Clinical practice guidelines on the screening and treatment of precancerous lesions for cervical cancer prevention in Saudi Arabia

BACKGROUND: Cervical cancer is the third most common gynecological malignancy in Saudi women with an estimated incidence rate of 1.9 cases per 100 000 women-years. More than 40% of cervical cancer cases are diagnosed at advanced stages due to lack of a routine screening program in Saudi Arabia. Thus, national guidelines for routine screening and treatment of precancerous cervical lesions are needed. METHODS: The Saudi Centre for Evidence-Based Healthcare invited a panel of local experts and partnered them with a team from McMaster University in Canada for methodological support, to develop national clinical practice guidelines on the screening and treatment of precancerous lesions for cervical cancer. After the panel identified key clinical questions, the McMaster University working group updated existing systematic reviews that had been used for the 2013 WHO Guidelines for screening and treatment of precancerous lesions for cervical cancer prevention. Recommendations were based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. Those recommendations took into account the available evidence, patient values and preferences, and resource use in the Saudi context. The panel provided recommendations on two major issues: screening for precancerous lesions (cervical intraepithelial neoplasia 2 & 3) and treatment of those lesions to prevent cervical cancer in women who tested positive after screening. CONCLUSIONS: The Saudi expert panel recommends using the HPV DNA test followed by colposcopy or cytology (Pap test) followed by colposcopy to screen for CIN2+ in women at risk of cervical cancer. The panel recommends cryotherapy or loop excision electrosurgery procedure (LEEP) over cold knife cone biopsy to treat women at risk of cervical cancer that tests positive for CIN2+. Universal screening for precancerous cervical dysplasia in women in Saudi Arabia is recommended using HPV testing and or cytology. Either cryotherapy or LEEP are preferred for treatment. CONCLUSIONS: National studies on cervical cancer screening modalities and treatment of precancerous cervical lesions, including HPV prevalence and its association with cervical cancer, are scarce.

Intubation learning curve: comparison between video and direct laryngoscopy by inexperienced students.

Background: Direct laryngoscopy (DL) is considered the most common method of tracheal intubation. On the other hand, evidence shows the growing role of video laryngoscopy in danger airway administration. Objectives: Due to the importance of a proper training to accomplish an accurate and fast intubation by the student of anesthesia, this research was conducted to assess the effects of DL and video laryngoscopy (Glidescope VL) training on the success rate of tracheal intubation by low-skill students. Materials/Patients and styles: 50 undergraduate students of anesthesiology took part in this randomized control educational intervention. Having no considerable experience in intubation, they were selected and divided randomly into two equal groups (n = 25); video-laryngoscopy via GlideScope VL and direct laryngoscopy (DL) via a Macintosh blade were prepared by the same experienced anesthesiologist. All the participants practiced intubation six times on the same mannequin within a routine airway situation. The maximum acceptable time for each intubation was 3 minutes and three times of successful intubation was considered as an appropriate intubation skill. The required time for laryngoscopy and intubation at each stage, the grade of glottis view, the reasons for an unsuccessful intubation and the amount of successful intubations were recorded and compared between groups. Results: There was a clear variation between the 2 teams, in all the steps, based on the required time for laryngoscopy and intubation (p = 0.0001). Data analysis was performed by using repeated measures data which demonstrated that the necessary time for laryngoscopy and intubation during the study was clearly lower in the GlideScope VL team (p = .0001). In first five rounds of training, the glottis view in the DL group was significantly better than in the VL group (p < 0.05). Conclusion: Based on the result of today' study, routine airway intubation by using GlideScope VL is significantly faster than direct laryngoscopy. It seems that further studies are needed to investigate the effect of the educational program on different laryngoscopy and intubation situations.

Interaction between canine and human visceral leishmaniases in a holoendemic focus of Central Tunisia.

Canine visceral leishmaniasis (CVL) is endemic in the Mediterranean basin. In Tunisia, CVL is spatially associated with human visceral leishmaniasis (HVL) affecting mostly children younger than 5 years old. In this study, seroprevalence of Leishmania infantum infection in dogs was assessed in highly endemic districts of the governorate of Kairouan where more than 50% of HVL cases in Tunisia were reported. An entomological investigation was also carried out in two endemic districts (Bouhajla and Haffouz) to assess sand fly fauna and infection status of sand flies with Leishmania. A total of 191 serum samples were collected from healthy dogs and tested for anti-L. infantum antibodies by indirect immunofluorescence antibody test (IFAT). Overall seroprevalence for L. infantum was 26.7% being highest among dogs in the district of Bouhajla (52.7%) and the lowest in the district of Chbika (5.2%). In dogs, seroprevalence did not differ significantly based on gender or age, with dogs younger than 1 year showing a higher seroprevalence compared to older dogs. These findings suggest strong force of infection in naïve animals in holoendemic regions leading to emerging high incidence of HVL. Concomitant to the high CVL prevalence observed in the Bouhajla district, a significantly high cumulative HVL incidence also was observed in this district. Phlebotomus perniciosus and Phlebotomus longicuspis were the most abundant sand fly species in Bouhajla and Haffouz districts. The rate of Leishmania-DNA infection in sand flies was 9.4%. This finding points to spatial correlation between the occurrence of disease in humans, a high rate of infection in dogs and a high abundance of P. pernicious and P. longicuspis. Thus, CVL is the main risk factor for transmission to humans and subsequently, it is an important parameter for controlling transmission to humans.

Klebsiella pneumoniae LO10 producing extended-spectrum beta-lactamase SHV-12 in Saudi Arabia.

Klebsiella pneumoniae LO10 was responsible for an outbreak that occurred in the neonatal unit at Security Forces Hospital, Kingdom of Saudi Arabia. Over a period of eight months nine cases of bacteremia resulted in two deaths. Resistance to third generation cephalosporins was transferred from strain LO10 to E. coli by both conjugation and transformation. Sequence determination of the plasmid gene from two transconjugants and one transformant indicated that resistance was carried by a ca.100-kb plasmid encoding beta-lactamase SHV-12. This is the first description of a K. pneumoniae producing a type SHV-12 extended spectrum beta-lactamase in Riyadh. Long term exposure to antibiotics, prolonged stay, and heavy use of third generation cephalosporins contributed to the spread of the resistant strain in the unit. Strict infection control measures led to control of the outbreak.

Loss of heterozygosity in the Hodgkin-Reed Sternberg cell line L1236.

Hodgkin-Reed Sternberg cells are derived from germinal centre B-cells in most cases. Somatic mutations affecting their rearranged immunoglobulin genes were detected, rendering potential functional rearrangements non-functional. Under physiological conditions such cells would be designated to undergo apoptosis within the germinal centre. In search for the specific transforming event that prevents Hodgkin-Reed Sternberg cells from programmed cell death, cytogenetic analyses were broadly performed but did not reveal specific chromosomal aberrations. Analysis of these cells on the molecular level is difficult to perform due to the scarcity of the cells in the lymphoma tissue and the given limitations of in situ studies. To overcome these limitations, the cell line L1236, known to be derived from Hodgkin-Reed Sternberg cells in situ, was chosen for allelotype analysis. Using a panel of microsatellite loci assigned to nearly all chromosomal arms, regions of loss of heterozygosity were detected on chromosomal arms 6p, 9q and 17p. The size of lost segments was estimated by amplification of additional microsatellite loci mapped to the respective regions. Further analyses of single Hodgkin-Reed Sternberg cells will reveal whether LOH affecting these regions is a recurrent event in HD and to which extent the smallest commonly affected region can be estimated.

Suppression of the tumorigenic growth of Burkitt's lymphoma cells in immunodeficient mice by cytokine gene transfer using EBV-derived episomal expression vectors.

Epstein-Barr virus (EBV)-based expression vectors were tested for cytokine gene transfer-mediated induction of an immune response against human lymphoma cells. These vectors express the EBV latent gene EBNA 1 and carry the EBV latent origin of replication (ori P) for episomal replication in transfected cells. In addition, 3 human immunoglobulin light chain enhancer elements augment expression in B-cells. The suitability of these vectors for expression of cytokine genes in human lymphoma cells in vitro has been demonstrated. In order to extend these experiments in vivo, highly tumorigenic Burkitt's lymphoma (BL) cells were transfected with different cytokine genes of human and murine origin cloned into the EBNA 1/ori P vectors. Tumorigenicity of the transfectants was measured after inoculation into nude mice. No effect on tumorigenicity was observed after hIL 6 transfection and an inconsistent effect after hTNFalpha transfection. In contrast, complete suppression of tumor outgrowth occurred in hIL 10 transfectants. This tumor suppressive effect, however, was restricted to the IL 10 transfectants themselves and not directed against non-transfected cells. By comparison, mIL 4 transfected BL cells also were non-tumorigenic. However, co-inoculation of mIL 4 transfected and non transfected cells resulted in suppression of the tumorigenicity of the non-transfected cells. Thus, highly tumorigenic BL cells in nude mice are sensitive to immune effector mechanisms triggered by cytokine expression. In this experimental model, EBNA 1/ori P expression vectors are a suitable tool for cytokine gene transfer mediated induction of an anti-lymphoma immune response of the host.

Suitability of Epstein-Barr virus-based episomal vectors for expression of cytokine genes in human lymphoma cells.

Plasmids carrying the Epstein-Barr virus (EBV) latent gene EBNA1 and the EBV latent origin of replication (oriP) stay in transfected human cells as autonomously replicating extrachromosomal genetic units. They thus might represent a suitable tool for cytokine gene introduction into human tumor cells with the prospect of therapeutic antitumor vaccination. The aim of this study was to analyze whether such plasmids permit stable and efficient expression of cytokine genes in human non-Hodgkin lymphoma cells. We tested physical stability and expression levels of plasmids carrying EBNA1 and oriP for episomal maintenance, immunoglobulin light chain enhancer elements for augmentation of expression, and cytokine or marker genes after introduction into human NHL cell lines in vitro and in vivo after inoculation into nude mice. Data obtained with these EBV-based vectors were compared with another plasmid, not carrying EBNA1 and oriP. cDNAs coding for GM-CSF, IL6, TNF alpha, the chloramphenicolacetyltransferase (CAT) and the beta-galactosidase (lacZ) gene were transfected into the EBV-positive Burkitt's lymphoma cell line BL60 and the EBV-negative B cell lymphoma cell line BJA-B. EBV-derived vectors permitted a high, host cell independent transfection efficiency and high and host cell independent levels of expression. After removal of the selection pressure (hygromycin B) cytokine expression could be detected for several weeks in vitro and in vivo but, however, declined continuously. These experiments suggest that episomal BC-derived vectors represent an effective tool for cytokine gene transfer in human lymphoma cells.