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Populations consuming soy have reduced risk for breast cancer, but the mechanisms are unclear. We tested the hypothesis that soy isoflavones, which have ovarian hormone-like effects, can reduce fibroglandular breast tissue (FGBT, 'breast density'), a strong risk marker for breast cancer.Premenopausal women (age 30-42 years) were randomized to consume isoflavones (136.6 mg as aglycone equivalents, n = 99) or placebo (n = 98) for 5 days per week up to 2 years, and changes in breast composition measured by magnetic resonance imaging at baseline and yearly intervals were compared after square root transformation using linear mixed effects regression models.By intention-to-treat analyses (n = 194), regression coefficients (β estimates) of the interaction of time and isoflavone treatment were -0.238 (P = 0.06) and -0.258 (P 0.05) before and after BMI adjustment, respectively for FGBT, 0.620 (P 0.05) and 0.248 (P = 0.160), respectively for fatty breast tissue (FBT), and -0.155 (P 0.05) and -0.107 (P 0.05), respectively for FGBT as percent of total breast (FGBT%). β Estimates for interaction of treatment with serum calcium were -2.705 for FBT, and 0.588 for FGBT% (P 0.05, before but not after BMI adjustment). BMI (not transformed) was related to the interaction of treatment with time (β = 0.298) or with calcium (β = -1.248) (P 0.05). Urinary excretion of isoflavones in adherent subjects (n = 135) significantly predicted these changes in breast composition. Based on the modeling results, after an average of 1.2, 2.2 and 3.3 years of supplementation, a mean decrease of FGBT by 5.3, 12.1, and 19.3 cc, respectively, and a mean decrease of FGBT% by 1.37, 2.43, and 3.50%, respectively, were estimated for isoflavone exposure compared to placebo treatment. Subjects with maximum isoflavone excretion were estimated to have 38 cc less FGBT (or ∼3.13% less FGBT%) than subjects without isoflavone excretion. Decrease in FGBT and FGBT% was more precise with daidzein than genistein.Soy isoflavones can induce a time- and concentration-dependent decrease in FGBT, a biomarker for breast cancer risk, in premenopausal women, and moderate effects of calcium on BMI and breast fat, suggesting a beneficial effect of soy consumption.www.gov identifier: NCT00204490.www.gov identifier: NCT00204490.

Background: Acute Intermittent Porphyria (AIP) is a rare inborn error of heme biosynthesis characterized clinically by life-threatening acute neurovisceral attacks. Few studies have assessed quality of life (QoL) tools in the AIP population, and none are validated for use in AIP. In this study, the Patient Reported Outcomes Measurement Information System 57 (PROMIS-57) scales were assessed in AIP patients to determine the factor structure of PROMIS items and to compare this to previously proposed factor structures in the general population.Methods: Baseline data from the Porphyrias Consortium’s Longitudinal Study of the Porphyrias was obtained for 259 AIP patients. This included detailed disease and medical history information as well as PROMIS-57 data. Exploratory and confirmatory factor analyses (EFA and CFA, respectively) were conducted on baseline PROMIS-57 data. CFA was used to test the hypothesized three-factor structure from the PROMIS literature. Results: Internal consistency was high for all the PROMIS scales assessed. The EFA revealed a five-factor model, each consisting of a separate domain: pain interference, anxiety, depression, sleep disturbance, and fatigue. Model fit was good overall. A CFA of the hypothesized three-factor model did not converge suggesting an inappropriate structural model. Conclusion: The EFA showed a five-factor model that fit the data well, however a CFA of the three-factor model observed in the general population did not fit the data well. These findings, together with previous studies assessing correlations with clinical features, indicate that the PROMIS scales may be valid and reliable measures for AIP patients. However, further analyses are needed to confirm this. Further studies should assess correlations with other tools, whether the PROMIS scales are responsive to treatment, if they capture QoL longitudinally, and a CFA in a second sample.

Background Porphyrias are a group of rare diseases leading to dysregulation in heme biosynthesis and the accumulation of heme precursors, including porphyrinogens, which in their oxidized states [porphyrins] are reddish or purple. Acute hepatic porphyrias (AHP) comprise four diseases that cause acute debilitating neurovisceral attacks. Despite diagnostic advances, AHP is often undiagnosed or misdiagnosed due to a lack of disease awareness, low clinical suspicion, variable presentation, and nonspecific symptoms that mimic more common diseases. Delays in diagnosis and treatment increase the risk of serious acute and chronic complications. Aim In order to assess whether symptoms alone or in combination might be utilized as important indicators or “purple flags” that, when present, should alert clinicians to suspect AHP and pursue specific diagnostic testing, we conducted a comprehensive review of the literature on AHP, including cohort studies and case reports over two epochs, from 1980 to 2006 and from 2012 to 2018. Results We found that severe abdominal pain, with or without acute central nervous system manifestations and peripheral neuropathy, continues to be recognized the most frequent symptom. Hyponatremia, change in urine color, and certain chronic symptoms were also identified as features that should raise suspicion of AHP. To improve diagnosis of AHP, clinicians need to take a broad perspective, including demographic data and medical history, into consideration. Conclusions The clinical features of AHP continue to be severe pain, especially pain in the abdomen. Other features that should raise suspicion are autonomic, peripheral, or central neuropathies, hyponatremia, and red-purple urine color.

ImportanceErythropoietic protoporphyria (EPP) is a rare and underdiagnosed genetic disease characterized by painful sensitivity to light. A better understanding and characterization of its light-induced cutaneous symptoms may aid in the identification of EPP in patients.ObjectivesTo describe the cutaneous symptoms of erythropoietic protoporphyria (EPP) and to determine if these symptoms are associated with the degree of light sensitivity.Design, Setting, and ParticipantsThis was a cross-sectional study of adolescent and adult (≥15 years) patients with EPP across the US conducted by a single academic hospital via a remotely administered survey, measurements of light sensitivity by light dosimetry and by text message symptom assessments. Data analyses were conducted from November 2020 to April 2022.ExposuresSunlight exposure.Main Outcomes and MeasuresSelf-reported symptoms and association with measured light sensitivity.ResultsThe study sample consisted of 35 patients with EPP (mean [SD] age, 39.1 (15.5) years; 21 [60%] female; 14 [40%] male; 35 [100%] White individuals). The patients’ median [range] skin tone was 3.0 (1.0-8.0), based on self-reporting from 1 (lightest) to 12 (darkest). A total of 24 participants completed the light dosimeter measurements. Phototoxic reactions were characterized by pain (97%; 34 patients), burning (97%; 34), tingling (97%; 34), pruritus (83%; 29), allodynia (89%; 31), improvement of symptoms with cold (89%; 31), achiness (24%; 12), fatigue (46%; 16), mild swelling (83%; 29), severe swelling (63%; 22), erythema (51%; 18), petechiae (40%; 14), skin cracking (43%; 15), scabbing (46%; 16), scarring (66%; 23), and other chronic skin changes (40%; 14). Patients with EPP reported that their hands, feet, and face were most sensitive to light and that their shoulders and legs were least sensitive; 25.7% (9 patient) reported no chronic skin changes, and 5.7% (2 patients) reported never having had any visible symptoms. None of these findings varied with the degree of light sensitivity except that lower overall light sensitivity was associated with lower ranked sensitivity of the neck and arms.Conclusions and RelevanceThe findings of this cross-sectional study suggest that patients with EPP have distinctive cutaneous symptoms that may aid in identification of this underdiagnosed disease. Characteristic EPP symptoms include light-induced cutaneous burning pain and occasional swelling, particularly over the hands, with a prodrome of pruritus and paresthesias. Minimal skin changes or the absence of visible skin changes during reactions to light, including lack of erythema, do not exclude an EPP diagnosis nor suggest low EPP disease burden.