Treatment modalities and survival outcomes in prostate cancer parenchymal brain metastasis.

BACKGROUND: Prostate cancer (PCa) parenchymal brain metastases are uncommon and troubling observations in the course of the disease. Our study aims to evaluate the prevalence of brain metastases among PCa patients while reporting various therapeutic modalities, clinical features, and oncological outcomes. METHODS: We retrospectively identified 34 patients with parenchymal brain metastasis out of 4575 patients using a prospectively maintained database that contains clinicopathologic characteristics of PCa patients between January 2012 and December 2021. Based on the three treatment modalities used, the patients were divided into three groups: stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), and systemic therapy alone. The Kaplan-Meier curve was used to calculate overall survival [OS] probability and the Cox proportional hazards regression model was used to compare between groups. RESULTS: At the time of brain metastasis diagnosis, the median age was 66 years, the median (interquartile range [IQR]) prostate-specific antigen (PSA) was 2.2 (0.1-26.6) ng/ml and the median (IQR) months from initial PCa diagnosis to brain metastasis development was 70.8 (27.6-100.9). The median (IQR) primary Gleason score was 8 (7-9) and over a median (IQR) follow-up time of 2.2 (1.2-16.5) months, 76.5% (n = 26) of the patients died. Thirteen (38.2%) patients had solitary lesion, whereas 21 (61.8%) had ≥2 lesions. The lesions were supratentorial in 19 (55.9%) patients, infratentorial in six (17.6%), and both sides in nine (26.5%). Among all 34 patients, 10 (29.4%) were treated with SRS, seven (20.6%) with WBRT, and 17 (50%) with systemic therapy alone. OS varied greatly between the three treatment modalities (log-rank test, p = 0.049). Those who were treated with SRS and WBRT had better OS compared with patients who were treated with systemic therapy alone (hazard ratio: 0.37, 95% confidence interval: 0.16-0.86, p = 0.022). CONCLUSIONS: In our single-institutional study, we confirmed that PCa brain metastasis is associated with poor survival outcomes and more advanced metastatic disease. Furthermore, we found that SRS and WBRT for brain metastasis in patients with recurrent PCa appear to be associated with improved OS as compared with systemic therapy alone and are likely secondary to selection bias.

Tick-borne infections in children in North America.

PURPOSE OF REVIEW: Because both incidence and awareness of tick-borne infections is increasing, review of major infections and recent advances related to their diagnosis and management is important. RECENT FINDINGS: A new algorithm, termed modified two-tier testing, for testing for antibodies to Borrelia burgdorferi , the cause of Lyme disease, has been approved and may replace traditional two-tier testing. In addition, doxycycline is now acceptable to use for treatment of and/or prophylaxis for Lyme disease for up to 21 days in children of any age. Borrelia miyamotoi , a bacterium in the relapsing fever type of Borrelia, is the first of this type of Borrelia that is transmitted by hard-bodied ticks such as Ixodes scapularis. SUMMARY: Awareness of these infections and advances in their diagnosis and treatment is important to assure the best outcomes for affected patients. Table 1 contains a summary of infections discussed.

Sentinel Surveillance System Implementation and Evaluation for SARS-CoV-2 Genomic Data, Washington, USA, 2020-2021.

Genomic data provides useful information for public health practice, particularly when combined with epidemiologic data. However, sampling bias is a concern because inferences from nonrandom data can be misleading. In March 2021, the Washington State Department of Health, USA, partnered with submitting and sequencing laboratories to establish sentinel surveillance for SARS-CoV-2 genomic data. We analyzed available genomic and epidemiologic data during presentinel and sentinel periods to assess representativeness and timeliness of availability. Genomic data during the presentinel period was largely unrepresentative of all COVID-19 cases. Data available during the sentinel period improved representativeness for age, death from COVID-19, outbreak association, long-term care facility-affiliated status, and geographic coverage; timeliness of data availability and captured viral diversity also improved. Hospitalized cases were underrepresented, indicating a need to increase inpatient sampling. Our analysis emphasizes the need to understand and quantify sampling bias in phylogenetic studies and continue evaluation and improvement of public health surveillance systems.

Coping Mechanisms for Financial Toxicity Among Patients With Metastatic Prostate Cancer: A Survey-based Assessment.

PURPOSE: Assessments of financial toxicity among patients with metastatic prostate cancer are lacking. Using patient surveys, we sought to identify coping mechanisms and assess characteristics associated with lower financial toxicity. MATERIALS AND METHODS: Surveys were administered to all patients seen at a single center's Advanced Prostate Cancer Clinic over a 3-month period. Surveys included the COST-FACIT (COmprehensive Score for Financial Toxicity) and coping mechanism questionnaires. Patients with metastatic disease (lymph nodes, bone, visceral) were included for analysis. Coping mechanisms were compared between patients experiencing low (COST-FACIT >24) vs high (COST-FACIT ≤24) financial toxicity using Fisher's exact test. Multivariable linear regression was used to evaluate characteristics associated with lower financial toxicity. RESULTS: Overall, 281 patients met inclusion criteria of which 79 reported high financial toxicity. In multivariable analysis, characteristics associated with lower financial toxicity included older age (estimate: 0.36, 95%CI: 0.21-0.52), applying for patient assistance programs (estimate: 4.42, 95%CI: 1.72-7.11), and an annual income of at least $100,000 (estimate: 7.81, 95%CI: 0.97, 14.66). Patients with high financial toxicity were more likely to decrease spending on basic goods (35% vs 2.5%, P < .001) and leisure activities (59% vs 15%, P > .001), as well as use savings (62% vs 17%, P < .001) to pay for their treatment. CONCLUSIONS: In this cross-sectional study, patients with metastatic prostate cancer and high financial toxicity were more likely to decrease spending on basic goods and leisure activities and use savings to pay for care. Understanding the impact of financial toxicity on patients' lives is crucial to inform shared decision-making and interventions designed to mitigate financial toxicity in this population.

Vincristine/irinotecan/temsirolimus upfront window treatment of high-risk hepatoblastoma: A report from the Children's Oncology Group AHEP0731 Study Committee.

BACKGROUND: Survival for children with metastatic hepatoblastoma (HB) remains suboptimal. We report the response rate and outcome of two courses of vincristine/irinotecan/temsirolimus (VIT) in children with high-risk (HR)/metastatic HB. PROCEDURES: Patients with newly diagnosed HB received HR window chemotherapy if they had metastatic disease or a serum alpha-fetoprotein (AFP) level less than 100 ng/mL. Patients received vincristine (days 1 and 8), irinotecan (days 1-5), and temsirolimus (days 1 and 8). Cycles were repeated every 21 days. Responders had either a 30% decrease using RECIST (Response Evaluation Criteria in Solid Tumors) criteria OR a 90% (>1 log10 decline) AFP decline after two cycles. Responders received two additional cycles of VIT intermixed with six cycles of cisplatin/doxorubicin/5-fluorouracil/vincristine (C5VD). Nonresponders received six cycles of C5VD alone. RESULTS: Thirty-six eligible patients enrolled on study. The median age at enrollment was 27 months (range: 7-170). Seventeen of 36 patients were responders (RECIST and AFP = 3, RECIST only = 4, AFP only = 10). The median AFP at diagnosis was 222,648 ng/mL and the median AFP following two VIT cycles was 19,262 ng/mL. Three-year event-free survival was 47% (95% confidence interval [CI]: 30%-62%), while overall survival was 67% (95% CI: 49%-80%). CONCLUSION: VIT did not achieve the study efficacy endpoint. Temsirolimus does not improve the response rate seen in patients treated with vincristine and irinotecan (VI) alone as part of the initial treatment regimen explored in this study. Additionally, AFP response may be a more sensitive predictor of disease response than RECIST in HB.

PheLiGe: an interactive database of billions of human genotype-phenotype associations.

Genome-wide association studies have provided a vast array of publicly available SNP × phenotype association results. However, they are often in disparate repositories and formats, making downstream analyses difficult and time consuming. PheLiGe (https://phelige.com) is a database that provides easy access to such results via a web interface. The underlying database currently stores >75 billion genotype-phenotype associations from 7347 genome-wide and 1.2 million region-wide (e.g. cis-eQTL) association scans. The web interface allows for investigation of regional genotype-phenotype associations across many phenotypes, giving insights into the biological function affected by the variant in question. Furthermore, PheLiGe can compare regional patterns of association between different traits. This analysis can ascertain whether a co-association is due to pleiotropy or linkage. Moreover, comparison of association patterns for a complex trait of interest and gene expression and protein levels can implicate causal genes.

Understanding the Factors Influencing Health Care Provider Recommendations about Adolescent Vaccines: A Proposed Framework.

Health care provider recommendations are among the most important factors influencing parents' decisions to vaccinate their adolescents. However, delivery of high-quality health care provider recommendations for vaccination is not universal. There is wide variation in the strength, timeliness and consistency of the delivery of recommendations for all adolescent vaccines. The factors that influence health care providers' recommendations are multi-level and can be conceptualized in much the same way as vaccine acceptance among parents. Health care providers are influenced by their own attitudes and beliefs about a vaccine and also by the patient they are treating and by the community in which they practice as well as state and national level vaccine policy. We propose a multi-level framework for understanding the factors that influence health care providers' recommendations at the individual, interpersonal and community level to both develop and adapt interventions to improve providers' recommendations.

Microvascular Skeletal-Muscle Crosstalk in Health and Disease.

As an organ system, skeletal muscle is essential for the generation of energy that underpins muscle contraction, plays a critical role in controlling energy balance and insulin-dependent glucose homeostasis, as well as vascular well-being, and regenerates following injury. To achieve homeostasis, there is requirement for "cross-talk" between the myogenic and vascular components and their regulatory factors that comprise skeletal muscle. Accordingly, this review will describe the following: [a] the embryonic cell-signaling events important in establishing vascular and myogenic cell-lineage, the cross-talk between endothelial cells (EC) and myogenic precursors underpinning the development of muscle, its vasculature and the satellite-stem-cell (SC) pool, and the EC-SC cross-talk that maintains SC quiescence and localizes ECs to SCs and angio-myogenesis postnatally; [b] the vascular-myocyte cross-talk and the actions of insulin on vasodilation and capillary surface area important for the uptake of glucose/insulin by myofibers and vascular homeostasis, the microvascular-myocyte dysfunction that characterizes the development of insulin resistance, diabetes and hypertension, and the actions of estrogen on muscle vasodilation and growth in adults; [c] the role of estrogen in utero on the development of fetal skeletal-muscle microvascularization and myofiber hypertrophy required for metabolic/vascular homeostasis after birth; [d] the EC-SC interactions that underpin myofiber vascular regeneration post-injury; and [e] the role of the skeletal-muscle vasculature in Duchenne muscular dystrophy.

Seroprevalence and Risk Factors of Sexually Transmitted Blood-Borne Infections among Pregnant Women Attending Antenatal Care in Jirapa, Upper West Region of Ghana.

Background: Sexually transmitted blood-borne infections (STBBIs) contribute to negative outcomes of pregnancy. Hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and syphilis infections in pregnancy contribute significantly to maternal and child morbidities and mortalities. This study assessed the prevalence, knowledge, and risk factors of STBBIs (HBV, HCV, HIV, and syphilis) among pregnant women attending antenatal clinics in Jirapa. Methods: A cross-sectional study design involving 246 pregnant women was employed for the study. A structured questionnaire was used to solicit information about the knowledge, prevalence, and risk factors of STBBIs. Results: The overall prevalence of STBBIs was 11.4%; HBV prevalence was 9.8% and 0.8% each for HCV, HIV, and syphilis. About 66% of mothers were aware of mother-to-child transmission of infections during pregnancy. Knowledge of transmission of HIV (93.9%), hepatitis (67.1%), and syphilis (53.7%) in pregnancy was relatively high. Knowledge of risk factors for HIV, hepatitis, and syphilis was 97.6%, 74.4%, and 76.0%, respectively. More than 98% of respondents knew about the prevention of HIV, hepatitis, and syphilis. Significant risk factors associated with and predictive of STBBIs were female genital mutilation (FGM) and gravidity. Conclusion: The occurrence of STBBIs among pregnant women was strongly associated with FGM and gravidity. Public health education should be directed at stopping the practice of FGM and improving reproductive health in the study area.

The Effectiveness of Varicella Vaccine: 25 Years of Postlicensure Experience in the United States.

We summarize studies of varicella vaccine's effectiveness for prevention of varicella and lessons learned during the first 25 years of the varicella vaccination program in the United States. One dose of varicella vaccine provided moderate protection (82%-85%) against varicella of any severity and high protection (100%) against severe varicella, with some waning of protection over time. The 1-dose program (1995-2006) had a substantial impact on the incidence both of varicella and of severe outcomes (71%-90% decrease) although it did not prevent low-level community transmission and some outbreaks continued to occur in highly vaccinated populations. Two doses of varicella vaccine improved the vaccine's effectiveness by at least 10% against varicella of any severity, with further declines in the incidence both of varicella and of severe outcomes as well as in both number and size of outbreaks. There is no evidence for waning of the effectiveness of 2 doses of the vaccine.

Prognostic role of 11C-choline PET/CT scan in patients with metastatic castrate resistant prostate cancer undergoing primary docetaxel chemotherapy.

BACKGROUND: We sought to assess the prognostic utility of 11C-choline positron emission tomography/computed tomography (PET/CT) in patients with metastatic castrate resistant prostate cancer (mCRPC) undergoing primary docetaxel chemotherapy. METHODS: We performed a single institution retrospective analysis of 77 mCRPC patients who were treated with 6 cycles of docetaxel chemotherapy, and who also underwent 11C-choline PET/CT scans at baseline (before chemotherapy), mid-course (after 3 cycles), and posttherapy (after 6 cycles). We evaluated treatment response based on percent change in blood pool-corrected maximum standardized uptake value (SUVmax) of the target lesion on PET/CT, as well as percent change in serum prostate specific antigen (PSA). Logistic regression analysis was used to identify factors associated with complete treatment response. Progression free survival (PFS) analysis was performed using log-rank test and shown on Kaplan-Meier plot. RESULTS: Percent change in blood pool-corrected SUVmax on mid-course scan was a significant predictor of complete response (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.96-0.99, p = .0003), whereas percent change in PSA was not (OR: 0.99, 95% CI: 0.99-1.01, p = .6025). 57 of 77 patients (74%) achieved ≥20% reduction in blood pool-corrected SUVmax on mid-course; these patients were 3.6 times more likely to achieve complete response after full 6 cycles of docetaxel chemotherapy, compared to patients with <20% reduction in blood pool-corrected SUVmax (OR: 3.56, 95% CI: 1.04-16.52, p = .0420). Median PFS in the complete response group was 35.1 months (95% CI: 26.0-52.7 months), compared to 9.4 months (95% CI: 6.9-13.0 months) in the incomplete response group (p = .0005). CONCLUSIONS: Our study showed that mid-course and posttherapy 11C-choline PET/CT evaluation for mCRPC patients undergoing primary docetaxel chemotherapy can predict full course treatment response and PFS, respectively. 11C-choline PET/CT imaging may provide valuable prognostic information to guide treatment choices for patients with mCRPC.

Doxorubicin in combination with cisplatin, 5-flourouracil, and vincristine is feasible and effective in unresectable hepatoblastoma: A Children's Oncology Group study.

BACKGROUND: The Children's Oncology Group (COG) adopted cisplatin, 5-flourouracil, and vincristine (C5V) as standard therapy after the INT-0098 legacy study showed statistically equivalent survival but less toxicity in comparison with cisplatin and doxorubicin. Subsequent experience demonstrated doxorubicin to be effective in patients with recurrent disease after C5V, and this suggested that it could be incorporated to intensify therapy for patients with advanced disease. METHODS: In this nonrandomized, phase 3 COG trial, the primary aim was to explore the feasibility and toxicity of a novel therapeutic cisplatin, 5-flourouracil, vincristine, and doxorubicin (C5VD) regimen with the addition of doxorubicin to C5V for patients considered to be at intermediate risk. Patients were eligible if they had unresectable, nonmetastatic disease. Patients with a complete resection at diagnosis and local pathologic evidence of small cell undifferentiated histology were also eligible for an assessment of feasibility. RESULTS: One hundred two evaluable patients enrolled between September 14, 2009, and March 12, 2012. Delivery of C5VD was feasible and tolerable: the mean percentages of the target doses delivered were 96% (95% CI, 94%-97%) for cisplatin, 96% (95% CI, 94%-97%) for 5-fluorouracil, 95% (95% CI, 93%-97%) for doxorubicin, and 90% (95% CI, 87%-93%) for vincristine. Toxicity was within expectations, with death as a first event in 1 patient. The most common adverse events were febrile neutropenia (n = 55 [54%]), infection (n = 48 [47%]), mucositis (n = 31 [30%]), hypokalemia (n = 39 [38%]), and elevated aspartate aminotransferase (n = 28 [27%]). The 5-year event-free and overall survival rates for the 93 patients who did not have complete resection at diagnosis were 88% (95% CI, 79%-93%) and 95% (95% CI, 87%-98%), respectively. CONCLUSIONS: The addition of doxorubicin to the previous standard regimen of C5V is feasible, tolerable, and efficacious, and this suggests that C5VD is a good regimen for future clinical trials.

Metastasis-directed Therapy Without Androgen Deprivation Therapy in Solitary Oligorecurrent Prostate Cancer.

PURPOSE: As controversy remains regarding the role of metastasis-directed therapy in patients with oligometastatic prostate cancer, we sought to characterize outcomes of metastasis-directed therapy without concomitant androgen deprivation therapy in the specific subset of patients with a solitary metastatic lesion on C-11 choline positron emission tomography imaging whose primary tumor has already been treated. MATERIALS AND METHODS: We identified 124 consecutive prostate cancer patients from 2008 to 2018 with a solitary oligorecurrent metastatic lesion on positron emission tomography imaging who were treated with metastasis-directed therapy without androgen deprivation therapy from the Mayo Clinic C-11 choline registry. Metastasis-directed therapy consisted of either stereotactic body radiation therapy or surgical excision. RESULTS: Of these 124 patients, 67 were treated with surgery (median follow-up 54 months) and 57 patients were treated with stereotactic body radiation therapy (median follow-up 53 months). Of patients treated with surgery, 80.5% had >50% decline in prostate specific antigen at first follow-up, and the 3-year radiographic progression-free survival was 29%. Median time to initiation of systemic therapy in this cohort was 18.5 months (interquartile range 8.4-44.7 months). Meanwhile, for patients treated with stereotactic body radiation therapy, 40.3% had >50% decline in prostate specific antigen at first follow-up, and the 3-year radiographic progression-free survival was 17%. Similarly, median time to initiation of systemic therapy was 17.8 months (interquartile range 7.1-42.3 months). CONCLUSIONS: This study represents the first reported series of metastasis-directed therapy without androgen deprivation therapy in patients with solitary oligorecurrent metastatic prostate cancer. These results suggest that metastasis-directed therapy without androgen deprivation therapy can delay initiation of systemic therapy and highlight the need for further prospective study for select patients with solitary metastatic recurrences of prostate cancer.

Out-of-Pocket Cost Burden Associated With Contemporary Management of Advanced Prostate Cancer Among Commercially Insured Patients.

PURPOSE: Out-of-pocket costs represent an important component of financial toxicity and may impact patients' receipt of care. Herein, we evaluated patient-level factors associated with out-of-pocket costs for contemporary advanced prostate cancer treatment options. MATERIALS AND METHODS: We identified all commercially insured men receiving treatment for advanced prostate cancer between 2007 and 2019 within the OptumLabs Data Warehouse®. Patients were categorized into 3 treatment groups: androgen deprivation monotherapy, novel hormonal therapy, and nonandrogen systemic therapy. The primary outcome was out-of-pocket costs in the first year of treatment. The associations of treatment and patient variables with out-of-pocket costs were assessed using multivariable regression models. All costs were adjusted to reflect 2019 U.S. dollars using the Consumer Price Index. RESULTS: In a cohort of 13,409 men 81% (n = 10,926) received androgen deprivation monotherapy, 6% (n = 832) novel hormonal therapy, and 12% (n = 1,651) nonandrogen systemic therapy. Mean treatment-related out-of-pocket costs in the first year were $165, $4,236, and $994 for androgen deprivation monotherapy, novel hormonal therapy, and nonandrogen systemic therapy, respectively. The adjusted difference in annual treatment-related out-of-pocket costs for novel hormonal therapy and nonandrogen systemic therapy were $2,581 (95% CI: $1,923-$3,240) and $752 (95% CI: $600-$903) higher than androgen deprivation monotherapy, respectively. Patient characteristics associated (P < .05) with higher treatment-related out-of-pocket costs included older age (65-74 years), Black race, lower comorbidity scores, and lower household income. CONCLUSIONS: Patients receiving novel hormonal therapy for advanced prostate cancer had substantially higher treatment-related out-of-pocket costs. In addition to raising awareness among prescribers, these data support the inclusion of treatment associated financial toxicity in shared decision making for advanced prostate cancer and call attention to subgroups of patients particularly vulnerable to financial toxicity.

Standing Intravenous Acetaminophen Is Associated With a Reduction of Post-operative Opioid Use in Infants Aged Less Than 1 Year Treated on the Acute Care Floor.

INTRODUCTION: Given the negative clinical effects opiates can have, the search for alternative forms of analgesia to treat post-operative pain continues. We implemented an opiate reduction strategy using standing intravenous (IV) acetaminophen for infants aged less than 1 y who underwent abdominal or anorectal surgery and recovered on the acute care floor. MATERIALS AND METHODS: Infants were administered standing IV acetaminophen every 6 h for a minimum of 48 h as the main form of post-operative analgesia. Pain severity was objectively scored using the Face, Legs, Activity, Cry, and Consolability (FLACC) scale. A before-and-after retrospective cohort analysis was performed and process control charts were used to examine trends in post-operative opiate use in our pre-intervention (January 2012 to January 2016), roll-out (January 2016 to December 2016), and post-intervention (December 2016 to December 2020) cohorts. RESULTS: A total of 131 infants were included: 56 in the pre-intervention, 17 in the roll-out, and 58 in the post-intervention group. Patient demographics were equivalent. The intervention was associated with a 36-fold reduction in post-operative morphine equivalents (median 0.36 mg/kg in the pre-intervention group versus 0.0 mg/kg in the post-intervention group, P < 0.0001). The median and maximum FLACC pain scores along with clinical safety profiles were statistically equivalent between the groups. The intervention was associated with a 2-d reduction in post-operative length of stay (P < 0.0001). CONCLUSIONS: Standing IV acetaminophen is associated with a reduction of post-operative opioid use in infants being treated on the acute care floor while maintaining equivalent FLACC pain scores. Similar opiate reduction strategies may be of value at other institutions.

Live Attenuated Varicella Vaccine: Prevention of Varicella and of Zoster.

Michiaki Takahashi developed the live attenuated varicella vaccine in 1974 . This was the first, and is still the only, herpesvirus vaccine. Early studies showed promise, but the vaccine was rigorously tested on immunosuppressed patients because of their high risk of fatal varicella; vaccination proved to be lifesaving. Subsequently, the vaccine was found to be safe and effective in healthy children. Eventually, varicella vaccine became a component of measles mumps rubella vaccine, 2 doses of which are administered in the USA to ~90% of children. The incidence of varicella has dropped dramatically in the USA since vaccine-licensure in 1995. Varicella vaccine is also associated with a decreased incidence of zoster and is protective for susceptible adults. Today, immunocompromised individuals are protected against varicella due to vaccine-induced herd immunity. Latent infection with varicella zoster virus occurs after vaccination; however, the vaccine strain is impaired for its ability to reactivate.

Maternal systemic vascular dysfunction in a primate model of defective uterine spiral artery remodeling.

Uterine spiral artery remodeling (UAR) is essential for placental perfusion and fetal development. A defect in UAR underpins placental ischemia disorders, e.g., preeclampsia, that result in maternal systemic vascular endothelial dysfunction and hypertension. We have established a model of impaired UAR by prematurely elevating maternal serum estradiol levels during the first trimester of baboon pregnancy. However, it is unknown whether this experimental paradigm is associated with maternal vascular endothelial dysfunction. Therefore, in the present study baboons were administered estradiol on days 25-59 of gestation to suppress UAR and maternal vascular function determined on day 165 (term = 184 days) peripherally and in skeletal muscle, which accounts for over 40% of body mass and 25% of resting systemic vascular resistance. Maternal serum sFlt-1 levels were 2.5-fold higher (P < 0.05), and skeletal muscle arteriolar endothelial nitric oxide synthase (eNOS) protein expression and luminal area, and skeletal muscle capillary density were 30-50% lower (P < 0.05) in UAR suppressed baboons. Coinciding with these changes in eNOS expression, luminal area, and capillary density, maternal brachial artery flow-mediated dilation and volume flow were 70% and 55% lower (P < 0.05), respectively, and mean arterial blood pressure 29% higher (P < 0.01) in UAR defective baboons. In summary, maternal vascular function was disrupted in a baboon model of impaired UAR. These results highlight the translational impact of this primate model and relevance to adverse conditions of human pregnancy underpinned by improper uterine artery transformation.NEW & NOTEWORTHY Maternal vascular dysfunction is a hallmark of abnormal human pregnancy, particularly early-onset preeclampsia, elicited by impaired UAR. The present study makes the novel discovery that maternal systemic vascular dysfunction was induced in a baboon experimental model of impaired UAR. This study highlights the translational relevance of this nonhuman primate model to adverse conditions of human pregnancy underpinned by defective UAR.

Ethical and professionalism issues in dermatopathology: A cross-sectional survey of American Society of Dermatopathology Members.

BACKGROUND: Data regarding ethical/professional issues affecting dermatopathologists are lacking despite their importance in establishing policy priorities and educational content for dermatopathology. METHODS: A 14-item cross-sectional survey about ethical/professional issues in dermatopathology was distributed over e-mail to members of the American Society of Dermatopathology from June to September 2019. RESULTS: Two hundred sixteen surveys were completed, with a response rate of 15.3%. Respondents ranked appropriate and fair utilization of healthcare resources (n = 83 or 38.6%) as the most often encountered ethical/professional issue. Conflict of interest was ranked as the most urgent or important ethical/professional issue (n = 83 or 39.3%). One hundred thirty-three (61.6%) respondents felt "somewhat" or "not at all" well equipped to handle ethical dilemmas in practice and 47 (22.8%) respondents identified a major or extreme burden (eg, have considered resigning/retiring) due to ethical challenges. CONCLUSIONS: Areas of priority in ethics and professionalism issues can guide future policy and educational content in dermatopathology.

Patterns of recommended vaccine receipt among women ages 24-45 years: a cross-sectional analysis.

BACKGROUND: Vaccine receipt among mid-adults remains low, with only one quarter of adults being up to date for all recommended vaccines. It is important to understand the myriad factors that influence vaccine receipt among mid-adult women to address these low rates. METHODS: We conducted a cross-sectional analysis of data from women ages 24-45 years collected as part of an ongoing case-control study of the effectiveness of HPV vaccine. We examined associations between demographic characteristics and healthcare utilization and receipt of individual vaccines and combinations of multiple vaccines using logistic regression analyses for three routinely recommended vaccines: tetanus, influenza and HPV. RESULTS: Among the 309 women enrolled in the study, only 19 (6.2%) were up to date for all three recommended vaccines and 41 (13.3%) had not received any of the recommended vaccines. A greater number of health care visits in the past year was associated with receipt of influenza (aOR = 6.37, 95% CI = 2.53, 16.1) and tetanus (aOR = 2.17, 95% CI = 1.14, 4.12) vaccines. White women were more likely to have received HPV vaccine (aOR = 2.39, 95% CI = 1.07, 5.36). CONCLUSIONS: Uptake of recommended vaccines is low among young and mid-adult women. There is a need for greater understanding of the underlying factors influencing vaccine receipt in this population.

Clinical regression of inguinal hernias in premature infants without surgical repair.

BACKGROUND: The incidence of inguinal hernias in premature infants is approximately 30%. Due to concerns about a high risk of incarceration, early repair is commonly performed. We present a series of patients whose families opted to delay repair until after 55 weeks corrected gestational age (GA) and experienced safe clinical regression of their hernias. METHODS: Between June 2015 and July 2020, premature infants (< 37 weeks GA) diagnosed with inguinal hernias on physical examination were identified. Families of eligible infants were offered either immediate or delayed repair after 55 weeks corrected GA. Infants whose families elected to delay were followed until their hernia(s) clinically regressed, or until older than 55 weeks. RESULTS: Families of 68 infants consented to delay repair. 23 infants (33.8%) had hernias that clinically regressed at median follow up from diagnosis of 14.1 weeks. Univariate analysis demonstrated female sex as a significant predictor of hernia clinical regression (OR: 3.08; p = 0.046). Of the 45 infants who underwent repair, 84.4% safely progressed to 55 weeks corrected GA prior to. CONCLUSION: Delaying inguinal hernia repair in this series of premature infants until after 55 weeks corrected GA revealed that one third of hernias, especially in females, safely regressed upon follow-up examination.