Lupus erythematosus-specific bullous lesions.

Lupus erythematosus (LE)-specific bullous lesions are often difficult to distinguish from other bullous diseases presenting in patients with systemic lupus erythematosus. Herein, we describe a 49-year-old woman with systemic lupus erythematosus with recurrent tense bullae on the forearms. Clinical, histopathologic, and serologic findings led to the diagnosis of LE-specific bullous lesions. We also summarize the diagnostic clues for distinguishing LE-specific bullous lesions, bullous systemic lupus erythematosus, and erythema multiforme-like lesions in LE (Rowell syndrome).

Pediatric pyoderma gangrenosum associated with leukocyte adhesion deficiency type 1: A case report and review of the literature.

Pyoderma gangrenosum is a rare neutrophilic dermatosis characterized by painful skin ulcers with necrotic, undermined margins. In severe cases, particularly in pediatric patients, work-up for an associated autoimmune, inflammatory, malignant, or genetic disorder should be considered based on the clinical presentation. We report a unique case of pediatric pyoderma gangrenosum with a leukemoid reaction, secondary to an autosomal recessive leukocyte adhesion deficiency type 1.

Impact of Skin Biopsy and Clinical-Pathologic Correlation in Dermatology Inpatient Consults.

Background While studies of hospital dermatology have demonstrated diagnostic discordance between primary teams and dermatology consultants, little is known about the impact of biopsy and clinical-pathologic correlation (CPC) in consultation. This study compares biopsy performance based on diagnostic discordance and evaluates the impact of CPC on the diagnosis. Methods This was a retrospective review of 376 dermatologic consultations at a single academic medical center between July 1, 2017, and June 27, 2018. Results Biopsy was significantly less likely to be performed when the diagnosis by the referring primary team was unspecified (p < 0.001). In 24 percent of cases, the diagnosis based on histopathology alone differed from the diagnosis reached by formal CPC consensus review with either potential or significant impact on management. Conclusion Dermatologists who perform inpatient consultations and rely on hospital-based pathology services may consider a consensus review for CPC. Requests to perform a biopsy may be interpreted as a request for diagnostic assistance rather than pressure to perform a procedure.

Intermittent Hypoxia Differentially Regulates Adenosine Receptors in Phrenic Motor Neurons with Spinal Cord Injury.

Cervical spinal cord injury (cSCI) impairs neural drive to the respiratory muscles, causing life- threatening complications such as respiratory insufficiency and diminished airway protection. Repetitive "low dose" acute intermittent hypoxia (AIH) is a promising strategy to restore motor function in people with chronic SCI. Conversely, "high dose" chronic intermittent hypoxia (CIH; ∼8 h/night), such as experienced during sleep apnea, causes pathology. Sleep apnea, spinal ischemia, hypoxia and neuroinflammation associated with cSCI increase extracellular adenosine concentrations and activate spinal adenosine receptors which in turn constrains the functional benefits of therapeutic AIH. Adenosine 1 and 2A receptors (A1, A2A) compete to determine net cAMP signaling and likely the tAIH efficacy with chronic cSCI. Since cSCI and intermittent hypoxia may regulate adenosine receptor expression in phrenic motor neurons, we tested the hypotheses that: 1) daily AIH (28 days) downregulates A2A and upregulates A1 receptor expression; 2) CIH (28 days) upregulates A2A and downregulates A1 receptor expression; and 3) cSCI alters the impact of CIH on adenosine receptor expression. Daily AIH had no effect on either adenosine receptor in intact or injured rats. However, CIH exerted complex effects depending on injury status. Whereas CIH increased A1 receptor expression in intact (not injured) rats, it increased A2A receptor expression in spinally injured (not intact) rats. The differential impact of CIH reinforces the concept that the injured spinal cord behaves in distinct ways from intact spinal cords, and that these differences should be considered in the design of experiments and/or new treatments for chronic cSCI.

Daily acute intermittent hypoxia enhances serotonergic innervation of hypoglossal motor nuclei in rats with and without cervical spinal injury.

Intermittent hypoxia elicits protocol-dependent effects on hypoglossal (XII) motor plasticity. Whereas low-dose, acute intermittent hypoxia (AIH) elicits serotonin-dependent plasticity in XII motor neurons, high-dose, chronic intermittent hypoxia (CIH) elicits neuroinflammation that undermines AIH-induced plasticity. Preconditioning with repeated AIH and mild CIH enhance AIH-induced XII motor plasticity. Since intermittent hypoxia pre-conditioning could enhance serotonin-dependent XII motor plasticity by increasing serotonergic innervation density of the XII motor nuclei, we tested the hypothesis that 3 distinct intermittent hypoxia protocols commonly studied to elicit plasticity (AIH) or simulate aspects of sleep apnea (CIH) differentially affect XII serotonergic innervation. Sleep apnea and associated CIH are common in people with cervical spinal injuries and, since repetitive AIH is emerging as a promising therapeutic strategy to improve respiratory and non-respiratory motor function after spinal injury, we also tested the hypotheses that XII serotonergic innervation is increased by repetitive AIH and/or CIH in rats with cervical C2 hemisections (C2Hx). Serotonergic innervation was assessed via immunofluorescence in male Sprague Dawley rats, with and without C2Hx (beginning 8 weeks post-injury) exposed to 28 days of: 1) normoxia; 2) daily AIH (10, 5-min 10.5% O2 episodes per day; 5-min normoxic intervals); 3) mild CIH (5-min 10.5% O2 episodes; 5-min intervals; 8 h/day); and 4) moderate CIH (2-min 10.5% O2 episodes; 2-min intervals; 8 h/day). Daily AIH, but neither CIH protocol, increased the area of serotonergic immunolabeling in the XII motor nuclei in both intact and injured rats. C2Hx per se had no effect on XII serotonergic innervation density. Thus, daily AIH may increases XII serotonergic innervation and function, enhancing the capacity for serotonin-dependent, AIH-induced plasticity in upper airway motor neurons. Such effects may preserve upper airway patency and/or swallowing ability in people with cervical spinal cord injuries and other clinical disorders that compromise breathing and airway defense.

Attitudes and practices about fertility preservation discussions among young adults with cancer treated at a comprehensive cancer center: patient and oncologist perspectives.

BACKGROUND: Young adults (YAs, ages 18-39) diagnosed with cancer face multiple challenges that affect their health-related quality of life, including the potential for cancer-related infertility. Providing information about the risk of infertility and options to maintain fertility is critical for YAs who are newly diagnosed. However, barriers to effective communication exist for oncologists and their patients. The purpose of this study was to interview medical oncologists and YAs from the same cancer center to examine attitudes and practices about fertility preservation. METHODS: Semi-structured interviews were conducted with medical oncologists (N=12) and YAs within 2 years post-treatment (N=24), representing the most common cancers affecting YAs. Interviews were audio-recorded, transcribed, and coded using qualitative methodologies with the analysis software NVivo 10. RESULTS: Twelve oncologists (50% female, 67% <50 years) and 24 YAs (67% female, M=29 years) completed interviews. Common themes across oncologist and YA interviews were the roles of cancer type or stage and patient interest or parity in influencing the decision. The most important factor for YAs was to receive accurate, in-depth information. Unique themes for oncologists focused on clinical aspects of their patient's disease. For YAs, they shared about the emotional impact of cancer-related infertility and desire for support from trusted others. CONCLUSIONS: Results provide a better understanding of the attitudes and practices about fertility preservation discussions among YAs. Given the common factors affecting fertility preservation decisions, models of shared decision-making may be ideal for YAs and oncologists. Future interventions should explore tailored applications of this approach for YAs newly diagnosed with cancer.

Serotonergic innervation of respiratory motor nuclei after cervical spinal injury: Impact of intermittent hypoxia.

Although cervical spinal cord injury (cSCI) disrupts bulbo-spinal serotonergic projections, partial recovery of spinal serotonergic innervation below the injury site is observed after incomplete cSCI. Since serotonin contributes to functional recovery post-injury, treatments to restore or accelerate serotonergic reinnervation are of considerable interest. Intermittent hypoxia (IH) was reported to increase serotonin innervation near respiratory motor neurons in spinal intact rats, and to improve function after cSCI. Here, we tested the hypotheses that spontaneous serotonergic reinnervation of key respiratory (phrenic and intercostal) motor nuclei: 1) is partially restored 12 weeks post C2 hemisection (C2Hx); 2) is enhanced by IH; and 3) results from sprouting of spared crossed-spinal serotonergic projections below the site of injury. Serotonin was assessed via immunofluorescence in male Sprague Dawley rats with and without C2Hx (12 wks post-injury); individual groups were exposed to 28 days of: 1) normoxia; 2) daily acute IH (dAIH28: 10, 5 min 10.5% O2 episodes per day; 5 min normoxic intervals); 3) mild chronic IH (IH28-5/5: 5 min 10.5% O2 episodes; 5 min intervals; 8 h/day); or 4) moderate chronic IH (IH28-2/2: 2 min 10.5% O2 episodes; 2 min intervals; 8 h/day), simulating IH experienced during moderate sleep apnea. After C2Hx, the number of ipsilateral serotonergic structures was decreased in both motor nuclei, regardless of IH protocol. However, serotonergic structures were larger after C2Hx in both motor nuclei, and total serotonin immunolabeling area was increased in the phrenic motor nucleus but reduced in the intercostal motor nucleus. Both chronic IH protocols increased serotonin structure size and total area in the phrenic motor nuclei of uninjured rats, but had no detectable effects after C2Hx. Although the functional implications of fewer but larger serotonergic structures are unclear, we confirm that serotonergic reinnervation is substantial following injury, but IH does not affect the extent of reinnervation.

Predictors and outcomes in breast cancer patients who did or did not pursue fertility preservation.

PURPOSE: Breast cancer is the most common cancer in reproductive age women, and treatment can affect fertility; however, there is often concern regarding the safety of increased estradiol (E2) levels and potential delays in treatment with ovarian stimulation for fertility preservation (FP). The aim of this study was to compare recurrence and survival in breast cancer patients who pursued FP without concurrent letrozole to those who did not (non-FP). METHODS: We reviewed charts of women with breast cancer who contacted the FP patient navigator (PN) at Northwestern University from 01/2005-01/2018. Oncology and fertility outcome data were collected. Data were analyzed by Chi-square test or regression, as appropriate. Kaplan-Meier curves were used to examine breast cancer recurrence and survival. Statistical analyses were performed with SPSS IBM Statistics 26.0 for Windows. RESULTS: 332 patients were included, of which 157 (47.3%) underwent FP. Median days to treatment after consulting the PN was 35 in the FP group and 21 in non-FP (p < 0.05). Cancer recurrence was noted in 7 (4.7%) FP patients and 13 (7.9%) non-FP patients (NS), and mortality in 5 (3.2%) FP patients and 7 (4.2%) non-FP patients (NS). Within the FP group, no significant differences were found in recurrence or mortality based on ER status, age, BMI, peak E2 level or total gonadotropin dose. Likelihood of pursuing FP was primarily a function of age and parity, and was not affected by breast cancer stage. To date, 21 have used cryopreserved specimens, and 13 (62%) had a live birth. CONCLUSIONS: FP is safe and effective in breast cancer patients, regardless of receptor status; E2 elevations and the 2-week delay in treatment start are unlikely to be clinically significant. These findings are unique in that our institution does not use concomitant letrozole during stimulation to minimize E2 elevations in breast cancer patients.

Ovarian Stimulation Is Safe and Effective for Patients with Gynecologic Cancer.

Purpose: To compare long-term outcomes of gynecologic cancer patients who pursued controlled ovarian hyperstimulation (COH) for fertility preservation (FP) with those who did not. Methods: Retrospective cohort, COH, and health outcomes in gynecologic cancer patients; data were analyzed by chi-square test, t-tests, and logistic regression. Results: Ninety patients with a gynecologic malignancy contacted the FP patient navigator: 45.6% (n = 41) had ovarian cancer, 25.6% (n = 23) endometrial cancer, 18.9% (n = 17) cervical cancer, 5.6% (n = 5) uterine cancer, and 4.4% (n = 4) multiple gynecologic cancers. From this cohort, 32 underwent COH, 43 did not, and 18 pursued ovarian tissue cryopreservation (OTC; 3 patients had both COH and OTC). Median age and type of cancer were not significantly different between the groups. COH patients had a range of 1-35 oocytes retrieved. Days to next cancer treatment in the COH group was 36 days; for those who declined COH, it was 22 days (not significant [NS], p > 0.05). There were two recurrences reported in the stimulation group and four in the no stimulation group (NS). Five deaths were reported, two in the stimulation group, none in the no stimulation group, and three in the OTC group (NS); 34% (n = 11) COH patients returned to use cryopreserved specimens, of which 45% (n = 5) had a live birth. Conclusion: Although time to next treatment was longer in the group of patients who underwent COH, this did not reach statistical significance. It appears that in selected patients with GYN malignancies, COH for oocyte or embryo cryopreservation is safe, with reasonable stimulation outcomes and no difference in long-term outcomes.

Ovarian stimulation is a safe and effective fertility preservation option in the adolescent and young adult population.

PURPOSE: The aim of this study is to describe the multidisciplinary approach and controlled ovarian hyperstimulation (COH) outcomes in adolescent and young adult (AYA) patients (ages 13-21) who underwent oocyte cryopreservation for fertility preservation (FP). METHODS: Multi-site retrospective cohort was performed from 2007 to 2018 at Northwestern University and Michigan University. Data were analyzed by chi-square test, t-test, and logistic regression. RESULTS: Forty-one patients began COH of which 38 patients successfully underwent oocyte retrieval, with mature oocytes obtained and cryopreserved without any adverse outcomes. To treat this group of patients, we use a multidisciplinary approach with a patient navigator. When dividing patients by ages 13-17 vs. 18-21, the median doses of FSH used were 2325 and 2038 IU, the median number of mature oocytes retrieved were 10 and 10, and median number frozen oocytes were 11 and 13, respectively. Median days of stimulation were 10 for both groups. There was no statistical difference in BMI, AMH, peak E2, FSH dosage, days stimulated, total oocytes retrieved, mature oocytes retrieved, and oocytes frozen between the two groups. Three patients were canceled for poor response. CONCLUSION: COH with oocyte cryopreservation is a feasible FP option for AYAs who may not have other alternatives when appropriate precautions are taken, such as proper counseling and having a support team. These promising outcomes correspond to similar findings of recent small case series, providing hope for these patients to have genetically related offspring in the future.

Long-term outcomes in cancer patients who did or did not pursue fertility preservation.

OBJECTIVE: To compare long-term outcomes of cancer patients who pursued fertility preservation (FP) with those who did not and compare random-start (RS) and menstrual cycle-specific (CS) protocols for FP. DESIGN: Retrospective cohort. SETTING: Single urban academic institution. PATIENT(S): Oncology patients who contacted the FP patient navigator, 2005-2015. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Time to cancer treatment, disease-free survival, and reproductive outcomes in FP versus no-FP patients and cycle outcomes for RS versus CS protocols. Data were analyzed by χ2 and logistic regression. RESULT(S): Of 497 patients who met the inclusion criteria, 41% elected FP. The median number of days to cancer treatment was 33 and 19 days in the FP and no-FP groups, respectively. There was no difference in cancer recurrence or mortality. There were no differences in stimulation parameters, outcomes, or days to next cancer treatment in RS versus CS protocols. Twenty-one patients returned to use cryopreserved specimens, resulting in 16 live births. Eight of 21 returning patients used a gestational carrier. Thirteen FP (6.4%) and 16 no-FP (5.5%) patients experienced a spontaneous pregnancy. CONCLUSION(S): FP is both safe and efficacious for eligible cancer patients. Only 10% of patients returned to use cryopreserved specimens, and almost half used a gestational carrier, suggesting the need for further research into reproductive decision-making in cancer survivors.

Disparities in Counseling Female Cancer Patients for Fertility Preservation.

BACKGROUND: Female cancer patients who are exposed to gonadotoxic chemotherapy are at risk of future infertility. Research suggests that disparities in fertility preservation counseling (FPC) may exist. Previous research is limited by recall bias; therefore, this study examined objective electronic medical chart data regarding FPC at an academic medical center. MATERIALS AND METHODS: This study included reproductive-aged women (18-45 years old) with a diagnosis of breast, gynecological, or hematological cancer and who were exposed to a gonadotoxic chemotherapeutic agent from 2009 to 2013. Chi-square and logistic regression analyses were utilized to analyze disparities in FPC. RESULTS: Two hundred fifty-nine women met the study criteria. One hundred eighty-one women were diagnosed with breast cancer, 52 with hematological cancer, and 26 with gynecological cancer. 160/259 (62%) women had documented counseling for fertility preservation (FP), 60 (23%) women were not counseled as counseling was determined to be "not applicable," 16 (6%) women were not counseled and no explanation was given for the lack of counseling, and counseling was not documented in 23 (9%) charts. Age, marital status, and racial/ethnic background were related to counseling status. Patients with gynecological or hematological cancer were more likely to be counseled than other patients. Logistic regression results demonstrated that FPC was largely driven by cancer diagnosis. CONCLUSIONS: Although cancer diagnosis was the greatest predictor of FPC, disparities were evident in the counseling of female cancer patients for FP treatment. Equality in counseling female patients for FP treatment is imperative to reduce the risk of emotional harm and future infertility.

Documentation of Fertility Preservation Discussions for Young Adults With Cancer: Examining Compliance With Treatment Guidelines.

BACKGROUND: Professional guidelines have been developed to promote discussion between providers and newly diagnosed young adults with cancer about the possibility of cancer treatment-related infertility, but previous research suggests many young adults fail to receive this information. The aim of this study was to examine rates of and factors predictive of oncologists' compliance with national guidelines for discussing potential treatment-related infertility with newly diagnosed young adults with cancer seen at an NCI-designated comprehensive cancer center. METHODS: We reviewed data from the electronic medical record for new clinic encounters between medical oncologists and young adults with cancer (ages 18-39 years) from 2010 to 2012. Data from oncologist discussions of fertility preservation were abstracted, as were patient (age, sex, race, ethnicity, cancer type) and oncologist (gender, graduation year from fellowship) characteristics. RESULTS: A total of 1,018 cases were reviewed, with 454 patients (mean, 31.5 years; 67.8% women) meeting inclusion criteria. Overall, 83% of patients were informed about potential treatment-related infertility, with patients with breast cancer (85% informed), Hodgkin lymphoma (95% informed), non-Hodgkin's lymphoma (94% informed), leukemia (88% informed), or testicular cancer (100% informed) more likely to be informed than those with other cancer types (60%-74% informed). There was a significant effect for patient sex (odds ratio, 3.57; CI, 1.33, 9.60; P=.012), with women being more likely to be informed than men. CONCLUSIONS: Reported compliance with fertility preservation guidelines was greater than published rates. Higher compliance rates in female patients and in patients with cancers more common among young adults may reflect greater awareness of fertility-related concerns among these patients and their providers.

In vitro follicle growth supports human oocyte meiotic maturation.

In vitro follicle growth is a potential approach to preserve fertility for young women who are facing a risk of premature ovarian failure (POF) caused by radiation or chemotherapy. Our two-step follicle culture strategy recapitulated the dynamic human follicle growth environment in vitro. Follicles developed from the preantral to antral stage, and, for the first time, produced meiotically competent metaphase II (MII) oocytes after in vitro maturation (IVM).

Psychological Counseling of Female Fertility Preservation Patients.

Young cancer patients are increasingly interested in preserving their fertility prior to undergoing gonadotoxic therapies. Although the medical safety and treatment protocols for fertility preservation have been well documented, limited research has addressed the emotional issues that arise in fertility preservation patients. We briefly review the literature on the psychosocial issues in adult female fertility preservation treatment and describe our experiences within this patient population. Our findings suggest that several important issues to be addressed during the psychological counseling of adult female fertility preservation patients include: (1) preexisting psychological distress in patients undergoing treatment, (2) choice of fertility preservation strategy in the face of an uncertain relationship future, (3) decision making regarding use of third-party reproduction (e.g., sperm/egg donation, gestational surrogacy), (4) treatment expectations regarding pregnancy and miscarriage, (5) ethical issues related to treatment including the creation, cryopreservation, and disposition of embryos/oocytes, and (6) decision regret from patients who declined fertility preservation.

Prospective study of depression and anxiety in female fertility preservation and infertility patients.

OBJECTIVE: To prospectively assess anxiety, depression, coping, and appraisal in female fertility preservation (FP) patients compared with infertile patients. DESIGN: Prospective pre- and post-treatment survey. SETTING: Academic medical center. PATIENT(S): Forty-seven women with cancer (FP patients) and 91 age-matched infertile patients. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Depression, anxiety, coping, infertility-related stress, appraisal of treatment, and medical outcomes. RESULT(S): FP patients reported more symptoms of anxiety and depression than infertile patients, but infertile patients' symptoms worsened over time; 44% of FP and 14% of infertile patients' scores exceeded the clinical cutoff for depression before treatment. The interval between surveys and medical treatment data did not predict changes in mood symptoms. Coping strategies and infertility-related stress did not differ between groups, and avoidant coping predicted higher depression and anxiety scores. CONCLUSION(S): FP patients reported more anxiety and depression than infertile patients at enrollment in treatment, with more than one-third of FP patients reporting clinically significant depressive symptoms. However, infertile patients' anxiety and depressive symptoms increased across treatment. This increase was not related to time between registration for IVF and oocyte retrieval or the medical aspects of treatment. FP and infertile patients should be provided psychologic consultation before treatment to identify mood and anxiety symptoms and to refer patients for counseling as needed to prevent worsening of symptoms.

Square Pegs, Round Hole? Ensuring Fit in the AYAO Spectrum for Adolescents and Young Adults with Genetic Risk for Cancer.

This paper presents a case example of a young woman at genetic risk for future cancer. We discuss psychosocial challenges that adolescents and young adults (AYAs) may share with their cancer survivor peers, and describe an example of psychosocial care. A scientific foundation denoting the needs of AYAs at risk for heritable cancers is lacking, and it is unknown if these AYAs receive adequate support services. This is a call to action for practitioners and researchers to engage in initiatives that assure these AYAs have access to valuable support and more clearly mark their place within the spectrum of AYA oncology.

Spinal 2-chloroprocaine: a dose-ranging study and the effect of added epinephrine.

UNLABELLED: With the availability of preservative- and antioxidant-free 2-chloroprocaine (2-CP), there may be an acceptable short-acting alternative to lidocaine for spinal anesthesia. We examined the safety, dose-response characteristics, and effects of epinephrine with spinal 2-CP. Six volunteers per group were randomized to receive 30, 45, or 60 mg of spinal 2-CP with and without epinephrine. Intensity and duration of sensory and motor blockade were assessed. When 11 of the 18 volunteers complained of vague, nonspecific flu-like symptoms, breaking of the blind revealed that all spinal anesthetics associated with the flu-like symptoms contained epinephrine. There were no complaints of flu-like symptoms in the volunteers who received 2-CP without epinephrine. No further spinal anesthetics containing epinephrine were administered, resulting in 29 anesthetics (11 with epinephrine, 18 without epinephrine.) Plain 2-CP demonstrated a dose-dependent increase in peak block height and duration of effect at all variables except time to 2-segment regression and time to regression to T10. Time to complete sensory regression with plain 2-CP was 98 +/- 20, 116 +/- 15, and 132 +/- 23 min, respectively. 2-CP with epinephrine produced times to complete sensory regression of 153 +/- 25, 162 +/- 33, and 148 +/- 29 min, respectively. Preservative and antioxidant free 2-CP can be used effectively for spinal anesthesia in doses of 30-60 mg. Epinephrine is not recommended as an adjunct because of the frequent incidence of side effects. IMPLICATIONS: Hyperbaric spinal 2-chloroprocaine is effective and has an anesthetic profile appropriate for use in the surgical outpatient over the dose range of 30-60 mg without signs of transient neurologic symptoms. The addition of epinephrine is not recommended because of the frequent incidence of side effects.