Sleep disruption is common among hematopoietic cell transplant (HCT) recipients, with over 50% of patients experiencing sleep disruption pre-transplant, up to 82% experiencing moderate to severe sleep disruption during hospitalization for transplant, and up to 43% in the post-transplant period. These rates of sleep disruption are substantially higher than the general population. Although sleep disruption can be distressing to patients and contribute to diminished quality of life, it is rarely discussed during clinical visits. The goal of the current review is to draw attention to sleep disruption as a clinical problem in HCT in order to facilitate patient education, intervention, and research. The review opens with a discussion of sleep disruption measurement and clinical diagnosis of sleep disorders. An overview of the prevalence, severity, and chronicity of sleep disruption and disorders in patients receiving HCT follows. Current evidence regarding sociodemographic and clinical predictors of sleep disruption and disorders is summarized. The review concludes with suggestions for behavioral and pharmacologic management of sleep disruption and disorders as well as directions for future research.
Autophagy is an intracellular molecular pathway that maintains cellular homeostasis. A role for autophagy in the development as well as in the treatment of gynecologic malignancies, while still under-investigated, is receiving increased interest. Depending on concomitant factors, autophagy can either promote or suppress development of cervical, endometrial and ovarian cancer. Moreover, these cancer cells can utilize autophagy to promote its resistance to chemotherapeutic agents or, conversely, autophagy can enhance the efficacy of cytotoxic agents by promoting autophagic cell death. In this review the key autophagyrelated mechanisms in development and treatment of cervical, endometrial and ovarian cancer are elucidated and evaluated.
Inhibition of autophagy is a characteristic of ovarian cancer. We determined whether inhibition of autophagy by vaginal fluid could provide a non-invasive test for cancer risk stratification in women presenting with an adnexal mass. Vaginal fluid supernatants from 90 women undergoing evaluation for a suspicious adnexal mass were incubated with peripheral blood mononuclear cells (PBMCs) obtained from healthy women under conditions that induce autophagy. Rapamycin, an autophagy inducer, was added to some cultures. After 48 hr the cells were collected, lysed and assayed by ELISA for intracellular p62 concentration. p62 is a cytoplasmic protein that is consumed during autophagy induction. Its concentration is inversely proportional to the extent of autophagy induction. Clinical information including pathological diagnoses was obtained after completion of laboratory studies. Mean p62 levels were 9.4 ng/ml in the 21 women with a subsequent malignant diagnosis, 4.5 ng/ml in the eight women with a borderline tumor diagnosis and 3.6 ng/ml in the 61 women with benign disease (p < 0.0001, malignant vs. others). When rapamycin was added to the vaginal fluid-PBMC co-incubation, p62 levels in samples from women with a malignant diagnosis decreased to 3.3 ng/ml, a level comparable to what was observed with the nonmalignant samples. Vaginal fluid inhibition of autophagy can differentiate between women with malignant and benign adnexal masses.Ovarian cancer is first detected in many women when a suspicious adnexal mass is discovered and histologic confirmation follows surgical intervention. However, only a minority of women with an adnexal mass have a malignant tumor. 1Various clinical strategies have been employed in the preoperative evaluation of women with adnexal masses in an attempt to differentiate benign and malignant lesions. The most common include transvaginal ultrasound and serum biomarker testing. There is, however, significant overlap between the sonographic features of benign and malignant ovarian masses. A morphology index developed by expert gynecologic sonographers to differentiate benign and malignant adnexal masses achieved a positive predictive value of only 0.45.2 Serum CA 125, the most commonly used biomarker, is elevated in approximately 80% of women with advanced ovarian cancer and is useful for monitoring the response of the disease to therapy 3 but its use in the preoperative evaluation of a woman with adnexal mass is limited. CA 125 is normal in 50% of stage I ovarian cancers, and is elevated in a number of benign gynecologic conditions. 4 The risk of malignancy index (RMI), a predictive model including ultrasound findings, menopausal status, and the serum CA 125 level, was developed to increase the accuracy of cancer detection in adnexal masses. Although it is associated with a sensitivity of 78% overall, the sensitivity drops to 65% when applied to patients with early-stage disease. 5,6 The Risk of Malignancy Algorithm, which includes both serum CA 125 and human epididymal protein 4 levels 7 is assoc...
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