Controlling glass forming kinetics in 2D perovskites using organic cation isomers.

The recent discovery of glass-forming metal halide perovskites (MHPs) provides opportunities to broaden the application domain beyond traditionally celebrated optoelectronic research fueled by associated crystalline counterparts. In this regard, it is crucial to diversify the compositional space of glass-forming MHPs and introduce varied crystallization kinetics via synthetic structural engineering. Here, we compare two MHPs with slightly varying structural attributes, utilizing isomer organic cations with the same elemental composition, and demonstrate how this change in functional group position impacts the kinetics of glass formation and subsequent crystallization by multiple orders of magnitude. (S)-(-)-1-(1-Naphthyl)ethylammonium lead bromide (S(1-1)NPB) exhibits a lower melting point (Tm) of 175 °C and the melt readily vitrifies under a critical cooling rate (CCR) of 0.3 °C s-1. In contrast, (S)-(-)-1-(2-naphthyl)ethylammonium lead bromide (S(1-2)NPB) displays a Tm ∼193 °C and requires a CCR of 2500 °C s-1, necessitating the use of ultrafast calorimetry for glass formation and study of the underlying kinetics. The distinct Tm and glass-formation kinetics of the isomer MHPs are further understood through a combination of calorimetric and single-crystal X-ray diffraction studies on their crystalline counterparts, highlighting the influence of altered organic-inorganic hydrogen bonding interactions and entropic changes around melting, providing insights into the factors driving their divergent behaviors.

Radiographic Outcomes of Titanium Augment vs Bone Graft in Lateral Column Lengthening for Adult-Acquired Flatfoot Deformity.

Background: Lateral column lengthening (LCL) is a surgical procedure used to manage forefoot abduction and, in theory, also increases the longitudinal arch by plantarflexion of the first ray through tensioning the peroneus longus for patients with stage IIB adult acquired flatfoot deformity (AAFD). This procedure utilizes an opening wedge osteotomy of the calcaneus, which is then filled with autograft, allograft, or a porous metal wedge. The primary aim of this study was to compare the radiographic outcomes of these different bone substitutes following LCL for stage IIB AAFD. Methods: We conducted a retrospective review of all patients who underwent LCL from October 2008 until October 2018. Preoperative weightbearing radiographs, initial postoperative radiographs, and 1-year weightbearing radiographs were reviewed. The following radiographic measurements were recorded: incongruency angle, talonavicular coverage angle (TNCA), talar-first metatarsal angle (T-1MT), and calcaneal pitch. Results: A total of 44 patients were included in our study. The mean age of the cohort was 54 (range, 18-74). The study cohort was divided into 2 groups. There were 17 (38.7%) patients who received a titanium metal wedge and 27 (61.5%) that received autograft or allograft. Patients that underwent LCL with the autograft/allograft group were significantly older (59 vs 47 years old, P = .006). Patients who underwent LCL with a titanium wedge had a significantly higher preoperative talonavicular angle (32 vs 27 degrees, P = .013). There were no significant differences in postoperative TNCA, incongruency angle, or calcaneal pitch at 6 months or 1 year. Conclusion: At 6 months and 1 year, no radiographic differences were found between autograft/allograft bone substitutes vs titanium wedge in LCL. Level of Evidence: Level III, retrospective cohort study.

Partisan polarization, historical heritage, and public health: Exploring COVID-19 outcomes.

When the COVID-19 virus first arrived in the United States in early 2020, many epidemiologists and public health officers counseled for shutdowns and advised policymakers to prepare for a major pandemic. In 2020, though, US society was rife with major political and cultural divides. Some elected leaders promoted policies at odds with the experts, and many people refused to heed the public health-based communications about the coming pandemic. Additionally, the capacity to respond to a pandemic was distributed in the country in a highly unequal fashion. This paper analyzes the noteworthy geopolitical patterns of COVID-19 illnesses, subsequent demands on hospitals, and resulting deaths. This description is based on a snapshot of archival data gathered in the midst of the pandemic during late January and early February of 2021. Demographic data, indicators of political party support, indicators of citizen attitudes, and public health compliance behaviors are combined in a multivariate analysis to explain COVID-19 outcomes at the local government (county) level. The analysis suggests strongly that regional political culture and local demographics played a substantial role in determining the severity of the public health impact of the COVID-19 pandemic.

Cuando el virus COVID­19 llegó por primera vez a los Estados Unidos a principios de 2020, muchos epidemiólogos y funcionarios de salud pública recomendaron cierres y aconsejaron a los legisladores que se prepararan para una gran pandemia. Sin embargo, en 2020, la sociedad estadounidense estaba plagada de grandes divisiones políticas y culturales. Algunos líderes electos promovieron políticas en desacuerdo con los expertos, y muchas personas se negaron a prestar atención a las comunicaciones basadas en la salud pública sobre la próxima pandemia. Además, la capacidad de respuesta ante una pandemia se distribuyó en el país de manera muy desigual. Este documento analiza los patrones geopolíticos notables de las enfermedades de COVID­19, las demandas posteriores en los hospitales y las muertes resultantes. Esta descripción se basa en una instantánea de los datos de archivo recopilados en medio de la pandemia a fines de enero y principios de febrero de 2021. Los datos demográficos, los indicadores de apoyo a los partidos políticos, los indicadores de las actitudes de los ciudadanos y los comportamientos de cumplimiento de la salud pública se combinan en un modelo multivariado. análisis para explicar los resultados de COVID­19 a nivel del gobierno local (condado). El análisis sugiere fuertemente que la cultura política regional y la demografía local desempeñaron un papel importante en la determinación de la gravedad del impacto de la pandemia de COVID­19 en la salud pública.

The impact of total knee arthroplasty on golfing activity.

Background: Total knee arthroplasty (TKA) is frequently performed among individuals who golf. This study examines the effect of TKA on pre- and postoperative pain, frequency of sport participation, handicap, driving distance, use of a cart, and overall game enjoyment. Methods: This is a survey-based retrospective review of 71 patients after primary TKA at a tertiary medical facility in upstate New York. Patients were evaluated using postoperative pain scores and asked to complete a survey that included questions about their return to sport. Results: A total of 71 patients were included, with an average age of 70 years old. Postoperatively 85% of patients returned to play within 7.9 months, driving distance increased by 4 yards, patients' golf game improved by 1.07 strokes, and pain during and after golf was significantly decreased. Most patients did not change golf cart usage, and reported unchanged or improved performance in and enjoyment of golf. Conclusions: We found that a majority of patients undergoing TKA returned to playing golf postoperatively. Patients were more likely to report decreased pain both before and after play and positive changes to their golf game. Our results suggest that most patients can expect to return to golf after TKA and the majority will enjoy the sport with less pain postoperatively.

Patient Positioning for Proximal Femur Fracture Fixation: a Review of Best Practices.

PURPOSE OF REVIEW: Proximal femur fractures are common traumatic injuries treated by orthopedic surgeons. Preparation and positioning for surgical intervention are critical in the proper management of proximal femur fractures. The purpose of this study was to review the current evidence on the various positioning options for patients and to highlight the principles and emerging techniques to help orthopedic surgeons treat this common injury. RECENT FINDINGS: Strategic patient positioning is key to the reduction and fixation of proximal femur fractures without complications. The use of intramedullary devices for the fixation of proximal femur fractures has led to an increased use of the modern fracture table. The fracture table should be used when surgeons are facile with its use to avoid significant complications. Recent best available evidence has suggested increased risk of malrotation associated with the use of the fracture table. The use of the radiolucent table offers the most flexibility, but limits surgeons as multiple assistants are needed to maintain reduction during fixation. Positioning for proximal femur fractures is an important technique for general and trauma orthopedic surgeons. Surgeons need to be aware of the various techniques for positioning of proximal femur fractures due to the diversity of injury patterns and patient characteristics. Each positioning technique has it benefits and potential complications that every orthopaedic surgeon should be familiar with while treating these injuries.

Evolving Patient Perception of Limb Length Discrepancy Following Total Hip Arthroplasty.

BACKGROUND: Limb length discrepancy (LLD) is a known complication of total hip arthroplasty (THA), leading to decreased patient function and satisfaction. It remains unknown how a patient's perception of LLD evolves over time. The aim of this study is to evaluate the relationship between measured and perceived LLD, and to assess whether perceived LLD resolved with time in most patients. METHODS: This study retrospectively reviewed radiographs of 140 consecutive patients undergoing primary THA by a single surgeon via a direct anterior approach, calculating postoperative change in limb length (ΔL). Patient perceptions of LLD were recorded at standard postoperative visit intervals. A P-value of .05 was used to determine statistical significance. RESULTS: Of 130 patients (mean ΔL = +7.9 mm), 22 patients endorsed perceived postoperative LLD and the remainder were asymptomatic (mean ΔL +11.1 mm vs +7.3 mm, P = .03). Seventeen patients reported mild symptoms and 5 reported severe symptoms (mean ΔL +10.2 mm vs +13.8 mm, P = .4). After 1 year, 45% (10) patients reported complete resolution of perceived LLD (mean follow-up 364 days), 18% (4) reported notable improvement, and 36% (8) reported no improvement. Four excluded patients endorsed perceived LLD (2 mild, 2 severe), which resolved after contralateral THA. CONCLUSION: This study noted a correlation between increasing postoperative ΔL and perceived LLD. A majority of patients (63%) experienced either improvement or full resolution of symptoms during the follow-up period. This data may have a role in reassuring the orthopedic surgeon and the patient regarding the natural course of postoperative LLD. Further investigation is needed to help identify risk factors for persistent LLD. LEVEL OF EVIDENCE: Level III (Prognostic).

Oral health implications in total hip and knee arthroplasty patients: A review.

Over the past two decades, oral health has emerged as a health care priority. Historically, patients greater than 65 years of age, the economically disadvantaged, members of racial or ethnic minority groups, or the disabled or home bound have experienced significant barriers to routine dental care. The connection between oral health care and periprosthetic joint infections (PJI) continues to be of importance to the orthopedic surgeon, as such infections are significantly morbid and costly. This review aims to introduce the importance of oral health as a small but crucial portion of an arthroplasty patient's overall perioperative management.

Outcomes of a Total Joint Arthroplasty Enhanced Recovery Program in a Community Hospital Setting.

BACKGROUND: Same-day discharge (SDD) total joint arthroplasty (TJA) is increasingly popular, yet there remain concerns regarding patient safety, complication rates, and unforeseen overnight admission (failure to launch; FTL). The aim of this study is to retrospectively examine the outcomes of a large consecutive SDD-TJA series in the community hospital setting. METHODS: We retrospectively reviewed 1200 consecutive SDD-TJA candidates between March 2017 and December 2019 by 5 surgeons at a community hospital. Patient demographics, perioperative data including anesthesia type, and 30-day complications were evaluated, including FTL, infection, intraoperative fracture, postoperative periprosthetic fracture or dislocation, return to operating room, and unplanned postoperative care. RESULTS: We included 1200 SDD patients (582/618 total hip arthroplasty/total knee arthroplasty, mean age 62.1 years, 595 females, 605 males). Spinal anesthesia was more common than general anesthesia (1087 vs 113 patients). There were 85 FTLs (7.1%), of this cohort 58.8% were female, with a mean age of 62.4 years. General anesthesia increased the risk of FTL (odds ratio 2.93). Complications resulting in FTL included block-induced neuropraxia (32.1%), orthostatic hypotension (26.1%), urinary retention (19.0%), and nausea (13.1%). Sixteen patients were readmitted within 30 days (1.3%). Six patients returned to the operating room for periprosthetic fracture (4), wound dehiscence (1), and superficial surgical site infection (1). CONCLUSION: SDD-TJA can be safely performed at community hospitals, but general anesthesia should be avoided to decrease risk of FTL. Inpatient programs may allow young surgeons to gain experience with SDD-TJA while retaining overnight admission as a safety net for their patients. LEVEL OF EVIDENCE: Level III (Prognostic).

The Quality of Online Orthopaedic Oncology Information.

"Cancer" is one of the top three health-related Internet searches, yet research shows over 30% of patients are confused after searching for medical information. The quality and accuracy of Internet oncology literature varies widely and can affect patient perceptions or seeking of care. Purpose: This study hypothesizes that online patient resources for orthopaedic oncology are often inconsistent, inaccurate, or incomprehensible by the standard patient and examines the readability, quality, and accuracy of common orthopaedic oncology websites. Methods: Three common search terms were searched in three popular search engines. The first 25 nonsponsored websites were identified for each term; randomized to search term; and evaluated via a 25-question quality score, DISCERN treatment-based score, predetermined accuracy score, and Flesch-Kincaid reading level. Results: Forty-eight websites were included. Website quality, DISCERN score, accuracy score, and reading level were not statistically different based on search term. Quality and DISCERN scores were markedly higher from websites without commercial gain. Websites were consistently written above the recommended reading level. Discussion: Online orthopaedic oncology literature is frequently confusing and complicated. The orthopaedic surgeon should be aware that patients frequently access this information and should ensure that patients receive accurate primary source material relevant to their care.

Chronic Obstructive Pulmonary Disease Is Associated With Higher Rates of Venous Thromboemboli Following Primary Total Knee Arthroplasty.

BACKGROUND: There is discordance in the literature regarding the presence of chronic obstructive pulmonary disease (COPD) and the development of venous thromboemboli (VTEs). Therefore, the purpose of this study is to determine whether COPD patients undergoing primary total knee arthroplasty (TKA) have higher rates of (1) in-hospital lengths of stay (LOS); (2) readmissions; (3) VTEs; and (4) costs of care. METHODS: COPD patients undergoing primary TKA were identified and matched to controls in a 1:5 ratio by age, gender, and medical comorbidities. Patients with a history of VTEs or hypercoagulable states were excluded. The query yielded 211,378 patients in the study (n = 35,230) and control (n = 176,148) cohorts. Outcomes analyzed included in-hospital LOS, readmission rates, VTEs, and costs of care. A P-value less than .01 was considered statistically significant. RESULTS: COPD patients were found to have significantly longer in-hospital LOS (4 vs 3 days, P < .0001). Study group patients were also found to have significantly higher incidence and odds ratio (OR) of readmission rates (20.9% vs 16.3%; OR 1.36, P < .0001) and VTEs (1.75 vs .93; OR 1.18, P < .0001). Additionally, the study demonstrated that COPD patients incurred higher 90-day episode-of-care costs ($15,626.85 vs $14,471.29, P < .0001). CONCLUSION: After adjusting for confounding variables, our study found an association between COPD and higher rates of developing VTEs following primary TKA. The study can be used by orthopedic surgeons to adequately counsel and educate these patients of the potential complications which may arise following their TKA.

Cannabinoid Use in Musculoskeletal Illness: a Review of the Current Evidence.

PURPOSE OF REVIEW: The use of cannabinoids has increased since legalization of recreational and medical use in the USA. It is likely that many orthopaedic patients consume cannabinoid products during the traumatic or perioperative period. The purpose of this study was to investigate the pre-clinical data evaluating the mechanism of action of cannabidiol (CBD) and Δ9-Tetrahydrocannabinol (Δ9-THC) and to evaluate the current clinical data on the use of cannabinoids in musculoskeletal illness. RECENT FINDINGS: Recent pre-clinical studies have demonstrated that cannabinoid use and the endocannabinoid system (ECS) has an important role in bone healing and bone homeostasis. There is data that suggests that the use of cannabidiol (CBD) may increase bone healing, whereas the use of Δ9-Tetrahydrocannabinol (Δ9-THC), the major psychoactive ingredient in marijuana, likely inhibits bone metabolism and repair. The clinical implications and consumption of marijuana by orthopaedic patients have not been thoroughly evaluated. Studies have demonstrated concern for negative cardiovascular and psychiatric effects caused by marijuana use, but have not yet elucidated outcomes in the orthopaedic literature. With the recent increase in advertising of CBD products and legalization of marijuana, it is likely that many orthopaedic patients are consuming cannabinoid products. The clinical implications and consumption of these products are unclear. We need more robust and well-designed clinical studies prior to making further recommendations to our patients on the consumption of these products.

Clinical and functional outcomes of total hip arthroplasty in patients with cerebral palsy: A systematic review.

Hip joint subluxation and dislocations are very common in cerebral palsy (CP) patients and are directly related to a patient's degree of spasticity. Hip dislocation and subluxation leads to hip pain and difficulty in hygiene maintenance by a caregiver. Most cases require surgical intervention to improve the quality of life in these patients. For many years pelvic and proximal femoral osteotomies with soft tissue releases were the mainstay of treatment for affected hips in CP patients. Recently, hip arthroplasty has been proposed as a very successful operation which provides a pain free and mobile joint in CP patients. The purpose of this review is to evaluate the current evidence for effectiveness of total hip arthroplasty in CP patients.

Diagnosis and Treatment of Peritalar Injuries in the Acute Trauma Setting: A Review of the Literature.

The bony and ligamentous structure of the foot is a complex kinematic interaction, designed to transmit force and motion in an energy-efficient and stable manner. Visible deformity of the foot or atypical patterns of swelling should raise significant concern for foot trauma. In some instances, disruption of either bony structure or supporting ligaments is identified years after injury due to chronic pain in the hindfoot or midfoot. This article will focus on injuries relating to the peritalar complex, the bony articulation between the tibia, talus, calcaneus, and navicular bones, supplemented with multiple ligamentous structures. Attention will be given to the five most common peritalar injuries to illustrate the nature of each and briefly describe methods for achieving the correct diagnosis in the context of acute trauma. This includes subtalar dislocations, chopart joint injuries, talar fractures, navicular fractures, and occult calcaneal fractures.

Acute Superficial Peroneal Nerve Entrapment Mimicking Compartment Syndrome: A Case Report.

CASE: A 48-year-old man presented with foot drop and peroneal nerve paresthesia after a suspected ankle sprain. The patient was taken to the operating room for nerve exploration and anterior and lateral compartment releases. Diagnosis of superficial peroneal nerve (SPN) entrapment was made intraoperatively. CONCLUSION: Motor deficits in the setting of SPN entrapment may indicate overlapping compartment syndrome or pseudoparalysis from pain inhibition and not neural compression. This adds an increased level of complexity to an already challenging diagnosis to make. Accurate diagnosis and immediate surgical interventionwith proper surgical exposure were all critical for the recovery of this patient.

Exploring the Incidence, Implications, and Relevance of Metal Allergy to Orthopaedic Surgeons.

INTRODUCTION: Allergic reactions to metal implants are increasingly recognized, but its relevance to the orthopaedic surgeon remains unclear. We evaluate the prevalence of metal allergies in a subset of the population and review the significance through a survey of the current literature. METHODS: Preoperative and postoperative patients referred for metal allergy testing were divided into two groups; those with a history of dermatitis and those without. Patients with a history of dermatitis were offered skin patch testing that included the North American Contact Dermatitis core allergen panels in addition to our metal screening series. Patients without dermatitis were tested to the more limited patch testing metal screening series. Some patients with dermatitis opted for the more limited screening, whereas some patients without dermatitis underwent more extensive testing at their request or at the request of the referring clinician. Patch tests were evaluated at 2 and 4 days after placement. RESULTS: Hundred patients were referred for metal allergy testing, 46 of whom were for reasons related to planned orthopaedic surgery. Of those tested, 60 patients had a history of dermatitis and 40 did not. Some patients were nonreactive to all tested allergens, whereas others demonstrated one or more positive skin patch test reactions. The number of positive reactions to each metal in patients with a history of dermatitis was the following: nickel 19, amalgam 10, palladium 10, copper 8, cobalt 5, mercury 5, tin 2, gold 1, titanium 1, and vanadium 1. The number of positive reactions to metals in patients without a history of dermatitis was the following: nickel 4, amalgam 5, palladium 4, mercury 4, cobalt 4, tin 2, copper 2, gold 1, vanadium 1, and molybdenum 1. DISCUSSION: Metal allergy was common in the individuals referred for testing, with reactions to nickel and amalgam being the most commonly encountered. Some individuals experience more notable allergic reactions to implanted devices than others. Localized and generalized skin reactions have been reported, along with implant failure and loosening. Surgeons should be aware of the incidence of metal allergies and the potential consequences.

Regulation of GLI Underlies a Role for BET Bromodomains in Pancreatic Cancer Growth and the Tumor Microenvironment.

PURPOSE: The initiation, progression, and maintenance of pancreatic ductal adenocarcinoma (PDAC) results from the interplay of genetic and epigenetic events. While the genetic alterations of PDAC have been well characterized, epigenetic pathways regulating PDAC remain, for the most part, elusive. The goal of this study was to identify novel epigenetic regulators contributing to the biology of PDAC. EXPERIMENTAL DESIGN: In vivo pooled shRNA screens targeting 118 epigenetic proteins were performed in two orthotopic PDAC xenograft models. Candidate genes were characterized in 19 human PDAC cell lines, heterotopic xenograft tumor models, and a genetically engineered mouse (GEM) model of PDAC. Gene expression, IHC, and immunoprecipitation experiments were performed to analyze the pathways by which candidate genes contribute to PDAC. RESULTS: In vivo shRNA screens identified BRD2 and BRD3, members of the BET family of chromatin adaptors, as key regulators of PDAC tumor growth. Pharmacologic inhibition of BET bromodomains enhanced survival in a PDAC GEM model and inhibited growth of human-derived xenograft tumors. BET proteins contribute to PDAC cell growth through direct interaction with members of the GLI family of transcription factors and modulating their activity. Within cancer cells, BET bromodomain inhibition results in downregulation of SHH, a key mediator of the tumor microenvironment and canonical activator of GLI. Consistent with this, inhibition of BET bromodomains decreases cancer-associated fibroblast content of tumors in both GEM and xenograft tumor models. CONCLUSIONS: Therapeutic inhibition of BET proteins offers a novel mechanism to target both the neoplastic and stromal components of PDAC. Clin Cancer Res; 22(16); 4259-70. ©2016 AACR.

Selective and reversible suppression of intestinal stem cell differentiation by pharmacological inhibition of BET bromodomains.

Absorptive and secretory cells of the small intestine are derived from a single population of Lgr5-expressing stem cells. While key genetic pathways required for differentiation into specific lineages have been defined, epigenetic programs contributing to this process remain poorly characterized. Members of the BET family of chromatin adaptors contain tandem bromodomains that mediate binding to acetylated lysines on target proteins to regulate gene expression. In this study, we demonstrate that mice treated with a small molecule inhibitor of BET bromodomains, CPI203, exhibit greater than 90% decrease in tuft and enteroendocrine cells in both crypts and villi of the small intestine, with no changes observed in goblet or Paneth cells. BET bromodomain inhibition did not alter the abundance of Lgr5-expressing stem cells in crypts, but rather exerted its effects on intermediate progenitors, in part through regulation of Ngn3 expression. When BET bromodomain inhibition was combined with the chemotherapeutic gemcitabine, pervasive apoptosis was observed in intestinal crypts, revealing an important role for BET bromodomain activity in intestinal homeostasis. Pharmacological targeting of BET bromodomains defines a novel pathway required for tuft and enteroendocrine differentiation and provides an important tool to further dissect the progression from stem cell to terminally differentiated secretory cell.

Nitrogen retention and partitioning at the initiation of lipid accumulation in nitrogen-deficient algae.

Nitrogen (N) deficiency promotes lipid accumulation in many oleaginous algae, but we have a poor understanding of the associations between the initiation of lipid accumulation and algal N retention and partitioning. Here, we report on total cell N, five bulk pools of N in the cell (protein, free amino acids, DNA, RNA, chl), and lipids from N saturation to growth cessation in three species. While the maximum level of N uptake differed among species, the ratio of minimum retained N to N retained at the initiation of lipid accumulation was consistent among species at 0.5 ± 0.04. This suggests that the cellular initiation of lipid accumulation was associated with a common magnitude of N deficiency among species. Concerning the partitioning of N, the concentration of RNA and the protein to RNA ratio were most similar among species at the initiation of lipid accumulation with averages of 3.2 ± 0.26 g · L(-1) (8.2% variation) and 16 ± 1.5 (9.2% variation), respectively. All other pools and physiologically relevant ratios were considerably more variable. The species commonalities in RNA and protein show a similar reduction in general cellular function due to N deficiency before cellular initiation of lipid accumulation. These results provide insight into the physiological drivers for lipid accumulation in N-deficient algae and data for modeling these associations.

MicroRNA-21 in pancreatic ductal adenocarcinoma tumor-associated fibroblasts promotes metastasis.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is projected to rise to the second leading cause of U.S. cancer-related deaths by 2020. Novel therapeutic targets are desperately needed. MicroRNAs (miRs) are small noncoding RNAs that function by suppressing gene expression and are dysregulated in cancer. miR-21 is overexpressed in PDAC tumor cells (TC) and is associated with decreased survival, chemoresistance and invasion. Dysregulation of miR regulatory networks in PDAC tumor-associated fibroblasts (TAFs) have not been previously described. In this study, we show that miR-21 expression in TAFs promotes TC invasion. METHODS: In-situ hybridization for miR-21 was performed on the 153 PDAC patient UCLA tissue microarray and 23 patient-matched lymph node metastases. Stromal and TC histoscores were correlated with clinicopathologic parameters by univariate and multivariate Cox regression. miR-21 positive cells were further characterized by immunofluorescence for mesenchymal/epithelial markers. For in vitro studies, TAFs were isolated from freshly resected human PDAC tumors by the outgrowth method. miR-21 was overexpressed/inhibited in fibroblasts and then co-cultured with GFP-MiaPaCa TCs to assess TC invasion in modified Boyden chambers. RESULTS: miR-21 was upregulated in TAFs of 78% of tumors, and high miR-21 significantly correlated with decreased overall survival (P = 0.04). Stromal miR-21 expression was also significantly associated with lymph node invasion (P = 0.004), suggesting that it is driving TC spread. Co-immunofluorescence revealed that miR-21 colocalized with peritumoral fibroblasts expressing α-smooth muscle actin. Moreover, expression of miR-21 in primary TAFs correlated with miR-21 in TAFs from patient-matched LN metastases; evidence that PDAC tumor cells induce TAFs to express miR-21. miR-21 expression in TAFs and TCs promotes invasion of TCs and is inhibited with anti-miR-21. CONCLUSIONS: miR-21 expression in PDAC TAFs is associated with decreased overall survival and promotes TC invasion. Anti-miR-21 may represent a novel therapeutic strategy for dual targeting of both tumor and stroma in PDAC.