Uniformly-sized preparations with average microbubble (MB) diameters from 1 µm to 7 µm were produced reliably by sonicating decafluorobutane-saturated solutions of serum albumin and dextrose. Detailed protocols for producing and size-separating the MBs are presented, along with the effects that changing each production parameter (serum albumin concentration, sonication power, sonication time, etc.) had on MB size distribution and acoustic stability. These protocols can be used to produce MBs for experimental applications or serve as templates for developing new protocols that yield MBs with physical and acoustic properties better suited to specific applications. Size stability and ultrasonic performance quality control tests were developed to assure that successive MB preparations perform identically and to distinguish the physical and acoustic properties of identically sized MBs produced with different serum albumin-dextrose formulations and sonication parameters. MBs can be stored at 5°C for protracted periods (2 weeks to one year depending on formulation).

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Background: Despite years of research, it is still unclear which women with node-negative (N-) breast cancer will need adjuvant chemotherapy and which women are being treated unnecessarily. Our goal was to determine which factors best predicted disease free survival (DFS) or cancer-specific overall survival (OS) and, therefore, select the correct patients for treatment. A total of 11 parameters were measured: estrogen receptor (ER), progesterone receptor (PR), age, race, ploidy status, %G0/G1 (% non-DNA synthesis), %S (% S-phase), cathepsin D status, size, stage, and histologic grade.Results: In this prospective study, we followed 556 N-patients diagnosed between 1991 and 1996. The tumors were 56% ER؉, 51% PR؉, 30% diploid, with a mean %S of 8.9%. The level of cathepsin D ranged from 0.50 to 155 pmol/mg of protein with a mean of 42.9 pmol/mg of protein. There were 87 recurrences (16%) and 72 cancer deaths (13%), with a median follow-up of 7.8 years. Ploidy status (p ‫؍‬ 0.01), S-phase activity (p ‫؍‬ 0.003), G1 phase activity (p ‫؍‬ 0.02) and age (p ‫؍‬ 0.01) were able to significantly predict DFS in a univariate manner. All of the measurable factors were significant or borderline significant in predicting OS in a univariate manner except for age, race, and ER status. In multivariate analysis with S-phase included, it was the only remaining factor in DFS and OS; with S-phase excluded, age and ploidy status remained as factors for DFS in stepwise regression, while PR, size, and cathepsin D were the remaining factors that predicted cancer-specific OS. The effect of adjuvant treatment on prognosis was also analyzed.Conclusions: Both biochemical and clinical parameters have the potential to predict prognosis for Nbreast cancer. In this large prospective clinical trial, with a median follow-up of 7.8 years, no individual marker adequately predicted the prognosis for an individual patient. %S activity was the best independent marker, but only 77% of the tumors provided this value. Subset analysis provided improved prognostication, but there were limits to its utility. These data represents a definitive study starting in 1991 and ending in 2002.

OBJECTIVES: The American Academy of Pediatrics National Registry for the Surveillance and Epidemiology of Perinatal coronavirus disease 2019 (COVID-19) (NPC-19) was developed to provide information on the effects of perinatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: National Registry for the Surveillance and Epidemiology of Perinatal COVID-19 participating centers entered maternal and newborn data for pregnant persons who tested positive for SARS-CoV-2 infection between 14 days before and 10 days after delivery. Incidence of and morbidities associated with maternal and newborn SARS-CoV-2 infection were assessed. RESULTS: From April 6, 2020 to March 19, 2021, 242 centers in the United States centers reported data for 7524 pregnant persons; at the time of delivery, 78.1% of these persons were asymptomatic, 18.2% were symptomatic but not hospitalized specifically for COVID-19, 3.4% were hospitalized for COVID-19 treatment, and 18 (0.2%) died in the hospital of COVID-related complications. Among 7648 newborns, 6486 (84.8%) were tested for SARS-CoV-2, and 144 (2.2%) were positive; the highest rate of newborn infection was observed when mothers first tested positive in the immediate postpartum period (17 of 125, 13.6%). No newborn deaths were attributable to SARS-CoV-2 infection. Overall, 15.6% of newborns were preterm: among tested newborns, 30.1% of polymerase chain reaction-positive and 16.2% of polymerase chain reaction-negative were born preterm (P < .001). Need for mechanical ventilation did not differ by newborn SARS-CoV-2 test result, but those with positive tests were more likely to be admitted to a NICU. CONCLUSIONS: Early in the pandemic, SARS-CoV-2 infection was acquired by newborns at variable rates and without apparent short-term effects. During a period that preceded widespread availability of vaccines, we observed higher than expected numbers of preterm births and maternal in-hospital deaths.

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Highlights Overall prognosis of uterine leiomyosarcoma (ULMS) is poor with a low 5-year survival rate. Microsatellite instability (MSI)-high ULMS is not well documented in current literature. Immune checkpoint inhibitors such as pembrolizumab have been shown to have good efficacy in treating MSI-high solid tumors. Targeting MSI-high ULMS with pembrolizumab can potentially maintain a patient’s quality of life and extend overall survival.

Exstrophy

An earlier impression of a high prevalence of hypothyroidism in a general practice (4,190 patients including 1,544 adult females aged 18 years or more with 544 aged 50 years or more) in the Rosses, a coastal area in the northwest of Ireland was confirmed by this study. The accumulated prevalence of overt spontaneous primary hypothyroidism was 8.6% in 544 females aged 50 years or more but only 0.9% in the 1,000 females between 18 and 50 years of age. This prevalence was approximately twice that of an Irish National general practice population sample of 4,314 females aged 50 years or more (8.6% vs. 4.6%) p < 0.001. The reasons for this difference are unclear but may reflect the high level of opportunistic screening carried out in West Donegal. Thyroid peroxidase antibodies measured by radioimmunoassay were found in 75.6% of hypothyroid patients compared to 18.6% of practice controls (p < 0.01). Neither HLA-DRB1, DQA1, and DQB1 phenotype frequencies nor dietary iodine intake (median urinary iodine excretion 104 microg/L) appeared to be contributory factors. The finding of an 8.6% accumulated prevalence of hypothyroidism in females greater than 50 years of age when a population is aggressively investigated demonstrates the relative importance of its contribution to total morbidity and suggests that the disorder may be underdiagnosed, thus supporting the concept of targeted screening in this age group.