Understanding Causes of Inferior Outcomes in Adolescents and Young Adults With Cancer.

Individuals diagnosed with cancer as adolescents and young adults (AYAs; ages 15-39 years) face unique vulnerabilities. Compared with individuals diagnosed when younger (≤14 years) or older (≥40 years), AYAs have not seen the same improvement in survival. Furthermore, they sit at a complex moment of social, emotional, and cognitive development, and have a unique interface with the healthcare system. With these observations, NCI prioritized addressing the unique vulnerabilities among AYAs with cancer, and NCCN developed guidelines regarding optimal AYA cancer care. Improvements in certain locales have been seen in the wake of this focus on AYAs, suggesting that continuing to consider AYA outcomes in the context of their specific needs is critical as we strive toward additional improvements. However, it is key to consider the drivers of these outcomes to continue this trajectory. This review presents a holistic conceptual model that includes factors that influence outcomes among AYAs with cancer, including domains in these levels that influence both clinical outcomes (such as relapse and survival) and health-related quality of life (HRQoL). These include domains at the patient level, such as social constructs (race/ethnicity, socioeconomic status), behavior (adherence, risk-taking), biologic characteristics (cancer biology, host genetics), medical treatment (treatment regimen, risk-based survivorship care), and treatment-related toxicities. The model also includes domains at the system level, which include treatment location (NCI designation, facility model, AYA program presence), clinical trial enrollment, transdisciplinary communication, fertility preservation, and psychosocial support. Recognizing these multiple factors at the level of the individual and the healthcare system influence AYA outcomes (from HRQoL to survival), it is key not only to consider patient-level interventions and development of novel cancer agents but also to develop systems-level interventions that can be executed in parallel. In this way, the impact can be expanded to a vast number of AYAs.

Current Issues in Fertility Preservation Among Pediatric and Adolescent Cancer Patients.

PURPOSE OF REVIEW: Although fertility preservation is not yet fully integrated into the comprehensive cancer care of pediatric and adolescent patients, advances continue to take place. This review summarizes recent updates and trends for health care professionals caring for these patients. RECENT FINDINGS: The creation of standardized infertility risk assessment guidelines offers the opportunity to provide greater consistency in clinical care and to provide a current baseline for future research studies seeking to refine risk stratification for individual patients. New agents are being introduced into cancer care; as their use increases, information about their impact on fertility is being studied. Ovarian tissue cryopreservation offers a new standard of care option for fertility preservation, but additional studies are needed to further assess efficacy and impact on ovarian reserve among pediatric and adolescent patients. Standardization of fertility preservation recommendations among certain sub-populations may also make it easier to provide greater consistency in clinical care. Advances continue to be made in the field of fertility preservation, but dissemination of this information is critical to moving toward fertility preservation truly being a part of comprehensive cancer care.

Maternal childbirth experience and time in labor: a population-based cohort study.

A negative childbirth experience may have long term negative effects on maternal health. New international guidelines allow a slower progress of labor in the early active phase. However, a longer time in labor may influence the childbirth experience. In this population-based cohort study including 26,429 women, who gave birth from January 2016 to March 2020, the association between duration of different phases of active labor and childbirth experience was studied. The women assessed their childbirth experience by visual analogue scale (VAS) score. Data was obtained from electronic medical records. The prevalence of negative childbirth experience (VAS 1-3) was 4.9%. A significant association between longer duration of all labor phases and a negative childbirth experience was found for primi- and multipara. The adjusted odds ratio (aOR (95%CI)) of negative childbirth experience and longer time in active labor (above the 90th percentile) in primipara was 2.39 (1.98-2.90) and in multipara 2.23 (1.78-2.79). In primi-and multipara with duration of labor ≥ 12 h or ≥ 6 h the aOR (95%CI) of negative childbirth experience were 2.22 (1.91-2.58) and 1.91 (1.59-2.26) respectively. It is of great importance to identify and optimize the clinical care of women with longer time in labor to reduce the risk of negative childbirth experience and associated adverse long-term effects.

The effect of systemic levels of TNF-alpha and complement pathway activity on outcomes of VEGF inhibition in neovascular AMD.

BACKGROUND/OBJECTIVES: Systemic levels of pro-inflammatory cytokines and activated complement components affect the risk and/or progression of neovascular age-related macular degeneration (AMD). This study investigated the effect of serum pro-inflammatory cytokine levels and complement pathway activity on the clinical response to vascular endothelial growth factor (VEGF) inhibition in neovascular AMD. METHODS: Sixty-five patients with a new diagnosis of neovascular AMD were observed over a six-month period in a single-centre, longitudinal cohort study. At each visit, the visual acuity score (VAS), central macular thickness (CMT), serum levels of CRP, pro-inflammatory cytokines (TNF-α, IL-1ß, IL-2, IL-6 and IL-8), and complement pathway activity were measured. Participant DNA samples were sequenced for six complement pathway single nucleotide polymorphisms (SNPs) associated with AMD. RESULTS: A statistically significant difference in VAS was observed for serum levels of TNF-α only: there was a gain in VAS (from baseline) of 1.37 for participants below the 1st quartile of mean concentration compared to a reduction of 2.71 for those above the 3rd quartile. Statistical significance was maintained after Bonferroni correction (P value set at <0.006). No significant differences in CMT were observed. In addition, statistically significant differences, maintained after Bonferroni correction, were observed in serum complement activity for participants with the following SNPs: CFH region (rs1061170), SERPING1 (rs2511989) and CFB (rs641153). Serum complement pathway components did not significantly affect VAS. CONCLUSIONS: Lower serum TNF-α levels were associated with an increase in visual acuity after anti-VEGF therapy. This suggests that targeting pro-inflammatory cytokines may augment treatment for neovascular AMD.

Success rate of external cephalic version in relation to the woman's body mass index and other factors-a population-based cohort study.

INTRODUCTION: The aim of this study was to evaluate the impact of women's body mass index (BMI) on the probability of a successful external cephalic version (ECV). MATERIAL AND METHODS: A retrospective population-based observational study including all women that underwent an ECV in the southeast region of Sweden from January 2014 to December 2019. Data were collected from electronic medical records, Obstetrix, Cerner. The women were divided into BMI categories according to the World Health Organization classification. Women with a BMI below 25 kg/m2 formed the reference group. Crude and adjusted odds ratios for unsuccessful ECV in each BMI group were calculated using binary logistic regression. Furthermore, the association between maternal characteristics and clinical and ultrasound variables at the time of the ECV and unsuccessful ECV was evaluated. RESULTS: A total of 2331 women were included. The overall success rate of ECV was 53.4%. Women with a BMI below 25 kg/m2 had a success rate of 51.3% whereas obese women had a success rate of 58.6%. The risk of an unsuccessful ECV among obese women (BMI ≥30 kg/m2 ) had an OR of 0.74 (95% CI 0.59-0.94) compared with women with a BMI below 25 kg/m2 . After adjusting for suitable confounding factors, the association was no longer significant. Higher maternal age, multiparity, higher gestational age, posterior placenta position, polyhydramnios and higher estimated weight of the fetus at the ECV significantly decreased the risk of an unsuccessful ECV. CONCLUSIONS: Maternal obesity does not seem to negatively influence the success rate of ECV. This is a finding that may encourage both caregivers and obese pregnant women to consider an ECV and so avoid a planned cesarean section for breech presentation in this group.

Targeting the HIF-1α-IGFBP2 axis therapeutically reduces IGF1-AKT signaling and blocks the growth and metastasis of relapsed anaplastic Wilms tumor.

For patients with anaplastic Wilms tumor (WiT), metastasis and recurrence are common, and prognosis is generally poor. Novel therapies are needed to improve outcomes for patients with this high-risk WiT. A potential contributor to WiT development is constitutive activation of AKT by insulin-like growth factor 1 (IGF1) and its receptor (IGF1R) signaling pathway, but the complete underlying mechanism remains unclear. Here, we demonstrate that the hypoxia-inducible factor 1α (HIF-1α)-IGF binding protein 2 (IGFBP2) axis and the tumor-specific IGF1A are key players for constitutive activation of IGF1-AKT signaling leading to the tumor malignancy. HIF-1α and IGFBP2 are highly expressed in a majority of WiT patient samples. Deficiency of either HIF-1α or IGFBP2 or IGF1 in the tumor cells significantly impairs tumor growth and nearly abrogates metastasis in xenografted mice. Pharmacologic targeting of HIF-1α by echinomycin delivered via nanoliposomes can efficiently restrain growth and metastasis of patient-derived relapsed anaplastic WiT xenografts. Liposomal echinomycin is more potent and effective in inhibiting WiT growth than vincristine in an anaplastic WiT mouse model, and eliminates metastasis by suppressing HIF-1α targets and the HIF-1α-IGFBP2 axis, which governs IGF1-AKT signaling.

Hepatocellular carcinoma as a complication of Niemann-Pick disease type C1.

Niemann-Pick disease type C (NPC) is a rare and fatal lysosomal storage disorder characterized by neurodegeneration and hepatic involvement. Mutations in either NPC1 or NPC2, two genes encoding lysosomal proteins, lead to an intracellular accumulation of unesterified cholesterol and sphingolipids in late endosomes/lysosomes. Early cholestatic disease is considered a hallmark of patients with early disease onset. This can potentially result in liver failure shortly after birth or subclinical hepatic inflammation. Previous reports suggest an association between NPC and hepatocellular carcinoma, a cancer that is rare during childhood. We present a 12-year-old male with a known diagnosis of NPC1 disease who was found to have a stage III hepatocellular carcinoma, underwent surgical resection with adjuvant chemotherapy, and subsequently died from metastatic disease. This report provides evidence of an increased risk of hepatocellular carcinoma in NPC patients, suggesting a need for screening in this patient population.

MYC oncogene is associated with suppression of tumor immunity and targeting Myc induces tumor cell immunogenicity for therapeutic whole cell vaccination.

BACKGROUND: MYC oncogene is deregulated in 70% of all human cancers and is associated with multiple oncogenic functions including immunosuppression in the tumor microenvironment. The role of MYC in the immune microenvironment of neuroblastoma and melanoma is investigated and the effect of targeting Myc on immunogenicity of cancer cells is evaluated. METHODS: Immune cell infiltrates and immunogenic pathway signatures in the context of MYCN amplification were analyzed in human neuroblastoma tumors and in metastatic melanoma. Dose response and cell susceptibility to MYC inhibitors (I-BET726 and JQ1) were determined in mouse cell lines. The influence of downregulating Myc in tumor cells was characterized by immunogenic pathway signatures and functional assays. Myc-suppressed tumor cells were used as whole cell vaccines in preclinical neuroblastoma and melanoma models. RESULTS: Analysis of immune phenotype in human neuroblastoma and melanoma tumors revealed that MYCN or c-MYC amplified tumors respectively are associated with suppressed immune cell infiltrates and functional pathways. Targeting Myc in cancer cells with I-BET726 and JQ1 results in cell cycle arrest and induces cell immunogenicity. Combining vaccination of Myc-inhibited tumor cells with checkpoint inhibition induced robust antitumor immunity and resulted in therapeutic cancer vaccine therapy in mouse neuroblastoma tumors. Despite vigorous antitumor immunity in the mouse melanoma model, upregulation of immunosuppressive pathways enabled tumor escape. CONCLUSIONS: This study demonstrates that the Myc oncogene is an appropriate target for inducing tumor cell immunogenicity and suggests that Myc-suppressed whole tumor cells combined with checkpoint therapy could be used for formulating a personalized therapeutic tumor vaccine.

New approaches to risk stratification for Wilms tumor.

PURPOSE OF REVIEW: The treatment of Wilms tumor is one of the great achievements in the field of oncology. One of the key success factors has been improved risk stratification, enabling augmentation or reduction of therapy depending on a patient's risk of relapse. This article highlights the evolution of clinical and biological prognostic markers that have been applied in the treatment of Wilms tumor. RECENT FINDINGS: Historically, tumor stage and histology were the sole determinants of Wilms tumor treatment. Recent clinical trials conducted by the Children's Oncology Group (COG) and the International Society of Pediatric Oncology (SIOP) Renal Tumor Study Group have expanded the menu of prognostic factors to include histologic and volumetric response to therapy and tumor-specific loss of heterozygosity (LOH) at chromosomes 1p and 16q. Augmentation of therapy has been able to overcome the adverse risk factors. An emerging prognostic marker is chromosome 1q gain, will be incorporated into future clinical trials. SUMMARY: The application of new clinical and biological prognostic factors has created unprecedented ability to tailor therapy for Wilms tumor, accompanied with improved outcomes. Current and future trials will continue to enhance precision medicine for Wilms tumor.

Long-term effects of the nine-item list intervention on obstetric and neonatal outcomes in Robson group 1 - A time series study.

INTRODUCTION: The nine-item list, with organizational and cultural changes, was implemented at the delivery unit in Linköping, Sweden between 2007 and 2010, aiming at improving the quality of care by offering more women a safe and attractive vaginal delivery. The target group for the intervention was nulliparous women at term with spontaneous onset of labor and cephalic presentation (Robson group 1). The aim of this study was to evaluate pregnancy outcomes before, during, early post and late post introduction of the nine-item list. MATERIAL AND METHODS: Robson group 1 births (n = 12 763) from 2004 to 2018 were divided into four time periods; before the nine-item list (2004-2006), during introduction of the nine-item list (2007-2010), early post introduction of the nine-item list (2011-2014) and late post introduction of the nine-item list (2015-2018). The nine-item list consists of monitoring of obstetric results, midwife coordinator, risk classification of women, three midwife-competence levels, teamwork-the midwife, obstetrician and nurse working as a team with the common goal of a normal delivery, obstetric morning round, fetal monitoring skills and obstetric skills training. Perinatal outcomes before, during, early post and late post introduction were compared using a Student's t test for numerical variables and a Pearson chi-squared test for categorical variables. RESULTS: Apgar score <7 at 5 minutes, Apgar score <4 at 5 minutes and umbilical cord arterial pH <7 did not differ significantly between the four time periods. Between before introduction and early post introduction, instrumental vaginal delivery decreased from 19.8% to 12.2% and cesarean section from 9.6% to 4.5%. The late post introduction period showed a maintained effect with 10.7% instrumental deliveries and 3.9% cesarean sections. Obstetric anal sphincter injury grade III decreased instantly during the introduction of the nine-item list from 7.8% to 5.1% and thereafter remained unchanged. CONCLUSIONS: Implementation of the nine-item list increased the proportion of spontaneous vaginal deliveries by reducing the number of instrumental deliveries and cesarean sections without affecting the neonatal outcomes in nulliparous women with spontaneous onset of labor. The nine-item list intervention seems to provide long-term sustainable results.

The impact of obstetric interventions and complications on women's satisfaction with childbirth a population based cohort study including 16,000 women.

BACKGROUND: As a quality marker and a tool for benchmarking between units, a visual analogue scale (VAS) (ranging from 1 to 10) to estimate woman's satisfaction with childbirth was introduced in 2014. This study aimed to assess how obstetric interventions and complications affected women's satisfaction with childbirth. METHODS: A retrospective cohort study including 16,775 women with an available VAS score who gave birth between January 2016 and December 2017. VAS score, maternal and obstetric characteristics were obtained from electronic medical records and crude and adjusted odds ratios (aOR) were calculated. RESULTS: The total prevalence of dissatisfaction with childbirth (VAS 1-3) was 5.7%. The main risk factors for dissatisfaction with childbirth were emergency cesarean section, aOR 3.98 95% confidence interval (CI) 3.27-4.86, postpartum hemorrhage ≥2000 ml, aOR 1.85 95%CI 1.24-2.76 and Apgar score < 7 at five minutes, aOR 2.95 95%CI 1.95-4.47. The amount of postpartum hemorrhage showed a dose-response relation to dissatisfaction with childbirth. Moreover, labor induction, instrumental vaginal delivery, and obstetric anal sphincter injury were significantly associated with women's dissatisfaction with childbirth. A total number of 4429/21204 (21%) women giving birth during the study period had missing values on VAS. A comparison of characteristics between women with and without a recorded VAS score was performed. There were statistically significant differences in maternal age and maternal BMI between the study population and excluded women due to missing values on VAS. Moreover, 64% of the women excluded were multiparas, compared to 59% in the study population. CONCLUSIONS: Obstetric interventions and complications, including emergency cesareans section and postpartum hemorrhage, were significantly related to dissatisfaction with childbirth. Such events are common and awareness of these associations might lead to a more individualized care of women during and after childbirth.

Ten years of simulation-based shoulder dystocia training- impact on obstetric outcome, clinical management, staff confidence, and the pedagogical practice - a time series study.

BACKGROUND: To assess the impact of 10 years of simulation-based shoulder dystocia training on clinical outcomes, staff confidence, management, and to scrutinize the characteristics of the pedagogical practice of the simulation training. METHODS: In 2008, a simulation-based team-training program (PROBE) was introduced at a medium sized delivery unit in Linköping, Sweden. Data concerning maternal characteristics, management, and obstetric outcomes was compared between three groups; prePROBE (before PROBE was introduced, 2004-2007), early postPROBE (2008-2011) and late postPROBE (2012-2015). Staff responded to an electronic questionnaire, which included questions about self-confidence and perceived sense of security in acute obstetrical situations. Empirical data from the pedagogical practice was gathered through observational field notes of video-recordings of maternity care teams participating in simulation exercises and was further analyzed using collaborative video analysis. RESULTS: The number of diagnosed shoulder dystocia increased from 0.9/1000 prePROBE to 1.8 and 2.5/1000 postPROBE. There were no differences in maternal characteristics between the groups. The rate of brachial plexus injuries in deliveries complicated with shoulder dystocia was 73% prePROBE compared to 17% in the late postPROBE group (p > 0.05). The dominant maneuver to solve the shoulder dystocia changed from posterior arm extraction to internal rotation of the anterior shoulder between the pre and postPROBE groups. The staff questionnaire showed how the majority of the staff (48-62%) felt more confident when handling a shoulder dystocia after PROBE training. A model of facilitating relational reflection adopted seems to provide ways of keeping the collaboration and learning in the interprofessional team clearly focused. CONCLUSIONS: To introduce and sustain a shoulder dystocia training program for delivery staff improved clinical outcome. The impaired management and outcome of this rare, emergent and unexpectedly event might be explained by the learning effect in the debriefing model, clearly focused on the team and related to daily clinical practice.

Enforcing a tobacco-free campus through an ambassador-based program: a phenomenology.

OBJECTIVE: This phenomenology explored the experiences of those involved in a campus-based Ambassador program that enforced a tobacco-free policy at a public university in Montana. PARTICIPANTS: During the program's initial implementation (spring 2014), researchers observed and interviewed 21 Ambassadors and 19 policy violators. METHODS: Researchers observed and recorded field notes of Ambassadors promoting the policy to the campus community and interacting with policy violators. Researchers invited Ambassadors and violators to be interviewed regarding their experiences with the program. RESULTS: Although Ambassadors enjoyed promoting the policy and sensed an increase in recognition by others, they also felt uncomfortable and had mixed feelings regarding their level of authority. Violators also felt uncomfortable, yet the majority described the experience with the program as positive. CONCLUSIONS: The findings from the study can be used to inform those considering the implementation of an Ambassador program on their campus.

Supporting fathers in the transition to parenthood.

Knowledge of the experience of parenthood is usually from a woman's perspective. The resulting outcome is that knowledge about the experience of fatherhood has been limited. Fathers are starting to change this situation by sharing their experience as is evidenced by the overall response of 267 fathers to this study. This paper focuses on the exploration of 22 men's feelings and beliefs about fatherhood; and their expectations and views about parenting. The paper will also investigate how fathers' antenatal expectations matched the reality of early family life including emotional well-being, attitudes to parenting, adjustment to family life and sources of support. The quantitative and qualitative data of the 22 fathers who responded to both the antenatal and postnatal questionnaires used within this paper are drawn from a larger Queensland survey of women and men during the antenatal and postnatal period.