Same-day discharge after laparoscopic appendectomy for non-perforated appendicitis is safe and cost effective.

AIM OF THE STUDY: To compare the outcomes and hospital charges of patients who underwent laparoscopic appendectomy for non-perforated appendicitis and were discharged home either shortly after the operation after being admitted for overnight observation. METHODS: Postoperative (30-day) emergency department (ED) visits, hospital readmissions, and reoperations were compared between patients who were discharged shortly after surgery (same-day discharge [SDD] group) and patients who were discharged after spending one night in the hospital (overnight observation group). STUDY PERIOD: July/2015 to June/2019. Patients with perforated appendicitis and/or who spent > 1 night in the hospital were excluded from the study. RESULTS: We did 1957 laparoscopic appendectomies within the 4-year study period. After excluding all non-eligible cases, 930 patients were included in the overnight observation group, and 511 in the SDD group. Mean age and mean operative time were similar in both groups: 11.5 (SD 3.6)/11.8 (SD 3.5) years, and 35 (SD 13)/33 (SD 12) minutes, respectively. There were 24 (2.6%) ED visits within the overnight observation group. Sixteen patients (1.7%) were discharged from the ED, and 8 (0.9%) required a re-admission. There were 11 (2.1%; P = 0.61) ED visits within the SDD group. Six patients (1.1%; P = 0.41) were discharged from the ED, and 5 (1%; P = 0.82) required a readmission. Six of the 11 ED visits within the SDD group occurred on the 5th postoperative day or later, whereas five (1%) occurred within the first 3 days post appendectomy. These five patients would have likely benefited from an overnight admission and were erroneously discharged on the same day of the appendectomy. There were no reoperations in the overnight observation group, but there were 3 reoperations in the SDD group (0.6%, P = 0.01). The reasons for the reoperations (two bowel obstructions and one bowel perforation) were in no way related to the time of the original discharge. The mean hospital charges per patient in the SDD group and the overnight observation group were significantly different: $32,450 and $35,420, respectively (> 9% margin, P < 0.01). CONCLUSION: Healthy children who undergo laparoscopic appendectomy for non-perforated appendicitis can be discharged home during the same day of the operation after a short period of observation. This approach is safe and does not result in more postoperative ED visits or hospital readmissions. In addition, there is a significant financial benefit when patients are discharged early. LEVEL-OF-EVIDENCE: Level III-retrospective comparative treatment study.

Role of genomics in eliminating health disparities.

The Texas Center for Health Disparities, a National Institute on Minority Health and Health Disparities Center of Excellence, presents an annual conference to discuss prevention, awareness education, and ongoing research about health disparities both in Texas and among the national population. The 2014 Annual Texas Conference on Health Disparities brought together experts in research, patient care, and community outreach on the "Role of Genomics in Eliminating Health Disparities." Rapid advances in genomics and pharmacogenomics are leading the field of medicine to use genetics and genetic risk to build personalized or individualized medicine strategies. We are at a critical juncture of ensuring such rapid advances benefit diverse populations. Relatively few forums have been organized around the theme of the role of genomics in eliminating health disparities. The conference consisted of three sessions addressing "Gene-Environment Interactions and Health Disparities," "Personalized Medicine and Elimination of Health Disparities," and "Ethics and Public Policy in the Genomic Era." This article summarizes the basic science, clinical correlates, and public health data presented by the speakers.

Overcoming Barriers: Sex Disparity in Surgeon Ergonomics.

BACKGROUND: Musculoskeletal discomfort is widely experienced by surgeons across multiple surgical specialties. Developing technologies and new minimally invasive techniques add further complexity and ergonomic stressors. These stressors differentially affect male and female surgeons, but little is known about the role these sex disparities play in surgical ergonomic stress. We reviewed existing literature to better understand how ergonomic stress varies between male and female surgeons. STUDY DESIGN: A literature search was performed via PubMed including but not limited to the following topics: ergonomics, surgeons, female surgeons, women surgeons, pregnancy, and operating room. A review of available quantitative data was performed. RESULTS: Female surgeons endure more pronounced ergonomic discomfort than their male counterparts, with added ergonomic stress associated with pregnancy. CONCLUSIONS: A 4-fold method is proposed to overcome ergonomic barriers, including (1) improved education on prevention and treatment of ergonomic injury for active surgeons and trainees, (2) increased departmental and institutional support for ergonomic solutions for surgeons, (3) partnerships with industry to study innovative ergonomic solutions, and (4) additional research on the nature of surgical ergonomic challenges and the differential effects of surgical ergonomics on female surgeons.

Intersection of Smoking, Human immunodeficiency virus/acquired immunodeficiency syndrome and Cancer: Proceedings of the 8(th) Annual Texas Conference on Health Disparities.

The Texas Center for Health Disparities, a National Institute on Minority Health and Health Disparities Center of Excellence, presents an annual conference to discuss prevention, awareness education and ongoing research about health disparities both in Texas and among the national population. The 2013 Texas Conference on Health Disparities brought together experts, in research, patient care and community outreach, on the "Intersection of Smoking, Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and Cancer". Smoking, HIV/AIDS and cancer are three individual areas of public health concern, each with its own set of disparities and risk factors based on race, ethnicity, gender, geography and socio-economic status. Disparities among patient populations, in which these issues are found to be comorbid, provide valuable information on goals for patient care. The conference consisted of three sessions addressing "Comorbidities and Treatment", "Public Health Perspectives", and "Best Practices". This article summarizes the basic science, clinical correlates and public health data presented by the speakers.

Breast cancer disparities: Frontline strategies, proceedings of the 7(th) annual texas conference on health disparities.

There are striking disparities in health status, access to health care, and risk factors among racial and ethnic minorities and the general population in Texas. The disparities are multifactorial comprising genetic, sociocultural, and environmental variables. The Texas Center for Health Disparities (TCHD), a NIMHD Center of Excellence (COE), aims to prevent, reduce, and eliminate health disparities in the communities through research, education, and community-based programs. As part of the center's outreach activities, an annual conference is organized to build awareness and knowledge on health disparities. The overall theme for the 2012 conference was "Battling Breast Cancer Disparities: Frontline Strategies". The scientific program consisted of three sessions: "Breakthroughs in Breast Cancer", "Triple Negative Breast Cancer," and "Hormone Resistant Breast Cancer" featuring different aspects of bench-research from molecular biology, proteomics, and genetics to the clinical aspects such as detection, diagnosis, and finally to community-based approaches. This article summarizes the proceedings of the meeting providing salient strategies and best practices presented by the speakers.

Global dissemination of knowledge through virtual platforms: Reflections and recommendations from APSA/IPEG.

BACKGROUND: The COVID-19 pandemic forced the cancelation of conventional in-person academic conferences due to the risk of virus transmission and limited ability to travel. Both the American Pediatric Surgical Association (APSA) and International Pediatric Endosurgery Group (IPEG) converted to a virtual format for their 2020 annual meetings. The purpose of this article is to review the successful implementation of the APSA and IPEG virtual meetings and reflect upon lessons learned for future virtual conferences. METHODS: Logistics, structure, and attendance statistics were reviewed. Informal interviews were conducted with key stakeholders and the number of presenters and participants were analyzed. Finally, post-meeting attendee surveys were conducted to elicit feedback after both virtual meetings. RESULTS: The meetings were organized in different ways, with APSA spreading a mix of scientific and clinical educational content over several months and IPEG keeping the meeting compressed, similar to previous in-person versions. Both meetings were free and therefore attracted a high proportion of participants (720 for APSA and 834 for IPEG). The meetings were felt to be educationally appropriate by most, although timing and lack of Continuing Medical Education (CME) opportunities were detractors. Most attendees said they would be willing to pay fees similar to in-person amounts. IPEG compressed presentations into four 2-hour sessions spread over 4 weeks, but also made material available on-line through a proprietary application. There was a broad range of international attendees. IPEG attracted a larger percentage of non-members than did APSA (3:1 nonmember to member ratio). Both societies reported net losses, largely due to lost registration revenue and non-refundable costs from having to switch from an in-person meeting. CONCLUSIONS: The main advantage of the virtual meeting was increased participation while disadvantages included the lack of networking. The key lessons learned from the meetings include methods to increase interactivity, adjustments of technical logistics, and creation of enduring material. In the future, hybrid conferences will likely become more prevalent with advantages of both platforms. LEVEL-OF-EVIDENCE: Level V - Expert Opinion.

Ionizable lipid nanoparticles for in utero mRNA delivery.

Clinical advances enable the prenatal diagnosis of genetic diseases that are candidates for gene and enzyme therapies such as messenger RNA (mRNA)-mediated protein replacement. Prenatal mRNA therapies can treat disease before the onset of irreversible pathology with high therapeutic efficacy and safety due to the small fetal size, immature immune system, and abundance of progenitor cells. However, the development of nonviral platforms for prenatal delivery is nascent. We developed a library of ionizable lipid nanoparticles (LNPs) for in utero mRNA delivery to mouse fetuses. We screened LNPs for luciferase mRNA delivery and identified formulations that accumulate within fetal livers, lungs, and intestines with higher efficiency and safety compared to benchmark delivery systems, DLin-MC3-DMA and jetPEI. We demonstrate that LNPs can deliver mRNAs to induce hepatic production of therapeutic secreted proteins. These LNPs may provide a platform for in utero mRNA delivery for protein replacement and gene editing.

In utero adenine base editing corrects multi-organ pathology in a lethal lysosomal storage disease.

In utero base editing has the potential to correct disease-causing mutations before the onset of pathology. Mucopolysaccharidosis type I (MPS-IH, Hurler syndrome) is a lysosomal storage disease (LSD) affecting multiple organs, often leading to early postnatal cardiopulmonary demise. We assessed in utero adeno-associated virus serotype 9 (AAV9) delivery of an adenine base editor (ABE) targeting the Idua G→A (W392X) mutation in the MPS-IH mouse, corresponding to the common IDUA G→A (W402X) mutation in MPS-IH patients. Here we show efficient long-term W392X correction in hepatocytes and cardiomyocytes and low-level editing in the brain. In utero editing was associated with improved survival and amelioration of metabolic, musculoskeletal, and cardiac disease. This proof-of-concept study demonstrates the possibility of efficiently performing therapeutic base editing in multiple organs before birth via a clinically relevant delivery mechanism, highlighting the potential of this approach for MPS-IH and other genetic diseases.

Comparative analysis of racial differences in breast tumor microbiome.

Studies have demonstrated that environmental, host genetic, and socioeconomic factors influence the breast cancer prevalence landscape with a far-reaching influence on racial disparity to subtypes of breast cancer. To understand whether breast tissue harbors race-specific microbiota, we performed 16S rRNA gene-based sequencing of retrospective tumor and matched normal tissue adjacent to tumor (NAT) samples collected from Black non-Hispanic (BNH) and White non-Hispanic (WNH) women. Analysis of Triple Negative Breast cancer (TNBC) and Triple Positive Breast Cancer (TPBC) tissues for microbiota composition revealed significant differences in relative abundance of specific taxa at both phylum and genus levels between WNH and BNH women cohorts. Our main findings are that microbial diversity as measured by Shannon index was significantly lower in BNH TNBC tumor tissue as compared to matched NAT zone. In contrast, the WNH cohort had an inverse pattern for the Shannon index, when TNBC tumor tissue was compared to the matched NAT. Unweighted Principle Coordinates Analysis (PCoA) revealed a distinct clustering of tumor and NAT microbiota in both BNH and WNH cohorts.

Brainstem glioma progression in juvenile and adult rats.

OBJECT: Brainstem gliomas are common in children and have the worst prognosis of any brain tumor in this age group. On the other hand, brainstem gliomas are rare in adults, and the authors of some clinical studies have suggested that this lesion behaves differently in adults than in children. In the present study, the authors test an orthotopic C6 brainstem glioma model in juvenile and adult rats, and investigate the biological behavior of this lesion in the 2 age groups. METHODS: The C6 glioma cells were stereotactically implanted into the pons of juvenile or adult male rats. Neurological presentation and survival time were recorded. Tumor proliferation and the number of apoptotic cells in brainstem gliomas of young and adult rats were determined by immunohistochemical staining with Ki 67 and terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate-mediated nick-end labeling assay. RESULTS: Striking differences in the onset of neurological signs, duration of symptoms, survival time, tumor growth pattern, tumor proliferation, and number of apoptotic cells were found between the gliomas in the 2 groups of rats. The lesions were relatively focal in adult rats but more diffuse in young rats. Furthermore, brainstem gliomas in adult rats were less proliferative and had more apoptotic cells than those in young rats. CONCLUSIONS: The authors found that the C6 brainstem glioma model in young and adult rats closely imitates the course of brainstem glioma in humans both in neurological findings and histopathological characteristics. Their findings also suggest that the different growth pattern and invasiveness of these lesions in children compared with that in adults could be due to different cellular environments in the 2 age groups, and warrants further investigation into the difference in the host response to brainstem gliomas in children and adults.

Establishment of human retinal microvascular endothelial cells with extended life-span.

AIM: To generate and characterize a telomerase-immortalized human retinal microvascular endothelial cell (HREC) line. This cell line may be utilized as an in vitro model to study the molecular basis of several diseases of the human retina. MATERIALS AND METHODS: Primary retinal neuronal cells were isolated and transfected with plasmid encoding full-length human telomerase reverse transcriptase (hTERT). Transfected cells were selected and characterized to determine telomerase activity, karyotype, proliferative capacity and functionality. RESULTS: HREC-hTERT cells appear morphologically similar to primary endothelial cells and have an extended in vitro life-span. HREC-hTERT cells express the progenitor/stem cell marker nestin. They have active telomerase and a high proliferative capacity. These cells also maintain a diploid karyotype. The HREC-hTERT cells showed high colony-formation capacity and plating efficiency compared to the primary cells. These cells are capable of differentiation into neuronal and glial cell phenotypes and the differentiated cells express the astrocyte marker glial fibrillary acidic protein (GFAP) and the neuronal marker microtubule-associated protein-2 (MAP2), respectively. CONCLUSION: The in vitro life-span of human retinal neuronal endothelial cells can be extended by ectopic expression of hTERT without altering the genetic stability and functionality of these cells. These cells will be a valuable tool to further our understanding on the role of HRECs in the human blood-retinal-barrier and in angiogenesis and neovascularization.