The varied spectrum of nephroblastomatosis,nephrogenic rests,and Wilms tumors: Review of current definitions and challenges of the field

The diagnosis of multiple or diffuse renal lesions in a child is challenging by imaging and/or pathology. Optimal management requires distinguishing benign lesions such as nephrogenic rests from cancerous lesions such as Wilms tumor, but this is often difficult or impossible. This difficulty is compounded by the overlapping nature of our current radiologic and pathologic definitions of lesions along the spectrum of nephrogenic rests/nephroblastomatosis. We provide a review of these issues, as a collaborative effort between the Children's Oncology Group Renal Tumor Committee and International Society of Pediatric Oncology Renal Tumor Study Group. Our aim is to discuss current challenges in diagnosis and management of these renal lesions, encouraging future work toward consensus definitions for research and patient care.     

Minimal intervention dentistry for managing dental caries – a review

This publication describes the history of minimal intervention dentistry (MID) for managing dental caries and presents evidence for various carious lesion detection devices, for preventive measures, for restorative and non‐restorative therapies as well as for repairing rather than replacing defective restorations. It is a follow‐up to the FDI World Dental Federation publication on MID, of 2000. The dental profession currently is faced with an enormous task of how to manage the high burden of consequences of the caries process amongst the world population. If it is to manage carious lesion development and its progression, it should move away from the ‘surgical’ care approach and fully embrace the MID approach. The chance for MID to be successful is thought to be increased tremendously if dental caries is not considered an infectious but instead a behavioural disease with a bacterial component. Controlling the two main carious lesion development related behaviours, i.e. intake and frequency of fermentable sugars, to not more than five times daily and removing/disturbing dental plaque from all tooth surfaces using an effective fluoridated toothpaste twice daily, are the ingredients for reducing the burden of dental caries in many communities in the world. FDI's policy of reducing the need for restorative therapy by placing an even greater emphasis on caries prevention than is currently done, is therefore, worth pursuing.     

Clinico-histopathological correlations of venous wall modifications in chronic venous insufficiency

The interest manifested for the conjunctive tissue pathology leaded to the study of the structural disorder that appears in the varicose veins walls. The study is a prospective one initiated in March 2007 made on 11 patients with varicose disease hospitalized at Cluj-Napoca within Surgery Clinic no. II. The purpose of this study is to point out the histopathological modifications in the varicose venous wall (great saphenous vein cross, communicating veins, perforating veins), as well as the correlation of histopathological results with the evolutive stage of chronic vein insufficiency (CEAP classification) and with the clinical score at these patients. The histopathological (HP) results for 2 of the patients revealed hypertrophy of the media, intimal hyperplasia (stage II) corresponding to a CEAP 3. Six patients were integrated in HP stage III due to the partial intimal fibrosis corresponding to a CEAP 6 for one case, CEAP 4 one case, CEAP 3 four cases. One patient had HP stage I with CEAP 3 and two patients had HP stage IV corresponding to CEAP 5, respectively CEAP 6.     

Phase 2 study of pegylated liposomal doxorubicin, vincristine, decreased-frequency dexamethasone, and thalidomide in newly diagnosed and relapsed-refractory multiple myeloma

OBJECTIVE: To evaluate the efficacy and safety of adding thalidomide to the pegylated liposomal doxorubicin, vincristine, and decreased-frequency dexamethasone (DVd) regimen for multiple myeloma. PATIENTS AND METHODS: Patients newly diagnosed as having active multiple myeloma and those with relapsed-refractory disease were studied between August 2001 and October 2003. Patients received DVd as previously described. Thalidomide was given at 50 mg/d orally and the dose increased slowly to a maximum of 400 mg/d. At the time of best response, patients received maintenance prednisone, 50 mg orally every other day, and daily thalidomide at the maximum tolerated dose for each patient. The primary end point was the rate of complete responses plus very good partial responses as defined by the European Group for Blood and Marrow Transplantation criteria and the Intergroupe Fran?ais du Myélome, respectively. RESULTS: Of 102 eligible patients, 53 were newly diagnosed as having multiple myeloma, and 49 had been previously treated for multiple myeloma. The complete response plus very good partial response rate was 49% and 45%, with an overall response rate of 87% and 90% for patients with newly diagnosed and previously treated multiple myeloma, respectively. Furthermore, better responses were associated with improved progression-free and overall survival. The most common grade 3 and 4 adverse events were thromboembolic events (25%), peripheral neuropathy (22%), and neutropenia (14%). CONCLUSIONS: The addition of thalidomide to the DVd regimen significantly improves the response rate and quality of responses compared with the DVd regimen alone. This improvement is associated with longer progression-free and overall survival. The rate of observed quality responses is comparable to responses seen with high-dose therapy.     

Systemic and local expression of perforin in lymphocyte subsets in acute and chronic rheumatoid arthritis

OBJECTIVE: To investigate the role of the cytolytic action mediated by perforin in the course of rheumatoid arthritis (RA), we studied the immunophenotypic characteristics of lymphocytes containing perforin in peripheral blood (systemic level), in synovial fluid (SF), and in the synovial membrane (local level) in patients during the acute or chronic phase of RA. Cells from patients with osteoarthritis were used as controls. METHODS: Flow cytometry was used for simultaneous detection of intracellular (perforin) and cell surface antigens. Mean fluorescence intensity (MFI) was a measure of the mean perforin content per cell. Immunocytochemical staining was used to visualize perforin in the cytoplasmic compartment of cells. RESULTS: In acute RA highly significant changes in perforin expression were found in all compartments (peripheral blood, SF, and synovial membrane): (1) increase of percentage of total perforin positive cells; (2) increase of both subsets of cytolytic cells, T (CD8+P+) and NK (CD56+P+) cells; (3) increase in the frequency of perforin positive cells in CD8+ and CD56+ cell populations; and (4) the highest content of perforin/cell (MFI values) in all compartments, except in the synovial membrane. CONCLUSION: Perforin positive cells may participate in the acute phase of RA by maintaining and perpetuating inflammation and contributing to tissue destruction.     

DNA immunization circumvents deficient induction of T helper type 1 and cytotoxic T lymphocyte responses in neonates and during early life

The relative deficiency of T helper type 1 (Th1) and cytotoxic T lymphocyte (CTL) responses in early life is associated with an increased susceptibility to infections by intracellular microorganisms. This is likely to reflect a preferential polarization of immature CD4 T cells toward a Th2 rather than a Th1 pattern upon immunization with conventional vaccines. In this report, it is shown that a single immunization within the first week of life with DNA plasmids encoding viral (measles virus hemagglutinin, Sendai virus nucleoprotein) or bacterial (C fragment of tetanus toxin) vaccine antigens can induce adult-like Th1 or mixed Th1/Th2 responses indicated by production of IgG2a vaccine-specific antibodies and preferential secretion of interferon-γ (IFN-γ) compared with interleukin (IL)-5 by antigen-specific T cells, as well as significant CTL responses. However, in spite of this potent Th1-driving capacity, subsequent DNA immunization was not capable of reverting the Th2-biased responses induced after early priming with a recombinant measles canarypox vector. Thus, DNA vaccination represents a novel strategy capable of inducing Th1 or mixed Th1/Th2 and CTL responses in neonates and early life, providing it is performed prior to exposure to Th2-driving conventional vaccine antigens.     

Increased plasma N-glycome complexity is associated with higher risk of type 2 diabetes

Aims/hypothesis

Better understanding of type 2 diabetes and its prevention is a pressing need. Changes in human plasma N-glycome are associated with many diseases and represent promising diagnostic and prognostic biomarkers. Variations in glucose metabolism directly affect glycosylation through the hexosamine pathway but studies of plasma glycome in type 2 diabetes are scarce. The aim of this study was to determine whether plasma protein N-glycome is changed in individuals who are at greater risk of developing type 2 diabetes.

Methods

Using a chromatographic approach, we analysed N-linked glycans from plasma proteins in two populations comprising individuals with registered hyperglycaemia during critical illness (increased risk for development of type 2 diabetes) and individuals who stayed normoglycaemic during the same condition: AcuteInflammation (59 cases vs 49 controls) and AcuteInflammation Replication (52 cases vs 14 controls) populations. N-glycome was also studied in individuals from FinRisk (37 incident cases of type 2 diabetes collected at baseline vs 37 controls), Orkney Complex Disease Study (ORCADES; 94 individuals with HbA_1c > 6.5% [47.5 mmol/mol] vs 658 controls) and Southall and Brent Revisited (SABRE) cohort studies (307 individuals with HbA_1c > 6.5% [47.5 mmol/mol] vs 307 controls).

Results

Individuals with increased risk for diabetes type 2 development (AcuteInflammation and AcuteInflammation Replication populations), incident cases of type 2 diabetes collected at baseline (FinRisk population) and individuals with elevated HbA_1c (ORCADES and SABRE populations) all presented with increased branching, galactosylation and sialylation of plasma protein N-glycans and these changes were of similar magnitude.

Conclusions/interpretation

Increased complexity of plasma N-glycan structures is associated with higher risk of developing type 2 diabetes and poorer regulation of blood glucose levels. Although further research is needed, this finding could offer a potential new approach for improvement in prevention of diabetes and its complications.

     

Dental practitioners’ use of health risk assessments for a variety of health conditions: Results from the South Atlantic region of The National Dental Practice-Based Research Network

BackgroundAn important step in integrating dental and medical care is improving understanding of the frequency and characteristics of dental practitioners who conduct health risk assessments (HRAs).MethodsFrom September 2017 through July 2018, active dentist and hygienist members of the South Atlantic region of The National Dental Practice-Based Research Network (N = 870) were invited to participate in a survey evaluating their HRA practices (screening, measuring, discussing, referring patients) for 6 health conditions (obesity, hypertension, sexual activities, diabetes, alcohol use, tobacco use). For each health condition, the authors used ordinal logistic regression to measure the associations among the practitioner’s HRA practices and the practitioner’s characteristics, barriers, and practice characteristics.ResultsMost of the 475 responding practitioners (≥ 72%) reported they at least occasionally complete 1 or more HRA steps for the health conditions except sexual activities. Most practitioners screened (that is, asked about) and gave referral information to affected patients for diabetes (56%) and hypertension (63%). Factors associated with each increased HRA practice for 2 or more outcomes were non-Hispanic white compared with Hispanic practitioner (cumulative odds ratio [COR] obesity, 0.4; 95% confidence interval [CI], 0.2 to 0.8; and COR diabetes, 0.3; 95% CI 0.2 to 0.8), male compared with female practitioner (COR tobacco, 0.3; 95% CI, 0.2 to 0.7; and COR hypertension, 0.4; 95% CI 0.2 to 0.8), and practitioner discomfort (COR, obesity and alcohol use, 0.7; 95% CI, 0.6 to 0.9; and COR, sexual activities 0.6; 95% CI 0.5 to 0.8).Conclusions and Practical ImplicationsDental practitioners are conducting HRA practices for multiple conditions. Interventions should focus on reducing practitioner discomfort and target non-Hispanic white, male practitioners.     

Baseline characteristics as 3-year predictors of tooth fracture and crack progression: Findings from The National Dental Practice-Based Research Network

BackgroundThe authors of this practice-based study estimated the risk of experiencing tooth fractures and crack progression over 3 years and correlated baseline patient-, tooth-, and crack-level characteristics with these outcomes.MethodsTwo-hundred-and-nine National Dental Practice-Based Research Network dentists enrolled a convenience sample of 2,601 participants with a cracked vital posterior tooth that had been examined for at least 1 recall visit over 3 years. Data were collected at the patient, tooth, and crack levels at baseline, annual follow-up visits, and any interim visits. Associations between these characteristics and the subsequent same-tooth fractures and crack progression were quantified.ResultsOf the 2,601 teeth with a crack or cracks at baseline, 78 (3.0%; 95% confidence interval, 2.4% to 3.7%) subsequently developed a fracture. Of the 1,889 patients untreated before year 1, 232 (12.3%; 95% confidence interval, 10.9% to 13.8%) had some type of crack progression. Baseline tooth-level characteristics associated with tooth fracture were the tooth was maxillary and had a wear facet through enamel and a crack was detectable with an explorer, on the facial surface, and in a horizontal direction. Crack progression was associated with males and teeth with multiple cracks at baseline; teeth with a baseline facial crack were less likely to show crack progression. There was no commonality between characteristics associated with tooth fracture and those associated with crack progression.ConclusionsDevelopment of tooth fractures and crack progression over 3 years were rare occurrences. Specific characteristics were associated with the development of tooth fracture and crack progression, although none were common to both.Practical ImplicationsThis information can aid dentists in assessing factors that place posterior cracked teeth at risk of experiencing adverse outcomes.