Assessing safe chemotherapy needs and practices in Ile-Ife, Nigeria: a multi-disciplinary quality improvement project.

OBJECTIVE: To explore the gaps in the safe handling, administration, preparation and disposal of chemotherapy agents in low and middle-income countries. DESIGN: Two surveys comprising a needs assessment survey and an American Cancer Society (ACS) ChemoSafe Facility Assessment. SETTING: 2019 African Research Group for Oncology Symposium in South-West Nigeria (needs assessment) and the 2021 virtual engagement (ChemoSafe Assessment). PARTICIPANTS: Health professionals (n=50 of 98) from multiple institutions across Nigeria (needs assessment survey) and a designated task force of health professionals (n=10) from one teaching hospital in Southwest Nigeria(ChemoSafe Facility Assessment). RESULTS: In 2019, 75% of survey respondents (n=50) reported a lack of training resources for safe handling of chemotherapy. Additionally, 61% felt dissatisfaction with assessment practices for preparing and administering chemotherapy. ChemoSafe is a programme developed by the ACS to assess the ability of a facility to handle hazardous drugs. The 2021 ACS ChemoSafe survey administered at one teaching hospital indicated several areas for improvement to promote concordance with international standards for safe handling. Thirty-three (19.5%) items received a 'Yes' response (ie, met compliance with international standards). CONCLUSION: There is a need for the implementation of training resources for handling, administering and disposing of chemotherapy at sites across Nigeria. Strategies to identify and prioritise areas of need must be implemented in the context of available resources.

Postoperative Casting of Below-Knee Amputation Reduces StumpComplications.

BACKGROUND: Against the technological advances in limb salvage, below-the-knee amputation (BKA) remains a common procedure. Although most elective BKA is classified as clean operation, the reported stump complication rate is much higher than predicted. Postoperative casting (PC) may reduce the number of these complications. The aim of this study was to compare the efficacy of elastic bandage with knee immobilizer (EBKI) and PC in BKA stump complications. METHODS: Retrospective cohort comparison design identified patients who underwent BKA between 2000 and 2023 for non-correctable critical limb ischemia (CLI), or excessive tissue loss secondary to CLI, infection, severe neuropathy, or the combination of these and stratified them into 2 cohorts based on their postoperative stump dressing: EBKI and PC. BKAs that were done for trauma or neoplastic processes were excluded. The primary outcome measures: wound healing in 6 weeks and length of stay (LOS). SECONDARY OUTCOME MEASURES: stump injury, infection, dehiscence, necrosis, number of higher-level amputations, knee contracture, and post-BKA mobility with Special Interest Group of Amputee Medicine score. RESULTS: One hundred sixteen patients with 122 limbs (52 EBKI and 70 PC) were found who met inclusion criteria and analyzed. The groups were comparable in demographics and comorbidities and preoperative variables, including mobility. The primary wound healing at 6 weeks was higher (P = 0.007); wound dehiscence (P = 0.01) and LOS (P = 0.006) was lower in the PC group compared to EBKI group. The PC group achieved higher Special Interest Group of Amputee Medicine mobility score and lower number of contractures developed compared to the EBKI group. CONCLUSIONS: Applying and maintaining PC to the BKA stump during the first month of healing reduced the incidence of stump complications, shortened the LOS, and improved postrehabilitation mobility results. We found no effect of PC on postoperative infections, stump necrosis, and higher-level amputations.

A closed surgical intensive care unit organization improves cardiac surgical patient outcomes.

Background: Intensive care unit (ICU) organization is a critical factor in optimizing patient outcomes. ICU organization can be divided into "OPEN" (O) and "CLOSED" (C) models, where the specialist or intensivist, respectively, assumes the role of primary physician. Recent studies support improved outcomes in closed ICUs, however, most of the available data is centered on ICUs generally or on subspecialty surgical patients in the setting of a subspecialized surgical intensive care unit (SICU). We examined the impact of closing a general SICU on patient outcomes following cardiac and ascending aortic surgery. Methods: A retrospective cohort of patients following cardiac or ascending aortic surgery by median sternotomy was examined at a single academic medical center one year prior and one year after implementation of a closed SICU model. Patients were divided into "OPEN" (O; n=53) and "CLOSED" (C; n=73) cohorts. Results: Cohorts were comparable in terms of age, race, and number of comorbid conditions. A significant difference in male gender (O: 60.4% vs. C: 76.7%, P=0.049), multiple procedure performed (O: 13.21% vs. C: 35.62%, P=0.019), and hospital readmission rates was detected (O: 39.6% vs. C: 9.6%, P=0.0003). Using a linear regression model, a closed model SICU organization decreased SICU length of stay (LOS). Using a multivariate logistic regression, being treated in a closed ICU decreased a patient's likelihood of having an ICU LOS greater than 48 hours. Conclusions: Our study identified a decreased ICU LOS and hospital readmission in cardiac and ascending aortic patients in a closed general SICU despite increased procedure complexity. Further study is needed to clarify the effects on surgical complications and hospital charges.

Methamphetamine spasm in the large caliber arteries-the severity is likely underestimated.

This report describes two cases of rarely reported, severe large arterial vascular spasms seen on computed tomography images after methamphetamine abuse. Although the effects of methamphetamine on the central nervous system and smaller arteries are relatively well known, its effects on large caliber arteries are rarely discussed. We present two cases of severe large arterial multisegmented vasospasm, captured on contrast-enhanced computed tomography, several hours after methamphetamine abuse. One of the patients was discharged without apparent tissue loss or organ failure. The other developed severe heart failure, liver failure, and toe gangrene. The publication of the de-identified images has been approved by the VA Central California Health Care System's Research and Development Committee and Privacy Officer. Vascular surgeons and, perhaps, acute care physicians, who are usually aware of small arterial vasospastic conditions, should also be aware of this methamphetamine-induced large arterial finding, which can be quite dramatic in appearance on imaging.

Trends in the Prevalence of Hepatitis C Infection During Pregnancy and Maternal-Infant Outcomes in the US, 1998 to 2018.

Importance: Injection drug use is the primary risk factor for hepatitis C virus (HCV) infection in adults. More than one-third of newly reported HCV cases occur in women, particularly among persons aged 20 to 39 years. However, nationally representative data on HCV during pregnancy are limited. Objective: To estimate the temporal trend of HCV-positive pregnancies during the opioid epidemic and identify HCV-associated maternal and perinatal outcomes. Design, Setting, and Participants: A cross-sectional study was performed with data from the US, from calendar year 1998 through 2018. Data analysis was conducted from November 14, 2021, to May 14, 2023. Participants included women during in-hospital childbirth or spontaneous abortion in the National Inpatient Sample of the Healthcare Cost and Utilization Project. Exposure: Maternal HCV infection. Main Outcomes and Measures: The main outcome was the temporal trend, measured as change in the annual prevalence, in the prevalence of HCV positivity among pregnant women since the start of the opioid epidemic in the late 1990s. Secondary outcomes were the associations shown as relative odds between maternal HCV infection and maternal and perinatal adverse events. Results: During the study period, more than 70 million hospital admissions resulted in childbirth or spontaneous abortion. Among them, 137 259 (0.20%; 95% CI, 0.19%-0.21%) involved mothers with HCV; these individuals were more often White (77.4%; 95% CI, 76.1%-78.6%), low-income (40.0%; 95% CI, 38.6%-41.5%), and likely to have histories of tobacco (41.7%; 95% CI, 40.6%-42.9%), alcohol (1.8%; 95% CI, 1.6%-2.0%), and opioid (28.9%; 95% CI, 27.3%-30.6%) use compared with HCV-negative mothers. The median age of women with HCV was 28.0 (IQR, 24.3-32.2) years, and the median age of HCV-negative women was 27.2 (IQR, 22.7-31.8) years. The prevalence of HCV-positive pregnancies increased 16-fold during the study period, reaching 5.3 (95% CI, 4.9-5.7) cases per 1000 pregnancies in 2018. Age-specific prevalence increases ranged from 3-fold (age, 41-50 years) to 31-fold (age, 21-30 years). Higher odds of cesarean delivery, preterm labor, poor fetal growth, or fetal distress were associated with HCV-positivity during pregnancy. However, no significant differences were observed in gestational diabetes, preeclampsia, eclampsia, or stillbirths. Conclusions and Relevance: In this cross-sectional study, the prevalence of HCV-positive pregnancies increased markedly, and maternal HCV infection was associated with increased risks for adverse perinatal outcomes. These data may support recent recommendations for universal HCV screening with each pregnancy.

Adherence to Extended Venous Thromboembolism Prophylaxis and Outcomes After Complex Gastrointestinal Oncologic Surgery.

BACKGROUND: Clinical guidelines recommend extended venous thromboembolism (VTE) prophylaxis for cancer patients after major gastrointestinal (GI) operations. However, adherence to the guidelines has been low, and the clinical outcomes not well defined. METHODS: This study retrospectively analyzed a random 10 % sample of the 2009-2022 IQVIA LifeLink PharMetrics Plus database, an administrative claims database representative of the commercially insured population of the United States. The study selected cancer patients undergoing major pancreas, liver, gastric, or esophageal surgery. The primary outcomes were 90-day post-discharge VTE and bleeding. RESULTS: The study identified 2296 unique eligible operations. During the index hospitalization, 52 patients (2.2 %) experienced VTE, 74 patients (3.2 %) had postoperative bleeding, and 140 patients (6.1 %) had a hospital stay of at least 28 days. The remaining 2069 operations comprised 833 pancreatectomies, 664 hepatectomies, 295 gastrectomies, and 277 esophagectomies. The median age of the patients was 49 years, and 44 % were female. Extended VTE prophylaxis prescriptions were filled for 176 patients (10.4 % for pancreas, 8.1 % for liver, 5.8 % for gastric cancer, and 6.5 % for esophageal cancer), and the most used agent was enoxaparin (96 % of the patients). After discharge, VTE occurred for 5.2 % and bleeding for 5.2 % of the patients. The findings showed no association of extended VTE prophylaxis with post-discharge VTE (odds ratio [OR], 1.54; 95 % confidence interval [CI], 0.81-2.96) or bleeding (OR, 0.72, 95 % CI, 0.32-1.61). CONCLUSIONS: The majority of the cancer patients undergoing complex GI surgery did not receive extended VTE prophylaxis according to the current guidelines, and their VTE rate was not higher than for the patients who received it.

Hanging under the ledge: synergistic consequences of UVA and UVB radiation on scyphozoan polyp reproduction and health.

Overexposure to ultraviolet radiation (UVR) emitted by the sun can damage and kill living cells in animals, plants, and microorganisms. In aquatic environments, UVR can penetrate nearly 47 m into the water column, severely impacting many marine organisms. Jellyfish are often considered resilient to environmental stressors, potentially explaining their success in environmentally disturbed areas, but the extent of their resilience to UVR is not well known. Here, we tested resiliency to UVR by exposing benthic polyps of the moon jellyfish, Aurelia sp., to UVA and UVB-the two types of UVR that reach Earth's surface-both separately and in combination. We quantified asexual reproduction rates and polyp attachment to hard substrate, in addition to qualitative observations of polyp health. There were no differences in asexual reproduction rates between polyps exposed to isolated UVA and polyps that received no UVR. Polyps reproduced when exposed to short term (∼7-9 days) isolated UVB, but long-term exposure limited reproduction and polyp attachment to the substrate. When exposed to both UVA and UVB, polyps were unable to feed and unable to remain attached to the substrate, did not reproduce, and ultimately, experienced 100% mortality within 20 days. Although many studies only examine the effects of UVB, the combination of UVA and UVB here resulted in greater negative impacts than either form of UVR in isolation. Therefore, studies that only examine effects of UVB potentially underestimate environmentally relevant effects of UVR. These results suggest that polyps are unsuccessful under UVR stress, so the planula larval stage must settle in low-UVR environments to establish the success of the polyp stage.

Clinical Utility of Reflex Testing with Cancer Biomarkers to Improve Diagnostic Accuracy of Primary Human Papillomavirus Screening.

BACKGROUND: Human papillomavirus (HPV) testing is the cornerstone of cervical cancer screening, with outstanding sensitivity but only moderate specificity. We evaluated whether reflex testing for cancer biomarkers improves the sensitivity/specificity balance of screening. METHODS: Cervical samples from women in Cape Town, South Africa, ages 30-65 years, were collected and tested with Xpert HPV and with real-time PCR to detect mRNA for cyclin-dependent kinase inhibitor 2A (CDKN2A), topoisomerase 2 alpha (TOP2A), and Ki67 (MKi67). Women with histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+; 85 women without and 166 with HIV) and women with no cervical disease (331 without and 257 with HIV) were included. RESULTS: When used as reflex tests after a positive HPV result, biomarkers discriminated well between women with and without CIN2+. The inclusion of both CDKN2A and MKi67 had the best performance, with area under the curve (AUC) of 0.9171 and 0.8734 in women without and with HIV, respectively. Although excellent, these performance parameters did not improve on an approach utilizing only HPV testing with more stringent cycle threshold cutoffs and HPV genotype selection, which achieved AUC of 0.9059 and 0.8705 in women without and with HIV, respectively. CONCLUSIONS: Biomarkers can be used as triage after positive HPV results but do not outperform an approach utilizing higher viral load cutoffs on selected high-risk genotypes. IMPACT: A screening approach using HPV testing alone can be more easily implemented at the point of care.

Impact of a Rheumatology Clinic Protocol on Tobacco Cessation Quit Line Referrals.

OBJECTIVE: Smoking increases cardiopulmonary and rheumatic disease risk, yet tobacco cessation intervention is rare in rheumatology clinics. This study aimed to implement a rheumatology staff-driven protocol, Quit Connect, to increase the rate of electronic referrals (e-referrals) to free, state-run tobacco quit lines. METHODS: We conducted a quasi-experimental cohort study of Quit Connect at 3 rheumatology clinics comparing tobacco quit line referrals from 4 baseline years to referrals during a 6-month intervention period. Nurses and medical assistants were trained to use 2 standardized electronic health record (EHR) prompts to check readiness to quit smoking within 30 days, advise cessation, and connect patients using tobacco quit line e-referral orders. Our objective was to use EHR data to examine the primary outcome of tobacco quit line referrals using pre/post design. RESULTS: Across 54,090 pre- and post-protocol rheumatology clinic visits, 4,601 were with current smokers. We compared outcomes between 4,078 eligible pre-implementation visits and 523 intervention period visits. Post-implementation, the odds of tobacco quit line referral were 26-fold higher compared to our pre-implementation rate (unadjusted odds ratio [OR] 26 [95% confidence interval (95% CI) 6-106]). Adjusted odds of checking readiness to quit in the next 30 days increased over 100-fold compared to pre-implementation (adjusted OR 132 [95% CI 99-177]). Intervention led to e-referrals for 71% of quit-ready patients in <90 seconds; 24% of referred patients reported a quit attempt. CONCLUSION: Implementing Quit Connect in rheumatology clinics was feasible and improved referrals to a state-run tobacco quit line. Given the importance of smoking cessation to reduce cardiopulmonary and rheumatic disease risk, future studies should investigate disseminating cessation protocols like Quit Connect that leverage tobacco quit lines.

Is image-guided core needle biopsy of borderline axillary lymph nodes in breast cancer patients clinically helpful?

BACKGROUND: When borderline axillary lymph nodes (bALN) are identified on ultrasound (US) for breast cancer (BC) patients, preoperative management is unclear. We aimed to evaluate if core needle biopsy (CNB) for bALN is clinically helpful or disruptive. METHODS: Retrospective review of BC patients with bALN from 2014 to 2019 was performed. Clinicopathologic data were compared for those who did and did not have CNB. RESULTS: CNB (n = 34) and no CNB (n = 31) were similar with respect to clinicopathologic factors. Surgical LN-positive rate was the same between cohorts (p = 0.26). CNB was disruptive in 58.8 %; all had CNB for pN0 disease. CNB was helpful in 34.2 %: 14.7 % proceeded directly to axillary dissection; 17.6 % had positive LN localized after neoadjuvant chemotherapy. CONCLUSIONS: CNB for bALN is more likely clinically disruptive and did not impact surgical LN positive rate. BC patients with bALN should undergo CNB only if it will change clinical management.

Hofbauer Cells Spread Listeria monocytogenes among Placental Cells and Undergo Pro-Inflammatory Reprogramming while Retaining Production of Tolerogenic Factors.

Pregnant women are highly susceptible to infection by the bacterial pathogen Listeria monocytogenes, leading to miscarriage, premature birth, and neonatal infection. L. monocytogenes is thought to breach the placental barrier by infecting trophoblasts at the maternal/fetal interface. However, the fate of L. monocytogenes within chorionic villi and how infection reaches the fetus are unsettled. Hofbauer cells (HBCs) are fetal placental macrophages and the only leukocytes residing in healthy chorionic villi, forming a last immune barrier protecting fetal blood from infection. Little is known about the HBCs' antimicrobial responses to pathogens. Here, we studied L. monocytogenes interaction with human primary HBCs. Remarkably, despite their M2 anti-inflammatory phenotype at basal state, HBCs phagocytose and kill non-pathogenic bacteria like Listeria innocua and display low susceptibility to infection by L. monocytogenes. However, L. monocytogenes can exploit HBCs to spread to surrounding placental cells. Transcriptomic analyses by RNA sequencing revealed that HBCs undergo pro-inflammatory reprogramming upon L. monocytogenes infection, similarly to macrophages stimulated by the potent M1-polarizing agents lipopolysaccharide (LPS)/interferon gamma (IFN-γ). Infected HBCs also express pro-inflammatory chemokines known to promote placental infiltration by maternal leukocytes. However, HBCs maintain the expression of a collection of tolerogenic genes and secretion of tolerogenic cytokines, consistent with their tissue homeostatic role in prevention of fetal rejection. In conclusion, we propose a previously unrecognized model in which HBCs promote the spreading of L. monocytogenes among placental cells and transition to a pro-inflammatory state likely to favor innate immune responses, while maintaining the expression of tolerogenic factors known to prevent maternal anti-fetal adaptive immunity. IMPORTANCE Infection of the placental/fetal unit by the facultative intracellular pathogen Listeria monocytogenes results in severe pregnancy complications. Hofbauer cells (HBCs) are fetal macrophages that play homeostatic anti-inflammatory functions in healthy placentas. HBCs are located in chorionic villi between the two cell barriers that protect fetal blood from infection: trophoblast cells at the maternal interface (in contact with maternal blood), and fetal endothelial cells at the fetal interface (in contact with fetal blood). As the only leukocytes residing in chorionic villi, HBCs form a critical immune barrier protecting the fetus from infection. Here, we show that although HBCs display low susceptibility to L. monocytogenes, the bacterium still replicates intracellularly and can spread to other placental and fetal cells. We propose that HBCs are permissive to L. monocytogenes transplacental propagation and can repolarize toward a pro-inflammatory phenotype upon infection. However, consistent with their placental homeostatic functions, repolarized HBCs maintain the expression of tolerogenic factors known to prevent maternal anti-fetal adaptive immunity, at least at early stages of infection.

Selecting human papillomavirus genotypes to optimize the performance of screening tests among South African women.

Human papillomavirus (HPV) testing is highly sensitive compared to cytology, with the trade-off of being less specific. We investigated whether select combinations of HPV genotypes, ascertained by Linear Array (LA) and Xpert HPV (GX), can optimize sensitivity/specificity trade-offs to detect high-grade cervical intraepithelial neoplasia (CIN2+). In a study in Cape Town, South Africa, 586 women living without and 535 living with HIV, aged 30-65 years, were recruited. Each woman underwent a pelvic exam to collect cervical samples (tested by LA and GX for 14 high-risk HPV genotypes) and underwent colposcopy with histological sampling to determine CIN2+. In multivariable logistic regression of LA results, only HPV genotypes 16, 18, 31, 33, 35, 52, 58 were significantly associated with CIN2+ (P < .05). Xpert includes these seven types along with HPV 45 within three of the test's five channels and we defined these eight types as restricted genotyping (ie 16, 18, 31, 33, 35, 45, 52, 58). Full genotyping was defined as all 14 high-risk types. Sensitivity estimates for full genotyping using LA were similar to that of restricted genotyping: 83.9% (full) vs 79.0% (restricted) in women without HIV and 93.0% (full) vs 88.9% (restricted) in women living with HIV. Specificity estimates improved for restricted vs full genotyping: 87.4% (full) vs 90.8% (restricted) in women without HIV and 63.7% (full) vs 71.4% (restricted) in women living with HIV. To optimize the performance of HPV testing for cervical cancer screening in high-burden, under-resourced settings like South Africa, only HPV 16, 18, 31, 33, 35, 45, 52, 58 could be included to define screen-positive. We recommend the inclusion of HPV45 for its known link to adenocarcinoma.

Pilot Study of Telehealth Evaluations in Patients Undergoing Hematopoietic Cell Transplantation.

Telehealth involves the use of telecommunication and information technology for the delivery of clinical care and may be a mechanism to alleviate the burden of visits faced by patients undergoing hematopoietic cell transplantation (HCT). Few studies have evaluated the feasibility and acceptability of telehealth visits in the care of HCT patients. We conducted 27 telehealth visits with 25 patients undergoing HCT using a videoconferencing system that allows for real-time, 2-way interactions and administered satisfaction surveys to patients and providers. Of the 25 patients included in the study, 20 (80%) and 5 (20%) were undergoing autologous and allogeneic HCT, respectively. The telehealth visits were distributed as follows: 3 inpatient visits upon admission for HCT; 11 inpatient visits between 2 and 14 days post-HCT; 4 inpatient visits prior to discharge after HCT; 8 outpatient, post-HCT follow-up visits; and 1 handoff to a community oncologist. Out of a total of 54 provider assessments, 7 providers (13%) were unable to complete some part of the physical examination, but no provider reported being unable to manage patients' symptoms through telehealth. Eighty-one percent of patients were either satisfied or very satisfied with the telemedicine session. Overall satisfaction was higher among patients than providers (mean scores 4.12 versus 2.64; scale 1 to 5, with 1 = very poor to 5 = excellent). Technological barriers resulting in delays and suboptimal physical examination were largely responsible for provider dissatisfaction. The use of telehealth to deliver comprehensive follow-up care to HCT patients is feasible across different HCT types but is dependent upon quality of data streaming and videoconferencing technologies.

Assessing Nurses' Adherence to the See-and-Treat Guidelines of Botswana's National Cervical Cancer Prevention Programme.

The see-and-treat approach for cervical cancer screening [visual inspection with acetic acid (VIA) followed by immediate cryotherapy] was first pilot tested in Botswana in 2009. Botswana's Ministry of Health and the Botswana-UPenn Partnership collaborated to expand see-and-treat to five additional sites throughout the country in 2014. The purpose of this study was to evaluate whether nurses' adherence to guideline-based screening was maintained during scale-up. Therefore, we compared nurses' adherence between the pilot and scaled-up sites and determined main drivers of nonadherence across all sites. We conducted a retrospective review of 6,644 medical charts from Botswana's National Cervical Cancer Prevention Programme between February 2014 and October 2015. Using multivariable regression modeled with generalized estimating equations, we determined whether nurses' adherence to the see-and-treat guideline differed between the pilot and scale-up sites after controlling for significant covariates. Overall, adherence to the guideline was high (88.4%). Although the scaled-up sites had higher adherence compared with the pilot site (90.9% vs. 80.2%, respectively), the difference between sites was not statistically significant in the multivariable model (P = 0.221). Of the nonadherent clinical encounters, the three most frequent visit types were VIA not performed (178, 23.3%), VIA negative: HIV unknown (163, 21.3%), and VIA negative: HIV negative (144, 18.9%). The most common reason for nonadherence was misspecification of follow-up times. Despite known challenges of scaling-up health innovations in resource-limited settings, our study shows that nurses maintained guideline-adherent care in Botswana's national see-and-treat program. The successful scale-up may have been attributable to the program's intensive quality assurance monitoring.

Preliminary assessment of aneuploidy rates between the polar, mid and mural trophectoderm.

The objective of this study is to compare aneuploidy rates between three distinct areas of the human trophectoderm: mural, polar and a region in between these two locations termed the 'mid' trophectoderm. This is a cohort study on in vitro fertilization (IVF) patients undergoing comprehensive chromosome screening at the blastocyst stage at a private IVF clinic. All embryos underwent assisted hatching on day 3 with blastocyst biopsy and comprehensive chromosome screening. Biopsied blastocysts were divided into three groups depending on which area (polar, mid, or mural) of the trophectoderm was protruding from the zona pellucida and biopsied. Aneuploidy rates were significantly higher with cells from the polar region of the trophectoderm (56.2%) compared with cells removed from the mural region of the trophectoderm (30.0%; P = 0.0243). A comparison of all three areas combined also showed a decreasing trend, but this did not reach clinical significance, polar (56.2%), mid (47.4%) and mural trophectoderm (30.0%; P = 0.1859). The non-concordance demonstrated between polar and mural trophectoderm can be attributed to biological occurrences including chromosomal mosaicism or procedural differences between embryologists.

Patient-specific parameter estimates of glioblastoma multiforme growth dynamics from a model with explicit birth and death rates.

Glioblastoma multiforme (GBM) is an aggressive primary brain cancer with a grim prog-nosis. Its morphology is heterogeneous, but prototypically consists of an inner, largely necrotic core surrounded by an outer, contrast-enhancing rim, and often extensive tumor-associated edema beyond. This structure is usually demonstrated by magnetic resonance imaging (MRI). To help relate the three highly idealized components of GBMs (i.e., necrotic core, enhancing rim, and maximum edema ex-tent) to the underlying growth "laws," a mathematical model of GBM growth with explicit motility, birth, and death processes is proposed. This model generates a traveling-wave solution that mimics tumor progression. We develop several novel methods to approximate key characteristics of the wave profile, which can be compared with MRI data. Several simplified forms of growth and death terms and their parameter identifiability are studied. We use several test cases of MRI data of GBM patients to yield personalized parameterizations of the model, and the biological and clinical implications are discussed.

Intratumoral delivery of an HPV vaccine elicits a broad anti-tumor immune response that translates into a potent anti-tumor effect in a preclinical murine HPV model.

Therapeutic cancer vaccines have met limited clinical success. In the setting of cancer, the immune system is either tolerized and/or has a limited tumor-specific T cell repertoire. In this study, we explore whether intratumoral (IT) vaccination with an HPV vaccine can elicit quantitative and qualitative differences in immune response as compared to intramuscular (IM) vaccination to overcome immune resistance in established tumors. We report that IT administration of an HPV-16 E7 peptide vaccine formulated with polyinosinic-polycytidylic acid [poly(I:C)] generated an enhanced antitumor effect relative to IM delivery. The elicited anti-tumor effect with IT vaccination was consistent among the vaccinated groups and across various C57BL/6 substrains. IT vaccination resulted in an increased frequency of PD-1hi TILs, which represented both vaccine-targeted and non-vaccine-targeted tumor-specific CD8+ T cells. Overall, the CD8+/Treg ratio was increased within the tumor microenvironment using IT vaccination. We also assessed transcriptional changes in several immune-related genes in the tumor microenvironment of the various treated groups, and our data suggest that IT vaccination leads to upregulation of a broad complement of immunomodulatory genes, including upregulation of interferon gamma (IFNγ) and antigen presentation and processing machine (APM) components. IT vaccine delivery is superior to traditional IM vaccination routes with the potential to improve tumor immunogenicity, which has potential clinical application in the setting of accessible lesions such as head and neck squamous cell carcinomas (HNSCCs).

Risk factors for sexual dysfunction in BRCA mutation carriers after risk-reducing salpingo-oophorectomy.

OBJECTIVE: The aim of the study was to identify risk factors for sexual dysfunction in BRCA mutation carriers who have undergone risk-reducing salpingo-oophorectomy (RRSO). METHODS: A cross-sectional study was performed. BRCA1/2 mutation carriers with and without RRSO were surveyed to determine sexual function (Female Sex Function Index [FSFI]), demographics, medical history, sleep quality, depression, and anxiety scores. Characteristics of patients with the lowest quartile of FSFI scores (<14 ±â€Š8.8) were analyzed to identify risk factors for the most severe phenotype. RESULTS: In the 804 women surveyed, 764 underwent RRSO. Of the 529 (69%) carriers with completed FSFI questionnaires in the RRSO cohort, sexual dysfunction was reported in 77.3%. Poor sleep (P = 0.002), hot flashes (P = 0.002), lack of current systemic hormone therapy (HT) use (P = 0.002), depression (P < 0.001), and anxiety (P = 0.001) were associated with sexual dysfunction. In adjusted analyses, depression (adjusted odds ratio [aOR] 2.4, 95% CI, 1.4-4.1) and hot flashes (aOR 1.9, 95% CI, 1.2-3.0) remained significantly associated with sexual dysfunction. Depression was also a significant risk factor for the most severe degree of sexual dysfunction (OR 2.1, 95% CI, 1.3-3.5) and had the greatest impact on Arousal and Satisfaction domain scores of the FSFI. Current systemic HT use seemed to decrease the risk for sexual dysfunction (aOR 0.6, 95% CI, 0.4-1.0). CONCLUSIONS: Sexual dysfunction is highly prevalent in BRCA mutation carriers after RRSO. Depression seems to be a significant risk factor for sexual dysfunction in this patient population and may be under-recognized and undertreated. Patient and provider education on sexual side effects after surgery and risk factors for sexual dysfunction is necessary to decrease postoperative sexual distress. HT may be associated with improved sexual function after surgery.

Association of Cadmium and Lead Exposure With the Incidence of Contrast Sensitivity Impairment Among Middle-aged Adults.

Importance: Contrast sensitivity (CS) is an important indicator of visual function that affects daily life, including mobility, visually intensive tasks, safety, and autonomy. Understanding the risk factors for CS impairment could prevent decreases in visual function. Objective: To determine the incidence of and factors associated with CS impairment in a large cohort. Design, Setting, and Participants: The Beaver Dam Offspring Study is an ongoing longitudinal cohort study of aging involving adults in Beaver Dam, Wisconsin. Participants who were free of CS impairment in both eyes at baseline were included (N = 1983). Baseline data collection occurred from June 8, 2005, through August 4, 2008, when the participants ranged from 21 to 84 years of age. Two follow-up examinations occurred at 5-year intervals: one was conducted between July 12, 2010, and March 21, 2013, and the other between July 1, 2015, and November 13, 2017. Data analysis was performed from November 27, 2017, to February 27, 2018. Main Outcomes and Measures: Contrast sensitivity testing was conducted with Pelli-Robson letter sensitivity charts, and incident impairment was defined as a log CS score less than 1.55 in either eye at any follow-up examination. Cadmium and lead levels were measured in whole blood with inductively coupled plasma mass spectrometry. Associations between baseline characteristics and CS impairment incidence were examined using Cox proportional hazard models and quantified as hazard ratios (HRs) with 95% CI. Results: Of the 1983 participants included, 1028 (51.8%) were female and 955 (48.2%) were male, with a mean (SD) age of 48 (9.3) years. The 10-year cumulative incidence of CS impairment was 24.8% (95% CI, 22.9-26.8), similar in women (24.9%) and men (24.6%), and highest in the oldest age group (65-84 years) at 66.3%. In multivariable models, cadmium level in the highest quintile (HR, 1.35; 95% CI, 1.02-1.78), older age (HR, 1.36; 95% CI, 1.25-1.47), larger waist circumference (HR, 1.06; 95% CI, 1.01-1.11), and more plaque sites (1-3 sites: HR, 1.43; 95% CI, 1.07-1.92; 4-6 sites: HR, 2.75; 95% CI, 1.26-6.05) were among the factors associated with increased risk, while male sex (HR, 0.77; 95% CI, 0.60-0.98) and any alcohol consumption (HR, 0.61; 95% CI, 0.43-0.88) were associated with decreased risk. Results were similar when smoking status replaced cadmium exposure in the models. Lead level was not associated with increased risk. Conclusions and Relevance: This study's findings suggest that incident CS impairment was common in the 10-year follow-up, with cadmium, but not lead, exposure associated with increased risk. The associations of diminished CS with other modifiable risk factors found appear to imply that changes in behavior may reduce future incidence of CS impairment.