Premature ovarian insufficiency in female adolescent and young adult survivors of non-gynecological cancers: a population-based cohort study.

BACKGROUND: The risk of premature ovarian insufficiency (POI) is increased in adolescent and young adult (AYA) cancer survivors, with the prevalence depending on cancer diagnosis, treatment, and patient factors. Prior studies are limited by sample size and type of cancer included. The objective of this study was to assess the risk of POI in female AYA survivors of non-gynecologic cancers, using a population-based approach. METHODS: This population-based retrospective cohort study comprises 21,666 females, 15-39 years old, diagnosed with a single non-gynecologic cancer in Ontario, Canada from 1995 to 2015. Through health administrative data linkage, participants were followed until their 40th birthday, December 31, 2018, bilateral oophorectomy, loss of health insurance eligibility or death. Each cancer survivor was matched to 5 females who were not diagnosed with cancer (unexposed, n = 108,330). Women with bilateral oophorectomy or a prior menopause diagnosis were excluded. POI was identified through use of the ICD-9 code for menopause (ICD9-627). Modified Poisson regression models were used to calculate the adjusted relative risk (aRR) of POI for AYA cancer survivors compared to unexposed individuals, adjusted for income, parity, age, and immigration status. RESULTS: The occurrence of POI was higher in survivors of AYA cancer versus unexposed patients (5.4% vs. 2.2%). Survivors of AYA cancer had an increased risk of POI relative to unexposed patients (aRR 2.49; 95% CI 2.32-2.67). Risk varied by type of cancer: breast (4.32; 3.84-4.86), non-Hodgkin's lymphoma (3.77; 2.88-4.94), Hodgkin's lymphoma (2.37; 1.91-2.96), leukemia (14.64; 10.50-20.42), thyroid (1.26; 1.09-1.46) and melanoma (1.04; 0.82-1.32). Risk varied by age at time of cancer diagnosis, with a higher risk among females diagnosed at age 30-39 years (3.07; 2.80-3.35) than aged 15-29 years (1.75; 1.55-1.98). CONCLUSIONS: AYA survivors of non-gynecologic cancers are at an increased risk of POI, particularly survivors of lymphomas, leukemia, breast, and thyroid cancer. The risk of POI is increased for those diagnosed with cancer at an older age. These results should inform reproductive counseling of female AYAs diagnosed with cancer.

Premature ovarian insufficiency is the onset of premature menopause in individuals less than 40-years-old. Previous research has shown that there is a higher risk of premature ovarian insufficiency in adolescent and young adult cancer survivors, due to the toxicity of cancer treatments on reproductive organs. Prior research was limited in its applicability by having small sample sizes, only including childhood cancer, excluding young adults, and studying fewer types of cancer. This study was conducted using a large population-based approach, on all females aged 15­39 years old with cancer in Ontario, Canada from 1995 to 2015. We found that there was nearly a 2.5 times greater risk of premature ovarian insufficiency in cancer survivors compared patients without cancer. Compared to patients without cancer, this risk was highest for survivors of leukemia (14 times higher risk), followed by breast cancer (4 times higher risk), lymphomas (2­4 times higher risk), and thyroid cancer (1.2 times higher risk). There is no increased risk in melanoma survivors. The risk was higher in individuals diagnosed with cancer at a later age (30­39 years), with a risk 3 times higher than the population without cancer, while a younger age of diagnosis (15­29 years) carries a risk only 1.75 times higher than the population without cancer. These results should help improve healthcare provider and patient understanding of the risk of premature ovarian insuficiency in young cancer survivors, and guide counseling at the time of cancer diagnosis and during survivorship on future reproductive function.

Preoperative ultrasound accurately characterizes surgically confirmed extracranial spinal accessory nerve injuries.

OBJECTIVE: To determine the accuracy of preoperative ultrasound and MRI in surgically confirmed spinal accessory nerve injuries and present the benefits of a multimodality image review. MATERIALS AND METHODS: A retrospective review of 38 consecutive patients referred to a peripheral nerve surgical practice at an academic teaching hospital with surgically confirmed spinal accessory nerve injuries. All cases were reviewed for patient demographics, date and cause of injury, preoperative EMG, and surgical diagnosis and management. Additionally, prospective interpretation of preoperative ultrasound and MRI reports were reviewed for concordance or discordance with the surgical diagnosis. RESULTS: Iatrogenic injury was present in 37 (97%) cases and most commonly a result of an excisional lymph node biopsy (68%). Surgically confirmed spinal accessory nerve injury diagnoses consisted of 25 (66%) stump neuromas and 13 (34%) incomplete nerve injuries. Nine months was the average time from injury to surgery. Twenty-nine patients underwent preoperative ultrasound and/or MRI evaluation: 12 ultrasound only, 10 MRI only, and seven with both ultrasound and MRI. Eighteen (95%) preoperative ultrasound reports compared to four (24%) preoperative MRI reports were concordant with the surgical diagnosis. In the seven cases with both preoperative ultrasound and MRI, six had discordant ultrasound and MRI imaging diagnoses for which the ultrasound was concordant with the surgical diagnoses in all cases. CONCLUSION: Preoperative ultrasound more accurately characterizes spinal accessory nerve injuries compared to MRI and should serve as the modality of choice when a spinal accessory nerve injury is suspected.

Fat quantification of the rotator cuff musculature using dual-energy CT-A pilot study.

PURPOSE: To assess the ability of dual-energy CT (DECT) as a novel technique to quantify the degree of rotator cuff fat degeneration. METHOD: Clinically indicated shoulder CT exams for evaluation of osteoarthritis, rotator cuff arthropathy, pain or instability, or preoperative planning were acquired using dual-source CT systems. Rotator cuff DECT fat fraction after material decomposition was calculated off the sagittal image. Fat fractions were also assessed using CT numbers from dual energy virtual monochromatic images (70 keV) and single-energy CT (SECT) images (100 kV). Visual subjective Goutallier scores of the rotator cuff muscles were used as the reference standard. RESULTS: 12 shoulders from 10 patients were analyzed, with bilateral shoulders evaluated in two patients (mean age 69 years (range 19-97)). Three patients were male and seven were female, with mean BMI of 32 (range 26-41). Mean fat fraction of the teres major and subcutaneous fat were, 2.9 % ± 4.0 % and 99.5 % ± 2.6 %, respectively, rendering these as reliable internal standards for 0% and 100 % fat. Mean DECT fat fractions of the rotator cuff were compared to Goutallier scores, revealing a high strength of rank correlation: ρ = 0.92, p < 0.0001. Mean fat fraction assessed with CT numbers also revealed high strengths of linear associations: ρ = 0.83, p < 0.0001 and ρ = 0.82, p < 0.0001, for DECT 70 keV and SECT 100 kV, respectively. CONCLUSIONS: DECT direct fat fraction after material decomposition presents a novel approach to quantitative assessment of fatty degeneration, which has excellent correlation with clinically accepted standards.

Intranasal deferoxamine can improve memory in healthy C57 mice, suggesting a partially non-disease-specific pathway of functional neurologic improvement.

INTRODUCTION: Intranasal deferoxamine (IN DFO) has been shown to decrease memory loss and have beneficial impacts across several models of neurologic disease and injury, including rodent models of Alzheimer's and Parkinson's disease. METHODS: In order to assess the mechanism of DFO, determine its ability to improve memory from baseline in the absence of a diseased state, and assess targeting ability of intranasal delivery, we treated healthy mice with IN DFO (2.4 mg) or intraperitoneal (IP) DFO and compared behavioral and biochemical changes with saline-treated controls. Mice were treated 5 days/week for 4 weeks and subjected to behavioral tests 30 min after dosing. RESULTS: We found that IN DFO, but not IP DFO, significantly enhanced working memory in the radial arm water maze, suggesting that IN administration is more efficacious as a targeted delivery route to the brain. Moreover, the ability of DFO to improve memory from baseline in healthy mice suggests a non-disease-specific mechanism of memory improvement. IN DFO treatment was accompanied by decreased GSK-3ß activity and increased HIF-1α activity. CONCLUSIONS: These pathways are suspected in DFO's ability to improve memory and perhaps represent a component of the common mechanism through which DFO enacts beneficial change in models of neurologic disease and injury.

Understanding Placentophagy.

OBJECTIVE: To evaluate the knowledge, attitudes, and beliefs of women during pregnancy and the postpartum period related to placentophagy. DESIGN: Mixed methods study (cross-sectional survey and online discussions). SETTING: We used social media to advertise the study to mother/parenting groups. Online discussion groups were conducted through Google Groups. PARTICIPANTS: Women during pregnancy and in the postpartum period and placenta encapsulation specialists with Internet access. METHODS: We summarized descriptive data and analyzed subgroups with the use of chi-square tests. We conducted a binary logistic regression to compare placentophagy with demographic variables and used constant comparative analysis to analyze online discussion group themes. RESULTS: Overall, 271 of 1,088 (24.9%) respondents consumed their placentas. Canadian respondents and those who experienced pregnancy/birth-related complications were significantly (p < .05) less likely to consume their placentas than respondents from the United States (odds ratio = 0.48, 95% confidence interval [0.28, 0.82]) and those who had no complications (odds ratio = 0.56, 95% confidence interval [0.37, 0.85]). Increased iron stores (521/1,030, 50.6%), prevention of postpartum depression (519/1,030, 50.4%), and increased energy/decreased fatigue (460/1,030, 44.7%) were the most commonly listed perceived benefits. Infection and improper handling/preparation of the placenta were important concerns, and hospital policy was noted as a barrier to placentophagy. CONCLUSION: Respondents who engaged in placentophagy were primarily motivated by unproven benefits, such as the prevention of postpartum depression and anemia, for which there are other management alternatives. Although placentophagy is gaining popularity, it remains unregulated, and safety and efficacy data are limited. A safe, standardized preparation process is needed to minimize potential harm before further efficacy studies can be done. Targeted educational material surrounding placentophagy is needed to improve woman-centered care.

Food consumption and activity levels increase in rats following intranasal Hypocretin-1.

Hypocretin-1 (HC, orexin-A) is a neuropeptide involved in regulating physiological functions of sleep, appetite and arousal, and it has been shown that intranasal (IN) administration can target HC to the brain. Recent clinical studies have shown that IN HC has functional effects in human clinical trials. In this study, we use rats to determine whether IN HC has an immediate effect on food consumption and locomotor activity, whether distribution in the brain after IN delivery is dose-dependent, and whether MAPK and PDK1 are affected after IN delivery. Food intake and wheel-running activity were quantified for 24h after IN delivery. Biodistribution was determined 30min after IN delivery of both a high and low dose of 125I-radiolabelled HC throughout the brain and other bodily tissues, while Western blots were used to quantify changes in cell signaling pathways (MAPK and PDK1) in the brain. Intranasal HC significantly increased food intake and wheel activity within 4h after delivery, but balanced out over the course of 24h. The distribution studies showed dose-dependent delivery in the CNS and peripheral tissues, while PDK1 was significantly increased in the brain 30min after IN delivery of HC. This study adds to the growing body of evidence that IN administration of HC is a promising strategy for treatment of HC related behaviors.

Biodegradable polyphosphazene biomaterials for tissue engineering and delivery of therapeutics.

Degradable biomaterials continue to play a major role in tissue engineering and regenerative medicine as well as for delivering therapeutic agents. Although the chemistry of polyphosphazenes has been studied extensively, a systematic review of their applications for a wide range of biomedical applications is lacking. Polyphosphazenes are synthesized through a relatively well-known two-step reaction scheme which involves the substitution of the initial linear precursor with a wide range of nucleophiles. The ease of substitution has led to the development of a broad class of materials that have been studied for numerous biomedical applications including as scaffold materials for tissue engineering and regenerative medicine. The objective of this review is to discuss the suitability of poly(amino acid ester)phosphazene biomaterials in regard to their unique stimuli responsive properties, tunable degradation rates and mechanical properties, as well as in vitro and in vivo biocompatibility. The application of these materials in areas such as tissue engineering and drug delivery is discussed systematically. Lastly, the utility of polyphosphazenes is further extended as they are being employed in blend materials for new applications and as another method of tailoring material properties.