Association of Socioeconomic Characteristics With Where Children Receive Emergency Care.

OBJECTIVE: Outcomes of emergency care delivered to children vary by patient-level socioeconomic factors and by emergency department (ED) characteristics, including pediatric volume. How these factors intersect in emergency care-seeking patterns among children is not well understood. The objective of this study was to characterize national associations of neighborhood income and insurance type of children with the characteristics of the EDs from which they receive care. METHODS: We conducted a cross-sectional study of ED visits by children from 2014 to 2017 using the Nationwide Emergency Department Sample. We determined the associations of neighborhood income and patient insurance type with the proportions of visits to EDs by pediatric volume category, both unadjusted and adjusted for patient-level factors including urban-rural status of residence. RESULTS: Of 107.6 million ED visits by children nationally from 2014 to 2017, children outside of the wealthiest neighborhood income quartile had lower proportions of visits to high-volume pediatric EDs (57.1% poorest quartile, 51.5% second, 56.6% third, 63.5% wealthiest) and greater proportions of visits to low-volume pediatric EDs (4.4% poorest, 6.4% second, 4.6% third, 2.3% wealthiest) than children in the wealthiest quartile. Adjustment for patient-level factors, particularly urban-rural status, inverted this association, revealing that lower neighborhood income was independently associated with visiting higher-volume pediatric EDs. Publicly insured children were modestly more likely to visit higher-volume pediatric EDs than privately insured and uninsured children in both unadjusted and adjusted analyses. CONCLUSIONS: Nationally, children in lower-income neighborhoods tended to receive care in pediatric EDs with lower volume, an association that appears principally driven by urban-rural differences in access to emergency care.

Neighborhood Conditions and Recurrent Emergency Department Utilization by Children in the United States.

OBJECTIVE: To determine the associations of social and physical neighborhood conditions with recurrent emergency department (ED) utilization by children in the US. STUDY DESIGN: This cross-sectional study was conducted with the National Survey of Children's Health from 2016 to 2018 to determine the associations of neighborhood characteristics of cohesion, safety, amenities, and detractors with the proportions of children aged 1-17 years with recurrent ED utilization, defined as 2 or more ED visits during the past 12 months. A multivariable regression model was used to determine the independent association of each neighborhood characteristic with recurrent ED utilization controlling for individual-level characteristics. RESULTS: In this study of 98 711 children weighted to a population of 70 million nationally, children had significantly greater rates of recurrent ED utilization if they lived in neighborhoods that were not cohesive, were not safe, or had detractors present (all P < .001). With adjustment for individual-level covariates and the other neighborhood characteristics, only neighborhood detractors were independently associated with recurrent ED utilization (1 detractor: aOR 1.32, 95% CI 1.03-1.68; 2 or 3 detractors: aOR 1.37, 95% CI 1.04-1.81). CONCLUSIONS: Among neighborhood characteristics, the presence of physical detractors such as rundown housing and vandalism was most strongly associated with recurrent ED utilization by children. Negative attributes of the built environment may be a potential target for neighborhood-level, place-based interventions to alleviate disparities in child healthcare utilization.

In vitro and in silico multidimensional modeling of oncolytic tumor virotherapy dynamics.

Tumor therapy with replication competent viruses is an exciting approach to cancer eradication where viruses are engineered to specifically infect, replicate, spread and kill tumor cells. The outcome of tumor virotherapy is complex due to the variable interactions between the cancer cell and virus populations as well as the immune response. Oncolytic viruses are highly efficient in killing tumor cells in vitro, especially in a 2D monolayer of tumor cells, their efficiency is significantly lower in a 3D environment, both in vitro and in vivo. This indicates that the spatial dimension may have a major influence on the dynamics of virus spread. We study the dynamic behavior of a spatially explicit computational model of tumor and virus interactions using a combination of in vitro 2D and 3D experimental studies to inform the models. We determine the number of nearest neighbor tumor cells in 2D (median = 6) and 3D tumor spheroids (median = 16) and how this influences virus spread and the outcome of therapy. The parameter range leading to tumor eradication is small and even harder to achieve in 3D. The lower efficiency in 3D exists despite the presence of many more adjacent cells in the 3D environment that results in a shorter time to reach equilibrium. The mean field mathematical models generally used to describe tumor virotherapy appear to provide an overoptimistic view of the outcomes of therapy. Three dimensional space provides a significant barrier to efficient and complete virus spread within tumors and needs to be explicitly taken into account for virus optimization to achieve the desired outcome of therapy.

Plasma CXCL9 elevations correlate with chronic GVHD diagnosis.

There are no validated biomarkers for chronic GVHD (cGVHD). We used a protein microarray and subsequent sequential enzyme-linked immunosorbent assay to compare 17 patients with treatment-refractory de novo-onset cGVHD and 18 time-matched control patients without acute or chronic GVHD to identify 5 candidate proteins that distinguished cGVHD from no cGVHD: CXCL9, IL2Rα, elafin, CD13, and BAFF. We then assessed the discriminatory value of each protein individually and in composite panels in a validation cohort (n = 109). CXCL9 was found to have the highest discriminatory value with an area under the receiver operating characteristic curve of 0.83 (95% confidence interval, 0.74-0.91). CXCL9 plasma concentrations above the median were associated with a higher frequency of cGVHD even after adjustment for other factors related to developing cGVHD including age, diagnosis, donor source, and degree of HLA matching (71% vs 20%; P < .001). A separate validation cohort from a different transplant center (n = 211) confirmed that CXCL9 plasma concentrations above the median were associated with more frequent newly diagnosed cGVHD after adjusting for the aforementioned factors (84% vs 60%; P = .001). Our results confirm that CXCL9 is elevated in patients with newly diagnosed cGVHD.

Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial.

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a barrier to more widespread application of allogeneic haemopoietic stem-cell transplantation. Vorinostat is an inhibitor of histone deacetylases and was shown to attenuate GVHD in preclinical models. We aimed to study the safety and activity of vorinostat, in combination with standard immunoprophylaxis, for prevention of GVHD in patients undergoing related-donor reduced-intensity conditioning haemopoietic stem-cell transplantation. METHODS: Between March 31, 2009, and Feb 8, 2013, we did a prospective, single-arm, phase 1/2 study at two centres in the USA. We recruited adults (aged ≥18 years) with high-risk haematological malignant diseases who were candidates for reduced-intensity conditioning haemopoietic stem-cell transplantation and had an available 8/8 or 7/8 HLA-matched related donor. All patients received a conditioning regimen of fludarabine (40 mg/m(2) daily for 4 days) and busulfan (3.2 mg/kg daily for 2 days) and GVHD immunoprophylaxis of mycophenolate mofetil (1 g three times a day, days 0-28) and tacrolimus (0.03 mg/kg a day, titrated to a goal level of 8-12 ng/mL, starting day -3 until day 180). Vorinostat (either 100 mg or 200 mg, twice a day) was initiated 10 days before haemopoietic stem-cell transplantation until day 100. The primary endpoint was the cumulative incidence of grade 2-4 acute GVHD by day 100. This trial is registered with ClinicalTrials.gov, number NCT00810602. FINDINGS: 50 patients were assessable for both toxic effects and response; eight additional patients were included in the analysis of toxic effects. All patients engrafted neutrophils and platelets at expected times after haemopoietic stem-cell transplantation. The cumulative incidence of grade 2-4 acute GVHD by day 100 was 22% (95% CI 13-36). The most common non-haematological adverse events included electrolyte disturbances (n=15), hyperglycaemia (11), infections (six), mucositis (four), and increased activity of liver enzymes (three). Non-symptomatic thrombocytopenia after engraftment was the most common haematological grade 3-4 adverse event (nine) but was transient and all cases resolved swiftly. INTERPRETATION: Administration of vorinostat in combination with standard GVHD prophylaxis after related-donor reduced-intensity conditioning haemopoietic stem-cell transplantation is safe and is associated with a lower than expected incidence of severe acute GVHD. Future studies are needed to assess the effect of vorinostat for prevention of GVHD in broader settings of haemopoietic stem-cell transplantation. FUNDING: Merck, Leukemia and Lymphoma Society, National Institutes of Health, St Baldrick's Foundation, Michigan Institute for Clinical and Health Research.

Participation in clinical research: perspectives of adult patients and parents of pediatric patients undergoing hematopoietic stem cell transplantation.

Despite major improvements over the past several decades, many patients undergoing hematopoietic stem cell transplantations (HSCT) continue to suffer from significant treatment-related morbidity and mortality. Clinical research studies (trials) have been integral to advancing the standard of care in HSCT. However, 1 of the biggest challenges with clinical trials is the low participation rate. Although barriers to participation in cancer clinical trials have been previously explored, studies specific to HSCT are lacking. The current study was undertaken to examine the knowledge, attitudes, and perceptions of HSCT patients regarding clinical trials. As members of focus groups, participants responded to open-ended questions that assessed factors influencing decision-making about HSCT clinical trials. Suggestions for improvements in the recruitment process were also solicited among participants. Seventeen adult HSCT patients and 6 parents of pediatric HSCT patients participated in the study. The median age was 56 years (range, 18 to 70) and 44 years (range, 28 to 54) for adult patients and parents, respectively. Participants universally indicated that too much information was provided within the informed consents and they were intimidated by the medical and legal language. Despite the large amount of information provided to them at the time of study enrollment, the participants had limited knowledge retention and recall of study details. Nevertheless, participants reported overall positive experiences with clinical trial participation and many would readily choose to participate again. A common concern among participants was the uncertainty of study outcome and general lack of feedback about results at the end of the study. Participants suggested that investigators provide more condensed and easier to understand informed consents and follow-up of study findings. These findings could be used to help guide the development of improved consent documents and enhanced participation in research studies, thereby affecting the future design of HSCT research protocols.

Engraftment syndrome after allogeneic hematopoietic cell transplantation predicts poor outcomes.

Engraftment syndrome (ES), characterized by fever, rash, pulmonary edema, weight gain, liver and renal dysfunction, and/or encephalopathy, occurs at the time of neutrophil recovery after hematopoietic cell transplantation (HCT). In this study, we evaluated the incidence, clinical features, risk factors, and outcomes of ES in children and adults undergoing first-time allogeneic HCT. Among 927 patients, 119 (13%) developed ES at a median of 10 days (interquartile range 9 to 12) after HCT. ES patients experienced significantly higher cumulative incidence of grade 2 to 4 acute GVHD at day 100 (75% versus 34%, P < .001) and higher nonrelapse mortality at 2 years (38% versus 19%, P < .001) compared with non-ES patients, resulting in lower overall survival at 2 years (38% versus 54%, P < .001). There was no significant difference in relapse at 2 years (26% versus 31%, P = .772). Suppression of tumorigenicity 2, interleukin 2 receptor alpha, and tumor necrosis factor receptor 1 plasma biomarker levels were significantly elevated in ES patients. Our results illustrate the clinical significance and prognostic impact of ES on allogeneic HCT outcomes. Despite early recognition of the syndrome and prompt institution of corticosteroid therapy, outcomes in ES patients were uniformly poor. This study suggests the need for a prospective approach of collecting clinical features combined with correlative laboratory analyses to better characterize ES.

Etanercept plus topical corticosteroids as initial therapy for grade one acute graft-versus-host disease after allogeneic hematopoietic cell transplantation.

Clinical diagnosis of grade 1 acute graft-versus-host disease (GVHD) marks the beginning of a potentially progressive and fatal course of GVHD after hematopoietic stem cell transplantation (HSCT). However, interventional studies to treat early GVHD are lacking. We conducted a single-arm prospective phase II trial to test the hypothesis that treatment of newly diagnosed grade 1 acute GVHD with etanercept and topical corticosteroids would reduce progression to grade 2 to 4 within 28 days. Study patients (n = 34) had a median age of 51 years (range, 10 to 67 years) and had undergone unrelated (n = 22) or related (n = 12) donor HSCT. Study patients were treated with etanercept (.4 mg/kg, maximum 25 mg/dose) twice weekly for 4 to 8 weeks. Ten of 34 patients (29%) progressed to grade 2 to 4 acute GVHD within 28 days. The cumulative incidence of grade 2 to 4 and grade 3 to 4 acute GVHD at 1 year was 41% and 3%, respectively. Nonrelapse mortality was 19% and overall survival was 63% at 2 years. Among a contemporaneous control cohort of patients who were diagnosed with grade 1 acute GVHD and treated with topical corticosteroids but not etanercept during the study period, 12 of 28 patients (43%) progressed to grade 2 to 4 GVHD within 28 days, with a 1-year incidence of grade 2 to 4 GVHD and grade 3 to 4 GVHD of 61% (41% versus 61%, P = .08) and 18% (3% versus 18%, P = .05), respectively. Patients treated with etanercept also experienced less increase in GVHD plasma biomarkers suppression of tumorigenicity 2 (P = .06) and regenerating islet-derived 3-alpha (P = .01) 28 days after grade 1 acute GVHD diagnosis compared with contemporaneous control patients. This study was terminated early because of poor accrual. Future prospective studies are needed to identify patients with grade 1 acute GVHD at risk of swift progression to more severe GVHD and to establish consensus for the treatment of grade 1 acute GVHD. This trial is registered with ClinicalTrials.gov, number NCT00726375.

Health-Related Social Risks Versus Needs in a Pediatric Emergency Department.

INTRODUCTION: Health-related social problems may be conceptualized as the presence of either a social risk (i.e., food insecurity as defined by a screening tool) or a social need (i.e., desire for referral to a food program). Identification of social risks may not correlate with patients' desire to receive help. This study aimed to identify and compare patients and families with social risks versus social needs in a pediatric emergency department. METHODS: This was a planned secondary analysis conducted in 2023 of a previously published prospective intervention study, which screened and referred caregivers and adult patients for health-related social problems in an urban tertiary pediatric emergency department between May 2019 and October 2020. Participants completed a screening tool for social risks and self-identified social needs by selecting desired assistance from a list of social service categories. Participants' social risk screening results were compared with their selection of resources for social needs across demographic and socioeconomic characteristics and the number of positive social risks using chi-squared or Fisher's exact tests. RESULTS: Of 258 participants, 42.2% (109) screened positive for any social risk, and 38.0% (98) self-selected a social need. Of those, only 59.2% (77/130) both screened positive and self-selected a need. Among those who screened positive for a social risk, several demographic and socioeconomic factors including race, ethnicity, and income were significantly different between those interested versus not interested in assistance. CONCLUSIONS: Both social risks and self-identified social needs should be considered within social care interventions in the pediatric healthcare setting.

Efficacy of genotypic resistance-guided sequential therapy in the third-line treatment of refractory Helicobacter pylori infection: a multicentre clinical trial.

OBJECTIVES: The efficacy of sequential therapy and the applicability of genotypic resistance to guide the selection of antibiotics in the third-line treatment of Helicobacter pylori have not been reported. We aimed to assess the efficacy of genotypic resistance-guided sequential therapy in third-line treatment. METHODS: Genotypic and phenotypic resistances were determined in patients who failed at least two eradication therapies by PCR with direct sequencing and agar dilution test, respectively. The patients were retreated with sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole plus clarithromycin, levofloxacin or tetracycline for another 7 days (all twice daily), according to genotypic resistance determined using gastric biopsy specimens. Eradication status was determined by the (13)C-urea breath test. Trial registered at clinicaltrials.gov (identifier: NCT01032655). RESULTS: The overall eradication rate was 80.7% (109/135, 95% CI 73.3%-86.5%) in the intention-to-treat analysis. The presence of amoxicillin resistance (OR 6.83, 95% CI 1.62-28.86, P = 0.009) and prior sequential therapy (OR 4.77, 95% CI 1.315-17.3, P = 0.017), but not tetracycline resistance (tetracycline group), were associated with treatment failure. The eradication rates in patients who received clarithromycin-, levofloxacin- and tetracycline-based sequential therapies were 78.9% (15/19), 92.2% (47/51) and 71.4% (25/35) in strains susceptible to clarithromycin, levofloxacin and tetracycline, respectively. CONCLUSIONS: A simple molecular method guiding sequential therapy can achieve a high eradication rate in the third-line treatment of refractory H. pylori infection.

Rapid reduction of central line infections in hospitalized pediatric oncology patients through simple quality improvement methods.

BACKGROUND: Pediatric hematology-oncology (PHO) patients are at significant risk for developing central line-associated bloodstream infections (CLA-BSIs) due to their prolonged dependence on such catheters. Effective strategies to eliminate these preventable infections are urgently needed. In this study, we investigated the implementation of bundled central line maintenance practices and their effect on hospital-acquired CLA-BSIs. MATERIALS AND METHODS: CLA-BSI rates were analyzed within a single-institution's PHO unit between January 2005 and June 2011. In May 2008, a multidisciplinary quality improvement team developed techniques to improve the PHO unit's safety culture and implemented the use of catheter maintenance practices tailored to PHO patients. Data analysis was performed using time-series methods to evaluate the pre- and post-intervention effect of the practice changes. RESULTS: The pre-intervention CLA-BSI incidence was 2.92 per 1,000-patient days (PD) and coagulase-negative Staphylococcus was the most prevalent pathogen (29%). In the post-intervention period, the CLA-BSI rate decreased substantially (45%) to 1.61 per 1,000-PD (P < 0.004). Early on, blood and marrow transplant (BMT) patients had a threefold higher CLA-BSI rate compared to non-BMT patients (P < 0.033). With additional infection control countermeasures added to the bundled practices, BMT patients experienced a larger CLA-BSI rate reduction such that BMT and non-BMT CLA-BSI rates were not significantly different post-intervention. CONCLUSIONS: By adopting and effectively implementing uniform maintenance catheter care practices, learning multidisciplinary teamwork, and promoting a culture of patient safety, the CLA-BSI incidence in our study population was significantly reduced and maintained.

Mobile Social Screening and Referral Intervention in a Pediatric Emergency Department.

OBJECTIVE: Many families in pediatric emergency departments (PED) have unmet social needs, which may be detected and addressed with the use of a digital social needs intervention. Our objective was to characterize the feasibility and effectiveness of utilizing personal phones or a PED tablet for screening and referral to social services. METHODS: We conducted a prospective single-arm intervention study using a convenience sample of caregivers and adult patients in an urban PED between May 2019 and October 2020. Participants chose either their personal phone or a PED-provided tablet to use an app, "HelpSteps." Participants self-selected need(s) then referrals to service agencies. Participants completed a 1-month follow-up. Clinicians were surveyed about screening and impact on visit. RESULTS: Of 266 participants enrolled, 55% of participants elected to use their personal phone. Of all participants, 67% self-selected at least 1 health-related social need; 34% selected 3 or more. The top 3 "most important" needs were housing (14%), education (12%), and fitness (12%). At one month follow-up, 44% of participants reported their top need was "completely" or "somewhat" solved. For 95% of encounters, clinicians reported the intervention did not increase length of stay. CONCLUSIONS: A mobile social needs intervention was feasible and effective at identifying and referring participants in the PED setting. While more than half of participants used their personal phones, several smartphone owners cited barriers and elected to use a tablet. Overall, participants found the app easy to use, appropriate for the PED, and the intervention had minimal impact on clinical flow.

Microglia-containing cerebral organoids derived from induced pluripotent stem cells for the study of neurological diseases.

Microglia play an important role in neuroinflammation and neurodegeneration. Here, we report an approach for generating microglia-containing cerebral organoids derived from human pluripotent stem cells involving the supplementation of growth factors (FGF, EGF, heparin) and 10% CO2 culture conditions. Using this platform, Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex (ALS-PDC) cerebral organoids were generated from patient-derived induced pluripotent stem cells (iPSCs). These ALS-PDC-affected organoids had more reactive astrocytes and M1 microglia, and had fewer M2 microglia than their unaffected counterparts, leading to impaired microglia-mediated phagocytosis. RNA-seq analysis of ALS-PDC and control organoids indicated that the most significant changes were microglia- and astrocyte-related genes (IFITM1/2, TGF-ß, and GFAP). The most significantly downregulated pathway was type I interferon signaling. Interferon-gamma supplementation increased IFITM expression, enhanced microglia-mediated phagocytosis, and reduced beta-amyloid accumulation in ALS-PDC-affected network. The results demonstrated the feasibility of using microglia-containing organoids for the study of neurodegenerative diseases.

Health-related quality of life in the phase III ASCENT trial of sacituzumab govitecan versus standard chemotherapy in metastatic triple-negative breast cancer.

BACKGROUND: The antibody-drug conjugate sacituzumab govitecan (SG) prolongs progression-free survival and overall survival in patients with refractory/relapsed metastatic triple-negative breast cancer (mTNBC). Here, we investigated its effect on health-related quality of life (HRQoL). METHODS: This analysis was based on the open-label phase III ASCENT trial (NCT02574455). Adults with refractory/relapsed mTNBC who had received ≥2 prior systemic therapies (≥1 in the metastatic setting) were randomised 1:1 to SG or treatment of physician's choice (TPC; capecitabine, eribulin, vinorelbine, or gemcitabine). HRQoL was assessed on day 1 of each treatment cycle using the EORTC QLQ-C30. Score changes from baseline were analysed using linear mixed-effect models for repeated measures. Stratified Cox regressions evaluated time to first clinically meaningful change of HRQoL. RESULTS: The analysis population comprised 236 patients randomised to SG and 183 to TPC. For global health status (GHS)/QoL, physical functioning, fatigue, and pain, changes from baseline were superior for SG versus TPC. Compared with TPC, SG was inferior regarding changes from baseline for nausea/vomiting and diarrhoea but non-inferior for other QLQ-C30 domains. Median time to first clinically meaningful worsening was longer for SG than for TPC for physical functioning (22.1 versus 12.1 weeks, P < 0.001), role functioning (11.4 versus 7.1 weeks, P < 0.001), fatigue (7.7 versus 6.0 weeks, P < 0.05), and pain (21.6 versus 9.9 weeks, P < 0.001). CONCLUSIONS: SG was generally associated with greater improvements and delayed worsening of HRQoL scores compared with TPC. This supports the favourable profile of SG as an mTNBC treatment.

The Incidence, Prevalence, and Associated Costs of Anemia, Malignancy, Venous Thromboembolism, Major Adverse Cardiovascular Events, and Infections in Rheumatoid Arthritis Patients by Treatment History in the United States.

OBJECTIVE: Comorbidities in rheumatoid arthritis (RA) can influence treatment selection, impact treatment persistency, and increase health care costs. This study assessed the magnitude of comorbidity burden via epidemiology (incidence and prevalence) and associated costs of select comorbidities in RA patients: anemia, malignancy, venous thromboembolism (VTE), major adverse cardiovascular events (MACE), and infections, stratified by history of disease-modifying antirheumatic drug (DMARD) exposure. METHODS: From the IQVIA PharMetrics® Plus database, we selected adult patients with RA (2 or more RA diagnostic codes at least 30 days apart) at initiation of a new DMARD (DMARD-naïve), after the first conventional synthetic DMARD (csDMARD) or after the first biologic DMARD (bDMARD). We assessed pre-index prevalence (percentage) and on-treatment incidence (per 100 patient-years [P100PY]) of the aforementioned comorbidities. For patients with versus without incident conditions, we compared total all-cause health care costs as unadjusted and adjusted for baseline characteristics and health care costs. RESULTS: Prior to initiating a new treatment, among DMARD-naïve patients (N = 28,201), csDMARD switchers (N = 7,816), or bDMARD switchers (N = 4,656), the overall prevalence ranged from 14.1% to 16.2% (anemia), from 1.3% to 5.2% (malignancy, evaluated in csDMARD and bDMARD switchers), from 1.5% to 2.1% (VTE), from 1.8% to 2.9% (MACE), and from 66.6% to 76.1% (infections). Once on index treatment, overall incidence (P100PY) among the cohorts ranged from 6.9 to 8.9 (anemia), from 2.0 to 2.3 (malignancy), from 0.7 to 0.9 (VTE), from 1.6 to 2.0 (MACE), and from 77.4 to 87.7 (infections). The incident comorbidities (except herpes zoster) were associated with increased adjusted health care costs. CONCLUSION: Anemia, malignancy, VTE, MACE, and infections affect patients with RA at all stages of their treatment journey and are associated with increased health care costs.

Cryotherapy-Enhanced Chemowrap Treatment of Squamous Cell Carcinoma: A Case Series.

An estimated 20% of all malignant cutaneous neoplasms are diagnosed as squamous cell carcinoma (SCC). Chemotherapeutic wraps, or chemowraps, consist of application of topical 5-fluorouracil (5-FU) 5% cream along with occlusive zinc oxide and a compressive bandage (e.g., Unna boot). This treatment modality is often used as a less invasive option compared to surgery, especially in the presence of numerous SCCs. Cryotherapy, the use of liquid nitrogen gas, can be utilized to obliterate pre-malignant and malignant skin lesions. In this report, we present four cases in which females between the ages of 65 and 80 with multiple lower extremity SCCs were treated with cryotherapy prior to each chemowrap application, resulting in favorable clinical tumor improvement. Our observations indicate that cryotherapy may enhance the effectiveness of chemowrap treatment when used before each application. To our knowledge, the use of cryotherapy to synergistically enhance the efficacy of chemowraps has not yet been reported. We hypothesize that cryotherapy induces edema and first strips the outer, hyperkeratotic layers of skin, which facilitates deeper penetration of the 5-FU cream from chemowraps. Chemowraps may also relieve the pain associated with cryotherapy. Therefore, dual cryotherapy and chemowrap treatment may be considered to maximize skin penetration, thus minimizing the extent of surgical intervention in patients with a significant number of SCC lesions.

COVID-19 Proned Ventilation and Its Possible Association With Foot Drop: A Case Series.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causing the coronavirus disease 2019 (COVID-19) pandemic is known to lead to the complicated sequelae of severe acute respiratory distress syndrome. Proning has been used as an adjunctive treatment to improve oxygenation in both ventilated and non-ventilated patients. Although patients respond well to this strategy, complications from this arise as well. It is hypothesized that COVID-19 intensive care unit (ICU) proned ventilation is associated with new cases of foot drops or compressive unilateral ankle dorsiflexion weakness during the early 2020 COVID-19 pandemic. Five patients presented to an acute rehabilitation facility with unilateral ankle dorsiflexion weakness after ICU proned ventilation during the COVID-19 pandemic. Three patients were found to have primarily subacute left sensory-motor dysmyelinating common peroneal neuropathies located around the fibular head. Two patients were found to have primarily subacute sensory-motor dysmyelinating right-sided common peroneal neuropathies above the fibular head and distal to biceps femoris muscle. Compressive unilateral common peroneal neuropathies during the pandemic are possibly related to the impromptu, unconventional, and unfamiliar use of proned ventilation.

Screening Discordance and Characteristics of Patients With Housing-Related Social Risks.

INTRODUCTION: Healthcare systems are increasingly interested in identifying patients' housing-related risks, but minimal information exists to inform screening question selection. The primary study aim is to evaluate discordance among 5 housing-related screening questions used in health care. METHODS: This was a cross-sectional multisite survey of social risks used in a convenience sample of adults seeking care for themselves or their child at 7 primary care clinics and 4 emergency departments across 9 states (2018-2019). Housing-related risks were measured using 2 questions from the Accountable Health Communities screening tool (current/anticipated housing instability, current housing quality problems) and 3 from the Children's HealthWatch recommended housing instability screening measures (prior 12-month: rent/mortgage strain, number of moves, current/recent homelessness). The 2-sided Fisher's exact tests analyzed housing-related risks and participant characteristics; logistic regression explored associations with reported health (2019-2020). RESULTS: Of 835 participants, 52% screened positive for ≥1 housing-related risk (n=430). Comparing the tools, 32.8% (n=274) screened discordant: 11.9% (n=99) screened positive by Children's HealthWatch questions but negative by Accountable Health Communities, and 21.0% (n=175) screened positive by the Accountable Health Communities tool but negative by Children's HealthWatch (p<0.001). Worse health was associated with screening positive for current/anticipated housing instability (AOR=0.56, 95% CI=0.32, 0.96) or current/recent homelessness (AOR=0.57, 95% CI=0.34, 0.96). CONCLUSIONS: The 5 housing questions captured different housing-related risks, contributed to different health consequences, and were relevant to different subpopulations. Before implementing housing-related screening initiatives, health systems should understand how specific measures surface distinct housing-related barriers. Measure selection should depend on program goals and intervention resources.

Bisphenol-A exposure induced neurotoxicity in glutamatergic neurons derived from human embryonic stem cells.

Bisphenol-A (BPA) is a lipophilic, organic, synthetic compound that has been used as an additive in polycarbonate plastics manufacturing since 1957. Studies have shown that BPA interferes with the development and functions of the brain, but little is known about the effects of BPA on human glutamatergic neurons (hGNs) at the molecular and cellular levels. We investigated the impact of chronic exposure to BPA to hGNs derived from human embryonic stem cells (hESCs). The results showed that chronic exposure of different concentrations of BPA (0, 0.1, 1.0 and 10 µM) to hGNs for 14 days reduced neurite outgrowth in a concentration-dependent manner. Using presynaptic protein synaptophysin and postsynaptic protein PSD-95 antibodies, immunofluorescence staining and western blotting results indicated that BPA exposure altered the morphology of dendritic spines and increased synaptophysin and PSD-95 expression. Furthermore, BPA exposure at concentrations higher than 1.0 µM resulted in the increase of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) expression and deterioration of dendritic spines. In addition, our results suggested that these BPA mediated neurotoxicity effects were due to an increased production of reactive nitrogen species (RNS) and reactive oxygen species (ROS) via increased nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), 3-nitrotyrosine expression and Ca2+ influx. These results imply that hESC-based neuronal differentiation is an excellent cellular model to examine BPA-induced neurotoxicity on human neurons at the cellular and molecular level.