Impact of Body Mass Index and Weight Change on Risk of Recurrence in Patients Treated for Endometrial Adenocarcinoma

Background: Obesity is a well-documented risk factor for EAC, but the relationship between obesity and disease recurrence is controversial. Additionally, body weight is an inherently dynamic variable and no studies have examined the relationship between interval weight change and risk of EAC recurrence. Objectives: To identify if there is a relationship between body mass index (BMI) or interval weight change and the risk of disease recurrence among women treated for EAC. Methods: We conducted a retrospective chart review of 337 women diagnosed and treated surgically for EAC at UMass Memorial Medical Center from 2010 to 2015. The effect of BMI on risk of disease recurrence was assessed by Cox proportional hazards model adjusting for age, FIGO stage, myometrial invasion, lymphovascular space involvement and status of adjuvant therapy. The effect of interval weight change on EAC recurrence was assessed using logistic regression, adjusting for BMI and recurrence free interval. Results: Among 337 women diagnosed with EAC, mean BMI at diagnosis was 35.9 pounds (SD: 8.9), mean weight at diagnosis was 201.5 pounds (SD: 52.7) and mean interval weight change was -8.1 pounds (SD: 18.8). At time of data extraction there were 19 patients (5.7%) with disease recurrence. The hazard ratio for recurrence in women with BMI \u3e50 was 11.4 [95%CI: 1.54-84.05] times that of women with BMI(p=0.02). Women who maintained or gained weight following primary surgical resection had no increased risk of recurrence compared to those who lost weight [OR: 1.02, 95%CI: 0.27-3.82] (p=0.97). Conclusion: Women with extreme obesity at diagnosis are more likely to have disease recurrence following primary surgical treatment for endometrial adenocarcinoma. However, women who lose weight following primary surgical treatment of EAC are just as likely to have disease recurrence as those who maintain or gain weight

Prevalence, Predictors, and Same Day Treatment of Positive VIA Enhanced by Digital Cervicography and Histopathology Results in a Cervical Cancer Prevention Program in Cameroon

BACKGROUND: In 2007, the Cameroon Baptist Convention Health Services (CBCHS) implemented a screen-and-treat cervical cancer prevention program using visual inspection with acetic acid enhanced by digital cervicography (VIA-DC). METHODS: We retrospectively analyzed 46,048 medical records of women who received care through the CBCHS Women\u27s Health Program from 2007 through 2014 to determine the prevalence and predictors of positive VIA-DC, rates of same day treatment, and cohort prevalence of invasive cervical cancer (ICC). RESULTS: Of the 44,979 women who were screened for cervical cancer, 9.0% were VIA-DC-positive, 66.8% were VIA-DC-negative, 22.0% were VIA-DC-inadequate (normal ectocervix, but portions of the transformation zone were obscured), and 2.2% were VIA-DC-uncertain (cervical abnormalities confounding VIA-DC interpretation). Risk factors significantly associated with VIA-DC-positive screen were HIV-positivity, young age at sexual debut, higher lifetime number of sexual partners, low education status and higher gravidity. In 2014, 31.1% of women eligible for cryotherapy underwent same day treatment. Among the 32,788 women screened from 2007 through 2013, 201 cases of ICC were identified corresponding to a cohort prevalence of 613 per 100,000. CONCLUSIONS: High rate of VIA-DC-positive screens suggests a significant burden of potential cervical cancer cases and highlights the need for expansion of cervical cancer screening and prevention throughout the 10 regions of Cameroon. VIA-DC-inadequate rates were also high, especially in older women, and additional screening methods are needed to confirm whether these results are truly negative. In comparison to similar screening programs in sub-Saharan Africa there was low utilization of same day cryotherapy treatment. Further studies are required to characterize possible program specific barriers to treatment, for example cultural demands, health system challenges and cost of procedure. The prevalence of ICC among women who presented for screening was high and requires further investigation

Resting and task-modulated high-frequency brain rhythms measured by scalp encephalography in infants with tuberous sclerosis complex.

The electrophysiological correlates of cognitive deficits in tuberous sclerosis complex (TSC) are not well understood, and modulations of neural dynamics by neuroanatomical abnormalities that characterize the disorder remain elusive. Neural oscillations (rhythms) are a fundamental aspect of brain function, and have dominant frequencies in a wide frequency range. The spatio-temporal dynamics of these frequencies in TSC are currently unknown. Using a novel signal decomposition approach this study investigated dominant cortical frequencies in 10 infants with TSC, in the age range 18-30 months, and 12 age-matched healthy controls. Distinct spectral characteristics were estimated in the two groups. High-frequency [in the high-gamma (>50 Hz) and ripple (>80 Hz) ranges], non-random EEG components were identified in both TSC and healthy infants at 18 months. Additional components in the lower gamma (30-50 Hz) ranges were also identified, with higher characteristic frequencies in TSC than in controls. Lower frequencies were statistically identical in both sub-groups. A significant shift in the high-frequency spectral content of the EEG was observed as a function of age, independently of task performance, possibly reflecting an overall maturation of developing neural circuits. This shift occurred earlier in healthy infants than in TSC, i.e., by age 20 months the highest dominant frequencies were in the high gamma range, whereas in TSC dominant frequencies above 100 Hz were still measurable. At age 28-30 months a statistically significant decrease in dominant high frequencies was observed in both TSC and healthy infants, possibly reflecting increased myelination and neuronal connection strengthening with age. Although based on small samples, and thus preliminary, the findings in this study suggest that dominant cortical rhythms, a fundamental aspect of neurodynamics, may be affected in TSC, possibly leading to impaired information processing in the brain

Visual evoked potentials detect cortical processing deficits in Rett syndrome

ObjectiveRett syndrome (RTT) is a neurodevelopmental disorder caused by mutation of the X-linked MECP2 gene and characterized by developmental regression during the first few years of life. The objective of this study was to investigate if the visual evoked potential (VEP) could be used as an unbiased, quantitative biomarker to monitor brain function in RTT. MethodsWe recorded pattern-reversal VEPs in Mecp2 heterozygous female mice and 34 girls with RTT. The amplitudes and latencies of VEP waveform components were quantified, and were related to disease stage, clinical severity, and MECP2 mutation type in patients. Visual acuity was also assessed in both mice and patients by modulating the spatial frequency of the stimuli. ResultsMecp2 heterozygous female mice and RTT patients exhibited a similar decrease in VEP amplitude that was most striking in the later stages of the disorder. RTT patients also displayed a slower recovery from the principal peak of the VEP response that was impacted by MECP2 mutation type. When the spatial frequency of the stimulus was increased, both patients and mice displayed a deficit in discriminating smaller patterns, indicating lower visual spatial acuity in RTT. InterpretationVEP is a method that can be used to assess brain function across species and in children with severe disabilities like RTT. Our findings support the introduction of standardized VEP analysis in clinical and research settings to probe the neurobiological mechanism underlying functional impairment and to longitudinally monitor progression of the disorder and response to treatmen

Implementing a Fee-for-Service Cervical Cancer Screening and Treatment Program in Cameroon: Challenges and Opportunities

BACKGROUND: Cervical cancer screening is one of the most effective cancer prevention strategies, but most women in Africa have never been screened. In 2007, the Cameroon Baptist Convention Health Services, a large faith-based health care system in Cameroon, initiated the Women\u27s Health Program (WHP) to address this disparity. The WHP provides fee-for-service cervical cancer screening using visual inspection with acetic acid enhanced by digital cervicography (VIA-DC), prioritizing care for women living with HIV/AIDS. They also provide clinical breast examination, family planning (FP) services, and treatment for reproductive tract infection (RTI). Here, we document the strengths and challenges of the WHP screening program and the unique aspects of the WHP model, including a fee-for-service payment system and the provision of other women\u27s health services. METHODS: We retrospectively reviewed WHP medical records from women who presented for cervical cancer screening from 2007-2014. RESULTS: In 8 years, WHP nurses screened 44,979 women for cervical cancer. The number of women screened increased nearly every year. The WHP is sustained primarily on fees-for-service, with external funding totaling about $20,000 annually. In 2014, of 12,191 women screened for cervical cancer, 99% received clinical breast exams, 19% received FP services, and 4.7% received treatment for RTIs. We document successes, challenges, solutions implemented, and recommendations for optimizing this screening model. CONCLUSION: The WHP\u27s experience using a fee-for-service model for cervical cancer screening demonstrates that in Cameroon VIA-DC is acceptable, feasible, and scalable and can be nearly self-sustaining. Integrating other women\u27s health services enabled women to address additional health care needs. IMPLICATION FOR PRACTICE: The Cameroon Baptist Convention Health Services Women\u27s Health Program successfully implemented a nurse-led, fee-for-service cervical cancer screening program using visual inspection with acetic acid-enhanced by digital cervicography in the setting of a large faith-based health care system in Cameroon. It is potentially replicable in many African countries, where faith-based organizations provide a large portion of health care. The cost-recovery model and concept of offering multiple services in a single clinic rather than stand-alone silo cervical cancer screening could provide a model for other low-and-middle-income countries planning to roll out a new, or make an existing, cervical cancer screening services accessible, comprehensive, and sustainable

Prevalence, Predictors, and Same Day Treatment of Positive VIA Enhanced by Digital Cervicography and Histopathology Results in a Cervical Cancer Prevention Program in Cameroon.

BACKGROUND:In 2007, the Cameroon Baptist Convention Health Services (CBCHS) implemented a screen-and-treat cervical cancer prevention program using visual inspection with acetic acid enhanced by digital cervicography (VIA-DC). METHODS:We retrospectively analyzed 46,048 medical records of women who received care through the CBCHS Women's Health Program from 2007 through 2014 to determine the prevalence and predictors of positive VIA-DC, rates of same day treatment, and cohort prevalence of invasive cervical cancer (ICC). RESULTS:Of the 44,979 women who were screened for cervical cancer, 9.0% were VIA-DC-positive, 66.8% were VIA-DC-negative, 22.0% were VIA-DC-inadequate (normal ectocervix, but portions of the transformation zone were obscured), and 2.2% were VIA-DC-uncertain (cervical abnormalities confounding VIA-DC interpretation). Risk factors significantly associated with VIA-DC-positive screen were HIV-positivity, young age at sexual debut, higher lifetime number of sexual partners, low education status and higher gravidity. In 2014, 31.1% of women eligible for cryotherapy underwent same day treatment. Among the 32,788 women screened from 2007 through 2013, 201 cases of ICC were identified corresponding to a cohort prevalence of 613 per 100,000. CONCLUSIONS:High rate of VIA-DC-positive screens suggests a significant burden of potential cervical cancer cases and highlights the need for expansion of cervical cancer screening and prevention throughout the 10 regions of Cameroon. VIA-DC-inadequate rates were also high, especially in older women, and additional screening methods are needed to confirm whether these results are truly negative. In comparison to similar screening programs in sub-Saharan Africa there was low utilization of same day cryotherapy treatment. Further studies are required to characterize possible program specific barriers to treatment, for example cultural demands, health system challenges and cost of procedure. The prevalence of ICC among women who presented for screening was high and requires further investigation

Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder mainly affecting females and is associated with mutations in MECP2, the gene encoding methyl CpG-binding protein 2. Mouse models suggest that recombinant human insulin-like growth factor 1 (IGF-1) (rhIGF1) (mecasermin) may improve many clinical features. We evaluated the safety, tolerability, and pharmacokinetic profiles of IGF-1 in 12 girls with MECP2 mutations (9 with RTT). In addition, we performed a preliminary assessment of efficacy using automated cardiorespiratory measures, EEG, a set of RTT-oriented clinical assessments, and two standardized behavioral questionnaires. This phase 1 trial included a 4-wk multiple ascending dose (MAD) (40–120 μg/kg twice daily) period and a 20-wk open-label extension (OLE) at the maximum dose. Twelve subjects completed the MAD and 10 the entire study, without evidence of hypoglycemia or serious adverse events. Mecasermin reached the CNS compartment as evidenced by the increase in cerebrospinal fluid IGF-1 levels at the end of the MAD. The drug followed nonlinear kinetics, with greater distribution in the peripheral compartment. Cardiorespiratory measures showed that apnea improved during the OLE. Some neurobehavioral parameters, specifically measures of anxiety and mood also improved during the OLE. These improvements in mood and anxiety scores were supported by reversal of right frontal alpha band asymmetry on EEG, an index of anxiety and depression. Our data indicate that IGF-1 is safe and well tolerated in girls with RTT and, as demonstrated in preclinical studies, ameliorates certain breathing and behavioral abnormalities.Rett Syndrome Foundation (Grant 2534)Autism Speaks (Organization) (Grant 5795)National Institutes of Health (U.S.) (Harvard Clinical and Translational Science Center, Grant 1 UL1 RR 025758-01)Boston Children’s Hospital (Translational Research Program)Boston Children’s Hospital (Intellectual and Developmental Disabilities Research Center P30 HD18655

Age-specific VIA-DC Results.

<p>Age-specific VIA-DC Results.</p

Adjusted Odds Ratios and 95% Confidence Intervals for VIA-DC-positive Screen.

<p>Adjusted Odds Ratios and 95% Confidence Intervals for VIA-DC-positive Screen.</p