AHCC® Supplementation to Support Immune Function to Clear Persistent Human Papillomavirus Infections.

Objective: To determine the efficacy, safety, and durability of the use of AHCC supplementation for 6 months to support the host immune system to clear high-risk human papillomavirus (HPV) infections. The AHCC supplement is a proprietary, standardized extract of cultured lentinula edodes mycelia (AHCC®, Amino Up, Ltd., Sapporo, Japan) that has been shown to have unique immune modulatory benefits. Study Design: This was a randomized, double-blind, placebo-controlled study (CTN: NCT02405533) in 50 women over 30 years of age with confirmed persistent high-risk HPV infections for greater than 2 years. Patients were randomized to placebo once daily for 12 months (N = 25) or AHCC 3-g supplementation by mouth once daily on empty stomach for 6 months followed by 6 months of placebo (N = 25). Every 3 months, patients were evaluated with HPV DNA and HPV RNA testing as well as a blood sample collected to evaluate a panel of immune markers including interferon-alpha, interferon-beta (IFN-ß), interferon-gamma (IFN-γ), IgG1, T lymphocytes, and natural killer (NK) cell levels. At the completion of the 12-month study period, patients on the placebo arm were given the option to continue on the study to receive AHCC supplementation unblinded for 6 months with the same follow-up appointments and testing as the intervention arm. Results: Fifty women with high-risk HPV were enrolled, and 41 completed the study. Fourteen (63.6%) of the 22 patients in the AHCC supplementation arm were HPV RNA/HPV DNA negative after 6 months, with 64.3% (9/14) achieving a durable response defined as being HPV RNA/HPV DNA negative 6 months off supplementation. On the placebo arm, two (10.5%) of 19 patients were HPV negative at 12 months. In the twelve placebo arm patients who elected to continue on the unblinded study, 50% (n = 6) were HPV RNA/HPV DNA negative after 6 months of AHCC supplementation. At the time of completion of the study, there were a total of 34 patients (22 blinded and 12 unblinded) who had received AHCC supplementation with an overall response rate of 58.8% that cleared HPV persistent infections. At the time of enrollment, the mean IFN-ß level was 60.5 ± 37.6 pg/ml in women with confirmed persistent HPV infections. Suppression of IFN-ß to less than 20 pg/ml correlated with an increase in T lymphocytes and IFN-γ and durable clearance of HPV infections in women who received AHCC supplementation. Conclusion: Results from this phase II study demonstrated that AHCC 3 g once daily was effective to support the host immune system to eliminate persistent HPV infections and was well tolerated with no significant adverse side effects reported. The duration of AHCC supplementation required beyond the first negative result needs more evaluation to optimize success for durable outcomes. The suppression of the IFN-ß level to less than 20 pg/ml correlated with clearance of HPV infections and merits further evaluation as a clinical tool for monitoring patients with HPV infections. Clinical Trial Registration: clinicaltrials.gov/ct2/, identifier NCT02405533.

From Bench to Bedside: Evaluation of AHCC Supplementation to Modulate the Host Immunity to Clear High-Risk Human Papillomavirus Infections.

Objective: There is currently no effective medicine or supplement for clearance of high risk- human papillomavirus (HR-HPV) infections. We have taken a systematic approach evaluating the potential use of AHCC supplementation to support clearance of HR-HPV infections. The primary objective of this research was to evaluate AHCC supplementation to modulation of the host immune system to clear HR-HPV infections from bench to bedside. Methods: Cervical cancer cells, CaSki (HPV16+), HeLa(HPV18+), SiHa(HPV16/18+), and C-33A(HPV-), were treated in vitro with AHCC 0.42 mg/mL daily x7 days then observed x7 days with daily sample collection. A confirmatory study in cervical cancer mouse models, SiHa(HPV16/18+) and C-33A(HPV-), was conducted: mice were divided into three groups per cell line then dosed with AHCC 50 mg/kg/d (N = 10), or vehicle alone (N = 10), or no supplementation (N = 10) for a total of 90 days followed by 30 days of observation. Tumors were measured 3x/week and blood samples collected bi-weekly to evaluate interferon (IFN) alpha(α), beta(ß), and gamma(γ) and immunoglobulin G(IgG) by immunoassays. Tumors were evaluated for HR-HPV expression by PCR. Two pilot studies of 10 patients each were conducted in women with confirmed persistent HR-HPV+ infections. The 1st study evaluated AHCC 3g from 5 weeks up to 6 months and 2nd study evaluated AHCC 1g < 8 months. HR-HPV DNA status and the immune panel were monitored at each visit. Results: HR-HPV clearance was observed in vitro and confirmed in the animal studies as a durable response. Four of six (66.7%) patients had confirmed HR-HPV clearance after 3-6 months of AHCC 3g. Similarly, 4 of 9 (44%) patients had confirmed HR-HPV clearance after 7 months of AHCC 1g. Suppression of IFNß <25 pg/mL was observed in those clearing the HR-HPV infection. Conclusion: Pre-clinical in vitro and in vivo studies demonstrated durable clearance of HR-HPV infections. The preliminary data from the two pilot studies suggested that AHCC supplementation supports the host immune system for successful clearance of HR-HPV infections. A confirmatory phase II randomized, double-blinded, placebo-controlled study is ongoing.

Unidirectional barbed suture versus interrupted vicryl suture in vaginal cuff healing during robotic-assisted laparoscopic hysterectomy.

This study examined the performance of unidirectional barbed suture versus polyglactin 910 with respect to vaginal cuff healing in robotic-assisted total laparoscopic hysterectomy (RATLH). This was a retrospective cohort study of 93 patients who underwent RATLH in a teaching hospital from July 2008 to June 2012. In the first 44 patients, the vaginal cuff was closed by interrupted polyglactin (Vicryl) 2-0 suture. In the following 49 patients, unidirectional barbed suture (V-loc) in a running fashion was used for cuff closure. Patients were seen 2 and 6 weeks postoperatively to evaluate cuff healing. Age, tobacco use, hemoglobin, deliveries, uterine weight, menopause, steroid use, underlying health problems, and concomitant procedures were found not to be significantly different between the two groups. There was one cuff dehiscence in the unidirectional barbed suture group and none in the interrupted polyglactin group (P > 0.05). The mean cuff healing time (8.5 vs. 7.7 weeks), incidence of cuff cellulitis (4.6 vs. 4.1 %), and postoperative bleeding (22.7 vs. 14.3 %) were not statistically significantly different between polyglactin and barbed suture closures, respectively (P > 0.05). However, polyglactin suture was associated with greater presence of granulation tissue than barbed suture (27.3 vs. 8.2 %, odds ratio = 3.34, P < 0.05). Unidirectional barbed suture cases were associated with shorter total operative times (220.2 vs. 272.8 min) and less estimated blood loss (164.8 vs. 274.9 ml); however, cuff closure times were not specifically measured. In our study, unidirectional barbed suture was identified as possibly superior to polyglactin cuff closure because of less observed granulation tissue, shorter operative duration, and lower estimated blood loss. However, there was no statistical difference in cuff healing time, cuff dehiscence, cellulitis, or postoperative bleeding between the two groups. A prospective randomized trial would be necessary to confirm these findings.

Accuracy of an accelerated, culture-based assay for detection of group B streptococcus.

OBJECTIVE: To determine the validity of a novel Group B Streptococcus (GBS) diagnostic assay for the detection of GBS in antepartum patients. STUDY DESIGN: Women were screened for GBS colonization at 35 to 37 weeks of gestation. Three vaginal-rectal swabs were collected per patient; two were processed by traditional culture (commercial laboratory versus in-house culture), and the third was processed by an immunoblot-based test, in which a sample is placed over an antibody-coated nitrocellulose membrane, and after a six-hour culture, bound GBS is detected with a secondary antibody. RESULTS: 356 patients were evaluated. Commercial processing revealed a GBS prevalence rate of 85/356 (23.6%). In-house culture provided a prevalence rate of 105/356 (29.5%). When the accelerated GBS test result was compared to the in-house GBS culture, it demonstrated a sensitivity of 97.1% and a specificity of 88.4%. Interobserver reliability for the novel GBS test was 88.2%. CONCLUSIONS: The accelerated GBS test provides a high level of validity for the detection of GBS colonization in antepartum patients within 6.5 hours and demonstrates a substantial agreement between observers.

Necrotizing soft-tissue infections in obstetric and gynecologic patients.

For the clinician, necrotizing soft-tissue infections have remained a daunting opponent since the first writings on the subject over 2000 years ago. Early disease may be incorrectly diagnosed as cellulitis, and this delay in correctly diagnosing and expeditiously proceeding to radical surgical debridement may lead to a high degree of mortality. Although several inciting events and risk factors have been described that allow for the development and progression of this disease, the diagnosis is still made clinically. Only aggressive surgical management in combination with broad-spectrum antibiotics will offer a chance at improving patient outcomes.

Optimization of a rapid diagnostic test for detection of group B streptococcus from antepartum patients.

We analyzed the performance of a new rapid diagnostic test for use in determining group B streptococcus colonization in pregnancy. Vaginal-rectal specimens were compared by the rapid test, a commercial laboratory culture result, and an in-house culture. Of 150 patient samples, 72 were positive by the rapid test, giving a prevalence of 48.0% versus 24.7% by traditional culture. Characterization of these results showed cross-reactivity with Enterococcus. The addition of bacitracin reduced this interference, and when reanalyzed, a colonization rate of 31.3% was found (P = 0.3961, chi-square), as well as a sensitivity of 100% (95% confidence interval [CI] 89.1-100) and a specificity of 93.6% (95% CI 86.9-97.2). The addition of bacitracin greatly improves the reliability of this diagnostic test and demonstrates a novel approach to reduce interference. An accurate determination of the test's sensitivity and specificity, however, awaits enrollment of the remaining subjects.

Small bowel perforation 17 months after robotic surgery for endometrial cancer: A case report.

► Robotic surgery offers several advantages in the management of endometrial cancer. ► No long-term data exist regarding recurrence in patients undergoing robotic surgery. ► Metastasis or recurrence may result in bowel obstruction post surgery.