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.

Repercussões do câncer infantil sobre a relação conjugal / Repercussions of pediatric cancer on marital relations

Investigaram-se as repercussões do câncer de um filho sobre a relação conjugal dos pais. Realizou-se um estudo de caso coletivo com quatro casais. Os dados foram obtidos a partir de entrevistas semiestruturadas, realizadas individualmente com cada cônjuge, no ambiente hospitalar. Após, foram submetidos à análise de conteúdo qualitativa, que teve como categorias: coesão, comunicação e intimidade/sexualidade. Relatou-se uma maior coesão, relacionada à sensação de poder contar com o cônjuge. Quanto à comunicação, constatou-se o predomínio de temas relacionados à enfermidade da criança, mas um silenciamento, entre os homens, quanto aos temores vivenciados. A intimidade/sexualidade mostrou-se influenciada pela ansiedade enfrentada. Constatou-se como o câncer infantil pode exacerbar características já presentes na relação, assim como apresentar novos desafios aos casais.(AU)

The repercussions of child's cancer on parent's marital relation were investigated. A collective case study with four couples was carried out. Data were obtained from individual semi-structured interviews, conducted in the hospital, and submitted to a qualitative content analysis, whose categories were: cohesion, communication, and intimacy/sexuality. An increase in the cohesion between the parents was observed. In relation to communication, a predominance of topics related to the child's disease was observed. Among the men, silence about their own fears was observed. The intimacy/sexuality was affected by the anxiety about the child's survival. It was shown how child's cancer can intensify characteristics already present in the marital relation, and can also raise new challenges for the couple.(AU)

Repercussões do câncer infantil sobre a relação conjugal / Repercussions of pediatric cancer on marital relations

Investigaram-se as repercussões do câncer de um filho sobre a relação conjugal dos pais. Realizou-se um estudo de caso coletivo com quatro casais. Os dados foram obtidos a partir de entrevistas semiestruturadas, realizadas individualmente com cada cônjuge, no ambiente hospitalar. Após, foram submetidos à análise de conteúdo qualitativa, que teve como categorias: coesão, comunicação e intimidade/sexualidade. Relatou-se uma maior coesão, relacionada à sensação de poder contar com o cônjuge. Quanto à comunicação, constatou-se o predomínio de temas relacionados à enfermidade da criança, mas um silenciamento, entre os homens, quanto aos temores vivenciados. A intimidade/sexualidade mostrou-se influenciada pela ansiedade enfrentada. Constatou-se como o câncer infantil pode exacerbar características já presentes na relação, assim como apresentar novos desafios aos casais.

The repercussions of child's cancer on parent's marital relation were investigated. A collective case study with four couples was carried out. Data were obtained from individual semi-structured interviews, conducted in the hospital, and submitted to a qualitative content analysis, whose categories were: cohesion, communication, and intimacy/sexuality. An increase in the cohesion between the parents was observed. In relation to communication, a predominance of topics related to the child's disease was observed. Among the men, silence about their own fears was observed. The intimacy/sexuality was affected by the anxiety about the child's survival. It was shown how child's cancer can intensify characteristics already present in the marital relation, and can also raise new challenges for the couple.

Continuous glucose monitoring in diabetic women following antenatal corticosteroid therapy: a pilot study.

To compare the timing, duration, and severity of corticosteroid-associated hyperglycemia in pregnant women with and without diabetes mellitus (DM). An observational study was conducted of pregnant women with DM and controls who received corticosteroids. Median glucose levels were calculated over 4-hour intervals after the first dose of corticosteroid with a continuous glucose monitor. A glucose level increase of at least 15% above baseline was considered significant. Nine pregnant women participated in this study (six with DM and three without DM). Elevations of glucose levels occurred at hour 20, 44, and 68 in both groups and lasted for up to 4 hours. In those with DM, glucose levels increased 33 to 48%, whereas in those without DM, glucose levels rose 16 to 33%. Several, relatively short episodes of glucose elevation occur in response to corticosteroids, and are more pronounced in diabetic women.