Thromboembolic risk and anticoagulant therapy in COVID-19 patients: emerging evidence and call for action

Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated with coagulopathy, namely disseminated intravascular coagulation, which has a rather prothrombotic character with high risk of venous thromboembolism. The incidence of venous thromboembolism among COVID-19 patients in intensive care units appears to be somewhat higher compared to that reported in other studies including such patients with other disease conditions. D-dimer might help in early recognition of these high-risk patients and also predict outcome. Preliminary data show that in patients with severe COVID-19, anticoagulant therapy appears to be associated with lower mortality in the subpopulation meeting sepsis-induced coagulopathy criteria or with markedly elevated d-dimer. Recent recommendations suggest that all hospitalized COVID-19 patients should receive thromboprophylaxis, or full therapeutic-intensity anticoagulation if such an indication is present.     

Salivary alkaline phosphatase activity and chronological age as indicators for skeletal maturity

Objectives:To investigate the relationship between salivary alkaline phosphatase activity (ALP), protein concentration, and chronological age with cervical vertebral maturation stages (CVMS) as noninvasive biomarkers for skeletal maturity assessment.Materials and Methods:This cross-sectional study included 79 subjects (48 females, 31 males; 7 to 23 years old) categorized into five CVMS based on lateral cephalographs evaluated by three examiners. ALP activity and protein concentration in unstimulated whole saliva were compared among five CVMS. The association between age and CVMS was assessed and five multinomial logistic regression models were utilized to predict CVMS based on salivary ALP activity, protein concentration, and chronological age.Results:Salivary ALP reached the peak at early pubertal stage and then declined with a significant difference between CVMS I and CVMS II (P < .001) and between CVMS I and CVMS V (P = .004). A significant positive correlation between age and CVMS was found (r_s = 0.763, P < .001). The models'' overall correct classification rates for predicting CVMS were 32.9% using protein concentration, 35.4% using ALP activity, and 53.2% using both ALP activity and age.Conclusions:The combination of salivary ALP activity and chronological age may provide the best CVMS prediction.     

Comparison of Gastrojejunal Anastomosis Techniques in Laparoscopic Roux-en-Y Gastric Bypass: Gastrojejunal Stricture Rate and Effect on Subsequent Weight Loss

Background

Different gastrojejunal anastomotic (GJA) techniques have been described in laparoscopic Roux-en-Y gastric bypass (LRYGB). There is conflicting data on whether one technique is superior to the other. We aimed to compare hand-sewn (HSA), circular-stapled (CSA) and linear-stapled (LSA) anastomotic techniques in terms of stricture rates and their impact on subsequent weight loss.

Methods

A prospectively collected database was used to identify patients undergoing LRYGB surgery between March 2005 and May 2012. Anastomotic technique (HSA, CSA, LSA) was performed according to individual surgeon preference. The database recorded patient demographics, relevant comorbidities and the type of GJA performed. Serial weight measurements and percentage excess weight loss (%EWL) were available at defined follow-up intervals.

Results

Included in the data were 426 patients, divided between HSA (n?=?174, 40.8 %), CSA (n?=?110, 25.8 %) and LSA (n?=?142, 33.3 %). There was no significant difference in the stricture rates (HSA n?=?17, 9.72 %; CSA n?=?9, 8.18 %; LSA n?=?8, 5.63 %; p?=?0.4006). Weight loss was similar between the three techniques (HSA, CSA and LSA) at 3 months (40.6 %?±?16.2 % vs 35.92 %?±?21.42 % vs 48.21 %?±?14.79 %; p?=?0.0821), 6 months (61.48 %?±?23.94 % vs 58.16 %?±?27.31 % vs 60.18 %?±?22.26 %; p?=?0.2296), 12 months (72.94 %?±?19.93 % vs 69.72?±?21.42 % vs 66.05 %?±?17.75 %; p?=?0.0617) and 24 months (73.29 %?±?22.31 % vs 68.75 %?±?24.71 % vs 69.40 %?±?23.10 %; p?=?0.7242), respectively. The stricture group lost significantly greater weight (%EWL) within the first 3 months compared to the non-stricture group (45.39 %?±?16.82 % vs 39.22 %?±?21.93 %; p?=?0.0340); however, this difference had resolved at 6 months (61.29 %?±?18.50 % vs 59.79 %?±?23.03 %; p?=?0.8802) and 12 months (71.59 %?±?18.67 % vs 68.69 %?±?22.19 %; p?=?0.5970).

Conclusions

There was no significant difference in the rate of strictures between the three techniques, although the linear technique appears to have the lowest requirement for post-operative dilatation. The re-intervention rate will, in part, be dictated by the threshold for endoscopy, which will vary between units. Weight loss was similar between the three anastomotic techniques. Surgeons should use techniques that they are most familiar with, as stricture and weight loss rates are not significantly different.     

Levels of Evidence for the Outcome of Regenerative Endodontic Therapy

Introduction

The aim of this systematic review was to assign levels of evidence (LOEs) to existing clinical articles related to the outcome of regenerative endodontic therapy and to evaluate the clinical and radiographic outcomes of this treatment modality.

Methods

Electronic search was executed in PubMed, Scopus, and Cochrane databases by using appropriate Medical Subject Headings terms covering the period from January 1993 to December 2013. Additional publications from hand-searching and reference section of each relevant article enriched the article list. The LOE of each article was assessed according to guidelines provided by the Oxford Centre of Evidence-Based Medicine. Quality assessment of the observational studies was executed by using the Newcastle-Ottawa scale.

Results

Fifty-one relevant publications were included in this review. There were 2 high-level cohort studies (LOE 2), 8 case series (LOE 4), and 41 case reports (LOE 5). The vast majority of the treated teeth in those publications showed resolution of clinical signs, symptoms, and periapical radiolucencies at follow-up period. Furthermore, the majority of treated teeth presented further increase in root length and root wall thickness and apical closure at the follow-up period. However, because of lack of sufficient high-level evidence it was not possible to answer totally the review question and determine definitely the outcome of regenerative endodontic therapy.

Conclusions

The lack of adequate high-level studies that could possibly strengthen the satisfactory current data and allow practicing more evidence-based dentistry constitutes a significant knowledge gap in the endodontic literature. However, the current best available evidence undeniably allows clinicians to provide this treatment modality safely to patients.     

Canonical pathway of nuclear factor kappa B activation selectively regulates proinflammatory and prothrombotic responses in human atherosclerosis

Nuclear factor kappa B (NF-kappa B) activation has been observed in human atherosclerotic plaques and is enhanced in unstable coronary plaques, but whether such activation has a protective or pathophysiological role remains to be determined. We addressed this question by developing a short-term culture system of cells isolated from human atherosclerotic tissue, allowing efficient gene transfer to directly investigate signaling pathways in human atherosclerosis. We found that NF-kappa B is activated in these cells and that this activity involves p65, p50, and c-Rel but not p52 or RelB. This NF-kappa B activation can be blocked by overexpression of I kappa B alpha or dominant-negative I kappa B kinase (IKK)-2 but not dominant-negative IKK-1 or NF-kappa B-inducing kinase, resulting in selective inhibition of inflammatory cytokines (tumor necrosis factor alpha, IL-6, and IL-8), tissue factor, and matrix metalloproteinases without affecting the antiinflammatory cytokine IL-10 or tissue inhibitor of matrix metalloproteinases. Our results demonstrate that the canonical pathway of NF-kappa B activation that involves p65, p50, c-Rel, and IKK-2 is activated in human atherosclerosis and results in selective up-regulation of major proinflammatory and prothrombotic mediators of the disease.     

Synchronous rectal and colon cancer caused by familial polyposis coli during pregnancy

The management of colon and rectal cancer during pregnancy is controversial and challenging. Rectal or colon cancer during pregnancy is a very rare event. A 29-year-old woman, pregnant with her second child, was diagnosed with rectal cancer causing bowel obstruction and synchronous colon cancer during the 27th week of gestation. Both cancers occurred as a result of familial polyposis. This is the first case of synchronous rectal and colon cancer caused by familial polyposis during pregnancy reported in the published literature. We discuss the therapeutic interventions and the surgical management of the cancer in relation to the gestation.     

Assessment of patient radiation doses during transcatheter closure of ventricular and atrial septal defects with Amplatzer devices.

The purpose of this study was to estimate the radiation dose to which children are exposed during cardiac catheterizations for the treatment of ventricular and atrial septal defects. Radiation doses were estimated for 46 children aged 1-18 years. These children were treated for secundum atrial septal defects (ASD group) for perimembranous ventricular septal defects (VSD group) or underwent a routine diagnostic catheterization (diagnostic group). Thermoluminescent dosimeters (TLDs) were attached in locations, representing the lateral entrance dose, the posterior entrance dose, the thyroid dose, and the gonad dose, respectively. A dose area product (DAP) meter was also attached externally on the posterior-anterior (PA) tube to give a direct value in cGy cm(2) for each procedure. The patient's entrance dose from the PA field ranged from 1.5 to 185.0 mGy for all patients, while the lateral entrance dose varied from 0.9 to 204 mGy. Radiation exposure to the thyroid and the gonads was found to vary from 0.4 to 8.3 and 0.1 to 2.1 mGy, respectively. The DAP meter recorded DAP values for the posterior tube, between 46 and 3,700 cGy cm(2). The mean effective dose was found to be 7.7, 16.2, and 33.3 mSv for the diagnostic, the ASD, and the VSD group, respectively. Very strong correlation was found between the DAP values and the entrance radiation dose measured with TLDs. The mean entrance dose received from therapeutic cardiac catheterizations using the Amplatzer devices was found approximately twice the dose received from a diagnostic one. Even for the most complex procedures, the maximum entrance dose was at least 10 times lower than the threshold, associated with skin erythema.     

Macrophage migration inhibitory factor promotes intestinal tumorigenesis

BACKGROUND & AIMS: The cytokine macrophage migration inhibitory factor (MIF) is expressed throughout the human gastrointestinal tract. Recently, protumorigenic activity of MIF has been described in several cancer models. Therefore, we investigated the expression and function of MIF during the early stages of intestinal tumorigenesis. METHODS: MIF messenger RNA, protein, and tautomerase activity were measured in normal intestinal mucosa and adenomas from patients with sporadic colorectal adenomas and in the adenomatous polyposis coli (Apc)Min/+ mouse model of intestinal tumorigenesis. MIF function was investigated by using VACO-235 human colorectal adenoma cells in vitro and by testing the effect of genetic deletion of Mif on ApcMin/+ mouse intestinal tumorigenesis. RESULTS: MIF expression and tautomerase activity were increased in human and ApcMin/+ mouse intestinal adenomas compared with adjacent normal mucosa. Up-regulation of MIF occurred mainly in epithelial cells (associated with an increasing grade of dysplasia), but also in stromal plasma cells. Exogenous MIF inhibited apoptosis and promoted anchorage-independent growth of VACO-235 cells (maximal at 100 ng/mL). Homozygous deletion of Mif was associated with a reduction in the number and size of ApcMin/+ mouse adenomas (P = .025 for the difference in large [>7-mm] tumors) and decreased angiogenesis (43% decrease in mean tumor microvessel density), but there was no alteration in epithelial cell apoptosis or proliferation. CONCLUSIONS: MIF expression is increased in sporadic human colorectal adenomas, and exogenous MIF drives tumorigenic behavior of epithelial cells in vitro. Mif also promotes intestinal tumorigenesis (predominantly via angiogenesis) in the ApcMin/+ mouse. Therefore, MIF is a potential colorectal cancer chemoprevention target.