Pretreatment antimüllerian hormone levels determine rate of posttherapy ovarian reserve recovery: acute changes in ovarian reserve during and after chemotherapy

To identify factors associated with ovarian reserve (OR) impairment during and immediately after chemotherapy

Fertility preservation for male patients with childhood, adolescent, and young adult cancer:recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group

Item does not contain fulltextMale patients with childhood, adolescent, and young adult cancer are at an increased risk for infertility if their treatment adversely affects reproductive organ function. Future fertility is a primary concern of patients and their families. Variations in clinical practice are barriers to the timely implementation of interventions that preserve fertility. As part of the PanCareLIFE Consortium, in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in male patients who are diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. Recognising the need for global consensus, this clinical practice guideline used existing evidence and international expertise to rigorously develop transparent recommendations that are easy to use to facilitate the care of male patients with childhood, adolescent, and young adult cancer who are at high risk of fertility impairment and to enhance their quality of life

A View from the Past Into our Collective Future: The Oncofertility Consortium Vision Statement

Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future

Preparedness of the CTSA's Structural and Scientific Assets to Support the Mission of the National Center for Advancing Translational Sciences (NCATS)

The formation of the National Center for Advancing Translational Sciences (NCATS) brings new promise for moving basic and discoveries to clinical practice, ultimately improving the health of the nation. The CTSA sites, now housed with NCATS, are organized and prepared to support in this endeavor. The CTSAs provide a foundation for capitalizing on such promise through provision of a disease-agnostic infrastructure devoted to C&T science, maintenance of training programs designed for C&T investigators of the future, by incentivizing institutional reorganization and by cultivating institutional support

Local Cerebral Glucose Utilization and Cytoskeletal Proteolysis as Indices of Evolving Focal Ischemic Injury in Core and Penumbra

To ascertain the tempo of progression to irreversible injury in focal ischemia, we subjected halothaneanesthetized Sprague–Dawley rats to photochemically induced distal middle cerebral artery occlusion (dMCAO) combined with permanent ipsilateral and 1 h contralateral common carotid artery occlusions. Head temperature was maintained at 36°C. At times centered at either 1.5 or 3 h post-dMCAO, the rate of local glucose metabolism (lCMRgl) was measured by 2-deoxyglucose autoradiography, and cytoskeletal proteolysis was assessed regionally by an immunoblotting procedure to detect spectrin breakdown products. At 1.5 h (n = 5), the cortical ischemic core was already severely hypometabolic (lCMRgl 15.5 ± 10.8 μmol 100 g−1 min−1, mean ± SD), whereas the cortical penumbral zone was hypermetabolic (69.0 ± 9.7). (The lumped constant was verified to be unchanged by methylglucose studies.) Neutral red pH studies at this time point showed that both the core and penumbral zones were equally acidotic. By 3 h post-dMCAO (n = 6), lCMRgl in the penumbral zone had fallen to low levels (15.4 ± 2.2 μmol 100 g−1 min−1) equal to those of the ischemic core (16.7 ± 4.5). Correspondingly, spectrin breakdown in the ischemic core was advanced at both 2 and 3.5 h post-dMCAO (36 ± 18% and 33 ± 18% of total spectrin, respectively), whereas in the penumbral zone spectrin breakdown was less extensive and more highly variable at both times (22 ± 23% and 29 ± 16%). We conclude that irreversible deterioration of the ischemic core, as evidenced by the onset of local cytoskeletal proteolysis, begins within 2 h of middle cerebral artery occlusion. In the ischemic penumbra, the transition from glucose hyper- to hypometabolism occurs by 3.5 h and is associated with a milder and more variable degree of spectrin breakdown

Factors impacting time to diagnosis in pediatric, adolescent and young adult (AYA) patients with solid tumors.

e21515 Background: While cancer is the leading cause of non-accidental death in children and AYAs, factors associated with delays in diagnosis in young patients with cancer are poorly understood; we sought to fill this knowledge gap. Methods: Using the OptumLabs Data Warehouse’s claims data for commercially insured enrollees in a large US health plan—we identified pediatric [0-14 years (y)] and AYA (15–39 y) patients diagnosed with soft tissue sarcomas (STS), bone tumors (BT) and germ cell tumors (GCT) during 2001–17 and continuously enrolled 6 months prior to diagnosis. Time to diagnosis was calculated as days between first medical encounter associated with a possible cancer symptom and diagnosis date. Median times from first symptom to diagnosis were compared using Wilcoxon Rank Sum test. Multivariable logistic regression identified sociodemographic and clinical factors associated with longer time ( > 3 months) from symptom to diagnosis. Results: Of the 11,395 patients, 86% presented to medical care with symptoms prior to diagnosis [STS: 2,228 (89%); BT: 1,565 (87%); GCT: 5,904 (84%)]. The most common symptoms were pain and swelling. STS had the longest median days to diagnosis (92), followed by BT (91) and GCT (49). There was a significant difference (p < 0.001) in median days to diagnosis by age for BT (0–14y: 69; 15–21y: 77; 22–39y: 105) and GCT (0–14y: 96; 15–21y: 34; 22–39y: 49), but not for STS. Patients in households with ≥ a college degree (OR 1.96, 95% CI 1.06–3.64, vs < high school) and seeing a specialist (excluding oncologists) (OR 2.54, CI 2.03–3.19, vs primary care) at first symptom presentation was associated with a longer delay, while older age (22–39y: OR 0.77, CI 0.63–0.94, vs 0-14y) and male sex (OR 0.58, CI 0.51–0.66) were associated with a shorter delay in diagnosis. Conclusions: This study demonstrates that, in a commercially insured population, time to diagnosis varies by cancer type and is impacted by clinical and sociodemographic factors. Shorter time to diagnosis may represent delays in presenting to medical care or more acute presentations of symptoms, therefore patient-reported symptoms and barriers to care data should be collected to better define strategies to reduce delays in diagnosis

Neuroprotection by LY341122, a novel inhibitor of lipid peroxidation, against focal ischemic brain damage in rats

LY341122 (2-(3,5-di- t-butyl-4-hydroxyphenyl)-4-(2-(4-methylethylaminomethyl-phenyloxy)ethyl)oxazole) is a potent inhibitor of lipid peroxidation which has been shown to protect against global ischemia and traumatic brain injury in rats. The purpose of this study was to examine the effect of LY341122 on ischemic injury in a highly reproducible model of focal cerebral ischemia in rats. Male Sprague–Dawley rats were anesthetized with halothane and subjected to 120 min of temporary middle cerebral artery occlusion by retrograde insertion of an intraluminal nylon suture coated with poly- l-lysine. The drug (LY341122, n=19) or vehicle (phosphate-buffered saline (PBS), n=10) was administered i.v. (as a 5 or 10 mg/kg bolus followed by a 5 or 10 mg/kg/h infusion for 20 h, respectively, starting 1 or 2 h after the onset of middle cerebral artery occlusion). Neurological status was evaluated during middle cerebral artery occlusion (60 min) and daily for 3 days thereafter. Three days after ischemia, brains were perfusion-fixed and infarct volumes and brain edema were determined. LY341122 significantly improved the neurological score compared to vehicle at 24, 48 and 72 h after middle cerebral artery occlusion. Treatment with LY341122 significantly reduced total infarct volume in all treated groups compared to vehicle rats. Cortical infarct volume was significantly reduced by LY341122 treatment in the 10 mg/kg (1 h) and LY341122 10 mg/kg (2 h) groups compared to vehicle rats (14.7±9.5 vs. 106.8±20.9 mm 3, and 36.9±20.1 vs. 106.8±20.9 mm 3, respectively (mean±S.E.M.)). Striatal infarct volume was also significantly reduced by treatment with LY341122 in the 10 mg/kg (1 h) group compared to vehicle (23.7±3.4 vs. 68.2±6.7 mm 3). These results demonstrate the neuroprotective efficacy of LY341122 in focal cerebral ischemia

Delays in diagnosis in young patients with leukemia and lymphoma.

e18138 Background: Patients diagnosed with leukemia and lymphoma typically present with nonspecific symptoms, making a timely diagnosis difficult. Little is known about factors associated with delays in diagnosis. We hypothesized that age, minority race/ethnicity, and low income are associated with greater time to diagnosis. Methods: Using the OptumLabs Data Warehouse, which includes claims data for privately insured enrollees in a large US health plan, we identified 17,536 pediatric (0-14 y), adolescent (15-21 y), and young adult (22-39 y) patients diagnosed with acute leukemia or lymphoma between 2001-17. Using this retrospective cohort, potential cancer-related symptoms occurring up to 6 months pre-diagnosis were identified. Delay was defined as > 3 months from symptom onset to diagnosis. Contingency table analysis with chi-squared tests and unconditional logistic regression were used to estimate the association between sociodemographic factors and delays in diagnosis. Results: Seventy-eight percent of patients had a diagnosis of a cancer-related symptom in the 6 months prior to diagnosis. The most common presenting symptoms were lymphadenopathy, fever, and cytopenias. The median days to diagnosis was longer in young adults (93) than children (86) or adolescents (81) (p = < 0.0001). For pediatric v. AYA patients, median days to diagnosis differed for those with constitutional symptoms (18 v. 37, p = < 0.001), infectious symptoms (93 v. 74, p = < 0.001), and cytopenias (11 v. 22, p = < 0.001). Multivariable analysis identified younger age, female sex, and low household income to be significantly associated with delays in diagnosis (table below). Conclusions: In this large cohort of privately insured patients, adolescents had the shortest time to diagnosis. We saw no disparities by race/ethnicity or education but observed that low income ( < $40K) and female patients had greater odds of delays in diagnosis. [Table: see text