Risk Factors of High Grade Squamous Intraepithelial Lesions of Cervix in HIV Infected Women at Khon Kaen Hospital

Objective:To determine risk factors associated of high grade squamous intraepithelial lesion (HSIL) in HIV infected women. Material and Methods: Retrospective cohort study of 250 HIV infected women registered in colposcopy clinic at Khon Kaen Hospital between January 1st 2008 and January 1st 2014 who had high grade histology (HSIL) was conducted. Risk factors associated with HSIL histology were studied between HSIL and low grade squamous intraepithelial lesion (LSIL) plus normal histology group. Risk factors were analyzed by logistic regression and recurrence of HSIL was analyzed by survival analysis.Results: The colposcopic records of 250 HIV infected women were analyzed. Mean age was 36.0 ± 7.5 years, and the mean CD4 cell count was 391.0 ± 229.3 cell/μL. Age ≥ 35 years was only significant risk factor associated with HSIL histology in HIV infected women (RR 2.06, 95% CI = 1.17 - 3.63). There were 32 (29.4%) and 7 (5.0%) women in HSIL and LSIL group had recurrent of HSIL histology respectively. Median time to recurrence of HSIL group compared with LSIL group was 55.6 months versus 59.8 months (p < 0.05).Conclusion: Age ≥ 35 years was a risk factor of HSIL histology in HIV infected women. Higher recurrence of HSIL was found in HSIL group

Subphrenic Saline Irrigation for Reducing Postoperative Shoulder Pain after Gynecologic Laparoscopic Surgery: A Randomized Controlled Trial

Objective:To determine the effectiveness of subphrenic saline irrigation for postoperative shoulder pain reduction in gynecologic laparoscopic surgery.Materials and Methods:A randomized controlled trial comparing subphrenic saline irrigation and no irrigation for shoulder pain reduction was conducted at Khon Kaen Hospital between May 1st and August 20th, 2014. A total of 62 patients were randomly allocated into two groups: Group A: Subphrenic saline Irrigation (n=31) and Group B: No irrigation (n=31). The primary outcomes were postoperative shoulder pain at 12, 24, and 48 hours, evaluated by using visual analog scale. The secondary outcomes were data of additional analgesics drug use, abdominal discomfort, fever, wound infection and bradycardia.Results: Postoperatively shoulder pain in subphrenic saline irrigation was significantly less than in no irrigation group at 12 hours [median (IQR) 2 (0-3) and 5 (0-6); P=0.01] and at 24 hours [median (IQR ) 0 (0) and 2 (0-4); P=0.004]. Abdominal discomfort was significantly higher in the control group [74.2% and 48.4%; P=0.03]. Mean additional analgesic drugs in intervention group was lower than in the control group [2.1±1.5 and 3.6±1.6; P=0.001]. There was no complication.Conclusions: Subphrenic saline irrigation significantly reduced postoperative shoulder pain in gynecologic laparoscopic surgery without serious complications

Membrane Stripping to Reduce Postdate Pregnancy: A Randomized Controlled Trial

Objectives: To compare delivery before 40 weeks of gestation between the pregnant women who had membrane stripping and those with no intervention.Materials and Methods: One hundred and seventy-eight pregnant women, gestational age of 38 weeks or more who attended antenatal care clinic at Khon Kaen Hospital from January to July, 2016 were randomized into two groups: membrane stripping group and no intervention group. The proportion of pregnant women who delivered before 40 weeks of gestation was analyzed.Results: Baseline characteristics were similar between groups. The proportion of women who delivered before 40 weeks of gestation in membrane stripping group was significantly higher than no intervention group (69.3% VS 51.1%, p=0.01) (RR=0.6, 95% CI 0.4-0.9). There was no significant difference in cesarean section rate, maternal complications and neonatal outcomes between groups.Conclusion: Membrane stripping can reduce postdate pregnancy

Sublingual Misoprostol for Unsatisfactory Colposcopic Finding: A randomized controlled trial

Objectives: To assess the effectiveness of 200 μg sublingual misoprostol for converting an unsatisfactory to satisfactory colposcopic finding.Materials and Methods: Forty-two participants with abnormal cervical cytology and unsatisfactory colposcopic finding who underwent colposcopy between September 2016 and June 2017 were randomized into two groups; either misoprostol or placebo given sublingually. Second colposcopy was performed 2 hours later, and the conversion rate of unsatisfactory to satisfactory colposcopic finding of both groups was analyzed.Results: Baseline characteristics were similar between two groups. Conversion rate of unsatisfactory to satisfactory colposcopic finding in participants who received sublingual misoprostol was statistically significant higher than placebo group (80.9% vs 38.1%, p = 0.011, relative risk = 2.1, 95% confidence interval 1.18-3.80). There was no significant difference in adverse effect between groups.Conclusion: Two hundred micrograms of sublingual misoprostol, 2 hours before performing colposcopy can convert an unsatisfactory finding to a satisfactory one

Validity of the Risk of Malignancy Index 4 to Preoperative Evaluation of Patients with Adnexal Masses

Objectives: To study the validity of the risk of malignancy index 4 in preoperative prediction for women with adnexal masses.Materials and Methods: A cross-sectional diagnostic study of women with adnexal masses admitted at Khon Kaen Hospital between 18th May to 31st July, 2015 for elective surgery. The sensitivity, specificity, positive predictive value and negative predictive value were calculated. Receiver operating characteristic (ROC) curve was used to evaluate the optimal cut-off point for the risk of malignancy index (RMI).Results: One hundred and sixteen women with adnexal masses were recruited (89 cases were benign and 27 cases were malignancy). The optimal cut-off point for RMI 4 in our study was 204 giving the sensitivity 82.8%, specificity 79.3%, positive predictive value 52.3%, and negative predictive value 93.2%. Using a cut-off at 450, sensitivity was 63%, specificity was 86.5%, PPV was 58.6% and NPV was 88.5%. The area under the ROC curve for the RMI 4 was 0.852. Conclusion: The RMI 4 had a validity to discriminate between benign and malignant ovarian tumors

HPV E2s expression in recombinant adenovirus HPV E2-transduced human primary keratinocytes.

<p>(A) GFP signals of recombinant adenoviruses GFP, GFP-HPV16 E2, GFP-HPV18 E2, GFP-HPV18 E2TAD, and GFP-HPV18 E2DBD under fluorescence microscope on live cells (10X). (B) GFP protein expression was detected by western blotting analysis. GFP, GFP-HPV16 E2, GFP-HPV18 E2, GFP-HPV18 E2TAD, and GFP-HPV18 E2DBD showed the expected protein sizes of ∼32 kD, 62 kD, 64 kD, 50 kD, and 45 kD, respectively and are indicated by asterisks. The β-actin protein was used as loading control. (C) The mRNA expression levels of recombinant adenoviruses GFP, GFP-HPV16 E2, GFP-HPV18 E2, GFP-HPV18 E2TAD, and GFP-HPV18 E2DBD are shown as CT values (mean±SD). (D) The suppressive effect of HPV E2 on HPV18 E6/E7 transcription in HeLa cells is shown as relative transcripts levels compared to cells not expressing E2 using real-time PCR. (*<i>P</i>≤0.05).</p

STING and IFN-κ transcripts were down-regulated by HPV E2s.

<p>(A) STING transcripts level analyzed by RT-PCR was significantly down-regulated by HPV16 E2, HPV18 E2 and the HPV18 E2 TAD in HPK and B) IFN-κ transcription level was significantly down-regulated by HPV16 E2, HPV18 E2 and HPV18 TAD in HPK. C) STING transcripts level was modulated by E2 in NUH49 as shown in (A). D) IFN-κ transcripts level was modulated by E2 in ITB3 and NUH49 as in (B). (A–D) HPV18 E2TAD significantly down-regulated STING and IFN-κ genes transcription when compared to HPV18 E2DBD. (*<i>P</i>≤0.05, **<i>P</i>≤0.01, ***<i>P</i>≤0.001).</p

Transcriptional reduction of IFN-κ in STING-silenced HPK and poly I:C stimulated HPK.

<p>(A) STING and IFN-κ transcription level in HPK cells after transfection with siSTING and siIFNK for 48 h. IFN-κ transcription level in STING-knockdown HPK was reduced by ∼20% (<i>P</i> = 0.06). STING transcription level in IFN-κ-knockdown HPK was not changed. (B) ISGs transcription levels were down-modulated in IFN-κ-knockdown HPK. (C) TAD of HPV18 E2 abrogated STING transcription in Poly I:C induced HPK cells. Cells transduced with GFP as control and GFP-E218TAD were stimulated with poly I:C (10 µg/ml) for 3, 6, and 12 h. STING transcription level was measured at each time point. (D) IFN-κ transcription level was abrogated by HPV18 E2TAD when examined at each time point of IFN-κ induction by poly I:C (E) ISGs were determined after stimulation of HPK expressing HPV18 E2TAD with poly I:C (10 µg/ml) for 3 h. (*<i>P</i>≤0.05, **<i>P</i>≤0.01, ***<i>P</i>≤0.001).</p

E2 Proteins of High Risk Human Papillomaviruses Down-Modulate STING and IFN-κ Transcription in Keratinocytes

<div><p>In the early stages of human papillomavirus (HPV) infection, the viral proteins elicit specific immune responses that can participate to regression of ano-genital lesions. HPV E6 protein for instance can reduce type I interferon (IFN) including IFN-κ that is involved in immune evasion and HPV persistence<b>.</b> To evaluate the role of E2 protein in innate immunity in HPV16-associated cervical lesions, genome-wide expression profiling of human primary keratinocytes (HPK) transduced by HPV16 E2 was investigated using microarrays and innate immunity associated genes were specifically analyzed. The analyses showed that the expression of 779 genes was modulated by HPV16E2 and 92 of them were genes associated with innate immunity. Notably IFN-κ and STING were suppressed in HPK expressing the E2 proteins of HPV16 or HPV18 and the trans-activation amino-terminal domain of E2 was involved in the suppressive effect. The relationship between STING, IFN-κ and interferon stimulated genes (ISGs) in HPK was confirmed by gene silencing and real time PCR. The expression of STING and IFN-κ were further determined in clinical specimens by real time PCR. STING and IFN-κ were down-modulated in HPV positive low grade squamous intraepithelial lesions compared with HPV negative controls. This study demonstrates that E2 proteins of high risk HPV reduce STING and IFN-κ transcription and its downstream target genes that might be an immune evasion mechanism involved in HPV persistence and cervical cancer development.</p></div

STING and IFN-κ down-regulation in HPV positive clinical specimens.

<p>(A) HPV E2s transcription level was significantly increased in HPV positive normal and LSIL when compared to HPV negative normal cases (<i>P</i><0.05). (B) STING transcription level was significantly decreased in LSIL with HPV positive and HPV E2 positive cases (<i>P</i><0.05). Normal cases with HPV positive also showed low STING transcription level when compared to normal HPV negative cases (<i>P</i><0.05). (C) IFN-κ transcription level was significantly down-regulated in normal HPV positive cases and HPV positive LSIL cases when compared to normal HPV negative cases (<i>P</i><0.05). (*<i>P</i>≤0.05, **<i>P</i>≤0.01, ***<i>P</i>≤0.001).</p