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1.
Surg Infect (Larchmt) ; 25(4): 315-321, 2024 May.
Article in English | MEDLINE | ID: mdl-38696615

ABSTRACT

Background: Surgical site complications (SSCs) are common, yet preventable hospital-acquired conditions. Single-use negative pressure wound therapy (sNPWT) has been shown to be effective in reducing rates of these complications. In the era of value-based care, strategic allocation of sNPWT is needed to optimize both clinical and financial outcomes. Materials and Methods: We conducted a retrospective analysis using data from the Premier Healthcare Database (2017-2021) for 10 representative open procedures in orthopedic, abdominal, cardiovascular, cesarean delivery, and breast surgery. After separating data into training and validation sets, various machine learning algorithms were used to develop pre-operative SSC risk prediction models. Model performance was assessed using standard metrics and predictors of SSCs were identified through feature importance evaluation. Highest-performing models were used to simulate the cost-effectiveness of sNPWT at both the patient and population level. Results: The prediction models demonstrated good performance, with an average area under the curve of 76%. Prominent predictors across subspecialities included age, obesity, and the level of procedure urgency. Prediction models enabled a simulation analysis to assess the population-level cost-effectiveness of sNPWT, incorporating patient and surgery-specific factors, along with the established efficacy of sNPWT for each surgical procedure. The simulation models uncovered significant variability in sNPWT's cost-effectiveness across different procedural categories. Conclusions: This study demonstrates that machine learning models can effectively predict a patient's risk of SSC and guide strategic utilization of sNPWT. This data-driven approach allows for optimization of clinical and financial outcomes by strategically allocating sNPWT based on personalized risk assessments.


Subject(s)
Artificial Intelligence , Negative-Pressure Wound Therapy , Surgical Wound Infection , Humans , Retrospective Studies , Surgical Wound Infection/prevention & control , Surgical Wound Infection/economics , Surgical Wound Infection/epidemiology , Negative-Pressure Wound Therapy/methods , Negative-Pressure Wound Therapy/economics , Female , Middle Aged , Male , Cost-Benefit Analysis , Aged , Machine Learning , Adult , Risk Assessment/methods
2.
Plast Reconstr Surg Glob Open ; 11(4): e4954, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37113309

ABSTRACT

One factor that can contribute to the development of hypertrophic scar contracture is mechanical stress. Mechanical cyclic stretch stimuli enhance the secretion of endothelin-1 (ET-1) from keratinocyte. Cyclical stretching of fibroblasts also increases the expression level of the transient receptor potential ion channel (TRPC3), which is known to couple with the endothelin receptor and induce intracellular Ca2+ signaling via the calcineurin/nuclear factor of activated T cells (NFAT) pathway. The aim of this study was to investigate the relationship between keratinocytes and fibroblasts when they are stretched. Methods: The conditioned medium from stretched keratinocyte was added to the fibroblast populated collagen lattice. Then, we analyzed the levels of endothelin receptor in the human hypertrophic scar tissue and stretched fibroblasts. To address the function of TRPC3, we have used an overexpression system with the collagen lattice. Finally, the TRPC3 overexpressing fibroblasts were transplanted to mouse dorsal skin, and the rate of skin wound contraction was assessed. Results: Conditioned medium from stretched keratinocytes increased the rate of contraction of fibroblast populated collagen lattice. In human hypertrophic scar and stretched fibroblasts, endothelin receptor type B was increased. Cyclic stretching of TRPC3 overexpressing fibroblasts activated NFATc4, and stretched human fibroblasts showed more activation of NFATc4 in response to ET-1. The wound treated with TRPC3 overexpressing fibroblasts showed more contraction than control wound. Conclusion: These findings suggest that cyclical stretching of wounds have an effect on both keratinocytes and fibroblasts, where keratinocytes secret more ET-1, and fibroblasts develop more sensitivity to ET-1 by expressing more endothelin receptors and TRPC3.

3.
Int J Health Econ Manag ; 21(4): 457-471, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33837491

ABSTRACT

More than 2.5 million people in the United States develop pressure injuries annually, which are one of the most common complications occurring in hospitals. Despite being common, hospital-acquired pressure injuries (HAPIs) are largely considered preventable by regular patient turning. Although current methodologies to prompt on-time repositioning have limited efficacy, a wearable patient sensor has been shown to optimize turning practices and improve clinical outcomes. The purpose of this study was to assess the cost-effectiveness of patient-wearable sensor in the prevention of HAPIs in acutely ill patients when compared to standard practice alone. A decision analytic model was developed to simulate the expected costs and outcomes from the payer's perspective using data from published literature, including a recently published randomized controlled trial. Both univariate and probabilistic sensitivity analysis were conducted. The patient-wearable sensor was found to be cost saving (dominant). It resulted in better clinical outcomes (77% reduction in HAPIs) compared to standard care and an expected cost savings of $6,621 per patient over a one-year period. Applying the model to a cohort of 1,000 patients, an estimated 203 HAPIs would be avoided with annualized cost reduction of $6,222,884 through all patient treatment settings. The probabilistic analysis returned similar results. In conclusion, the patient-wearable sensor was found to be cost-effective in the prevention of HAPIs and cost-saving to payers and hospitals. These results suggest that patient-wearable sensors should be considered as a cost-effective alternative to standard care in the prevention of HAPIs.


Subject(s)
Pressure Ulcer , Wearable Electronic Devices , Cost-Benefit Analysis , Hospitals , Humans , Pressure Ulcer/prevention & control , United States
4.
Int Wound J ; 17(6): 1924-1934, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32830460

ABSTRACT

Pressure injuries are one of the most common and costly complications occurring in US hospitals. With up to 3 million patients affected each year, hospital-acquired pressure injuries (HAPIs) place a substantial burden on the US healthcare system. In the current study, US hospital discharge records from 9.6 million patients during the period from October 2009 through September 2014 were analysed to determine the incremental cost of hospital-acquired pressure injuries by stage. Of the 46 108 patients experiencing HAPI, 16.3% had Stage 1, 41.0% had Stage 2, 7.0% had Stage 3, 2.8% had Stage 4, 7.3% had unstageable, 14.6% had unspecified, and 10.9% had missing staging information. In propensity score-adjusted models, increasing HAPI severity was significantly associated with higher total costs and increased overall length of stay when compared with patients not experiencing a HAPI at the index hospitalisation. The average incremental cost for a HAPI was $21 767. Increasing HAPI severity was significantly associated with greater risk of in-hospital mortality at the index hospitalisation compared with patients with no HAPI, as well as 1.5 to 2 times greater risk of 30-, 60-, and 90-day readmissions. Additionally, increasing HAPI severity was significantly associated with increasing risk of other hospital-acquired conditions, such as pneumonia, urinary tract infections, and venous thromboembolism during the index hospitalisation. By preventing pressure injuries, hospitals have the potential to reduce unreimbursed treatment expenditures, reduce length of stay, minimise readmissions, prevent associated complications, and improve overall outcomes for their patients.


Subject(s)
Patient Discharge , Pressure Ulcer , Hospitals , Humans , Iatrogenic Disease/epidemiology , Patient Readmission , Pressure Ulcer/epidemiology , Retrospective Studies
5.
Wounds ; 30(8): 229-234, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30212372

ABSTRACT

BACKGROUND: Compliance with turning protocols in the intensive care unit (ICU) is low; however, little is known about the quality of turning, such as turn angle magnitude or depressurization time. Wearable sensors are now available that provide insight into care practices. OBJECTIVE: This secondary descriptive study describes the turning practices of nurses from 2 ICUs at an academic medical center among consecutive ICU patients. MATERIALS AND METHODS: A wearable patient sensor was applied to patients on hospital admission. The sensor continuously recorded position data but was not visible to staff. A qualified turn was one that reached > 20° angle and was held for 1 minute after turning. The institution's clinical research repository provided clinical data. RESULTS: A total of 555 patients were analyzed over a 5-month period (September 2015-January 2016); 44 870 hours of monitoring data (x- = 73 hours ± 97/patient) and 27 566 individual turns were recorded. Compliant time was recorded as 54%, with 39% of observed turns reaching the minimum angle threshold and 38% of patients remaining in place for > 15 minutes (depressurization). Turn magnitude was similar for medical and surgical patients. Factors associated with lower compliant time included male sex, high body mass index, and low Braden score. Patients were supine for 72% of the observed time. CONCLUSIONS: The investigators found dynamically measured turning frequency, turn magnitude, and tissue depressurization time to be suboptimal. This study highlights the need to reinforce best practices related to preventive turning and to consider staff and patient factors when developing individualized turn protocols.


Subject(s)
Guideline Adherence/statistics & numerical data , Iatrogenic Disease/prevention & control , Intensive Care Units , Patient Positioning/standards , Practice Patterns, Nurses'/statistics & numerical data , Pressure Ulcer/prevention & control , Wearable Electronic Devices/statistics & numerical data , Adolescent , Adult , Aged , Body Mass Index , Female , Humans , Intention to Treat Analysis , Male , Middle Aged , Outcome Assessment, Health Care , Patient Positioning/instrumentation , Quality Improvement , Sex Distribution , Time Factors , Young Adult
6.
Sci Rep ; 5: 11620, 2015 Jun 25.
Article in English | MEDLINE | ID: mdl-26108359

ABSTRACT

Wound healing process is a complex and highly orchestrated process that ultimately results in the formation of scar tissue. Hypertrophic scar contracture is considered to be a pathologic and exaggerated wound healing response that is known to be triggered by repetitive mechanical forces. We now show that Transient Receptor Potential (TRP) C3 regulates the expression of fibronectin, a key regulatory molecule involved in the wound healing process, in response to mechanical strain via the NFkB pathway. TRPC3 is highly expressed in human hypertrophic scar tissue and mechanical stimuli are known to upregulate TRPC3 expression in human skin fibroblasts in vitro. TRPC3 overexpressing fibroblasts subjected to repetitive stretching forces showed robust expression levels of fibronectin. Furthermore, mechanical stretching of TRPC3 overexpressing fibroblasts induced the activation of nuclear factor-kappa B (NFκB), a regulator fibronectin expression, which was able to be attenuated by pharmacologic blockade of either TRPC3 or NFκB. Finally, transplantation of TRPC3 overexpressing fibroblasts into mice promoted wound contraction and increased fibronectin levels in vivo. These observations demonstrate that mechanical stretching drives fibronectin expression via the TRPC3-NFkB axis, leading to intractable wound contracture. This model explains how mechanical strain on cutaneous wounds might contribute to pathologic scarring.


Subject(s)
Cicatrix, Hypertrophic/metabolism , NF-kappa B/metabolism , TRPC Cation Channels/metabolism , Wound Healing/physiology , Animals , Blotting, Western , Cells, Cultured , Cicatrix, Hypertrophic/genetics , Cicatrix, Hypertrophic/physiopathology , Contracture/genetics , Contracture/metabolism , Contracture/physiopathology , Dermis/cytology , Embryo, Mammalian/cytology , Fibroblasts/metabolism , Fibroblasts/physiology , Fibroblasts/transplantation , Fibronectins/genetics , Fibronectins/metabolism , Gene Expression , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Microscopy, Fluorescence , NIH 3T3 Cells , Reverse Transcriptase Polymerase Chain Reaction , Stress, Mechanical , TRPC Cation Channels/genetics , Wound Healing/genetics
7.
Ann Plast Surg ; 69(1): 85-90, 2012 Jul.
Article in English | MEDLINE | ID: mdl-21712703

ABSTRACT

In mammals, the early-gestation fetus has the regenerative ability to heal skin wounds without scar formation. This observation was first reported more than 3 decades ago, and has been confirmed in a number of in vivo animal models. Although an intensive research effort has focused on unraveling the mechanisms underlying scarless fetal wound repair, no suitable model of in vitro fetal skin healing has been developed. In this article, we report a novel model for the study of fetal wound healing. Fetal skin from gestational day 16.5 Balb/c mice (total gestation, 20 days) was grafted onto the chorioallantoic membrane of 12-day-old chicken embryos and cultured for up to 7 days. At 48 hours postengraftment, circular wounds (diameter = 1 mm) were made in the fetal skin using a rotating titanium sapphire laser (N = 45). The tissue was examined daily by visual inspection to look for signs of infection and ischemia. The grafts and the surrounding host tissue were examined histologically. In all fetal skin grafts, the wounds completely reepithelialized by postinjury day 7, with regeneration of the dermis. Fetal mouse skin xenografts transplanted onto the chorioallantoic membrane of fertilized chicken eggs provides a useful model for the study of fetal wound healing. This model can be used as an adjunct to traditional in vivo mammalian models of fetal repair.


Subject(s)
Chorioallantoic Membrane , Fetal Tissue Transplantation , Models, Animal , Skin Physiological Phenomena , Skin Transplantation , Skin/injuries , Wound Healing/physiology , Animals , Chick Embryo , Cicatrix , Lasers, Solid-State , Mice , Mice, Inbred BALB C , Skin/embryology
8.
PLoS One ; 6(11): e27106, 2011.
Article in English | MEDLINE | ID: mdl-22073267

ABSTRACT

INTRODUCTION: Nanoparticles (NPs) are small entities that consist of a hydroxyapatite core, which can bind ions, proteins, and other organic molecules from the surrounding environment. These small conglomerations can influence environmental calcium levels and have the potential to modulate calcium homeostasis in vivo. Nanoparticles have been associated with various calcium-mediated disease processes, such as atherosclerosis and kidney stone formation. We hypothesized that nanoparticles could have an effect on other calcium-regulated processes, such as wound healing. In the present study, we synthesized pH-sensitive calcium-based nanoparticles and investigated their ability to enhance cutaneous wound repair. METHODS: Different populations of nanoparticles were synthesized on collagen-coated plates under various growth conditions. Bilateral dorsal cutaneous wounds were made on 8-week-old female Balb/c mice. Nanoparticles were then either administered intravenously or applied topically to the wound bed. The rate of wound closure was quantified. Intravenously injected nanoparticles were tracked using a FLAG detection system. The effect of nanoparticles on fibroblast contraction and proliferation was assessed. RESULTS: A population of pH-sensitive calcium-based nanoparticles was identified. When intravenously administered, these nanoparticles acutely increased the rate of wound healing. Intravenously administered nanoparticles were localized to the wound site, as evidenced by FLAG staining. Nanoparticles increased fibroblast calcium uptake in vitro and caused contracture of a fibroblast populated collagen lattice in a dose-dependent manner. Nanoparticles also increased the rate of fibroblast proliferation. CONCLUSION: Intravenously administered, calcium-based nanoparticles can acutely decrease open wound size via contracture. We hypothesize that their contraction effect is mediated by the release of ionized calcium into the wound bed, which occurs when the pH-sensitive nanoparticles disintegrate in the acidic wound microenvironment. This is the first study to demonstrate that calcium-based nanoparticles can have a therapeutic benefit, which has important implications for the treatment of wounds.


Subject(s)
Calcium/pharmacology , Nanoparticles , Skin/drug effects , Wound Healing/drug effects , Animals , Female , Mice , Mice, Inbred BALB C
9.
Plast Reconstr Surg ; 126(4): 1172-1180, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20885241

ABSTRACT

SUMMARY: Scar formation is a major medical problem that can have devastating consequences for patients. The adverse physiological and psychological effects of scars are broad, and there are currently no reliable treatments to prevent scarring. In contrast to adult wounds, early gestation fetal skin wounds repair rapidly and in the absence of scar formation. Despite extensive investigation, the exact mechanisms of scarless fetal wound healing remain largely unknown. For some time, it has been known that significant differences exist among the extracellular matrix, inflammatory response, cellular mediators, and gene expression profiles of fetal and postnatal wounds. These differences may have important implications in scarless wound repair.


Subject(s)
Cell Transdifferentiation , Cicatrix/prevention & control , Embryonic Stem Cells/cytology , Fetus/physiology , Wound Healing/physiology , Blastocyst Inner Cell Mass/cytology , Blastocyst Inner Cell Mass/physiology , Embryonic Stem Cells/physiology , Fetus/metabolism , Forecasting , Humans , Research Design/trends , Science , Stem Cell Transplantation
10.
Mol Pharmacol ; 73(2): 461-8, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17978167

ABSTRACT

ATP7B is a P-type ATPase that mediates the efflux of copper. Recent studies have demonstrated that ATP7B regulates the cellular efflux of cisplatin (DDP) and controls sensitivity to the cytotoxic effects of this drug. To determine whether DDP is a substrate for ATP7B, DDP transport was assayed in vesicles isolated from Sf9 cells infected with a baculovirus that expressed either the wild-type ATP7B or a mutant ATP7B that was unable to transport copper as a result of conversion of the transmembrane metal binding CPC motif to CPA. Only the wild-type ATP7B-expressing vesicles exhibited copper-dependent ATPase activity, copper-induced acyl-phosphate formation, and ATP-dependent transport of copper. The amount of DDP that became bound was higher for vesicles expressing either type of ATP7B than for those not expressing either form of ATP7B, but only the vesicles expressing wild-type ATP7B mediated ATP-dependent accumulation of the drug. At pH 4.6, the vesicles expressing the wild-type ATP7B exhibited ATP-dependent accumulation of DDP with an apparent K(m) of 1.2 +/- 0.5 (S.E.M.) muM and V(max) of 0.03 +/- 0.002 (S.E.M.) nmol/mg of protein/min. DDP also induced the acyl-phosphorylation of ATP7B but at a much slower rate than copper. Copper and DDP each inhibited the ATP-dependent transport of the other. These results establish that DDP is a substrate for ATP7B but is transported at a much slower rate than copper.


Subject(s)
Adenosine Triphosphatases/metabolism , Cation Transport Proteins/metabolism , Cisplatin/metabolism , Adenosine Triphosphatases/biosynthesis , Adenosine Triphosphatases/genetics , Animals , Biological Transport/physiology , Cation Transport Proteins/biosynthesis , Cation Transport Proteins/genetics , Cell Line , Copper/metabolism , Copper-Transporting ATPases , Protein Binding/physiology , Spodoptera
11.
Mol Cancer Ther ; 4(10): 1595-604, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16227410

ABSTRACT

Previous work has shown that cisplatin (CDDP) becomes concentrated in lysosomes, and that acquired resistance to CDDP is associated with abnormalities of protein trafficking and secretion. The lysosomal compartment in CDDP-sensitive 2008 human ovarian carcinoma cells was compared with that in CDDP-resistant 2008/C13*5.25 subline using deconvoluting imaging and specific dyes and antibodies. The lysosomal compartment in CDDP-resistant cells was reduced to just 40% of that in the parental CDDP-sensitive cells (P<0.002). This was accompanied by a reduced expression of the lysosome-associated proteins 1 and 2 (LAMP1 and LAMP2) as determined by both microscopy and Western blot analysis. The CDDP-resistant cells released more protein as exosomes and Western blot analysis revealed that these exosomes contained substantially more LAMP1 than those released by the CDDP-sensitive cells. Following loading of the whole cell with CDDP, the exosomes released from 2008/C13*5.25 cells contained 2.6-fold more platinum than those released from sensitive cells. Enhanced exosomal export was accompanied by higher exosomal levels of the putative CDDP export transporters MRP2, ATP7A, and ATP7B. Expression profiling identified significant increases in the expression of several genes whose products function in membrane fusion and vesicle trafficking. This study shows that the lysosomal compartment of human ovarian carcinoma cells selected for stable resistance to CDDP is markedly reduced in size, and that these cells abnormally sort some lysosomal proteins and the putative CDDP transporters into an exosomal pathway that also exports CDDP.


Subject(s)
Cisplatin/pharmacokinetics , Lysosomes/metabolism , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Animals , Cisplatin/pharmacology , Drug Resistance , Drug Resistance, Neoplasm , Female , Humans , Lysosomal-Associated Membrane Protein 1/metabolism , Lysosomal-Associated Membrane Protein 2/metabolism , Secretory Vesicles/metabolism , Tumor Cells, Cultured
12.
Clin Cancer Res ; 11(2 Pt 1): 756-67, 2005 Jan 15.
Article in English | MEDLINE | ID: mdl-15701866

ABSTRACT

PURPOSE: We sought to identify the subcellular compartments in which cisplatin [cis-diamminedichloroplatinum (DDP)] accumulates in human ovarian carcinoma cells and define its export pathways. EXPERIMENTAL DESIGN: Deconvoluting digital microscopy was used to identify the subcellular location of fluorescein-labeled DDP (F-DDP) in 2008 ovarian carcinoma cells stained with organelle-specific markers. Drugs that block vesicle movement were used to map the traffic pattern. RESULTS: F-DDP accumulated in vesicles and were not detectable in the cytoplasm. F-DDP accumulated in the Golgi, in vesicles belonging to the secretory export pathway, and in lysosomes but not in early endosomes. F-DDP extensively colocalized with vesicles expressing the copper efflux protein, ATP7A, whose expression modulates the cellular pharmacology of DDP. Inhibition of vesicle trafficking with brefeldin A, wortmannin, or H89 increased the F-DDP content of vesicles associated with the pre-Golgi compartments and blocked the loading of F-DDP into vesicles of the secretory pathway. The importance of the secretory pathway was confirmed by showing that wortmannin and H89 increased whole cell accumulation of native DDP. CONCLUSIONS: F-DDP is extensively sequestered into vesicular structures of the lysosomal, Golgi, and secretory compartments. Much of the distribution to other compartments occurs via vesicle trafficking. F-DDP detection in the vesicles of the secretory pathway is consistent with a major role for this pathway in the efflux of F-DDP and DDP from the cell.


Subject(s)
Antineoplastic Agents/pharmacology , Biological Transport , Cisplatin/pharmacology , Fluorescein , Ovarian Neoplasms/metabolism , Adenosine Triphosphatases/metabolism , Androstadienes/pharmacology , Antineoplastic Agents/metabolism , Brefeldin A/pharmacology , Cation Transport Proteins/metabolism , Cell Nucleus/metabolism , Cisplatin/metabolism , Contrast Media , Copper/chemistry , Copper/metabolism , Copper-Transporting ATPases , Cytoplasm/metabolism , Female , Golgi Apparatus/metabolism , Humans , Isoquinolines/pharmacology , Lysosomes/metabolism , Microscopy, Confocal , Microscopy, Fluorescence , Ovarian Neoplasms/drug therapy , Protein Kinase Inhibitors/pharmacology , Protein Synthesis Inhibitors/pharmacology , Recombinant Fusion Proteins/metabolism , Subcellular Fractions , Sulfonamides/pharmacology , Tumor Cells, Cultured , Wortmannin
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