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Cholecystitis Fast Track Pathway Provides Safe, Value Based Care on Busy Acute Care Surgery Service
No full textThe general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.BACKGROUND: Fast track (FT) pathways have been adopted across a multitude of elective surgeries, with the culmination of their progress resulting in higher value-based care of the patient. However, these programs have been slow to be adopted into the acute care surgery (ACS) realm. We hypothesized that a FT pathway implemented in an ACS service would safely hasten patient progress to the operating room while decreasing patient length of stay. To minimize variation, we have selected a singular, common operation, the cholecystectomy, which can be compared across two hospitals with well-established ACS services, one with a FT pathway and one with a traditional pathway.
METHODS: All patients at both hospitals that underwent an urgent or emergent laparoscopic cholecystectomy for acute cholecystitis between May 1, 2019 and October 31, 2019 were queried using CPT codes. Patients that required a conversion to open or partial cholecystectomy were excluded because they no longer qualified for the fast track pathway. Retrospective chart review was used to gather information relating to the patients' demographics, presentation, operative and hospital course, and outcomes. Time to OR and hospital length of stay were the primary outcomes.
RESULTS: There was a total of 479 urgent or emergent laparoscopic cholecystectomies performed during the 6 months for acute cholecystitis. Four hundred and thirty (89.8%) were performed under the FT pathway and 49 (10.2%) were performed under the traditional pathway. The median [IQR] time to the OR following surgical consultation was not different between the two pathways: 14.1 hours [8.3-29.0 hours] for FT and 18.5 hours [11.9-25.9 hours] for traditional (p=0.316). However, the median length of stay was shorter by 15.9 hours in the FT cohort (22.6 hours, [14.2-40.4] vs 38.5 hours, [28.3-56.3]; p0.2 for all). On multivariate analysis, having a fast track pathway was an independent predictor of discharge within 24 hours of surgical consultation (OR 7.6, 95% CI 2.9-20.2, p<0.0001).
CONCLUSION: Use of a fast track program for patients with acute cholecystitis has a significant positive impact on hospital resource utilization without compromise of clinical outcomes. Shorter times in the hospital and fewer clinic appointments benefit the hospital, surgeon, and patient. Incorporation of a FT pathway into all areas of ACS should be investigated
The Mechanism of cGAS-STING Signaling in Antiviral Immunity
No full textThe general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.Unlike inflammatory cell death pathways, apoptosis is a highly regulated process that leads to cell death without the secretion of pro-inflammatory cytokines. The intrinsic apoptosis pathway (IAP) is triggered upon sensing cellular stress, activating pro-death B cell lymphoma 2-associated X (BAX) and B cell lymphoma 2 homologous antagonist killer (BAK) proteins. BAX and BAK induce mitochondrial outer membrane permeabilization (MOMP), spilling cytochrome C (cyt C) into the cytoplasm where it forms the apotosome complex with the apoptotic protease activating factor 1 (Apaf-1). Apaf-1 subsequently induces a cysteine-aspartic protease (caspase) activation cascade culminating in activation of caspases-3/7. Nevertheless, the purpose of the caspase activation cascade remained an interesting conundrum as BAX and BAK, not Apaf-1 and caspases, are necessary for induction of apoptosis.
Recent publications seem to indicate that the main function of caspases after activation of apoptosis is to prevent the induction of type I interferons by cyclic GMP-AMP synthase (cGAS) or stimulator of interferon genes (STING) to maintain an immunologically quiescent cell death. I utilized the drug ABT-737 to inhibit the B-cell lymphoma (BCL) family of proteins to prevent the activation of BAK and BAX, leading to MOMP. MOMP causes leakage of cyt C and mitochondrial DNA (mtDNA), activating Apaf-1 and cGAS, respectively. cGAS catalyzes the creation of the cyclic dinucleotide cyclic GMP-AMP (cGAMP) to activate STING which activates downstream targets such as TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) to induce the expression of interferonβ (IFNβ) and interferon-stimulated genes (ISGs) such as C-X-C motif chemokine ligand 10 (CXCL10). However, the mechanism behind caspase-dependent inhibition of the cGAS-STING pathway is currently unknown. My central hypothesis is that caspases-3/7 activate a downstream regulator that inhibits cGAS-mediated cGAMP production. These findings will further our understanding of the regulatory mechanics behind immune responses.
As STING is necessary for the production of IFNs downstream of cGAS, it plays an important role in activating the innate immune response during infections. Specifically, mice lacking cGAS or STING are highly susceptible to acute herpes simplex encephalitis (HSE). STING-induced type I IFNs and immune-priming of other cell types were suggested to be critical for protecting mice from HSE. Recent work from our lab has identified an additional primordial downstream pathway of STING: autophagy; in addition, these results indicate that the interferon- and autophagy-inducing function of STING can be uncoupled. To better understand how STING-induced autophagy is controlled, I investigated the necessity of certain canonical autophagy-related genes. To also understand the exact mechanisms downstream of STING activation required for antiviral immunity, I utilized several different STING mutant mice generated in our lab and assessed their response to HSV-1 infection. My results indicate that a novel interferon-independent function of STING was essential to protect against infection and improve the overall survival rates of infected mice; however, STING-induced autophagy was not sufficient to protect against viral challenge
High-Performance Software Development for Genomic Sequence Alignment and Analysis
Get PDFNucleic acid sequencing technology is a powerful tool for understanding genetic information. Genomic data analysis software is critical for transforming complex sequencing results into meaningful biological information. Emerging sequencing technologies help scientists to understand biological processes from multiple angles, but they also raise the challenge of developing new sequence analysis tools, especially new alignment methods, to support these techniques.
In this dissertation, I developed a rapid and accurate sequence alignment software, HISAT-3N, to solve the alignment problem of nucleotide conversion sequencing (NC) technologies. NC technologies, such as BS-seq and SLAM seq, involve converting one type of nucleotide to another, which allows researchers to identify specific chemical modifications in DNA or RNA molecules. However, the conversions generated in these NC technologies make it difficult to align the reads back to the reference genome. To solve this issue, I implemented the 3-letter alignment algorithm into HISAT2, which was developed by our lab previously, to create HISAT-3N. I thoroughly tested HISAT-3N and demonstrated that it is more than seven times faster and more accurate than widely used sequence aligners, and can support all types of nucleotide conversion sequencing technologies, including those that have not yet been developed.
Additionally, to generalize the process of developing new alignment methods to support new sequencing technologies, I created a platform that allows for the modularized design of sequence alignment software. This platform incorporates algorithms from HISAT2, STAR, and BWA, providing greater efficiency for developers to create novel sequence alignment software and more flexibility for users to analyze different types of data in a variety of computational environments.
Finally, I developed a metagenomics analysis pipeline that effectively organizes and manages multiple well-known sequence analysis software for rapid and accurate soil microbial analysis. The successful development and implementation of these tools demonstrate the robustness of a well-designed bioinformatics software and pipeline framework in bioinformatics analysis.
Overall, my work emphasizes the significance of continuously improving genomics data analysis tools. This is important to support emerging sequencing technologies and deliver more precise results, which assist researchers in revealing valuable genetic information
Regulation of Reparative Macrophage Transition by the B-cell Adapter for PI3K (BCAP)
Get PDFMacrophages respond to microbial ligands and various noxious cues by initiating an inflammatory response aimed at eliminating the original pathogenic insult. Transition of macrophages from a pro-inflammatory state to a reparative state, however, is vital for resolution of inflammation and return to homeostasis. The molecular players governing this transition remain poorly defined. Here, we find that the reparative macrophage transition is dictated by B-cell adapter for PI3K (BCAP). Mice harboring a macrophage specific deletion of BCAP fail to recover from and succumb to DSS-induced colitis due to prolonged intestinal inflammation and impaired tissue repair. Following microbial stimulation, gene expression in WT macrophages switches from an early inflammatory signature to a late reparative signature, a process that is hampered in BCAP deficient macrophages. We find that absence of BCAP hinders inactivation of FOXO1 and GSK3b that contributes to their enhanced inflammatory state. BCAP deficiency also results in defective aerobic glycolysis and reduced lactate production. This translates into reduced histone lactylation and decreased expression of reparative macrophage genes. Thus, our results reveal BCAP to be critical cell intrinsic switch that regulates transition of inflammatory macrophages to reparative macrophages by imprinting epigenetic changes
Bear in a Bowtie
Get PDFThe author submitted this entry in the Creative Non-FIction category (Professional division) for the 2023 On My Own Time (OMOT) Art Show.This work received a Third Place Award in the "Creative Non-Fiction" category from all literary works submitted in the 2023 On My Own Time show.I participated in a 5-day 100-word memoir challenge, and one of the prompts was to write about an item from your childhood. I was stuck until I remembered one of my first stuffed animals and the story behind her name, which may have been an early indication that I never latched onto gender stereotypes. This piece was published earlier this year in Exist Otherwise
Smooth transitions: facilitating appropriate, timely hospice referrals in advanced diseases
No full textDetailed formal protocol with illustrations and extensive bibliography.A recording of the protocol presentation is available on UT Southwestern's Mediasite. Note: Access to the video is restricted to authorized UT Southwestern users only.UT Southwestern--Internal Medicin
Paradoxically Sparse Chemosensory Tuning in Broadly-Integrating External Granule Cells in the Mouse Accessory Olfactory Bulb
Get PDFThe file named "ZHANG-PRIMARY-2022-1.pdf" is the primary dissertation file. Seven (7) supplemental video files are also available and may be viewed individually.Most terrestrial animal species heavily rely on non-volatile chemosignals for conspecific and heterospecific communication. The sensory system responsible for detecting such signals is especially important in guiding animal behavior. Such sensory system in rodents is called accessory olfactory system (AOS). The chemostimulation detection is done by the vomeronasal sensory neurons in the vomeronasal organ (VNO), with their ligand-specific receptors. The electrophysiological signals generated here are then projected to the accessory olfactory bulb (AOB), where the local circuit performs preliminary filtering to the signal.
GABAergic interneurons are known to exert their signal sculpturing effect onto principal cells in many brain areas. However, the roles of the AOB GABAergic interneurons are poorly understood. Here, I focus on one genetically defined subtype of GABAergic interneuron, called external granule cell (EGC). Using fast non-ratiometric Ca2+ indicator GCaMP6f specifically expressed in target cell populations on a specialized ex vivo preparation that preserves the functional connections of VNO and AOB, I characterized and compared the tuning properties of EGC and the mitral cells (MC). EGCs show generally narrow tuning preferences towards naturalistic stimulation such as mouse fecal extract and urinal extract, but MCs are much more excitable upon monomolecular sulfated steroid ligands. The result on its appearance contradicts the integrative model as indicated by the circuitry architecture, in which individual EGC broadly connects with MCs by dendrodendritic reciprocal synapses.
One explanation is that EGC activation has relatively high threshold. In the presence of sulfated steroids, the excitatory inputs from the activated MCs may not be strong enough to elicit action potentials. Nevertheless, such inputs should be reflected by membrane potential recording of EGCs, in the form of subthreshold depolarizations. To verify this hypothesis, I performed ex vivo electrophysiological recording on EGCs upon the chemostimulation. As expected, subthreshold activities were reliably triggered by sulfated steroid ligands, displaying a 'tuning' profile indistinguishable from that of MCs as indicated by GCaMP6f imaging.
AOB granule cells are widely believed to be the information gating module under various behavioral contexts. This unexpected discovery of EGCs might suggest a unique information processing logic of AOS fitting the purpose of rodent social communication
Evaluating the Effectiveness of a Teledermatology on System Utilization in a Safety-Net Public Health and Hospital System
No full textThe general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.BACKGROUND: Teledermatology is a potentially useful and cost-effective modality for triaging patients in a primary care setting. However, the effect of teledermatology on health system utilization in a safety net hospital system has not been studied.
OBJECTIVE: To determine the effect teledermatology on dermatological-problem related healthcare system utilization. Our hypothesis was that teledermatology would be associated with decreased dermatological-problem related healthcare system utilization.
METHODS: The design is a retrospective cohort study comparing patients referred by Parkland Community Outpatient Clinics (COPC) primary care providers for dermatology evaluation during Fiscal Year 2016 (October 1st, 2015 and September 30th, 2016): 1) Patients evaluated through SAF teledermatology, 2). Patients from COPCs that did not have teledermatology available to them and were referred for a face-to-face visit. 3.) Patients from the COPCs in cohort 1 that had teledermatology available but were referred for a face-to-face visit instead. Data from 6 months prior to originating encounter and 18 months post originating encounter were measured. Statistical analysis with binary categorical repeated measures for a saturated model analyzed for significant variations in utilization. Health system utilization was measured at primary care clinics, dermatology and other specialty care clinics, urgent care clinic, and Emergency Room visits at Parkland Memorial Hospital. We compared the demographic, diagnostic, and clinical management data of the 3 cohorts. We measured sex, age, race/ethnicity, health care coverage, and diagnostic category for all 3 cohorts. The patients were classified as either having an inflammatory or neoplastic skin condition. The primary outcome was the percentage of patients with at least 1 visit in a 6-month time interval. Secondary outcomes measured were referral treatment capture rate, time to definitive treatment, and teledermatology response time.
RESULTS: There were 809 total participants comprising the 3 cohorts, which were 64% female and with a mean age of 50.4 years. Baseline characteristics among groups were similar except for a higher proportion of eczematous conditions in the teledermatology cohort. Over the 24 month study period, total health system utilization, defined as the percentage of patients with at least 1 visit in each 6-month time interval measured over 4 intervals, was significantly greater for patients with inflammatory conditions receiving a face-to-face referral from both teledermatology and non-teledermatology-utilizing clinics compared to patients receiving teledermatology consults. There are no significant differences all combined, dermatology, and PCP clinic utilization between the face-to-face referrals from teledermatology and non-teledermatology-utilizing groups.
CONCLUSION: This study provides evidence for the potential effectiveness of teledermatology improving access to care and reducing system utilization for patients with an inflammatory skin condition in a large safety-net public hospital system. There was no significant difference in utilization in patients with a neoplastic condition. Our results suggest additional benefits of utilizing a teledermatology system in a safety net hospital system
Efficacy and Safety Comparison of Robotic-Assisted Sacrocolpopexy Using Light-Weight and Heavy-Weight Polypropylene Mesh
Get PDFAIMS: This study compares long-term surgical outcomes of light-weight polypropylene mesh (LWPPM) and heavy-weight polypropylene mesh (PPM) for robotic sacrocolpopexy (RSC).
METHODS: Following IRB approval, a 2-surgeon POP database of women who underwent RSC at a single institution was reviewed. Minimum follow-up time was 6 months. Patients were stratified by mesh weight: Boston Scientific MarlexTM natural Trelex mesh or AtriumTM ProLite mesh (PPM) versus Caldera Medical Vertessa(r) Lite Y Polypropylene Mesh (LWPPM). Success was defined using a composite of absence of prolapse symptoms at the patient's most recent visit, no POP-Q point beyond the hymen, and no reoperation for POP.
RESULTS: From 2007 to 2018, 110 patients met study criteria: 67 with LWPPM and 43 with PPM. The success rate of RSC using LWPPM at 12 months was 91.0% versus 90.7% for RSC with PPM (p =1). Over time, the mean follow-up length was 23.3 months in the LWPPM groups compared to 44.7 months in the PPM group (p <0.0002). The success rate at the last follow-up of RSC using LWPPM was significantly higher than that of RSC with PPM - 89.6% versus 72.1% (p =0.0221). Regarding complications, mesh extrusion rates varied (3.0% for LWPPM versus 11.6% for PPM at the last follow-up); however, this difference was not statistically significant (p=0.11) nor was the difference in management (p=0.15).
CONCLUSIONS: RSC using LWPPM is a safe and effective procedure. Success rates using LWPPM are not inferior to those using PPM. Complication rates were low with either mesh
Walk the Line
Get PDFThis poem is inspired by life. In today's world there are so many things that we have to process daily. Our minds have to triage the intricacies of every day decisions. People have expectations and others try to live up to those expectations. These hidden battles people face every day but in the end hopefully there is something or someone that holds us together to keep us from falling