The OHStat Guidelines for Reporting Observational Studies and Clinical Trials in Oral Health Research: Explanation and Elaboration.

Adequate and transparent reporting is necessary for critically appraising research. Yet, evidence suggests that the design, conduct, analysis, interpretation, and reporting of oral health research could be greatly improved. Accordingly, the Task Force on Design and Analysis in Oral Health Research-statisticians and trialists from academia and industry-empaneled a group of authors to develop methodological and statistical reporting guidelines identifying the minimum information needed to document and evaluate observational studies and clinical trials in oral health: the OHstat Guidelines. Drafts were circulated to the editors of 85 oral health journals and to Task Force members and sponsors and discussed at a December 2020 workshop attended by 49 researchers. The final version was subsequently approved by the Task Force in September 2021, submitted for journal review in 2022, and revised in 2023. The checklist consists of 48 guidelines: 5 for introductory information, 17 for methods, 13 for statistical analysis, 6 for results, and 7 for interpretation; 7 are specific to clinical trials. Each of these guidelines identifies relevant information, explains its importance, and often describes best practices. The checklist was published in multiple journals. The article was published simultaneously in JDR Clinical and Translational Research, the Journal of the American Dental Association, and the Journal of Oral and Maxillofacial Surgery. Completed checklists should accompany manuscripts submitted for publication to these and other oral health journals to help authors, journal editors, and reviewers verify that the manuscript provides the information necessary to adequately document and evaluate the research.

Mitochondrial neurogastrointestinal encephalomyopathy: Clinical and biochemical impact of allogeneic stem cell transplantation in a Greek patient with one novel TYMP mutation.

We describe the case of a Greek female patient with the Classic form of the ultra- rare and fatal autosomal recessive disorder Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and the impact of allogeneic hematopoietic stem cell transplantation on the biochemical and clinical aspects of the disease. The patient presented at the age of 15 years with severe gastrointestinal symptoms, cachexia, peripheral neuropathy and diffuse leukoencephalopathy. The diagnosis of MNGIE disease was established by the increased levels of thymidine and deoxyuridine in plasma and the complete deficiency of thymidine phosphorylase activity. The novel c.[978dup] (p.Ala327Argfs*?) variant and the previously described variant c.[417 + 1G > A] were identified in TYMP. The donor for the allogeneic hematopoietic stem cell transplantation was her fully compatible sister, a carrier of the disease. The patient had a completely uneventful post- transplant period and satisfactory PB chimerism levels. A marked and rapid decrease in thymidine and deoxyuridine plasma levels and an increase of the thymidine phosphorylase activity to the levels measured in her donor sister was observed and is still present sixteen months post-transplant. Disease symptoms stabilized and some improvement was also observed both in her neurological and gastrointestinal symptoms. Follow up studies will be essential for determining the long term impact of allogeneic hematopoietic stem cell transplantation in our patient.

Tooth loss strongly associates with malnutrition in chronic kidney disease.

BACKGROUND: In chronic kidney disease (CKD), inadequate nutritional intake, inflammation, and increased oxidative stress have been the major contributing factors in malnutrition pathogenesis. However, there is still a paucity of evidence assessing the magnitude of the effect of tooth loss on malnutrition in CKD populations. The authors hypothesize that among patients with CKD, tooth loss may affect nutritional status, using the National Health and Nutrition Examination Survey 1988 to 1994 (NHANES III). METHODS: Glomerular filtration rate (GFR) was estimated based on cystatin C levels using the relevant equation. Urinary albumin-to-creatinine ratio (albuminuria) was calculated in milligrams per gram with a cutoff point of 30 mg/g. CKD was defined based on estimated GFR <60 mL/minute/1.73m(2) and albuminuria ≥30 mg/g. The cutoff point for serum albumin was set at 3.7 g/dL. Tooth loss categories were based on the number of missing and replaced teeth. RESULTS: A total of 2,749 patients was included and stratified based on their oral health status. There was a statistically significant correlation between tooth loss and the proportion of patients with low protein and caloric intake (P = 0.02 and 0.01, respectively). Serum albumin reached a frequency peak in the fully edentulous group without dentures (group 4, 19.2%). In the same group, individuals had lower protein (30.1%) and caloric intake (30.2%) (P = 0.01 and 0.02, respectively). Furthermore, logistic regression analysis confirmed the significant role of tooth loss on serum albumin and protein and energy intake in this population even after adjusting for confounding variables. CONCLUSION: Tooth loss independently predicts low energy and protein intake, as well as serum albumin levels, biomarkers of malnutrition in CKD.

Absence of JAK2V617F mutation in patients with beta-thalassemia major and thrombocytosis due to splenectomy.

The report of Janus Kinase 2 (JAK2) mutations in myeloid malignancies with high frequency in myeloproliferative neoplasms has been well known since 2005. By monitoring allele burden, it is found that the expression of JAK2V617F mutation is increasing significantly from essential thrombocytosis to polycythemia vera. Furthermore, JAK2 abnormalities are reported in the majority of unexplained thrombotic episodes. Thalassemic syndromes are characterized by ineffective erythropoiesis and thrombocytosis, mainly due to splenectomy. The high incidence of thromboembolic events has led to the identification of a prothrombotic state in these patients. The contribution of JAK2 mutations to the hypercoagulable state of thalassemic patients is still unknown. Furthermore, the potential role of Janus Kinase mutations in hepcidin expression and consequently in ineffective erythropoiesis is still under investigation. This study was scheduled to determine whether the presence of JAK2V617F mutation in thalassemic patients is associated with thrombocytosis. We studied 20 patients DNA with beta-thalassemia for JAK2V617F mutation by using RG-PCR method. None of the patients were positive for this particular mutation. More studies are needed to prove the role of JAK2 in ineffective erythropoiesis, iron metabolism and thrombocytosis and to determine if using JAK2 inhibitors in thalassemic patients can be a potential therapeutic option.

Periodontitis predicts elevated C-reactive protein levels in chronic kidney disease.

Based on the existing evidence supporting a state of chronic inflammation in chronic kidney disease (CKD), we hypothesized that periodontal infection may affect the systemic inflammatory status of a nationally representative CKD population as measured by serum C-reactive protein (CRP). We examined this hypothesis using the National Health and Nutrition Examination Survey 1988-1994 (NHANES III) dataset including 2303 individuals. We followed the American Academy of Periodontology (AAP)/Centers for Disease Control and Prevention (CDC) case definition for periodontitis. We used a cutoff point of 30% sites with (PD) ≥ 5 mm and (CAL) ≥ 4 mm to define generalized periodontitis cases. We estimated glomerular filtration rate based on cystatin C levels using the relevant equation. Urinary albumin-to-creatinine ratio was calculated in milligrams per gram with a cutoff point of 30 mg/g. CKD was defined based on eGFR < 60 mL/min/1.73 m(2) and albuminuria ≥ 30 mg/g. Periodontitis was found in 427 (12.3%) individuals. Of individuals with periodontitis, 41.8% had serum CRP higher than 0.3 mg/dL compared with 27.1% of non-periodontitis and 53.1% of edentulous individuals (p = 0.001 for all comparisons). When the extent of periodontitis was used as one of the independent variables, the parsimonious model showed a strong independent association between extent of periodontitis and serum CRP levels (OR = 2.0, CI95% = 1.2-3.6).

Increased levels of proinflammatory cytokines in children with family history of coronary artery disease.

BACKGROUND: Parental history of coronary artery disease (CAD) is considered an important risk factor for early atherosclerosis HYPOTHESIS: The onset of the inflammatory process of atherosclerosis initiates early during childhood in children with positive family history (PFH) of CAD. METHODS: We studied 55 healthy children (5-15 years), 30 (16 male) with PFH and 25 age and sex matched control subjects. Blood samples were taken to measure white blood count (WBC), glucose, total cholesterol, triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), erythrocyte sedimentation rate (SDE), C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-a). We performed cultures on monocytes (from peripheral blood) measuring in the cell culture supernatants the proinflammatory cytokines IL-6 and TNF-a, by using the immunoassay ELISA method. RESULTS: : Higher values of body mass index (BMI), total cholesterol, LDL, cholesterol, TG, SDE, leucocytes, and CRP were calculated in children with PFH. Significantly higher values of cytokines in monocell cultures were measured in the PFH group compared to the control group (IL-6 = 139.32 +/- 80.84 pg/ml versus 14.30 +/- 12.97 pg/ml, p < 0.001 and TNF-a = 39.91 +/- 11.80 pg/ml versus 8.65 +/- 4.35 pg/ml, p < 0.001). IL-6 values in plasma and cultures were found independently associated with PFH of premature CAD (p < 0.001, p = 0.005, respectively). A similar relation was found for TNF-a values measured in cultures (p = 0.005) and CRP values in plasma (p < 0.001). The values of IL-6 were found proportionally related to TG. CONCLUSION: In individuals with PFH of CAD the inflammatory process of atheromatosis appears to begin early in childhood. Except for triglycerides, this inflammatory process appears to occur independently of several traditional cardiovascular risk factors.

Oral Candida infection and colonization in solid organ transplant recipients.

INTRODUCTION: Oral Candida carriage and infection have been reported to be associated with a greater risk for systemic infection in transplant recipients; however, a systematic analysis of the oral Candida titers and species has not been previously conducted. The objectives of this study were to determine the prevalence of oropharyngeal candidiasis, the oral carrier status, Candida titers and species in this population. METHODS: Ninety kidney and heart transplant subjects and 72 age-matched healthy controls were included. Swabs from the oral mucosa and a standardized amount of unstimulated saliva were plated on Chromagar Candida, and colony-forming units per millilitre were calculated. Initial speciation was based on colony color and was confirmed by standard germ tube, biotyping, or polymerase chain reaction assays. RESULTS: Infection with C. albicans was detected in seven transplant subjects and none of the controls. The transplant group had significantly higher oral Candida titers than the control group. There were no statistically significant relationships between the dose or type of immunosuppressants and oral Candida titers or infection. A significantly higher percentage of transplant subjects were colonized by more than one species, compared with control subjects. The most frequent species combination in transplant subjects was C. albicans and C. glabrata. C. glabrata was isolated from 13.5% of transplant carriers and none of the controls. CONCLUSIONS: Increased oral Candida infection and carriage titers were found in the transplant population. Although the majority of transplant patients were colonized by C. albicans, C. glabrata appears to emerge as the second most prevalent species.

Keratinocyte growth factor is effective in the prevention of intestinal mucositis in patients with hematological malignancies treated with high-dose chemotherapy and autologous hematopoietic SCT: a video-capsule endoscopy study.

Oral and/or intestinal mucositis is a severe complication of hematopoietic SCT. Keratinocyte growth factor (KGF) has proven activity in the prevention of oral mucositis. We examined the efficacy of KGF in the prevention of intestinal mucositis. From January 2006 until December 2007, 35 consecutive patients underwent autologous SCT (auto-SCT) in our institution. A total of 15 consecutive patients who underwent auto-SCT from March 2007 to December 2007 received KGF for the prevention of mucositis and were included in the study group A, whereas 20 consecutive patients treated from January 2006 to March 2007, were included in the historical control group B. Oral and intestinal mucositis were significantly less severe in group A (P=0.002 and P<0.001, respectively). These results were confirmed with the use of video-capsule endoscopy. Patients in group A had a significantly lower incidence of neutropenic fever (P=0.026). Severe intestinal mucositis was significantly associated with a higher incidence of documented infections too (P=0.019). KGF is effective in the prevention of intestinal mucositis in patients undergoing auto-SCT. Patients with severe intestinal mucositis run a higher risk to develop infections.

Severity of asymptomatic carotid stenosis and risk of ipsilateral hemispheric ischaemic events: results from the ACSRS study.

OBJECTIVES: This study determines the risk of ipsilateral ischaemic neurological events in relation to the degree of asymptomatic carotid stenosis and other risk factors. METHODS: Patients (n=1115) with asymptomatic internal carotid artery (ICA) stenosis greater than 50% in relation to the bulb diameter were followed up for a period of 6-84 (mean 37.1) months. Stenosis was graded using duplex, and clinical and biochemical risk factors were recorded. RESULTS: The relationship between ICA stenosis and event rate is linear when stenosis is expressed by the ECST method, but S-shaped if expressed by the NASCET method. In addition to the ECST grade of stenosis (RR 1.6; 95% CI 1.21-2.15), history of contralateral TIAs (RR 3.0; 95% CI 1.90-4.73) and creatinine in excess of 85 micromol/L (RR 2.1; 95% CI 1.23-3.65) were independent risk predictors. The combination of these three risk factors can identify a high-risk group (7.3% annual event rate and 4.3% annual stroke rate) and a low risk group (2.3% annual event rate and 0.7% annual stroke rate). CONCLUSIONS: Linearity between ECST per cent stenosis and risk makes this method for grading stenosis more amenable to risk prediction without any transformation not only in clinical practice but also when multivariable analysis is to be used. Identification of additional risk factors provides a new approach to risk stratification and should help refine the indications for carotid endarterectomy.

Interaction of granulocyte-macrophage colony-stimulating factor and interleukin 3 in human long-term bone marrow culture.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), or a combination of both growth factors were added weekly to normal human long-term bone marrow cultures (LTBMC). GM-CSF had a greater effect on the total nonadherent cell population than the committed progenitor cells (granulocyte-macrophage colony-forming units, CFUgm), whereas IL-3 had the opposite effect and stimulated the expansion of greater numbers of CFUgm than GM-CSF. The combination of both factors had an additive effect on CFUgm. The longevity of the growth factor-treated cultures was not reduced. These data indicate that IL-3 stimulates an earlier progenitor cell population than GM-CSF and that a combination of the two factors should be more effective in vivo and could be applied to the expansion of bone marrow progenitor cells in culture before bone marrow transplantation.

Synergistic induction of cytogenetic damage by alkylating antineoplastics and 5-azacytidine in human lymphocytes.

We studied the effects of the inhibitor of DNA methylation, 5-azacytidine (Aza-C), alone and in combination with three antitumor alkylating agents, on sister chromatid exchanges (SCEs) and lymphocyte proliferation kinetics. Aza-C was found to act synergistically on induction of SCEs when administered in combination with either melphalan (MEL) or chlorambucil (CBC) or cis-platinum-(II)diamine dichloride (cis-Pt). Cell-division delays were consistently observed in cultures treated with each of the antineoplastics when introduced concomitantly with Aza-C, compared with cultures treated with antineoplastics alone. Mitotic indices (MI) in cultures treated with each of the three alkylating agents were found to be suppressed by Aza-C. These results support the premise that hypomethylation of DNA causes cytotoxic effects by interfering with DNA repair mechanisms and by inhibiting DNA synthesis, or other cell growth mechanisms, which human lymphocytes undertake after being damaged by alkylation.

Anaerobic bacteria in jaw cysts.

The bacterial flora of the fluid content of 54 cysts of the jaws with a history suggestive of infection were studied. Forty-seven of these cysts were subsequently considered to be infected and from 78.6% of these, positive bacterial cultures were developed. Of the bacterial strains 89.2% were anaerobes and only 10.8% were pure aerobes or facultative anaerobes. Microorganisms isolated from each specimen ranged from 1 to 4 bacterial species. Gram positive anaerobic cocci revealed to be the most frequent bacterial group (36.9%), followed by Gram negative anaerobic rods (29.8%), Gram positive aerobic cocci being the third most common group of the isolates (19.0%). Antibiotic sensitivity tests of the isolated anaerobic cocci to a group of nine antibiotics revealed chloramphenicol and minocycline as the most effective. All anaerobic rods tested, were sensitive to metronidazole.