Guidelines in Practice: Sterile Technique.

Sterile technique is the collective actions taken to reduce potential contaminants in the OR and maintain a sterile field during operative or other invasive procedures. Practicing and applying the principles of sterile technique is a cornerstone of perioperative nursing and providing safe patient care. The recently updated AORN "Guideline for sterile technique" provides perioperative nurses with information on the principles of and processes associated with sterile technique. This article provides an overview of the guideline and discusses recommendations for actions to take before preparing the sterile field, while preparing and maintaining the sterile field, for limiting movement, for surgical wound classification, and for quality. It also includes a scenario describing the implementation of isolation technique (ie, clean closure) for colon procedures. Perioperative nurses should review the guideline in its entirety and apply the recommendations when practicing sterile technique.

Guidelines in Practice: Surgical Attire.

Perioperative team members wear surgical attire when working in the OR. Wearing clean surgical attire is important to maintain a high level of cleanliness for patient safety. The recently updated AORN "Guideline for surgical attire" provides perioperative nurses with recommendations for wearing surgical attire in the semirestricted and restricted areas of the perioperative setting. This article discusses recommendations for laundering; head coverings; shoes; and identification badges, access cards, and personal items. It also includes a scenario describing compliance monitoring for an updated policy related to cleaning cell phones and performing hand hygiene after cell phone use. Perioperative nurses should review the guideline in its entirety and apply the recommendations for wearing surgical attire in the perioperative environment.

Guidelines in Practice: Safe Patient Handling and Movement.

The perioperative environment presents unique ergonomic challenges related to lifting and moving patients. These challenges place perioperative team members and patients at an increased risk for injury. The updated AORN "Guideline for safe patient handling and movement" provides perioperative nurses with guidance on safe patient handling and movement practices to help minimize the incidence of injuries to patients and health care workers. This article provides an overview of the guideline and discusses recommendations for a safe patient handling and mobility (SPHM) program, ergonomic planning and facility design, SPHM technology, an individualized SPHM and ergonomic plan, and fall risk and mobility assessments. It also includes a scenario describing concerns related to patient and perioperative team member safety. Perioperative nurses should review the guideline in its entirety and apply the recommendations for safe patient handling and movement.

Guidelines in Practice: Team Communication.

The perioperative setting is a complex environment requiring interdisciplinary team collaboration to avoid adverse events. To protect the safety of patients and perioperative team members, communication among personnel should be clear and effective. The recently updated AORN "Guideline for team communication" provides perioperative nurses with recommendations on the topic. To promote effective communication in perioperative areas, all personnel should value and commit to a culture of safety. This article discusses recommendations for supporting a culture of safety, developing and implementing an effective hand-off process and surgical safety checklist, and developing education strategies for team communication. It also includes a scenario describing the implementation of a standardized, electronic surgical safety checklist in the OR. Perioperative nurses should review the guideline in its entirety and apply the recommendations for team communication in their working environments.

MAPK phosphatase 1 inhibition of p38α within lung myofibroblasts is essential for spontaneous fibrosis resolution.

Fibrosis following tissue injury is distinguished from normal repair by the accumulation of pathogenic and apoptosis-resistant myofibroblasts (MFs), which arise primarily by differentiation from resident fibroblasts. Endogenous molecular brakes that promote MF dedifferentiation and clearance during spontaneous resolution of experimental lung fibrosis may provide insights that could inform and improve the treatment of progressive pulmonary fibrosis in patients. MAPK phosphatase 1 (MKP1) influences the cellular phenotype and fate through precise and timely regulation of MAPK activity within various cell types and tissues, yet its role in lung fibroblasts and pulmonary fibrosis has not been explored. Using gain- and loss-of-function studies, we found that MKP1 promoted lung MF dedifferentiation and restored the sensitivity of these cells to apoptosis - effects determined to be mainly dependent on MKP1's dephosphorylation of p38α MAPK (p38α). Fibroblast-specific deletion of MKP1 following peak bleomycin-induced lung fibrosis largely abrogated its subsequent spontaneous resolution. Such resolution was restored by treating these transgenic mice with the p38α inhibitor VX-702. We conclude that MKP1 is a critical antifibrotic brake whose inhibition of pathogenic p38α in lung fibroblasts is necessary for fibrosis resolution following lung injury.

Guidelines in Practice: Manual High-Level Disinfection.

There are several steps involved when performing high-level disinfection (HLD) of semicritical devices. The recently updated AORN "Guideline for manual high-level disinfection" provides perioperative nurses with evidence-based best practices for performing safe and effective HLD of reusable semicritical items. The guideline also addresses preventing injury to patients and health care workers associated with the handling of high-level disinfectants. This article provides an overview of the guideline and discusses recommendations for selection of a processing method, sterile processing areas, preparation of items for HLD, preparation of high-level disinfectants, manual HLD, drying and storage of items after HLD, and processing records. It also includes a scenario that illustrates specific concerns related to performing quality tests on high-level disinfectant solutions. Perioperative nurses should review the guideline in its entirety and apply the recommendations when performing manual HLD.

GTP Signaling Links Metabolism, DNA Repair, and Responses to Genotoxic Stress.

How cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links metabolism to DNA repair and has significant therapeutic implications. GTP, but not other nucleotides, regulates the activity of Rac1, a guanine nucleotide-binding protein, which promotes the dephosphorylation of serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5). Dephosphorylated Abi-1, a protein previously not known to activate DNA repair, promotes nonhomologous end joining. In patients and mouse models of glioblastoma, Rac1 and dephosphorylated Abi-1 mediate DNA repair and resistance to standard-of-care genotoxic treatments. The GTP-Rac1-PP5-Abi-1 signaling axis is not limited to brain cancer, as GTP supplementation promotes DNA repair and Abi-1-S323 dephosphorylation in nonmalignant cells and protects mouse tissues from genotoxic insult. This unexpected ability of GTP to regulate DNA repair independently of deoxynucleotide pools has important implications for normal physiology and cancer treatment. SIGNIFICANCE: A newly described GTP-dependent signaling axis is an unexpected link between nucleotide metabolism and DNA repair. Disrupting this pathway can overcome cancer resistance to genotoxic therapy while augmenting it can mitigate genotoxic injury of normal tissues. This article is featured in Selected Articles from This Issue, p. 5.

Guidelines in Practice: Design and Maintenance of the Surgical Suite.

Hospital construction and renovation is an ongoing occurrence in the health care setting. The recently updated AORN "Guideline for design and maintenance of the surgical suite" provides perioperative nurses with information on the layout design and maintenance of perioperative spaces; safety measures to use during construction and renovation; monitoring and maintenance of the heating, ventilation, and air conditioning; and how to respond to unintended utility failures. This article provides an overview of the guideline and discusses recommendations for the interdisciplinary team, planning and designing the surgical suite, construction-related environmental contamination, ORs, and OR maintenance. It also includes a scenario describing specific concerns associated with the construction of an additional OR. Perioperative nurses should review the guideline in its entirety and apply the recommendations when participating in perioperative construction and renovation projects.

Guidelines in Practice: Medication Safety.

Medication errors are preventable events that health care professionals, consumers, and medication manufacturers report to the US Food and Drug Administration. The agency receives more than 100,000 medication-related reports each year, and some reports involve patient death. A variety of sources provide perioperative nurses with information on interventions and practices to prevent medication errors, including the US Pharmacopeia, The Joint Commission, medication manufacturers' instructions for use, safety data sheets, and the updated AORN "Guideline for medication safety." This article provides an overview of the guideline and discusses recommendations for organizational oversight, procurement and storage, retrieval and preparation, labeling, and hazardous medications. It also includes a scenario that illustrates perioperative nursing practices for administering an antineoplastic medication intraoperatively. Perioperative nurses should review the guideline in its entirety and implement recommendations in operative or procedural settings.

Guidelines in Practice: Prevention of Venous Thromboembolism.

Venous thromboembolism (VTE), a condition involving deep vein thrombosis and embolism, can cause death when left untreated. Hospitalized patients and those who have recently undergone surgery or have a cancer diagnosis are at increased risk for VTE development. The updated AORN "Guideline for prevention of venous thromboembolism" provides perioperative nurses with a variety of evidence-based recommendations associated with the topic. This article provides an overview of the guideline and discusses recommendations for a VTE protocol, VTE and bleeding risk assessments, pharmacologic and mechanical VTE prophylaxis, postoperative ambulation, and patient and family education. It also includes a scenario that illustrates the importance of the VTE assessment and the use of mechanical prophylaxis for high-risk patients undergoing operative or other invasive procedures. Perioperative nurses should review the guideline in its entirety and implement recommendations in operative and procedural settings.

Guidelines in Practice: Minimally Invasive Surgery.

During minimally invasive surgery (MIS), surgeons create small and percutaneous incisions to access internal structures without open surgical incisions. Some MIS equipment is complex and challenging for perioperative nurses to manage. Patients also can experience life-threatening complications during MIS procedures. The updated AORN "Guideline for minimally invasive surgery" provides recommendations that perioperative nurses can use when caring for patients undergoing MIS procedures. This article provides an overview of the guideline and discusses several recommendations, including creating a safe environment in which to perform MIS procedures; using gas distension media, irrigation and fluid distension media, and computer-assisted navigation and robotics; and performing intraoperative magnetic resonance imaging in a hybrid OR. It also includes a scenario describing care of a patient undergoing a hysteroscopy. Perioperative nurses who care for patients undergoing MIS procedures should review the guideline in its entirety and apply the recommendations as applicable in their practice.

Guidelines in Practice: Processing Flexible Endoscopes.

Flexible endoscopes allow surgeons and proceduralists to view patients' internal organs through small incisions or natural orifices. These devices may be difficult to clean and dry adequately, and the formation of biofilm can further complicate effective cleaning. The updated AORN "Guideline for processing flexible endoscopes" provides perioperative personnel with evidence-based best practice recommendations on a variety of concepts associated with this topic. This article provides an overview of the guideline and discusses recommendations for point-of-use treatment, transport, cleaning (including verification and drying), and storage of flexible endoscopes. It also includes a scenario that illustrates the importance of adequately drying and storing flexible endoscopes. When processing flexible endoscopes, personnel should adhere to the endoscope and processing equipment manufacturers' instructions for use. Perioperative nurses should review the guideline in its entirety and implement recommendations in practice settings where flexible endoscopes are used.

Guidelines in Practice: Hand Hygiene.

Effective hand hygiene is an important part of infection prevention, especially in perioperative areas. The revised AORN "Guideline for hand hygiene" provides perioperative personnel with evidence-based practice recommendations for hand hygiene. This article presents an overview of the guideline and discusses specific recommendations for maintaining appropriate fingernail and hand condition; wearing or removing hand and wrist jewelry; performing general hand hygiene; performing surgical hand antisepsis with a traditional hand scrub or surgical hand rub; selecting sinks, faucets, and drains to avoid hand contamination; and implementing quality activities to enhance hand hygiene compliance. It also includes a scenario illustrating how nurses can use the guideline to mitigate hand dermatitis associated with surgical hand antisepsis. Perioperative nurses should review the revised guideline in its entirety and apply the recommendations as applicable for their practice.

Guidelines in Practice: Prevention of Perioperative Pressure Injury.

Immobility and lack of sensation during perioperative procedures increase the risk of patients developing pressure injuries (PIs). Such injuries can cause pain and result in serious infections, thereby leading to increased health care costs. The recently developed AORN "Guideline for prevention of perioperative pressure injury" provides perioperative nurses and leaders with applicable recommendations for preventing these injuries. In addition to a brief overview of a health care facility's interdisciplinary perioperative PI prevention program, this article discusses a variety of concepts related to PI prevention, including prophylactic materials, intraoperative considerations, hand-over communication, pediatric patient concerns, policies and procedures, quality management, and education. It also provides a pediatric patient-specific scenario that illustrates the implementation of the described recommendations. Perioperative nurses and leaders should review the guideline in its entirety and apply the recommendations to prevent PIs as appropriate for their facility and patient population.

Guidelines in Practice: Positioning the Patient.

Positioning the patient is an important perioperative task; the recently updated AORN "Guideline for positioning the patient" provides perioperative personnel with background information and evidence-based best practices for perioperative patient positioning and focuses on maintaining patient and staff member safety. The revised guideline includes recommendations for placing patients safely in a variety of positions and avoiding positioning injuries, such as postoperative vision loss. This article provides an overview of positioning recommendations for assessing patients' risk for injury, implementing safe positioning practices, placing patients in the Trendelenburg position, and preventing intraocular injuries. It also includes a patient-focused scenario on preventing adverse events associated with the Trendelenburg position that aligns with information discussed in the article. Perioperative nurses should review the guideline in its entirety and implement appropriate recommendations for positioning patients during procedures.

GTP signaling links metabolism, DNA repair, and responses to genotoxic stress.

How cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links metabolism to DNA repair and has significant therapeutic implications. GTP, but not other nucleotides, regulates the activity of Rac1, a G protein, that promotes the dephosphorylation of serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5). Dephosphorylated Abi-1, a protein previously not known to activate DNA repair, promotes non-homologous end joining. In patients and mouse models of glioblastoma, Rac1 and dephosphorylated Abi-1 mediate DNA repair and resistance to standard of care genotoxic treatments. The GTP-Rac1-PP5-Abi-1 signaling axis is not limited to brain cancer, as GTP supplementation promotes DNA repair and Abi-1-S323 dephosphorylation in non-malignant cells and protects mouse tissues from genotoxic insult. This unexpected ability of GTP to regulate DNA repair independently of deoxynucleotide pools has important implications for normal physiology and cancer treatment.

KLF4 is a therapeutically tractable brake on fibroblast activation that promotes resolution of pulmonary fibrosis.

There is a paucity of information about potential molecular brakes on the activation of fibroblasts that drive tissue fibrosis. The transcription factor Krüppel-like factor 4 (KLF4) is best known as a determinant of cell stemness and a tumor suppressor. We found that its expression was diminished in fibroblasts from fibrotic lung. Gain- and loss-of-function studies showed that KLF4 inhibited fibroblast proliferation, collagen synthesis, and differentiation to myofibroblasts, while restoring their sensitivity to apoptosis. Conditional deletion of KLF4 from fibroblasts potentiated the peak degree of pulmonary fibrosis and abrogated the subsequent spontaneous resolution in a model of transient fibrosis. A small molecule inducer of KLF4 was able to restore its expression in fibrotic fibroblasts and elicit resolution in an experimental model characterized by more clinically relevant persistent pulmonary fibrosis. These data identify KLF4 as a pivotal brake on fibroblast activation whose induction represents a therapeutic approach in fibrosis of the lung and perhaps other organs.

ATP citrate lyase links increases in glycolysis to diminished release of vesicular suppressor of cytokine signaling 3 by alveolar macrophages.

Extracellular vesicles (EVs) are important vectors for intercellular communication. Lung-resident alveolar macrophages (AMs) tonically secrete EVs containing suppressor of cytokine signaling 3 (SOCS3), a cytosolic protein that promotes homeostasis in the distal lung via its actions in recipient neighboring epithelial cells. AMs are metabolically distinct and exhibit low levels of glycolysis at steady state. To our knowledge, whether cellular metabolism influences the packaging and release of an EV cargo molecule has never been explored in any cellular context. Here, we report that increases in glycolysis following in vitro exposure of AMs to the growth and activating factor granulocyte-macrophage colony-stimulating factor inhibit the release of vesicular SOCS3 by primary AMs. Glycolytically diminished SOCS3 secretion requires export of citrate from the mitochondria to the cytosol and its subsequent conversion to acetyl-CoA by ATP citrate lyase. Our data for the first time implicate perturbations in intracellular metabolites in the regulation of vesicular cargo packaging and secretion.

Bortezomib Inhibits Lung Fibrosis and Fibroblast Activation without Proteasome Inhibition.

The U.S. Food and Drug Administration-approved proteasomal inhibitor bortezomib (BTZ) has attracted interest for its potential antifibrotic actions. However, neither its in vivo efficacy in lung fibrosis nor its dependence on proteasome inhibition has been conclusively defined. In this study, we assessed the therapeutic efficacy of BTZ in a mouse model of pulmonary fibrosis, developed an in vitro protocol to define its actions on diverse fibroblast activation parameters, determined its reliance on proteasome inhibition for these actions in vivo and in vitro, and explored alternative mechanisms of action. The therapeutic administration of BTZ diminished the severity of pulmonary fibrosis without reducing proteasome activity in the lung. In experiments designed to mimic this lack of proteasome inhibition in vitro, BTZ reduced fibroblast proliferation, differentiation into myofibroblasts, and collagen synthesis. It promoted dedifferentiation of myofibroblasts and overcame their characteristic resistance to apoptosis. Mechanistically, BTZ inhibited kinases important for fibroblast activation while inducing the expression of DUSP1 (dual-specificity protein phosphatase 1), and knockdown of DUSP1 abolished its antifibrotic actions in fibroblasts. Collectively, these findings suggest that BTZ exhibits a multidimensional profile of robust inhibitory actions on lung fibroblasts as well as antifibrotic actions in vivo. Unexpectedly, these actions appear to be independent of proteasome inhibition, instead attributable to the induction of DUSP1.

PGE2 accounts for bidirectional changes in alveolar macrophage self-renewal with aging and smoking.

Alveolar macrophages (AMs) are resident immune cells of the lung that are critical for host defense. AMs are capable of proliferative renewal, yet their numbers are known to decrease with aging and increase with cigarette smoking. The mechanism by which AM proliferation is physiologically restrained, and whether dysregulation of this brake contributes to altered AM numbers in pathologic circumstances, however, remains unknown. Mice of advanced age exhibited diminished basal AM numbers and contained elevated PGE2 levels in their bronchoalveolar lavage fluid (BALF) as compared with young mice. Exogenous PGE2 inhibited AM proliferation in an E prostanoid receptor 2 (EP2)-cyclic AMP-dependent manner. Furthermore, EP2 knockout (EP2 KO) mice exhibited elevated basal AM numbers, and their AMs resisted the ability of PGE2 and aged BALF to inhibit proliferation. In contrast, increased numbers of AMs in mice exposed to cigarette smoking were associated with reduced PGE2 levels in BALF and were further exaggerated in EP2 KO mice. Collectively, our findings demonstrate that PGE2 functions as a tunable brake on AM numbers under physiologic and pathophysiological conditions.