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Objective To investigate factors associated with early IVF treatment discontinuation. Design Retrospective cohort study. Setting Academic medical center. Patient(s) Six hundred sixty-nine first-attempt IVF patients who did not have a live birth. Intervention(s) None. Main Outcome Measure(s) Treatment discontinuation and time to return for a second IVF cycle. Result(s) Women without IVF insurance coverage were more likely to discontinue treatment than women with insurance coverage (adjusted odds ratio [aOR] = 3.12; 95% confidence interval [CI], 2.22–4.40). African-American women were more likely to discontinue treatment (aOR = 2.95; 95% CI, 1.54–5.66) and returned for treatment more slowly (adjusted hazard ratio [aHR] = 0.44; 95% CI, 0.28–0.71) than non-Hispanic white women, regardless of IVF insurance coverage or income. Women with a poor prognosis were more likely to discontinue treatment than women with a good prognosis. Older women with IVF insurance coverage or a good prognosis had a shorter time to return for a second IVF cycle than older women without IVF insurance coverage or with a poor prognosis. Estimated income, distance to clinic, fertility diagnosis, number of oocytes retrieved, and history of previous live birth were not associated with treatment discontinuation or time to return for a second IVF cycle after adjustment for covariates. Conclusion(s) IVF insurance coverage, race, age, and future treatment prognosis are associated with IVF treatment discontinuation and time to return.

A 16-year-old white boy with a history of chronic lung disease of prematurity, cough-variant asthma, and incidental lung nodules presented to the emergency center in spring 2020 with acute onset dry cough, shortness of breath, and fever. An initial history, gathered from his mother because of the patient’s respiratory distress, revealed no recent travel. However, his mother is a health care worker at a hospital, and sick contacts included ongoing contact with a friend with cold-like symptoms. He had a variety of animals at home, including a dog, cats, fish, rodents, and reptiles. He had a history of vaping tobacco products >6 months ago. Fever and respiratory symptoms were associated with fatigue, chest tightness, abdominal pain, and myalgias. On examination, he was ill appearing and had tachycardia, tachypnea, borderline hypoxia with an oxygen saturation of 91% on room air, diminished breath sounds at the lung bases, and unremarkable abdominal examination results. A chest radiograph was consistent with the lung examination, revealing bilateral lower lobe hazy infiltrates. He showed initial improvement for 48 hours with antibiotics, intravenous fluid resuscitation, oxygen via nasal cannula, albuterol, and prednisone. Subsequently, he worsened with persistent high fever, increasing respiratory distress with pulmonary findings, and severe persistent epigastric pain, which added a layer of diagnostic complexity. As this patient’s clinical course evolved and further history became available, pulmonary medicine and infectious diseases services were consulted to guide diagnostic evaluation and treatment of this patient early in the era of coronavirus disease 2019.

Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration-resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways. We hypothesized that these Sigma1-mediated responses could be exploited to suppress AR protein levels and activity. Here we demonstrate that treatment with a small-molecule Sigma1 inhibitor prevented 5α- dihydrotestosterone-mediated nuclear translocation of AR and induced proteasomal degradation of AR and ARV, suppressing the transcriptional activity and protein levels of both full-length and splice-variant AR. Consistent with these data, RNAi knockdown of Sigma1 resulted in decreased AR levels and transcriptional activity. Furthermore, Sigma1 physically associated with ARV7 and ARv567es as well as full-length AR. Treatment of mice xenografted with ARV-driven CRPC tumors with a drug-like small-molecule Sigma1 inhibitor significantly inhibited tumor growth associated with elimination of AR and ARV7 in responsive tumors. Together, our data show that Sigma1 modulators can be used to suppress AR/ARV–driven prostate cancer cells via regulation of pharmacologically responsive Sigma1-AR/ARV interactions, both in vitro and in vivo. Cancer Res; 77(9); 2439–52. ©2017 AACR.

Background Thrombelastography (TEG) is a viscoelastic hemostatic assay. We have observed that end-stage renal disease (ESRD) and trauma-induced coagulopathy (TIC) produce distinctive TEG tracings. We hypothesized that rigorously definable TEG patterns could discriminate between healthy controls and patients with ESRD and TIC. Methods TEG was performed on blood from ESRD patients (n = 54) and blood from trauma patients requiring a massive blood transfusion (n = 16). Plots of independent TEG parameters were analyzed for patterns coupled to disease state, compared with controls. Decision trees for taxonomic classification were then built using the “R-Project” statistical software. Results Minimally overlapping clusters of TEG results were observed for the three patient groups when coordinate pairs of maximum amplitude (MA) and TEG-activated clotting time (ACT) were plotted on orthogonal axes. Based on these groupings, a taxonomical classification tree was constructed using MA and TEG ACT. Branch points were set at an ACT of 103 s, and these branches subdivided for MA at 60.8 mm for the high ACT branch and 72.6 mm for the low ACT branch, providing a correct classification rate of 93.4%. Conclusions ESRD and TIC demonstrate distinct TEG patterns. The coagulopathy of ESRD is typified by a prolonged enzymatic phase of clot formation, with normal-to-elevated final clot strength. Conversely, TIC is typified by prolonged clot formation and weakened clot strength. Our taxonomic categorization constitutes a rigorous system for the algorithmic interpretation of TEG based on cluster analysis. This will form the basis for clinical decision support software for viscoelastic hemostatic assays.

Coagulase-negative staphylococci (CoNS) are the most common cause of late-onset sepsis in the neonatal intensive care unit (NICU) and usually require vancomycin treatment. Our objective was to determine whether CoNS are associated with neonatal morbidity and mortality. This was a retrospective cohort study of very-low-birth-weight (VLBW, ≤ 1500 g) infants from 1989 to 2015. Exclusion criteria were major congenital anomaly or death within 72 h. CoNS was considered a pathogen if recovered from ≥ 2 cultures, or 1 culture if treated for ≥ 5 days and signs of sepsis were present. Logistic regression was used to examine factors associated with morbidity and mortality. Of 2242 VLBW infants, 285 (12.7%) had late-onset sepsis. CoNS (125, 44%), Staphylococcus aureus (52, 18%), and Escherichia coli (36, 13%) were the most commonly recovered organisms. In multivariate analysis, CoNS sepsis was not associated with mortality [OR 0.6 (95% CI 0.2–2.6)), but sepsis with other organisms was [OR 4.5 (95% CI 2.6–8.0)]. CoNS sepsis was associated with longer hospitalization but not risk for bronchopulmonary dysplasia, intraventricular hemorrhage, or retinopathy of prematurity. CoNS sepsis was not associated with mortality or morbidities other than length of stay. These findings support vancomycin-reduction strategies in the NICU.

The purpose of this paper is to share lessons learned from a collaborative, community-informed mixed-methods approach to adapting an evidence-based intervention to meet the needs of Latinos with chronic disease and minor depression and their family members. Mixed-methods informed by community-based participatory research (CBPR) were employed to triangulate multiple stakeholders' perceptions of facilitators and barriers of implementing the adapted intervention in community settings. Community partners provided an insider perspective to overcome methodological challenges. The study's community informed mixed-methods: research approach offered advantages to a single research methodology by expanding or confirming research findings and engaging multiple stakeholders in data collection. This approach also allowed community partners to collaborate with academic partners in key research decisions.