Effectiveness of extracellular vesicles derived from hiPSCs in repairing hyperoxia-induced injury in a fetal murine lung explant model.

BACKGROUND: Despite advances in neonatal care, the incidence of Bronchopulmonary Dysplasia (BPD) remains high among preterm infants. Human induced pluripotent stem cells (hiPSCs) have shown promise in repairing injury in animal BPD models. Evidence suggests they exert their effects via paracrine mechanisms. We aim herein to assess the effectiveness of extracellular vesicles (EVs) derived from hiPSCs and their alveolar progenies (diPSCs) in attenuating hyperoxic injury in a preterm lung explant model. METHODS: Murine lung lobes were harvested on embryonic day 17.5 and maintained in air-liquid interface. Following exposure to 95% O2 for 24 h, media was supplemented with 5 × 106 particles/mL of EVs isolated from hiPSCs or diPSCs by size-exclusion chromatography. On day 3, explants were assessed using Hematoxylin-Eosin staining with mean linear intercept (MLI) measurements, immunohistochemistry, VEGFa and antioxidant gene expression. Statistical analysis was conducted using one-way ANOVA and Multiple Comparison Test. EV proteomic profiling was performed, and annotations focused on alveolarization and angiogenesis signaling pathways, as well as anti-inflammatory, anti-oxidant, and regenerative pathways. RESULTS: Exposure of fetal lung explants to hyperoxia induced airspace enlargement, increased MLI, upregulation of anti-oxidants Prdx5 and Nfe2l2 with decreased VEGFa expression. Treatment with hiPSC-EVs improved parenchymal histologic changes. No overt changes in vasculature structure were observed on immunohistochemistry in our in vitro model. However, VEGFa and anti-oxidant genes were upregulated with diPSC-EVs, suggesting a pro-angiogenic and cytoprotective potential. EV proteomic analysis provided new insights in regard to potential pathways influencing lung regeneration. CONCLUSION: This proof-of-concept in vitro study reveals a potential role for hiPSC- and diPSC-EVs in attenuating lung changes associated with prematurity and oxygen exposure. Our findings pave the way for a novel cell free approach to prevent and/or treat BPD, and ultimately reduce the global burden of the disease.

Plain language summary and patient perspective of the 2020 lung cancer screening recommendations by the US Preventive Services Task Force.

WHAT IS THIS SUMMARY ABOUT?: This summary describes the research carried out by the United States Preventive Services Task Force (USPSTF for short) during a review and update of their lung cancer screening recommendations made in 2013. The USPSTF reviewed the results of clinical studies that used a type of scan called low dose computed tomography (LDCT for short). They wanted to see how successful LDCT was at finding lung cancers in people ho hadn't shown any physical signs of lung cancer, but had a history of smoking and were over 50 years of age. WHAT WERE THE RESULTS?: The review found that performing yearly LDCT scans in people who are at high risk of developing lung cancer is beneficial, as it means that some patients will be diagnosed earlier than they would be without this type of screening. People considered to be at high risk of developing lung cancer include: Adults aged 50 to 80 years who have smoked a pack of 20 cigarettes per day for 20 years or two packs per day for 10 years; OR Adults aged 50 to 80 years who currently smoke or have stopped smoking within the last 15 years. WHAT DO THE RESULTS OF THE STUDY MEAN?: The information gained from reviewing the research enabled the USPSTF to update their lung cancer screening recommendations.

Plain language summary and patient perspective of the European Society for Medical Oncology expert consensus statements on treating EGFR-positive non-small-cell lung cancer.

WHAT IS THIS SUMMARY ABOUT?: This article provides a plain language summary and patient perspective of a new set of recommendations made by the European Society for Medical Oncology (ESMO for short). These recommendations are also called expert consensus statements. They cover the management of people with a type of lung cancer called epidermal growth factor receptor-positive non-small-cell lung cancer (EGFR-positive NSCLC for short). WHY WERE THE RECOMMENDATIONS DEVELOPED?: The ESMO Clinical Practice Guidelines are used by healthcare professionals when treating people with cancer, but they don't necessarily have all the information healthcare professionals need to make decisions for with people with EGFR-positive NSCLC. So, in 2021, 32 healthcare professionals who are experts in treating people with EGFR-positive NSCLC worked together to produce recommendations to fill these gaps about EGFR-positive NSCLC. This was called a consensus-building process and it also included patient advocates. WHAT RECOMMENDATIONS DID THEY MAKE?: The experts discussed four main topics including how people with different stages of EGFR-positive NSCLC are diagnosed and treated, and how clinical studies are done. They reviewed the scientific information that exists on these subjects. They reached an agreement and developed the recommendations that are summarized here.

Plain language summary and patient perspective of the American Society for Clinical Oncology guideline: management of stage 3 non-small-cell lung cancer.

WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of a guideline on the management of stage 3 non-small-cell lung cancer, also known as NSCLC. This guideline was written by the American Society for Clinical Oncology (ASCO for short) and published in the Journal of Clinical Oncology. WHY WERE THE GUIDELINES DEVELOPED?: The purpose of the ASCO guideline is to provide recommendations to healthcare professionals in the US including oncologists, surgeons, pathologists, radiologists, and nurses on how best to diagnose and treat people with stage 3 NSCLC. HOW WERE THE GUILDEINES DEVELOPED?: The ASCO guideline is based on the latest research and scientific evidence to make certain the recommendations are up to date and based on reliable data and best practice. In 2021, a group of experts were asked by ASCO to form an Expert Panel. The Expert Panel reviewed the results of 127 clinical research studies on NSCLC that were done between 1990 and 2021. They looked at how NSCLC had been diagnosed and treated in these studies, as well as at patients' survival and quality of life. The Expert Panel used these findings and their own expertise to form their recommendations and produce the 2021 ASCO Guideline called 'Management of Stage 3 Non-Small-Cell Lung Cancer: ASCO Guideline'. WHAT INFORMATION DOES THE GUIDELINE CONTAIN?: The guideline aims to answer the following questions: What are the most precise ways to confirm and stage NSCLC in people suspected of having a stage 3 disease? Which patients with stage 3 NSCLC can be treated most successfully with surgery? Which patients who can be treated with surgery could also have an additional therapy before their surgery? Which patients who can be treated with surgery could also have an additional treatment after their surgery? Which treatment and/or management is most suitable for patients who cannot have surgery?

2022 cancer statistics: Focus on lung cancer.

WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of a medical journal article called 'Cancer statistics, 2022'. The data in this summary provides detailed information about lung cancer and less detailed information about other cancers. The researchers from the original study used data gathered from previous years to produce a cancer forecast, predicting the number of new cancer diagnoses and deaths in the United States in 2022. WHAT WERE THE RESULTS?: The review of the data up to 2019 found that compared to previous years: Advanced lung cancer diagnoses had decreased Local stage lung cancer diagnoses had increased Deaths had slowed for lung cancer Deaths continued to reduce for breast cancer, but the rate of this reduction had slowed down Female breast cancer diagnoses were slowly increasing each year Prostate cancer diagnoses stayed similar Local stage prostate cancer diagnoses stayed similar Advanced prostate cancer diagnoses had increased each year The researchers estimated that over 1.9 million new cancer cases would be diagnosed and over half a million cancer deaths would occur in the United States in 2022. This figure includes approximately 350 deaths per day from lung cancer, which was found to be the leading cause of cancer death in the United States. WHAT DO THE RESULTS OF THE STUDY MEAN?: The study found that progress in reducing the number of people being diagnosed with breast and prostate cancer has stalled. Although there were fewer lung cancers diagnosed, this reduction was likely caused by changes in screening and advancements in lung cancer treatments. The American Cancer Society recommended that investing more funds in detecting cancers early as well as developing targeted treatments would help to reduce cancer death rates. This would also help to address the differences in access to cancer care that exist based on racial, social and economic inequalities.

Plain language summary and patient perspective of the revised STARS study: long-term results of a study that compared the effectiveness of radiotherapy to surgery in people with non-small-cell lung cancer.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a research study called revised STARS. The STARS study involved people with non-small-cell lung cancer, also known as NSCLC. The cancer was less than 5 cm in size and had not spread to other parts of the body (known as stage 1 cancer). The study compared the effectiveness of surgery versus a type of radiotherapy treatment, called stereotactic ablative radiotherapy (also known as SABR) as a treatment for people with NSCLC. Researchers wanted to find out how likely people were to be alive after treatment or if their cancer had grown or spread to other parts of their body (also known as progressed). WHAT WERE THE RESULTS?: The study found that the long term outcomes were similar between SABR and surgery. People with NSCLC were as likely to be alive 3 years after treatment with SABR compared to surgery. WHAT DO THE RESULTS OF THE STUDY MEAN?: SABR may be an alternative to surgery for people with stage 1 NSCLC which is less than 5 cm in size and has not spread to other parts of the body Clinical Trial Registration: NCT02357992 (ClinicalTrials.gov).

Obesity and Adipose Tissue Dysfunction: From Pediatrics to Adults.

Obesity is a growing health problem that affects both children and adults. The increasing prevalence of childhood obesity is associated with comorbidities such as cardiovascular disease, type 2 diabetes and metabolic syndrome due to chronic low-grade inflammation present at early stages of the disease. In pediatric patients suffering from obesity, the role of epigenetics, the gut microbiome and intrauterine environment have emerged as causative factors Interestingly, pediatric obesity is strongly associated with low birth weight. Accelerated weight gain oftentimes occurs in these individuals during the post-natal period, which can lead to increased risk of adiposity and metabolic disease. The pathophysiology of obesity is complex and involves biological and physiological factors compounded by societal factors such as family and community. On a cellular level, adipocytes contained within adipose tissue become dysregulated and further contribute to development of comorbidities similar to those present in adults with obesity. This review provides an overview of the current understanding of adipose tissue immune, inflammatory and metabolic adaptation of the adipose tissue in obesity. Early cellular changes as well as the role of immune cells and inflammation on the progression of disease in pivotal pediatric clinical trials, adult studies and mouse models are emphasized. Understanding the initial molecular and cellular changes that occur during obesity can facilitate new and improved treatments aimed at early intervention and subsequent prevention of adulthood comorbidities.

Hidden in plain sight? Identifying patient-authored publications.

BACKGROUND: Patient advocates are increasingly authoring peer-reviewed publications that could enhance patient care and understanding of the lived experience. Although patient authorship may be seen as an innovation in the peer-reviewed publication environment and some may not be aware of or accept patient authorship, we know patient-authored publications exist. However, identifying patient-authored publications is often challenging and time-consuming. MAIN BODY: In this commentary, we propose a definition for a patient author and patient-authored publications. We outline factors driving the increase in patient authorship, including patient interest, recognition of the value of including the patient voice and major funders recognising the importance of involving patient advocates in research. Evidence and experience-based guidance on patient authorship is emerging, and we highlight practical guidance for patient advocates on authoring peer-reviewed publications. To gain a better understanding of patient authorship, an efficient method is needed to identify patient-authored publications. A dataset on patient-authored publications could be used for a range of quantitative and qualitative research studies. The affiliation search function in PubMed can provide an easy, and reproducible way to identify a dataset of patient-authored publications in the international peer-reviewed literature, but only if patient authors include a standard metatag, (e.g. Patient Author) as one of their listed affiliations, combined with other affiliations as appropriate. From 2020 to 2021, there was a nine-fold increase in patient-authored publications in PubMed identified using the Patient Author tag. We recognize that terminology can be contentious and some authors may prefer alternative metatags. Further efforts are required to gain consensus on a suitable, standard metatag or set of metatags to use to show the true extent of patient authorship. CONCLUSION: Patient authorship is not only legitimate, but it also exemplifies the principles of diversity, equity and inclusion. Stakeholders in the publication community need to review their policies and procedures to identify and address barriers to patient authorship. Patient advocates, funders, researchers and publishers could all help to promote awareness and acceptance of patient authorship and the merits of using a standard metatag or set of metatags, so that patient-authored publications are no longer hidden in plain sight.

Some patients are leading or helping with medical research to improve understanding of their condition and patient care. To share research findings, patients can author articles published in scientific journals. These articles are reviewed by experts and are known as peer-reviewed publications. Patient authors can provide unique and valuable insights from their experience of living with a condition. Demonstrating that patients can be authors would be easier if there was a quick way to find patient-authored publications. In this article, we describe who a patient author is and what patient-authored publications are. We identify factors that may encourage patients to author research publications. We highlight the practical guidance available to help patient authors and those working with them. To help future research about patient authorship, we need a way to find patient-authored publications. One way is for patients to include a standard search term, such as 'Patient Author' in the affiliation section of their publication. Like all authors, patient authors can list more than one affiliation, such as their workplace if they wish. We used the 'Patient Author' search term to look at publications in PubMed, a free resource to access scientific publications. We found the number of patient-authored publications using the 'Patient Author' tag increased nine times from 2020 and 2021. We encourage patients, funders, researchers and publishers to use a standard metatag or an agreed set of metatags. This could make it easier to find and raise awareness of patient-authored publications.

Fentanyl, Heroin, and Cocaine Overdose Fatalities are Shifting to the Black Community: An Analysis of the State of Connecticut.

BACKGROUND: Historically, Blacks and Hispanics have had lower opioid-involved overdose death rates in Connecticut (CT). We examined if a shift has taken place where rates of Black fatal overdoses have now surpassed Whites in the state. METHODS: Drug overdose fatality rates were calculated by number of deaths per year per 100,000 population from 2012 to 2019 in Connecticut. Measures were by race (White, Hispanic, Black, and Asian or Pacific Islander), age groups, and types of drugs, including fentanyl, heroin, cocaine, and other opioids. Poisson regression was used to test the interactions (race × age); joinpoint regression analysis was used to evaluate trend lines of fatality rate by racial/ethnic group within each age group with a significance level of p < 0.05. RESULTS: Drug overdose fatality rates in CT from 2012 to 2019 showed a significant increase for all races combined, estimated 3.6 deaths per 100,000 population per year. For Whites, overdose deaths were 4.6 per year from 2012 to 2017 with no change from 2017 to 2019. The overdose fatality rate for Hispanics was 3.0 and for Asian or Pacific Islanders 0.6 per year from 2012 to 2019. For Blacks, the death rates were statistically flat between 2012 and 2014; however, from 2015 to 2019, this group saw the largest average increase of 6.0 overdose deaths per 100,000 population each year. By 2019, the overdose fatality rate was higher in Blacks than in Whites, (39 vs. 38 per 100,000, respectively). Further, Blacks ages 50 years and over reported the highest overdose fatality rates among all race/age groups, an increase of 8.5 deaths per 100,000 population since 2014. CONCLUSIONS AND RELEVANCE: Connecticut is a microcosm of the opioid overdose trend in the New England region of our country. The majority of overdose deaths in CT involved illicit drugs, fentanyl, heroin, and cocaine, rather than prescription drugs. Blacks 50-years-old and over showed the fastest growing overdose death rates. Opioid deaths are now shifting to the Black community, creating an urgent public health crisis.

Changes in COVID-19-Associated Deaths During a Year Among Blacks and Hispanics Compared to Whites in the State of Connecticut.

BACKGROUND: With recent COVID-19 vaccination rates relatively high in the USA, the USA still maintains the most documented cases globally,[1] even though COVID-19 cases, hospitalization, and mortality have been declining. However, the health burden has been largely felt in communities involving racial and ethnic minorities. Thus, in order to provide a clearer picture of what is happening in Black, Indigenous, and people of color communities, we examined the racial/ethnic differences of monthly COVID-19 deaths in Connecticut. METHODS: This is an epidemiological study analyzing mortality data from March 1, 2020, to February 28, 2021, obtained from the Connecticut State Department of Public Health. The data include cause of death (COVID-19 death identified by ICD-10 code U071), race/ethnicity (non-Hispanic White (White), non-Hispanic Black (Black), and Hispanic), sex, and age. Both crude and age-adjusted rates were reported by racial/ethnic groups. To compare age-adjusted rates between racial groups, with estimated age-adjusted death counts as outcomes, between-racial group rate ratios, 95% confidence intervals, and p values significant at < 0.05 were derived from the Poisson regression model. RESULTS: From March 2020 to May 2020 (wave 1) of COVID-19 cases, the COVID-19-related mortality rates were the highest for all three race groups (Whites, Blacks, and Hispanics) with statistical group differences (p < 0.05). Blacks had the highest rates of deaths followed by Hispanics and then Whites. Further, more Whites died in a nursing home when compared to Blacks and Hispanics. From June 2010 to October 2020 (wave 2), COVID-19 mortality declined significantly for all three race groups with no statistical differences between groups. COVID-19 deaths in nursing homes declined for all three racial/ethnic groups. From November 2020 to February 2021 (wave 3), COVID-19 mortality rates were significantly higher compared to wave 2 but lower than wave 1 for all three race groups. The mortality rates for Blacks and Hispanics were higher than Whites. Hispanics had the highest rates of deaths, followed by Blacks, and then Whites (p < 0.05). Whites showed the lowest mortality rates among all three racial/ethnic groups. CONCLUSIONS: In summary, COVID-19 health disparities among Black and Hispanic populations were evident in this study. Blacks and Hispanics had significantly higher mortality rates when compared to Whites. Blacks had the highest mortality rates during wave 1, and in wave 3, Hispanics has the highest mortality rates. Our data are important because they show monthly COVID-19 deaths data by race. Data reported this way gives a better and more accurate understanding of what is really happening in Black, Indigenous, and people of color populations.

Excess Deaths Among Blacks and Latinx Compared to Whites During Covid-19.

IMPORTANCE: Blacks and Latinx are disproportionately affected by Coronavirus disease 2019 (Covid-19) and experience higher mortality rates than Whites and Asians in the USA. Such racial disparities, in Covid-19 testing, cases, and mortality are visible in Connecticut too. Recently, excess deaths have become an important consideration in news reports and academic research. However, data on racial differences in excess death is limited. OBJECTIVE: This study examines racial/ethnic differences in excess deaths in the state of Connecticut during the Covid-19 pandemic. DESIGN: This is a cross-sectional epidemiological study to estimate excess deaths by racial/ethnic status utilizing mortality data during the peak months of Covid-19 infections from March 1 to June 30, 2020, in Connecticut. The following assumption is applied: expected non-Covid-19 deaths from March 1 to June 30, 2020, are equal to the number of deaths occurring during the period of March 1 to June 30, 2019. Race/ethnicity are defined as Non-Hispanic White, Non-Hispanic Black, and Latinx. Descriptive statistics and rates with 95% confidence intervals are presented. Chi-square analyses are performed where applicable. SETTING: Connecticut PARTICIPANTS: All deaths in Connecticut from March 1 to June 30, 2020. EXPOSURE: Covid-19 and race/ethnicity RESULTS: From March 1 to June 30, 2020, a total of 14,226 all-cause deaths occurred including 1514 Blacks (10.6%), 1095 Latinx (7.7%), and 11,617 Whites (81.7%). This represented a 74% increase in mortality for Blacks; 63% for Latinx, and 30% for Whites. In addition, 42.70% of the deaths in Blacks were attributed to Covid-19; 38.5% for Latinx, and 23.0% for Whites (p<0.001). Covid-19 deaths accounted for over 90% of the excess deaths in Blacks and Hispanics. In contrast, in Whites, Covid-19 deaths exceeded the number of excess deaths by 353 cases (113.2%), indicating that some Whites may have died from other underlined health conditions with a positive Covid-19 diagnosis. Furthermore, there was an increase in undetermined deaths in 2020, which accounted for 10.8% of deaths in Blacks, 13% in Latinx, and 6.2% of deaths in Whites. CONCLUSIONS AND RELEVANCE: Excess deaths in Blacks and Latinx were found above the numbers of deaths determined to have occurred due to Covid-19. The fact that a large number of undetermined deaths were found for Blacks and Latinx individuals, and testing rates for Blacks and Latinx individuals (as determined by positivity rates) were lacking during this period strongly suggests, these excess deaths were Covid-19-related deaths. The study findings indicate that Black and Latinx COVID-19-related deaths may be underreported in this pandemic. We advocate for targeted strategies that increase testing capacity, treatment, and vaccine availability in Black and Latinx communities.

An Unanticipated Role for Sphingosine Kinase-2 in Bone and in the Anabolic Effect of Parathyroid Hormone.

Sphingosine-1-phosphate (S1P) is an anabolic clastokine. Sphingosine kinase (SPHK) is the rate-limiting enzyme in S1P production and has 2 isoforms. To evaluate the roles of SPHK1 and SPHK2 in bone, we examined the skeletal phenotype of mice with selective deletion of SPHK1 in osteoclasts (SPHK1-Oc-/-) and mice in which the SPHK2 gene was deleted in all tissues (SPHK2-/-). SPHK1-Oc-/- had normal bone mass. By contrast, SPHK2-/- female mice had a 14% lower spinal bone mineral density (BMD; P < 0.01) and males a 22% lower BMD at the same site (P < 0.001). SPHK2-/- and control mice were subsequently treated either with daily parathyroid hormone [PTH](1-34) or vehicle for 29 days. The response to PTH was significantly attenuated in the SPHK2-/-mice. The mean femoral bone volume to total volume fraction (BV/TV) increased by 24.8% in the PTH-treated female control animals vs 10.6% in the vehicle-treated female controls (P < 0.01). In contrast, in the SPHK2-/- female mice the difference in femoral trabecular BV/TV at the end of treatment was not significant (20.5 vs13.3%, PTH vs vehicle, P = NS). The anabolic response to PTH was significantly attenuated in the spine of male SPHK2-/- mice (29.7% vs 23.1%, PTH vs vehicle, in controls, P < 0.05; 26.9% vs 19.5% PTH vs vehicle in SPHK2-/- mice, P = NS). The spine responded normally in the SPHK2-/- female mice. Interestingly, suppression of sclerostin was blunted in the SPHK2-/- mice when those animals were treated with an anabolic PTH regimen. We conclude that SPHK2 has an important role in mediating both normal bone remodeling and the anabolic response to PTH.

A Pandemic on a Pandemic: Racism and COVID-19 in Blacks.

Racism and COVID-19 represent a pandemic on a pandemic for Blacks. The pandemics find themselves synergized to the detriment of Blacks and their health. The complexity of the combination of these pandemics are evident when examining the interplay between racist policing practices and health.

Racial Profiling Is a Public Health and Health Disparities Issue.

Racial profiling is a public health and health disparities issue through its disparate and adverse health impact on those targeted by this practice, as well as members of their communities. We discuss six ways police profiling and racial discrimination adversely impact Black American health. We identify four direct and two indirect ways. Four direct ways are (1) violent confrontation with police that causes injury or death; (2) police language that escalates a confrontation through micro-aggressions or macro-aggressions; (3) sub-lethal confrontations with police; (4) adverse health consequences of perceived or vicarious threat, i.e., the mere belief in potential harm by police injures health. There are two indirect ways: (5) through knowledge of or personal relationship with someone who directly experienced racial profiling; (6) through public events without a personal knowledge of the unarmed person threatened or killed by police as a result of racial profiling, but where such events cause both individuals and the community at large to perceive a threat. We support recognition of racial profiling as a public health and health disparities issue. We recommend support for community programs that address the clinical health effects of racial profiling. We also recommend widespread engagement of trauma-informed policing (TIP) that acknowledges the clinical effects of racial profiling.

Identification of a 22 bp DNA cis Element that Plays a Critical Role in Colony Stimulating Factor 1-Dependent Transcriptional Activation of the SPHK1 Gene.

Sphingosine-1-phosphate (S1P) is an anabolic clastokine. Colony Stimulating Factor 1 (CSF1) induces expression of the rate limiting enzyme required for S1P synthesis, sphingosine kinase 1 (SPHK1) in bone in vivo, and in osteoclasts in vitro. To study the mechanism of CSF1-induced SPHK1 gene expression, a 2608 bp fragment of the murine SPHK1 gene (- 2497 to + 111 bp relative to the transcription start site) was cloned and transfected into pZen cells (murine fibroblasts engineered to express c-fms). SPHK1 promoter activity was assessed using a dual-luciferase reporter assay system. By analyzing a series of 5'-deletions, a CSF1-responsive region was identified in the region - 1250 to - 1016 bp. To define putative DNA binding site(s) in this fragment, two biotin-labeled fragments that completely overlapped this region were generated, one 163 bp in length (- 1301 to - 1139) and one 169 bp in length (- 1157 to - 989). EMSAs revealed the 163 bp fragment as the target for protein binding. Using EMSAs, the nuclear protein binding region was further narrowed to an 85 bp fragment, (- 1223 to - 1139). Using a series of unlabeled DNA sequences as "cold competitors" in EMSAs, a 22 bp sequence is identified as the smallest fragment that could successfully compete away protein binding. The same 22 bp sequence also competed DNA binding in EMSAs using nuclear protein isolated from primary murine osteoclasts. A full-length wild-type SPHK1 promoter and an SPHK1 promoter in which the ATGGGGG motif was mutated were subsequently expressed in pZen cells. Mutating this ATGGGGG motif nearly completely abrogated the ability of CSF1 to activate the promoter. Although two transcription factors, KLF6 and Sp1 have been reported to bind to this sequence, supershift EMSAs failed to detect either among the proteins bound to the 85 bp DNA fragment.

Evaluation of Incisional Negative Pressure Wound Therapy in the Prevention of Surgical Site Occurrences After Radical Cystectomy: A New Addition to Enhanced Recovery After Surgery Protocol.

BACKGROUND: Surgical site infection (SSI) remains a significant complication after radical cystectomy (RC). Enhanced recovery after surgery (ERAS) focuses on interventions to decrease length of stay, but few address wound-related complications directly. OBJECTIVE: To determine the impact that prophylactic incisional negative pressure wound therapy (iNPWT) will have to reduce the rate of surgical site occurrences (SSOs = SSI + seroma + superficial dehiscence) after RC. DESIGN, SETTINGS, AND PARTICIPANTS: We retrospectively reviewed patients undergoing RC by a single surgeon from 2012 to 2017. As part of our ERAS pathway, we employed prophylactic iNPWT during abdominal closure and compared it with a contemporary cohort of standard wound closure. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We compared 90-d SSIs, SSOs, and readmissions between iNPWT and standard skin staple closure. Univariate and multivariate regressions were used to compare the two groups. RESULTS AND LIMITATIONS: We identified 158 (104 iNPWT, 54 standard) patients from 2012 to 2017. The rates of SSIs and SSOs were 9.7% and 19.0%, respectively. The overall readmission rate for the cohort was 21.5%, with 4.4% of patients requiring readmission for SSI. The iNPWT group had lower rates of SSIs (5.8% vs 16.7%, p = 0.03) and SSOs (11.5% vs 33.3%, p < 0.01). There was no difference between the groups for readmission (21.1% vs 22.2%, p = 0.5). The iNPWT protected against both SSI (odds ratio [OR] 0.89, 95% confidence interval [CI]: 0.81-0.98) and 90-d SSO (OR 0.77, 95% CI: 0.68-0.87). CONCLUSIONS: Prophylactic iNPWT is feasible after RC with a modest decrease in both 90-d SSIs and 90-d SSOs, but not readmissions. Wound closure assisted by iNPWT should be considered in RC ERAS pathways. PATIENT SUMMARY: In this report, we looked at the impact of new vacuum suction dressing on the prevention of surgical infections after radical cystectomy (RC). We found that this wound dressing can decrease the impact of surgical infections and aid in recovery after RC.