Breast cancer in young women: Imaging and clinical course

The purpose of this study was to characterize presenting imaging findings in women younger than 40 diagnosed with invasive breast cancer in the context of pathology and clinical course. Retrospective chart and imaging reviews were performed in patients under 40 diagnosed with breast cancer between July 1, 2004, and December 31, 2013. Patient demographic, imaging, pathology, and clinical data were collected. Overall and recurrence-free survival were estimated using the Kaplan-Meier method. Univariate Cox proportional hazards models were performed to identify factors associated with recurrence-free survival. Our study cohort consisted of 110 patients with invasive mammary carcinoma. One hundred one (91.8%) presented with a palpable mass. The mean size of all lesions on imaging was 3.5 cm ± 2.9 cm. Malignant calcifications were present in 54 (49.1%) cases. Imaging demonstrated multifocal or multicentric disease in 45 (40.9%) cases. Seventy four (67.3%) cancers were high grade. Luminal genomic subtypes were the most common (n = 61, 55.5%). At presentation, 4 (3.6%) patients had bilateral malignancy and 8 (7.3%) patients had distant metastatic disease. Ninety seven (88.2%) underwent neoadjuvant chemotherapy and 67 (60.9%) underwent radiation therapy. Seventy five (68.2%) of the patients underwent mastectomy. The restricted mean time to recurrence was 9.01 years (standard error 3.162 months). ER positivity was associated with compromised recurrence-free survival. The overall survival rate was 0.962 at 10 years. Young patients diagnosed with breast cancer typically present with advanced breast imaging findings and undergo aggressive treatment. Recurrence often occurs >5 years from diagnosis, and ER positive subtypes are at increased risk for recurrence.     

Quantifying infection risks in incompatible living donor kidney transplant recipients

Desensitization has enabled incompatible living donor kidney transplantation (ILDKT) across HLA/ABO barriers, but added immunomodulation might put patients at increased risk of infections. We studied 475 recipients from our center from 2010 to 2015, categorized by desensitization intensity: none/compatible (n = 260), low (0-4 plasmaphereses, n = 47), moderate (5-9, n = 74), and high (≥10, n = 94). The 1-year cumulative incidence of infection was 50.1%, 49.8%, 66.0%, and 73.5% for recipients who received none, low, moderate, and high-intensity desensitization (P < .001). The most common infections were UTI (33.5% of ILDKT vs. 21.5% compatible), opportunistic (21.9% vs. 10.8%), and bloodstream (19.1% vs. 5.4%) (P < .001). In weighted models, a trend toward increased risk was seen in low (wIRR = _0.771.40_2.56,P = .3) and moderately (wIRR = _0.881.35_2.06,P = .2) desensitized recipients, with a statistically significant 2.22-fold (wIRR = _1.332.22_3.72,P = .002) increased risk in highly desensitized recipients. Recipients with ≥4 infections were at higher risk of prolonged hospitalization (wIRR = _2.623.57_4.88, P < .001) and death-censored graft loss (wHR = _1.154.01_13.95,P = .03). Post–KT infections are more common in desensitized ILDKT recipients. A subset of highly desensitized patients is at ultra-high risk for infections. Strategies should be designed to protect patients from the morbidity of recurrent infections, and to extend the survival benefit of ILDKT across the spectrum of recipients.     

Effects of two stressors on behaviour in the elevated X-maze: preliminary investigation of their interaction with 8-OH-DPAT

Effects of water deprivation and restraint were compared in the rat elevated X-maze. Water deprivation for 12–48 h increased corticosterone and had a duration-dependent anxiolytic effect in the elevated X-maze, increasing the ratio of open/total arm entries (OTR) and the proportion of time spent on the open arms (% time) without affecting total entries. Brain 5HIAA/5HT was increased only after 24 or 48 h deprivation. Restraint for 15 min also increased plasma corticosterone and brain 5HIAA/5HT but had no effect on behaviour in the elevated X-maze when rats were tested immediately afterwards. However, 1 h restraint was anxiogenic in the elevated X-maze immediately after release, reducing OTR and % time, but with a less consistent reduction in total entries; reductions in OTR and % time were still present 24 h later. The 5HT_1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.1–0.2 mg/kg), administered 10 min before testing in the elevated X-maze, had anxiogenic actions in non-stressed rats. The effect of 0.1 mg/kg 8-OH-DPAT was not significantly altered by 24 or 48 h water deprivation but was abolished by restraint for 1 h immediately beforehand, despite the anxiogenic effect of restraint alone. Similar mutual antagonism of 8-OH-DPAT and restraint occurred when the dose of 8-OH-DPAT was increased to 0.2 mg/kg. Twenty-four hours after restraint, restrained rats which had received 8-OH-DPAT (0.1–0.2 mg/kg) still did not show any significant anxiogenic effect compared with non-restrained vehicle treated controls. Restraint-induced deficits in elevated X-maze exploration may prove a useful model with which to study the pharmacology of depression-related anxiety. However, the effects of the stressors examined, and their interaction with 8-OH-DPAT in the elevated X-maze, appear to depend on the nature of the stressor.     

Destruction of WiDr multicellular tumor spheroids with the novel thymidylate synthase inhibitor 1843U89 at physiological thymidine concentrations

The activity of a novel thymidylate synthase inhibitor, 1843U89, against WiDr human colon carcinoma multicellular tumor spheroids was investigated. Continuous exposure of the spheroids to 3 nM 1843U89 for 10 days resulted in spheroid disruption, whereas 100 nM methotrexate (MTX) was required for similar effects. Short-term treatment experiments demonstrated that a 3-day exposure to 100 nM 1843U89 caused spheroid disruption 9 days after drug removal. A 4-day exposure to 10 nM 1843U89 caused spheroid disruption 8 days after drug removal. In contrast, treatment with 10 or 100 nM 1843U89 for 6–48 h or treatment with 1 nM 1843U89 for up to 5 days caused only growth delay. Continuous exposure of spheroids to 30 nM 1843U89 in the presence of 0.05–0.3 M thymidine was as effective in causing spheroid disruption as treatment in the absence of thymidine, but treatment in the presence of 0.7–3.0 M thymidine caused partial reversal of spheroid disruption. The results of these experiments suggest that 1843U89 should have potent solid tumor activity in humans but should be less effective in mice due to differences in circulating thymidine levels (0.1 vs 1 M, respectively).     

Metaphyseal chondrodysplasia, type Jansen

The Jansen type of metaphyseal dysplasia is a rare disorder with significant clinical and radiographic variability. Two cases of classical Jansen disease and one with some distinctive features suggestive of the Jansen variant are reported.     

Quality assurance in a children's psychiatric hospital

The use of short-term isolation (STI) in a children's psychiatric hospital was examined using the Joint Commission on Accreditation of Hospitals (JCAH) quality assurance mode. A Clinical Care Evaluation addressed two questions: Are we providing quality use of STI? And are we adequately documenting its use? A medical record audit of 78 discharged patients and a review of unit records provided hospital staff with utilization and demographic statistics; structured interviews with staff and inpatients were conducted that provided information about their opinions of STI. The data gathered served as the basis for recommendations that led to planned, informed program changes.     

Recruit,screen, and hire: Staff selection and the decision-making process

This article focuses on the role of the clinician-manager in staff selection. The duties of the clinician-manager in a mental health center include those tasks described as recruit, screen, and hire but little or no guidance on the steps involved in this sequence of events is available. The how of hiring is transmitted by word of mouth, by following another's example, or by trial and error. This article examines the component parts of staff selection from the assimilation of procedures, rules, and regulation of the public authority under which a particular mental health center operates, to the compilation of a short list of those to be screened and finally the risk taking and decision-making process by the clinician-manager who makes the choice. Some speculation on the emotional impact it has on the clinician-manager is examined. The impact of personal value judgments of the selector are considered. Recommendations are made for the inclusion of training in staff selection by academic programs for mental health administrators.Sheila Melville, A.C.S.W., is the Director, Partial Hospitalization, Mt. Vernon Center for Community Mental Health, 8119 Holland Road, Alexandria, Virginia 22306.     

Utilization of acute inpatient psychiatric services: “Heavy users” in New York State

The severely and persistently mentally ill (SPMI) population are often forced to rely on emergency/acute inpatient services. The authors analyze Medicaid expenditures and state hospital utilization data to identify and describe the characteristics of heavy users of these services. Also described is New York State's intensive case management (ICM) initiative targeted at this heavy user group. It is postulated that ICM will alter the utilization patterns of participants from over-reliance on the most costly services and more effectively and efficiently serve the SPMI population, specifically the heavy user subpopulation.     

Sputum cytological atypia as a predictor of incident lung cancer in a cohort of heavy smokers with airflow obstruction.

Individuals with cytological atypia in sputum may be at increased risk for lung cancer. We conducted a longitudinal analysis of the association between lung cancer incidence and cytological atypia in sputum samples collected prospectively from an ongoing cohort of adults at high risk for lung cancer. Cohort members had a smoking history of > or = 30 pack-years and chronic obstructive pulmonary disease documented by pulmonary airflow testing. Sputum samples collected at baseline and periodically thereafter were examined by standard cytological methods. From the cohort of 2,006 people, there were 83 incident lung cancers over 4,469 person-years of observation. At baseline, the association between personal and behavioral characteristics, and sputum cytological atypia was assessed by multiple logistic regression. The association between sputum cytological atypia and incident lung cancer was then assessed by hazard ratios using proportional hazards regression analysis, adjusting for potential confounding factors. Cytological atypia graded as moderate or worse was associated with continuing cigarette smoking (adjusted odds ratio, 2.5; 95% confidence interval, 1.5-4.1), and with lower levels of intake of fruits and vegetables (P for trend = 0.04). Atypia was not associated with several other factors, including the degree of airflow obstruction, the use of vitamin supplements, nonsteroidal anti-inflammatory drugs, or metered-dose steroid inhalers. Incident lung cancer was increased among those with moderate or worse cytological atypia (adjusted hazards ratio, 2.8; 95% confidence interval, 1.4-5.5). This association was not confounded by other risk factors. We conclude that in this high-risk cohort, cytological atypia is associated with continuing smoking and low intake of fruits and vegetables, but that independent of these and other factors, the risk of incident lung cancer is increased among those with moderate or worse grades of cytological atypia in their sputum.