Association Between Uveal Melanoma and Allostatic Load.

BACKGROUND/AIM: Allostatic load (AL) is a measure of chronic stress that is associated with worse cancer outcomes. The purpose of this retrospective cohort study was to investigate the relationship between AL and uveal melanoma (UM) clinical features. PATIENTS AND METHODS: AL score was calculated as a composite of ten biomarkers in 111 patients with UM from the University of Illinois Hospital. One point was assigned to an AL score for each biomarker based on predetermined cutoff values. Linear and logistic regression analyses evaluated the relationship between AL score and several tumor clinical characteristics. RESULTS: High AL score had a significant relationship with extraocular extension (p=0.015). There was also a significant difference in mean blood glucose levels between the different tumor size groups (p=0.029). Higher AL scores also had a trend of being associated with a smaller tumor size (p=0.069). CONCLUSION: AL score was significantly associated with the presence of extraocular extension for uveal melanoma, while the smallest tumor size group was associated with the highest blood glucose level. No other significant correlations were found between AL and other clinical features of UM. The relationship between AL score and extraocular extension warrants further investigation. Additional research is needed to evaluate socioeconomic factors and their effect on the relationship between chronic stress and the clinical features of UM.

Trajectories of Allopregnanolone and Allopregnanolone to Progesterone Ratio across the Six Subphases of Menstrual Cycle.

Background: Allopregnanolone is one of the most studied neuroactive steroids; yet, despite its relevance to neuropsychiatric research, it is not known how it, as well as its ratio to progesterone, varies across all six subphases of the menstrual cycle. Two enzymes-5α-dihydroprogesterone and 5α-reductase-convert progesterone to allopregnanolone, and, based on immunohistochemical studies in rodents, the activity of 5α-reductase is considered the rate-limiting step in the formation of allopregnanolone. It is not clear, however, whether the same phenomenon is observed across to the menstrual cycle, and, if so, at what point this takes place. Methods: Thirty-seven women completed the study during which they attended eight clinic visits across one menstrual cycle. We analyzed their allopregnanolone and progesterone serum concentrations using ultraperformance liquid chromatography-tandem mass spectrometry, and we implemented a validated method to realign the data from the original eight clinic study visits, following which we imputed the missing data. Hence, we characterized allopregnanolone concentrations, and the ratio of allopregnanolone:progesterone at six menstrual cycle subphases: (1) early follicular, (2) mid-follicular, (3) periovulatory, (4) early luteal, (5) mid-luteal, and (6) late luteal. Results: There were significant differences in allopregnanolone levels between (1) early follicular and early luteal, (2) early follicular and mid-luteal, (3) mid-follicular and mid-luteal, (4) periovulatory and mid-luteal, and (5) mid-luteal and late luteal. We detected a sharp drop in allopregnanolone:progesterone ratio in the early luteal subphase. Within the luteal subphase, the ratio was the lowest in the mid-luteal subphase. Conclusions: Allopregnanolone concentrations are the most distinct, relative to the other subphases, in the mid-luteal subphase. The shape of the allopregnanolone trajectory across the cycle is similar to that of progesterone; however, the proportion of the two neuroactive steroid hormones is drastically different due to enzymatic saturation, which takes place at the start of the early luteal subphase, but continuing through, and peaking, in the mid-luteal subphase. Hence, the estimated activity of 5α-reductase decreases, but does not cease, at any point across the menstrual cycle.

Development and validation of an asthma exacerbation prediction model using electronic health record (EHR) data.

Objective: Asthma exacerbations are associated with significant morbidity, mortality, and cost. Accurately identifying asthma patients at risk for exacerbation is essential. We sought to develop a risk prediction tool based on routinely collected data from electronic health records (EHRs).Methods: From a repository of EHRs data, we extracted structured data for gender, race, ethnicity, smoking status, use of asthma medications, environmental allergy testing BMI status, and Asthma Control Test scores (ACT). A subgroup of this population of patients with asthma that had available prescription fill data was identified, which formed the primary population for analysis. Asthma exacerbation was defined as asthma-related hospitalization, urgent/emergent visit or oral steroid use over a 12-month period. Univariable and multivariable statistical analysis was completed to identify factors associated with exacerbation. We developed and tested a risk prediction model based on the multivariable analysis.Results: We identified 37,675 patients with asthma. Of those, 1,787 patients with asthma and fill data were identified, and 979 (54.8%) of them experienced an exacerbation. In the multivariable analysis, smoking (OR = 1.69, CI: 1.08-2.64), allergy testing (OR = 2.40, CI: 1.54-3.73), obesity (OR = 1.66, CI: 1.29-2.12), and ACT score reflecting uncontrolled asthma (OR = 1.66, CI: 1.10-2.29) were associated with increased risk of exacerbation. The area-under-the-curve (AUC) of our model in a combined derivation and validation cohort was 0.67.Conclusion: Despite use of rigorous methodology, we were unable to produce a predictive model with an acceptable degree of accuracy and AUC to be clinically useful.

Clinical profile of comorbid dysmenorrhea and bladder sensitivity: a cross-sectional analysis.

BACKGROUND: Antecedents of chronic pelvic pain are not well characterized, but pelvic organ visceral sensitivity is a hallmark of these disorders. Recent studies have identified that some dysmenorrhea sufferers are much more likely to exhibit comorbid bladder hypersensitivity. Presumably, these otherwise healthy women may be at higher risk of developing full-blown chronic bladder pain later in life. To encourage early identification of patients harboring potential future risk of chronic pain, we describe the clinical profile of women matching this putative pain-risk phenotype. OBJECTIVE(S): The objectives of the study were to characterize demographic, menstrual, pelvic examination, and psychosocial profiles of young women with comorbid dysmenorrhea and bladder hypersensitivity, defined using a standardized experimental visceral provocation test, contrasted with healthy controls, pure dysmenorrhea sufferers, and women with existing bladder pain syndrome. STUDY DESIGN: This prospective cohort study acquired data on participants with moderate to severe dysmenorrhea (n = 212), healthy controls (n = 44), and bladder pain syndrome (n = 27). A subgroup of dysmenorrhea patients was found on screening with noninvasive oral water challenge to report significantly higher bladder pain during experimentally monitored spontaneous bladder filling (>15 out of 100 on visual analogue scale, based on prior validation studies) and separately defined as a group with dysmenorrhea plus bladder pain. Medical/menstrual history and pain history were evaluated with questionnaires. Psychosocial profile and impact were measured with validated self-reported health status Patient Reported Outcomes Measurement Information System short forms and a Brief Symptom Inventory for somatic sensitivity. Pelvic anatomy and sensory sensitivity were examined via a standardized physical examination and a tampon provocation test. RESULTS: In our largely young, single, nulliparous cohort (24 ± 1 years old), approximately a quarter (46 out of 212) of dysmenorrhea sufferers tested positive for the dysmenorrhea plus bladder pain phenotype. Dysmenorrhea-only sufferers were more likely to be African American (24%) than healthy controls (5%, post hoc χ2, P = .007). Pelvic examination findings did not differ in the nonchronic pain groups, except for tampon test sensitivity, which was worse in dysmenorrhea plus bladder pain and dysmenorrhea sufferers vs healthy controls (2.6 ± 0.3 and 1.7 ± 0.2 vs 0.7 ± 0.2, P < .05). Consistent with heightened pelvic sensitivity, participants with dysmenorrhea plus bladder pain also had more nonmenstrual pain, dysuria, dyschezia, and dyspareunia (P's < .05). Participants with dysmenorrhea plus bladder pain had Patient Reported Outcomes Measurement Information System Global Physical T-scores of 47.7 ± 0.9, lower than in women with dysmenorrhea only (52.3 ± 0.5), and healthy controls 56.1 ± 0.7 (P < .001). Similarly, they had lower Patient Reported Outcomes Measurement Information System Global Mental T-score than healthy controls (47.8 ± 1.1 vs 52.8 ± 1.2, P = .017). Similar specific impairments were observed on Patient Reported Outcomes Measurement Information System scales for anxiety, depression, and sleep in participants with dysmenorrhea plus bladder pain vs healthy controls. CONCLUSION: Women with dysmenorrhea who are unaware they also have bladder sensitivity exhibit broad somatic sensitivity and elevated psychological distress, suggesting combined preclinical visceral sensitivity may be a precursor to chronic pelvic pain. Defining such precursor states is essential to conceptualize and test preventative interventions for chronic pelvic pain emergence. Dysmenorrhea plus bladder pain is also associated with higher self-reported pelvic pain unrelated to menses, suggesting central nervous system changes are present in this potential precursor state.

Clinical outcomes in ovarian cancer patients receiving three versus more cycles of chemotherapy after neoadjuvant treatment and interval cytoreductive surgery.

OBJECTIVES: To compare clinical outcomes for stage IIIC and IV ovarian cancer patients receiving neoadjuvant chemotherapy and interval cytoreductive surgery followed by up to three versus more cycles of post-operative chemotherapy. METHODS: We conducted a multi-institution retrospective cohort study of patients treated from January 2005 to February 2016 with neoadjuvant platinum-based therapy followed by interval surgery and post-operative chemotherapy. The following were exclusion criteria: more than four cycles of neoadjuvant chemotherapy, bevacizumab with neoadjuvant chemotherapy, non-platinum therapy, prior chemotherapy, and elevated CA125 values after three post-operative chemotherapy cycles. Progression-free and overall survival and toxicity profiles were compared between groups receiving up to three cycles versus more that three cycles post-operatively. RESULTS: A total of 100 patients met inclusion criteria: 41 received up to three cycles and 59 received more than three cycles. The groups were similar in terms of age, body mass index, performance status, tumor histology, optimal cytoreduction rates, and median number of neoadjuvant chemotherapy cycles. Median progression-free survival was 14 vs 16.6 months in those receiving up to three cycles versus more than three cycles, respectively (HR 0.99, 95% CI 0.58 to 1.68, p=0.97). Similarly, median overall survival was not different at 47.1 vs 69.4 months, respectively (HR 1.96, 95% CI 0.87 to 4.42, p=0.10). There were no differences in grade 2 or higher chemotherapy-related toxicities. CONCLUSIONS: Extending post-operative chemotherapy beyond three cycles in patients receiving neoadjuvant chemotherapy and interval cytoreductive surgery with normalization of CA125 levels was not associated with improved survival or greater toxicity. Future study in a larger cohort is warranted to define optimal length of cytotoxic treatment.

Identification of experimental bladder sensitivity among dysmenorrhea sufferers.

BACKGROUND: Dysmenorrhea is a common risk factor for chronic pain conditions including bladder pain syndrome. Few studies have formally evaluated asymptomatic bladder pain sensitivity in dysmenorrhea, and whether this largely reflects excess pelvic symptom reporting due to comorbid psychological dysfunction. OBJECTIVE: We sought to determine whether bladder hypersensitivity is more common among women reporting moderate or greater dysmenorrhea, without chronic pain elsewhere, after accounting for anxiety and depression. Demonstrating this would suggest that dysmenorrhea might be an early clue for visceral or widespread pain hypersensitivity and improve understanding of potential precursors to bladder pain syndrome. STUDY DESIGN: We compared cohorts of regularly menstruating women, without symptoms of chronic pain elsewhere, reporting (1) moderate-to-severe dysmenorrhea (n = 98) and (2) low levels or no menstrual pain (n = 35). Participants underwent rapid bladder filling following a standard water ingestion protocol, serially rating bladder pain and relative urgency during subsequent distension. Potential differences in bladder volumes were controlled for by sonographic measurement at standard cystometric thresholds. Bladder sensitivity was also measured with complementary measures at other times separately including a simplified rapid filling test, palpation of the bladder wall, and through ambulatory self-report. Anxiety and depression were evaluated with the National Institutes of Health Patient-Reported Outcomes Measurement Information System measures. RESULTS: Women with moderate-to-severe dysmenorrhea reported more urinary symptoms than controls and had a lower maximum capacity (498 ± 18 mL vs 619 ± 34 mL, P < .001) and more evoked bladder filling pain (0-100 visual analog scale: 25 ± 3 vs 12 ± 3, P < .001). The dysmenorrhea-bladder capacity relationship remained significant irrespective of menstrual pain severity, anxiety, depression, or bladder pain (R2 = 0.13, P = .006). Severity of menstrual pain predicted evoked bladder pain (R2 = 0.10, P = .008) independent of anxiety (P = .21) and depression (P = .21). Women with moderate-to-severe dysmenorrhea exhibiting provoked bladder pain (24/98, 24%) also reported higher pain during the screening rapid bladder test (P < .001), in response to transvaginal bladder palpation (P < .015), and on prospective daily diaries (P < .001) than women with dysmenorrhea without provoked bladder pain. CONCLUSION: Women experiencing moderate-to-severe dysmenorrhea also harbor a higher pain response to naturally evoked bladder distension. Noninvasive bladder provocation needs to be tested further longitudinally in those with dysmenorrhea to characterize the course of visceral sensitivity and determine if it may help predict individuals at risk for developing subsequent pain in the bladder or elsewhere.

The Shifting Paradigm for Breast Cancer Surgery in Patients Undergoing Neoadjuvant Chemotherapy.

INTRODUCTION: Surgical therapy for newly diagnosed breast cancer has changed over the past decade, but these trends have not been well documented in patients undergoing neoadjuvant therapy (NAC). METHODS: In a retrospective cohort study of the National Cancer Database (NCDB), we selected 285,514 women with clinical stage I-III breast cancer who underwent NAC or adjuvant therapy (AC) from 2006 to 2014. Breast-conserving surgery (BCS), unilateral mastectomy (UM), and bilateral mastectomy (BM) rates were compared between patients undergoing NAC and AC. RESULTS: Of 285,514 women, 68,850 (24.1%) underwent NAC. Of NAC patients, 18,158 (26.4%) underwent BM and 27,349 (39.7%) BCS compared with 31,886 (14.7%) and 120,626 (55.7%) AC patients, respectively. From 2006 to 2014, BM increased from 16.1 to 28.8% (p < 0.001) for NAC and from 7.4 to 17.5% (p < 0.001) for AC. After adjusting for patient, tumor, and facility factors, NAC patients were 1.50 times [odds ratio (OR) 1.50, confidence interval (CI) 1.42-1.51] more likely to undergo BM then AC patients. The difference in BM rates between patients receiving NAC versus AC varied significantly by cT classification. This difference was the greatest among cT1 tumors between NAC and AC (31.7 vs. 13.0%, p < 0.001), followed by cT2 tumors (24.1 vs. 16.6%, p < 0.001) and cT3 tumors (24.3 vs. 22.3%). CONCLUSIONS AND RELEVANCE: More NAC patients are undergoing BM while fewer are undergoing BCS compared with patients undergoing AC. This trend is particularly striking for those patients with smaller tumors who would otherwise be candidates for BCS.