Three-dimensional finite element analysis of the stress distribution in the endodontically treated maxillary central incisor by glass fiber post and dentin post.

INTRODUCTION: From the point of dental practice, the restoration of endodontically treated teeth has become an important aspect as it involves a range of treatment options of variable complexity. Restoring teeth with insufficient coronal tooth structure, it is always indicated to use the post to retain a core for definitive restoration. Fiber post has a modulus of elasticity in analogs to dentin structure, thus reducing the stress areas at the dowel dentin interface. However, the only material that can substantiate all these properties can be none other than dentin itself. MATERIALS AND METHODOLOGY: Three-dimensional (3D) models of the maxillary central incisor were developed incorporating all the nonlinearities. Continuum 3D elements were used in three dimensions. Maxillary central incisor was laser scanned, duplicated with the help of reverse engineering into STL format, and it was converted into 3D model for finite element analysis (FEA). For the model, fixed boundary conditions were applied at the outer bone, while 100 N static vertical occlusal loads were prescribed at 135° on the loading component of the simulated tooth. The stress distribution was evaluated using dentin and fiber post with prescribed materials, loading and boundary conditions in endontically treated teeth by 3D FEA. RESULTS: The analysis for von Misses stress for dentin post showed that the stress in the dentin post at the cervical area was 127 MPa. The displacement in the dentin post was <0.025 mm. Von Misses stress for the fiber post at the cervical area was approximately 182 MPa and the displacement was <0.035 mm. CONCLUSION: The FEA results showed that the stress in the cervical area of the dentin was more for fiber post when compared to dentin post, and maximum displacement values were less for dentin post in comparison to fiber post.

Metachronous colorectal cancer following segmental or extended colectomy in Lynch syndrome: a systematic review and meta-analysis.

Around 5% of colorectal cancers are due to mutations within DNA mismatch repair genes, resulting in Lynch syndrome (LS). These mutations have a high penetrance with early onset of colorectal cancer at a mean age of 45 years. The mainstay of surgical management is either a segmental or extensive colectomy. Currently there is no unified agreement as to which management strategy is superior due to limited conclusive empirical evidence available. A systematic review and meta- analysis to evaluate the risk of metachronous colorectal cancer (MCC) and mortality in LS following segmental and extensive colectomy. A systematic review of the PubMed database was conducted. Studies were included/ excluded based on pre-specified criteria. To assess the risk of MCC and mortality attributed to segmental or extensive colectomies, relative risks (RR) were calculated and corresponding 95% confidence intervals (CI). Publication bias was investigated using funnel plots. Data about mortality, as well as patient ascertainment [Amsterdam criteria (AC), germline mutation (GM)] were also extracted. Statistical analysis was conducted using the R program (version 3.2.3). The literature search identified 85 studies. After further analysis ten studies were eligible for inclusion in data synthesis. Pooled data identified 1389 patients followed up for a mean of 100.7 months with a mean age of onset of 45.5 years of age. A total 1119 patients underwent segmental colectomies with an absolute risk of MCC in this group of 22.4% at the end of follow-up. The 270 patients who had extensive colectomies had a MCC absolute risk of 4.7% (0% in those with a panproctocolecomy). Segmental colectomy was significantly associated with an increased relative risk of MCC (RR = 5.12; 95% CI 2.88-9.11; Fig. 1), although no significant association with mortality was identified (RR = 1.65; 95% CI 0.90-3.02). There was no statistically significant difference in the risk of MCC between AC and GM cohorts (p = 0.5, Chi-squared test). In LS, segmental colectomy results in a significant increased risk of developing MCC. Despite the choice of segmental or extensive colectomies having no statistically significant impact on mortality, the choice of initial surgical management can impact a patient's requirement for further surgery. An extensive colectomy can result in decreased need for further surgery; reduced hospital stays and associated costs. The significant difference in the risk of MCC, following segmental or extensive colectomies should be discussed with patients when deciding appropriate management. An individualised approach should be utilised, taking into account the patient's age, co-morbidities and genotype. In order to determine likely germline-specific effects, or a difference in survival, larger and more comprehensive studies are required.

The association of low penetrance genetic risk modifiers with colorectal cancer in lynch syndrome patients: a systematic review and meta-analysis.

Lynch syndrome (LS) is a highly penetrant inherited cancer predisposition syndrome accounting for approximately 1000 cases of colorectal cancer (CRC) in the UK annually. LS is characterised by autosomal dominant inheritance and germline mutations in DNA mismatch repair genes. The penetrance is highly variable and the reasons for this have not been fully elucidated. This study investigates whether low penetrance genetic risk factors may result in phenotype modification in LS patients. To conduct a systematic literature review and meta-analysis to assess the association between low penetrance genetic risk modifiers and CRC in LS patients. A systematic review was conducted of the PubMed and HuGENet databases. Eligibility of studies was determined by pre-defined criteria. Included studies were analysed via the per-allele model and assessed by pooled odds ratios and establishing 95% confidence intervals. Study heterogeneity was assessed via Cochrane's Q statistic and I2 values. Publication bias was evaluated with funnel plots. Subgroup analysis was conducted on gender. Statistical software used was the Metafor package for the R programme version 3.1.3. Sixty-four polymorphisms were identified and sufficient data was available for analysis of ten polymorphisms, with between 279 and 1768 CRC cases per polymorphism. None demonstrated association with CRC risk in LS patients. However in sub-group analysis the polymorphism rs16892766 (8q23.3) was significant in males (OR 1.53, 95% CI 1.12-2.10). The variable phenotype presentation of the disease still remains largely unexplained, and further investigation is warranted. Other factors may also be influencing the high variability of the disease, such as environmental factors, copy number variants and epigenetic alterations. Investigation into these areas is needed as well as larger and more definitive studies of the polymorphisms analysed in this study.

The Association of Low-Penetrance Variants in DNA Repair Genes with Colorectal Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: Approximately 35% of colorectal cancer (CRC) risk is attributable to heritable factors known hereditary syndromes, accounting for 6%. The remainder may be due to lower penetrance polymorphisms particularly of DNA repair genes. DNA repair pathways, including base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), direct reversal repair (DRR), and double-strand break repair are complex, evolutionarily conserved, and critical in carcinogenesis. Germline mutations in these genes are associated with high-penetrance CRC syndromes such as Lynch syndrome. However, the association of low-penetrance polymorphisms of DNA repair genes with CRC risk remains unclear. METHODS: A systematic literature review of PubMed, Embase, and HuGENet databases was conducted. Pre-specified criteria determined study inclusion/exclusion. Per-allele, pooled odds ratios disclosed the risk attributed to each variant. Heterogeneity was investigated by subgroup analyses for ethnicity and tumor location; funnel plots and Egger's test assessed publication bias. RESULTS: Sixty-one polymorphisms in 26 different DNA repair genes were identified. Meta-analyses for 22 polymorphisms in 17 genes revealed that six polymorphisms were significantly associated with CRC risk within BER (APE1, PARP1), NER (ERCC5, XPC), double-strand break (RAD18), and DRR (MGMT), but none within MMR. Subgroup analyses revealed significant association of OGG1 rs1052133 with rectal cancer risk. Egger's test revealed no publication bias. CONCLUSIONS: Low-penetrance polymorphisms in DNA repair genes alter susceptibility to CRC. Future studies should therefore analyze whole-genome polymorphisms and any synergistic effects on CRC risk.Translational impact:This knowledge may enhance CRC risk assessment and facilitate a more personalized approach to cancer prevention.

The characteristics of very short stay ICU admissions and implications for optimizing ICU resource utilization: the Saudi experience.

OBJECTIVE: Patients with very short stays (<24 hours) in intensive care units (ICUs) constitute a distinct group with a high turnover rate and a unique patient mix. Our aim was to study their characteristics with the aim of developing strategic approaches for better and more appropriate utilization of ICU resources. DESIGN: Prospective cohort study. SETTING: Adult medical/surgical ICU in a tertiary care teaching hospital. STUDY PARTICIPANTS: All admissions in an adult ICU from March 1999 to February 2001 and staying <24 hours were enrolled. Relevant data were collected on these patients, their course and outcome, and analyzed after categorizing patients according to: (i) the nature of admission; and (ii) risk of death (ROD) estimated by Mortality Probability Model II(0). RESULTS: Patients staying <24 hours (n = 304) formed 27.8% of all ICU admissions, with an ICU mortality rate of 26.3%. Only 45.4% of them utilized ICU-specific procedures. Around one-third (32.6%) were elective admissions comprising younger patients, with a significantly lower prevalence of chronic illness, a lower ROD, and utilization of less ICU-specific procedures, with very few mortalities. When stratified using RODs into low-, intermediate-, and high-risk groups, significant differences were found with respect to age, nature of ICU admission, presence of chronic illness, utilization of ICU-specific procedures, having do-not-resuscitate (DNR) orders, length of ICU stay, and ICU and hospital outcomes. CONCLUSIONS: Our study has provided crucial input for the study of strategic change towards more optimal utilization of scarce ICU resources. Implementing protocols to target ICU care to patients most likely to benefit, making DNR decisions early in the hospital stay, and operating an Intermediate Care Unit have been proposed as strategic approaches.

A prospective study of prolonged stay in the intensive care unit: predictors and impact on resource utilization.

OBJECTIVE: To evaluate the predictors of prolonged Intensive Care Unit (ICU) stay and the impact on resource utilization. DESIGN: Prospective study. SETTING: Adult medical/surgical ICU in a tertiary-care teaching hospital. STUDY PARTICIPANTS: All admissions to the ICU (numbering 947) over a 20-month period were enrolled. Data on demographic and clinical profile, length of stay, and outcome were collected prospectively. The ICU length of stay and mechanical ventilation days were used as surrogate parameters for resource utilization. Potential predictors were analyzed for possible association with prolonged ICU stay (length of stay > 14 days). RESULTS: Patients with prolonged ICU stay formed only 11% of patients, but utilized 45.1% of ICU days and 55.5% of mechanical ventilation days. Non-elective admissions, readmissions, respiratory or trauma-related reasons for admission, and first 24-hour evidence of infection, oliguria, coagulopathy, and the need for mechanical ventilation or vasopressor therapy had significant association with prolonged ICU stay. Mean APACHE II and SAPS II were slightly higher in patients with prolonged stay. ICU outcome was comparable to patients with < or = 14 days ICU stay. CONCLUSIONS: Patients with prolonged ICU stay form a small proportion of ICU patients, yet they consume a significant share of the ICU resources. The outcome of this group of patients is comparable to that of shorter stay patients. The predictors identified in the study can be used in targeting this group to improve resource utilization and efficiency of ICU care.

Assessment of performance of four mortality prediction systems in a Saudi Arabian intensive care unit.

INTRODUCTION: The purpose of this study is to assess the performance of Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II, Mortality Probability Model MPM II0 and MPM II24 systems in a major tertiary care hospital in Riyadh, Saudi Arabia. METHODS: The following data were collected prospectively on all consecutive patients admitted to the Intensive Care Unit between 1 March 1999 and 31 December 2000: demographics, APACHE II and SAPS II scores, MPM variables, ICU and hospital outcome. Predicted mortality was calculated using original regression formulas. Standardized mortality ratio (SMR) was computed with 95% confidence intervals (CI). Calibration was assessed by calculating Lemeshow-Hosmer goodness-of-fit C statistics. Discrimination was evaluated by calculating the Area Under the Receiver Operating Characteristic Curves (ROC AUC). RESULTS: Predicted mortality by all systems was not significantly different from actual mortality [SMR for MPM II0: 1.00 (0.91-1.10), APACHE II: 1.00 (0.8-1.11), SAPS II: 1.09 (0.97-1.21), MPM II24 0.92 (0.82-1.03)]. Calibration was best for MPM II24 (C-statistic: 14.71, P = 0.06). Discrimination was best for MPM II0 (ROC AUC:0.85) followed by MPM II24 (0.84), APACHE II (0.83) then SAPS II (0.79). CONCLUSIONS: In our ICU population: 1) Overall mortality prediction, estimated by standardized mortality ratio, was accurate, especially for MPM II0 and APACHE II. 2) MPM II24 has the best calibration. 3) SAPS II has the lowest calibration and discrimination. The local performance of MPM II24 in addition to its ease-to-use makes it an attractive model for mortality prediction in Saudi Arabia.

Can we predict prognosis using mortality probability model IIo?

OBJECTIVE: To evaluate Mortality Probability Model (MPM) IIo as a tool to predict very poor prognosis after intensive care unit admission. METHODS: The study was conducted as a prospective observational study in a medical-surgical intensive care unit in a tertiary care teaching hospital, Riyadh, Kingdom of Saudi Arabia. Data necessary to calculate MPM IIo predicted mortality was collected from March 1999 through to February 2000 on all intensive care unit admissions. The hospital outcome was documented. We calculated the sensitivity, specificity, positive predictive value and negative predictive value of MPM IIo using cutoff points of 90% and 95%. RESULTS: Data was complete on 557/569 patients (98%). Thirty-one patients had predicted mortality of >95% and all died yielding a specificity of 100% and positive predictive value of 100%. However, sensitivity was only 18% and negative predictive value 73%. Forty-four patients had predicted mortality of >90% of whom only one survived yielding a specificity of 99.7% and a positive predictive value of 97.7%. Sensitivity was only 25% and negative predictive value of 75%. CONCLUSIONS: Using a decision-cutoff of 95% predicted mortality using MPMI IIo had a very high specificity in predicting death after intensive care unit admission, although with a low sensitivity. This information can be used to support clinical judgment regarding the very ill patients who are unlikely to benefit from intensive care unit admission.