The scope of computerized simulation in competency-based maxillofacial training: a systematic review.

Oral and maxillofacial surgery (OMS) teaching is set to undergo a paradigm shift towards competency-based training. With increasing focus on resident skill development and patient safety, computerized simulators are likely to play a more mainstream role in OMS training. A systematic review of the available literature was conducted, in accordance with the PRISMA guidelines, to highlight the scope of computerized simulation in OMS teaching. A PubMed search was performed by two independent reviewers, and 35 articles published in English between 2010 and 2021 that reported the use of computerized simulation for teaching maxillofacial procedures were included in the analysis. Eight articles on minor oral surgery, seven on orthognathic surgery, five on maxillofacial trauma, five on cleft lip and palate surgery, three articles each on nerve block techniques, endoscopic procedures, and reconstructive surgery, and one article on fibre-optic intubation reported the use of computerized simulation that can be applied to OMS training. Ten randomized controlled trials were identified in the search. However there was marked heterogeneity among the studies. Simulator training for skill acquisition mentored by an expert OMS educator could offer holistic resident training; however more studies that test common themes of resident training such as knowledge acquisition and skill development are necessary.

Continuously evaluating performance in deceased donation: the Spanish quality assurance program.

The Spanish Quality Assurance Program applied to the process of donation after brain death entails an internal stage consisting of a continuous clinical chart review of deaths in critical care units (CCUs) performed by transplant coordinators and periodical external audits to selected centers. This paper describes the methodology and provides the most relevant results of this program, with information analyzed from 206,345 CCU deaths. According to the internal audit, 2.3% of hospital deaths and 12.4% of CCU deaths in Spain yield potential donors (clinical criteria consistent with brain death). Out of the potential donors, 54.6% become actual donors, 26% are lost due to medical unsuitability, 13.3% due to refusals to donation, 3.1% due to maintenance problems and 3% due to other reasons. Although the national pool of potential donors after brain death has progressively decreased from 65.2 per million population (pmp) in 2001 to 49 pmp in 2010, the number of actual donors after brain death has remained at about 30 pmp. External audits reveal that the number of actual donors could be 21.6% higher if all potential donors were identified and preventable losses avoided. We encourage other countries to develop similar comprehensive approaches to deceased donation performance.

E-cadherin contributes to the bystander effect of TK/GCV suicide therapy and enhances its antitumoral activity in pancreatic cancer models.

The thymidine kinase/ganciclovir (TK/GCV) cancer gene therapy approach is based on inducing GCV metabolite cytotoxicity in tumor cells expressing the herpes simplex virus TK gene and exposed to GCV. A bystander effect, mediated by gap junctions, accounts for the transfer of toxic metabolites from TK-expressing cells to neighboring cells. It has been proposed that E-cadherin participates in the formation and function of such gap junctions. In this study we investigate the influence of E-cadherin on TK/GCV suicide therapy with a panel of cellular and in vivo models of pancreatic ductal adenocarcinoma. We observed a strong correlation of E-cadherin expression and the TK/GCV bystander effect, associated with the modulation of gap junction communication and connexin expression or localization. Importantly, the co-expression of TK and E-cadherin genes in the adenoviral vector AdTat8TKIE improved TK/GCV cytotoxicity and triggered a potent antitumoral effect, superior to standard AdTat8TK/GCV in MIAPaCa-2 xenografts. The increased expression of E-cadherin resulted in the reduction of the bcl-2 content. Interestingly, the knockdown of bcl-2 sensitized cells to TK/GCV. Thus, we propose that by restoring E-cadherin in pancreatic tumor cells we will improve TK/GCV therapy, both by enhancing the bystander effect and by facilitating the induction of apoptosis.

The functional polymorphisms -429T>C and -374T>A of the RAGE gene promoter are not associated with gestational diabetes in Euro-Brazilians.

The receptor for advanced glycation end products (RAGE or AGER) is a multiligand member of the immunoglobulin superfamily. RAGE is expressed in several tissues, including human myometrium, chorionic villi and placenta. Advanced glycation end products are the best studied ligands of RAGE; they have pro-inflammatory actions in human gestational tissues, increasing oxidative stress and the release of cytokines and prostaglandins. We investigated the association of RAGE gene promoter polymorphisms -429T>C (rs1800625) and -374T>A (rs1800624) with gestational diabetes. A sample of 750 unrelated European origin pregnant Brazilian women were classified as nondiabetic (control group, N = 600) or having gestational diabetes (N = 150) according to American Diabetes Association 2009 criteria. Genotyping was performed by PCR-RFLP. The frequencies of the rare alleles -429C (6.3 versus 9.1%) and -374A (26 versus 30%) were not significantly different between the gestational diabetes patients and healthy pregnant women. Also, the -429T>C and -374T>A polymorphisms were not associated with body mass index, lipid profile, fasting glycemia, HbA1C, or insulin requirement. We found that functional promoter polymorphisms of the RAGE gene were not associated with gestational diabetes or its complications in these Euro-Brazilian patients.

Increased organ donations from people born outside Spain.

Organs donated from persons born outside Spain are becoming increasingly numerous. These persons now account for 26.1% of all donors in the "Malaga sector," an area of tourism with a high percentage of immigrants. Acceptance to donation among persons from Europe and South America is similar to that of Spanish persons but lower among those born in Africa. We must recognize the great help that cultural mediators provided not only by assistance with the language barrier but also by generating confidence among families and understanding their emotions, feelings, and traditions, mainly during interviews with families from different social and cultural miliere. To be efficient, the interpreters or cultural mediators need to have received specific training in the organ donation process and to be involved and convinced that organ donation and transplantation is the best solution for severe health problems.

Organ donors with exceptional medical conditions also count!

All organ donors, even those who have died under exceptional conditions, can provide at least one valid organ for transplantation. It is thus necessary to evaluate the outcomes of donors with unusual diseases. We reviewed 909 organ donors at six hospitals over the last 15 years. Of these, 29 (3.19%) were considered to be exceptional either because of prior disease, the circumstance of death, or complications arising during admission. Among the 53 organs transplanted from all these donors (except two), the mean number of valid organs per donor was 1.88 rather than 2.36 for standard donors. One patient who received a liver transplant died due to the same infection as that diagnosed in the donor. The remaining recipients experienced no primary graft failure or transmission of problems present in the donor.

Profile of organ donors not authorized for judicial reasons.

Loss of donors as a consequence of a coroner's refusal to authorize is an unusual problem that prevents organs becoming available for transplantation. Of 1123 effective donors, 433 (38.5%) died of accidental death. In these latter, it was therefore necessary to request judicial authorization for donation during the coroner's examination. Organ extraction was not performed because of judicial refusal in 15 of these donors (3.46% of the total number of judicial extractions requested and 1.33% of the total number of donors). Despite the lack of differences in the cause of death profile in the four provinces, large differences were noted between the provinces, with most judicial refusals in Malaga (10 refusals; 6.6% of the total judicial refusals), followed by Granada with five refusals (2.9%), Seville with two refusals (1.7%), and zero in Almería. To minimize these judicial refusals, we propose joint action protocols between transplant coordinators, judges, and coroners for these donors to be examined in the hospital prior to extraction and in the operating room during extraction. Any external lesion of judicial interest can then be examined, photographed, and evaluated.

GCV modulates the antitumoural efficacy of a replicative adenovirus expressing the Tat8-TK as a late gene in a pancreatic tumour model.

Replication-competent adenoviruses carrying the herpes simplex thymidine kinase (TK) gene have shown contradictory evidence with regard to their antitumoural efficacy in combination with ganciclovir (GCV) treatment. We generated a replication-competent adenovirus carrying Tat8-TK, a modified form of the TK gene, under the control of the adenoviral major late promoter (AdRGDTat8-TK-L). Pancreatic cancer cell lines with different sensitivity to the TK/GCV system were infected with AdRGDTat8-TK-L, both in the presence and absence of GCV, and tested for treatment efficacy. We observed that, although the presence of GCV reduced viral replication in all infected cell lines, in three out of four GCV significantly enhanced the efficacy of the virotherapy. Interestingly, the cytotoxicity of the AdRGD-Tat8-TK-L/GCV was found more potent than that of a first generation AdTK/GCV system. In tumour xenografts from BxPC-3 and NP-18 pancreatic cells, both AdRGDTat8-TK-L and AdRGDTat8-TK-L/GCV treatment showed antitumoural activity. In BxPC-3 tumours scheduling of virus and prodrug was a key factor to determine the outcome of the therapy. Importantly, the addition of GCV enhanced the antitumoural effect of AdRGDTat8-TK-L only when applied in two rounds of virus+GCV. Interestingly, in spite of interfering with viral replication in vitro, GCV treatment of NP-18 tumours did not compromise the antitumoural efficacy of the AdRGDTat8-TK-L adenovirus. Thus, our results show that the combination therapy of a replicative adenovirus and the Tat8-TK/GCV suicide system can prove beneficial, when the appropriate regimen of virus and GCV is applied.

Expanded donor criteria due to age: an effort rewarded.

The life expectancy of the current Spanish population is 78 years, with some 20% of the population aged over 65 years. The continuing increase in the demand for transplants has led to widening of the criteria for acceptance of donors without worsening the results, but without reducing transplant waiting lists or mortality. This has resulted in the need to include the concept of the expanded criteria donor (ECD). We undertook a retrospective study of 77 donors from a hospital with no neurosurgery service from January 2000 to December 2005. Four of the donors younger than 60 years of age (n = 38) were not appropriate (10.5%), whereas five of the donors older than 60 years of age (n = 39) were not appropriate (12.8%; P = NS). The older donors provided 47 used kidneys (60.2%) and 22 livers (56.4%), slightly fewer than those obtained from the younger donors, though the difference was not significant. Thus, ECDs, those older than 60 years of age, did not result in a significant loss of kidneys or livers available for transplantation. Other factors associated with systemic vascular disease and accompanying disorders could be determinant when predicting the usefulness of organs for transplantation.

Prostate-specific antigen in the assessment of organ donors.

Transplantation is limited worldwide by the shortage of organs, thus, donors of older ages are necessary to be used to meet the increasing demand for transplants. To minimize the transmission of cancer from this population, it is mandatory to rule out the presence of neoplasms. We present our experience with analysis of the prostate-specific antigen (PSA) for male donors older than 50 years of age. Eleven (5.9%) had PSA levels >6 ng/mL, 2 had prostate cancer. In 7 donors with high PSA levels postextraction study of the whole prostate gland showed carcinoma in 1 and prostate infarction in 1; the other 5 were reported as normal or having benign prostatic hypertrophy (BPH). Donors with high PSA levels are suitable for transplantation if urgent pathological studies do not find prostate cancer. Nevertheless, in most donors, increased PSA levels are secondary to causes other than malignant tumors, thus, the risk of transmission of prostate cancer with transplants is minimal. In conclusion, measurements of PSA levels alone prior to extraction are not sufficient to diagnose cancer in organ donors. We conclude that this analysis must be restricted to donors with a past history of prostate disease. Meanwhile, better tests to avoid false-positive results are required.