cortex in aging. Interestingly, the major glycosaminoglycan content of the medulla was hyaluronic acid, which showed a sharp increase during aging, whereas heparan sulfate declined. Chondroitin sulfate was not altered due to age in either tissue. The molecular weight of hyaluronic acid was determined by column chromatography. Results indicate that the size of hyaluronate in the cortex was small and did not vary with age. In the medulla of the younger age group, a considerable amount of large size hyaluronate was observed. As age increased, the size decreased. The results strongly suggest that alteration in the renal glycosaminoglycans may be partly responsible for the age related protinuria and ionic imbalance.

In an attempt to better prepare students for dental practice in a litigious environment with cost-containment pressures, quality assurance requirements, and increased patient expectations, the New Jersey Dental School has begun planning and implementing various programs to teach students and faculty ethics, jurisprudence, and risk management. In addition to formal course work, the New Jersey Dental School is implementing a quality assurance and risk management clinical program.