Increased revision rates in shoulder arthroplasty following shoulder arthroscopy.

Introduction: Total shoulder arthroplasty (TSA) and reverse TSA (rTSA) are successful treatments for end-stage shoulder arthritis. However, it is unknown whether prior arthroscopy is associated with an increased risk for revision surgery. This study investigates if undergoing a shoulder arthroscopy in the year prior to primary arthroplasty increases risk of revision surgery within 2 years. Methods: Patients who underwent TSA or rTSA between 2005 and 2017 were identified in a natinal claims database and stratified into two cohorts: (1) individuals with a history of shoulder arthroscopy prior to arthroplasty and (2) individuals with no documented history of arthroscopy prior to arthroplasty. These cohorts were propensity matched based on demographic and comorbidity factors. Univariate analysis was used to determine differences in revision rates, aseptic loosening, periprosthetic fracture, and infection between the two cohorts. Results: Seven hundred and eighty-eight patients were successfully matched from the two cohorts. Revision surgery (3.4% vs. 1.4%, p = 0.001) and aseptic loosening (2.2% vs. 0.8% p = 0.021) were significantly more common in the arthroscopy cohort. Periprosthetic fracture and periprosthetic infection were not found to be significantly different between cohorts. Discussion: Shoulder arthroscopy in the year prior to shoulder arthroplasty is associated with an increased risk of complications, including revision and aseptic loosening.

Risk Factors for Sacroiliac Joint Fusion after Instrumented Spinal Fusion.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: To identify risk factors for sacroiliac (SI) joint fusion after instrumented spinal fusion. METHODS: Patients were identified from the PearlDiver BiscayneBay database. Patients who underwent 1 level (CPT: 22840), 3-6 vertebral segment (22842), and 7+ vertebral segment spinal fusions (22843 and 22844) were identified. Patients were separated based on whether they received an SI joint fusion (27280 and 27279) after their spinal fusion. A univariate analysis and multivariate logistic regression was performed to evaluate the associations between patient factors and incidence of SI joint fusion. RESULTS: 549,625 patients who underwent posterior spinal fusions were identified, 6068 of whom underwent subsequent SI joint fusion (1.1%). Factors associated with future SI joint fusion included female gender, patients with obesity, fibromyalgia, diabetes, tobacco use, increased construct length, and prior SI joint injection. Prior SI joint injection had the highest odds ratio (OR: 8.70; 95% CI: 8.25-9.16; P < 0.001), followed by 7+ vertebral segment (OR: 2.17; 95% CI: 2.03-2.33; P < 0.001) and 3-6 vertebral segment fusion (OR: 1.49; 95% CI: 1.42-1.57; P < 0.001). CONCLUSIONS: The highest predictor of requiring subsequent SI joint fusion is a prior SI joint injection. We also found that longer fusion constructs are associated with increased risk for future SI joint fusion.

Algorithms and Resources for the Monitoring of Very-Low-Frequency Signal Deviations Due to Solar Activity Using a Web-Based Software-Defined Radio-Distributed Network.

This work presents the development and testing of an experimental web-based SDR (software-defined radio) monitoring system for indirect solar activity detection, which has the ability to estimate and potentially predict various events in space and on earth, including solar flares, coronal mass ejections, and geomagnetic storms. The proposed system can be used to investigate the effect of solar activity on the propagation of very-low-frequency (VLF) signals. The advantages and benefits of the given approach are as follows: increasing measurement accuracy and eventual solar activity identification by combining measurements from multiple spatially distributed SDRs. The verification process involves carrying out several experiments comparing data from the GOES satellite system and the Dunksin SuperSID system with information received by the SDR monitoring system. Then, utilizing Pearson correlation coefficients, the measured data from the SDRs, along with those from the GOES satellite system and the Dunsing monitoring station, are investigated. At the time of a solar flare, the correlation value is above 90% for most of the stations used. Combining the signal-to-noise ratio via summation also shows an improvement in the results, with a correlation above 98%.

Predicting Delayed In-Hospital Recovery of Physical Function After Total Knee Arthroplasty.

Objective: To identify patients at high risk of delayed in-hospital functional recovery after knee replacement surgery by developing and validating a prediction model, including a combination of preoperative physical fitness parameters and patient characteristics. Design: Retrospective cohort study using binary logistic regression. Setting: University hospital, orthopedic department. Participants: 260 adults (N=260) (≥18y) with knee osteoarthritis awaiting primary unilateral total knee arthroplasty and assessed during usual care between 2016 and 2020. Intervention: Not applicable. Main Outcome Measures: Time to reach in-hospital functional independence (in days), measured by the modified Iowa Level of Assistance Scale. A score of 0 means completely independent. Potential predictor variables are a combination of preoperative physical fitness parameters and patient characteristics. Results: Binary logistic regression modeling was applied to develop the initial model. A low de Morton Mobility Index (DEMMI), walking aid use indoors, and a low handgrip strength (HGS) were the most important predictors of delayed in-hospital recovery. This model was internally validated and had an optimism-corrected R2 of 0.07 and an area under curve of 61.2%. The probability of a high risk of delayed in-hospital recovery is expressed by the following equation:Phighrisk=(1/(1+e(-(2.638-0.193×DEMMI+0.879×indoorwalkingaid-0.007×HGS))))×100%. Conclusions: The model has a low predictive value and a poor discriminative ability. However, there is a positive association between preoperative physical fitness and postoperative recovery of physical function. The validity of our model to distinguish between high and low risk, based on preoperative fitness values and patient characteristics, is limited.

Increased Complications in Octogenarians Undergoing Same-Day Discharge following Total Knee Arthroplasty: A Matched Cohort Analysis.

Same-day discharge pathways in total knee arthroplasty (TKA) are gaining popularity as a means to increase patient satisfaction and reduce overall costs, but these pathways have not been thoroughly evaluated in potentially at-risk populations, such as in patients ≥80 years old. The purpose of this study was to compare 90-day complications and mortality following same-day discharge after primary TKA in patients ≥80 years old and those <80 years old. Patients who underwent unilateral primary TKA, were discharged on postoperative day 0, and had a minimum 90-day follow-up were identified in a national insurance claims database (PearlDiver Technologies) using Current Procedural Terminology code 27447. These patients were stratified into two cohorts based upon age: (1) nonoctogenarians (<80 years old) and (2) octogenarians (≥80 years old). These cohorts were propensity matched based upon sex, Charlson comorbidity index, and obesity status. Univariate analysis was performed to determine differences in 90-day complications and mortality between the two cohorts. In total, 1,111 patients were included in each cohort. Both cohorts were successfully matched, with no observed differences in matched parameters for demographics or comorbidities. There was no significant difference in 90-day mortality between the two cohorts (p = 0.896). However, octogenarians were at significantly increased risk of postoperative atrial fibrillation (20.8 vs. 10.4%; p < 0.001), nonatrial fibrillation arrhythmias (8.4 vs. 5.6%; p = 0.009), pneumonia (4.5 vs. 2.2%; p = 0.002), stroke (3.1 vs. 1.7%; p = 0.037), heart failure (10.5 vs. 7.5%; p = 0.012), and urinary tract infection (UTI; 14.3 vs. 9.4%; p < 0.001) compared with the nonoctogenarian cohort. Relative to matched controls, octogenarians were at significantly increased risk of numerous 90-day medical complications following same-day primary TKA, including cardiopulmonary complications, stroke, and UTI. Clinicians should be cognizant of these complications and counsel patients appropriately when electing to perform same-day TKA in the octogenarian population.

Identification of a Hypomorphic FANCG Variant in Bernese Mountain Dogs.

Bernese mountain dogs (BMDs), have an overall cancer incidence of 50%, half of which is comprised of an otherwise rare tumor, histiocytic sarcoma (HS). While recent studies have identified driver mutations in the MAPK pathway, identification of key predisposing genes has been elusive. Studies have identified several loci to be associated with predisposition to HS in BMDs, including near the MTAP/CDKN2A region, but no causative coding variant has been identified. Here we report the presence of a coding polymorphism in the gene encoding FANCG, near the MTAP/CDKN2A locus. This variant is in a conserved region of the protein and appears to be specific to BMDs. Canine fibroblasts derived from dogs homozygous for this variant are hypersensitive to cisplatin. We show this canine FANCG variant and a previously defined hypomorphic FANCG allele in humans impart similar defects in DNA repair. However, our data also indicate that this variant is neither necessary nor sufficient for the development of HS. Furthermore, BMDs homozygous for this FANCG allele display none of the characteristic phenotypes associated with Fanconi anemia (FA) such as anemia, short stature, infertility, or an earlier age of onset for HS. This is similar to findings in FA deficient mice, which do not develop overt FA without secondary genetic mutations that exacerbate the FA deficit. In sum, our data suggest that dogs with deficits in the FA pathway are, like mice, innately resistant to the development of FA.

Follicular Hyperstimulation Dysgenesis: New Explanation for Adverse Effects of Excessive FSH in Ovarian Stimulation.

High follicle-stimulating hormone (FSH) doses during ovarian stimulation protocols for assisted reproductive technologies (ART) are detrimental to ovulatory follicle function and oocyte quality. However, the mechanisms are unclear. In a small ovarian reserve heifer model, excessive FSH doses lead to phenotypic heterogeneity of ovulatory size follicles, with most follicles displaying signs of premature luteinization and a range in severity of abnormalities. By performing whole transcriptome analyses of granulosa cells, cumulus cells, and oocytes from individual follicles of animals given standard or excessive FSH doses, we identified progressive changes in the transcriptomes of the 3 cell types, with increasing severity of follicular abnormality with the excessive doses. The granulosa and cumulus cells each diverged progressively from their normal phenotypes and became highly similar to each other in the more severely affected follicles. Pathway analysis indicates a possible dysregulation of the final stages of folliculogenesis, with processes characteristic of ovulation and luteinization occurring concurrently rather than sequentially in the most severely affected follicles. These changes were associated with disruptions in key pathways in granulosa and cumulus cells, which may account for previously reported reduced estradiol production, enhanced progesterone and oxytocin production and diminished ovulation rates. Predicted deficiencies in oocyte survival, stress response, and fertilization suggest likely reductions in oocyte health, which could further compromise oocyte quality and ART outcomes.

Small Molecule 20S Proteasome Enhancer Regulates MYC Protein Stability and Exhibits Antitumor Activity in Multiple Myeloma.

Despite the addition of several new agents to the armamentarium for the treatment of multiple myeloma (MM) in the last decade and improvements in outcomes, the refractory and relapsing disease continues to take a great toll, limiting overall survival. Therefore, additional novel approaches are needed to improve outcomes for MM patients. The oncogenic transcription factor MYC drives cell growth, differentiation and tumor development in many cancers. MYC protein levels are tightly regulated by the proteasome and an increase in MYC protein expression is found in more than 70% of all human cancers, including MM. In addition to the ubiquitin-dependent degradation of MYC by the 26S proteasome, MYC levels are also regulated in a ubiquitin-independent manner through the REGγ activation of the 20S proteasome. Here, we demonstrate that a small molecule activator of the 20S proteasome, TCH-165, decreases MYC protein levels, in a manner that parallels REGγ protein-mediated MYC degradation. TCH-165 enhances MYC degradation and reduces cancer cell growth in vitro and in vivo models of multiple myeloma by enhancing apoptotic signaling, as assessed by targeted gene expression analysis of cancer pathways. Furthermore, 20S proteasome enhancement is well tolerated in mice and dogs. These data support the therapeutic potential of small molecule-driven 20S proteasome activation for the treatments of MYC-driven cancers, especially MM.

Cross-species meta-analysis of transcriptome changes during the morula-to-blastocyst transition: metabolic and physiological changes take center stage.

The morula-to-blastocyst transition (MBT) culminates with formation of inner cell mass (ICM) and trophectoderm (TE) lineages. Recent studies identified signaling pathways driving lineage specification, but some features of these pathways display significant species divergence. To better understand evolutionary conservation of the MBT, we completed a meta-analysis of RNA sequencing data from five model species and ICMTE differences from four species. Although many genes change in expression during the MBT within any given species, the number of shared differentially expressed genes (DEGs) is comparatively small, and the number of shared ICMTE DEGs is even smaller. DEGs related to known lineage determining pathways (e.g., POU5F1) are seen, but the most prominent pathways and functions associated with shared DEGs or shared across individual species DEG lists impact basic physiological and metabolic activities, such as TCA cycle, unfolded protein response, oxidative phosphorylation, sirtuin signaling, mitotic roles of polo-like kinases, NRF2-mediated oxidative stress, estrogen receptor signaling, apoptosis, necrosis, lipid and fatty acid metabolism, cholesterol biosynthesis, endocytosis, AMPK signaling, homeostasis, transcription, and cell death. We also observed prominent differences in transcriptome regulation between ungulates and nonungulates, particularly for ICM- and TE-enhanced mRNAs. These results extend our understanding of shared mechanisms of the MBT and formation of the ICM and TE and should better inform the selection of model species for particular applications.

Ultrasensitive small molecule fluorogenic probe for human heparanase.

Heparanase (HPA) is a critical enzyme involved in the remodeling of the extracellular matrix (ECM), and its elevated expression has been linked with diseases such as various types of cancer and inflammation. The detection of heparanase enzymatic activity holds tremendous value in the study of the cellular microenvironment, and search of molecular therapeutics targeting heparanase, however, no structurally defined probes are available for the detection of heparanase activity. Here we present the development of the first ultrasensitive fluorogenic small-molecule probe for heparanase enzymatic activity via tuning the electronic effect of the substrate. The probe exhibits a 756-fold fluorescence turn-on response in the presence of human heparanase, allowing one-step detection of heparanase activity in real-time with a picomolar detection limit. The high sensitivity and robustness of the probe are exemplified in a high-throughput screening assay for heparanase inhibitors.

Activating Mutations in PTPN11 and KRAS in Canine Histiocytic Sarcomas.

While the genetic contributions to the predisposition of Bernese mountain dogs (BMDs) to histiocytic sarcoma (HS) remains unclear, some insights into key genetic drivers have been gained. Our group recently reported a mutation in the PTPN11 gene (E76K). We have now identified a second missense mutation in PTPN11 (G503V), and a mutation in KRAS (Q61H) present in HS cell lines. These mutations are associated with malignancies in humans, and known to be gain-of-function mutations that result in activation of the mitogen-activated protein kinase (MAPK) pathway. The goal of the present study was to evaluate the prevalence of these mutations in a large sample of HS cases from BMDs and golden retrievers, and in lymphoma cases, from a cohort of BMDs. Mutations in PTPN11 were present in HS in 41/96 (43%) BMDs, and in 3/13 (23%) golden retrievers. PTPN11 mutations E76K and G503V did not coexist in the same neoplasm. The KRAS mutation was much less frequent, with a prevalence of 3.1% (3/96). We did not identify either PTPN11 nor KRAS mutations in any of the lymphoma samples. These results point out the potential relevance of PTPN11 and KRAS mutations as activators of the oncogenic MAPK pathway for canine HS, particularly in BMDs.

Enhanced recovery in usual health care improves functional recovery after total knee arthroplasty.

BACKGROUND: The success of total knee arthroplasty (TKA) is determined by an effective surgical procedure as well as a well-organized clinical care pathway. Research has shown that day-of-surgery mobilization decreases length of stay (LOS) and complication rates. We developed, implemented, and evaluated a new clinical care pathway for patients undergoing TKA, that included early mobilization, using 'Lean Six Sigma (LSS)', with the aim of accelerating functional recovery and reducing LOS. METHODS: Data derived from physical therapy reports and LOS were compared between the old (n = 85) and the new (n = 85) clinical care pathways for time to functional recovery (using the modified Iowa Level of Assistance Scale), LOS and joint-related readmission. Group differences were evaluated using Mann-Whitney and Chi-Square tests. The clinical care pathway was redesigned using LSS-methods. RESULTS: After implementation of the new pathway, median time to functional recovery improved from 4 (2-5) to 2 days (1-8)(P < 0.001) and LOS from 7 (5-11) to 4 days (3-12)(P < 0.001), joint-related readmission declined (3.5-2.4%)(P = 0.65). CONCLUSION: Implementation of the new clinical care pathway accelerated functional recovery and reduced LOS for patients undergoing TKA. Future research should focus on having multiple discharge moments per day which might encourage patients to achieve functional recovery as soon as possible.

Femoral Contact Forces in the Anterior Cruciate Ligament Deficient Knee: A Robotic Study.

PURPOSE: To measure contact forces (CFs) at standardized locations representative of clinical articular cartilage defects on the medial and lateral femoral condyles during robotic tests with simulated weightbearing knee flexion. METHODS: Eleven human knees had 20-mm-diameter cylinders of native bone/cartilage cored from both femoral condyles at standardized locations, with each cylinder attached to a custom-built load cell that maintained the plug in its precise anatomic position. A robotic test system was used to flex the knee from 0° to 50° under 200-N tibiofemoral compression without and with a 2 Nm internal tibial torque, 5 Nm external tibial torque, and 45 N anterior tibial force (AF). CFs and knee kinematics were recorded before and after cutting the anterior cruciate ligament (ACL). RESULTS: ACL sectioning did not significantly increase medial or lateral CFs for any loading condition, with the exception of AF, in which increases in medial CF ranged from 38 N (at 15° flexion, P < .01) to 77 N (at 50° flexion, P < .002). Compared with the intact condition, ACL sectioning significantly increased anterior tibial translation by 12.33 mm (at 15° flexion, P < .001) and 17.4 mm (at 50° flexion, P < .001), and increased valgus rotation by 2.4° (at 15° flexion, P < .001) and 3.8° (at 50° flexion, P < .001). CONCLUSIONS: Our hypothesis that CF would increase after ACL section was confirmed for the AF test condition only, and only for the medial condyle beyond 10° flexion. With the ACL sectioned, it appeared that the increased CF was owing to the medial condyle riding up over the posterior tibial plateau resulting from the large anterior tibial displacements. CLINICAL RELEVANCE: Aside from our limited finding with AF, we concluded that CFs were generally unaffected by ACL section.

Variations in the Organisms Causing Deep Surgical Site Infections in Fracture Patients at a Level I Trauma Center (2006-2015).

OBJECTIVES: To quantify the current bacteriology of deep surgical site infections (SSIs) after fracture surgery at 1 institution and to compare those data with historical controls at the same institution, assessing variations in infecting organisms over the past decade. DESIGN: Retrospective review. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS: Two hundred forty-three patients requiring surgical intervention for deep SSI between January 2011 and December 2015 were compared with 211 patients requiring surgical intervention for deep SSI between December 2006 and December 2010. INTERVENTION: None. MAIN OUTCOME MEASUREMENTS: Bacteria were categorized as Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus, Enterococcus, gram-negative rods (GNR), gram-positive rods, anaerobes, or negative cultures. The proportion of each bacterial type was determined and compared with previously published data from the same trauma center (December 2006 to December 2010). RESULTS: Patients most commonly had S. aureus infections (48%), followed by GNR (40%) and CoNS (19%). The proportion of CoNS species (26% vs. 12%, P < 0.01) in infected patients was significantly higher during the current study period compared with historical controls. The proportion of S. aureus species in infected patients was significantly less during the current study period (39% vs. 56%, P < 0.01). The reduction in the proportion of S. aureus species in infected patients was driven by a decrease in the proportion of methicillin-resistant S. aureus (MRSA) in the overall sample. CONCLUSIONS: Bacteriology of deep SSI of fractures has changed substantially over the past decade at our center, specifically the proportions of GNR, CoNS, and MRSA. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Periapical Microsurgery: Do Root Canal-retreated Teeth Have More Dentinal Defects?

INTRODUCTION: This microsurgical clinical study evaluated if teeth that have undergone endodontic retreatment are associated with more dentinal defects than primary root canal-treated teeth. METHODS: One hundred fifty-five patients who underwent periapical microsurgery treatment in a private practice setting were evaluated. The root ends were resected, and the roots were inspected for the presence of dentinal defects through the surgical operating microscope with the help of a 0.8-mm-diameter light-emitting diode probe light and methylene blue dye. The root canal treatment history (primary vs retreatment) of the teeth was documented and related to the presence or absence of dentinal defects. Bivariate analysis was performed using the chi-square test, and a multivariate analysis was performed using logistic regression to evaluate possible confounding effects of patient age, sex, and tooth location on the association between treatment and the presence of dentinal defects. RESULTS: Of the 155 treated teeth, 33 were excluded (3 fractured and 30 missing treatment history). Of the remaining 122 included teeth, 73 (59.8%) had undergone primary root canal treatment and 49 (40.2%) retreatment. Sixteen teeth (22.5%) of the primary root canal group versus 33 (64.7%) of the retreatment group had dentinal defects. The proportion of retreated teeth with dentinal defects compared with primary treatment was statistically significant (P < .001) with a higher proportion of retreated teeth having dentinal defects. In the multivariate analysis, only the type of treatment was statistically significant (P < .001). CONCLUSIONS: This clinical study showed that root canal-retreated teeth are associated with more dentinal defects than primary root canal-treated teeth.

Differences in the Radius of Curvature Between Femoral Condyles: Implications for Osteochondral Allograft Matching.

BACKGROUND: The radius of curvature (ROC) is an important variable related to potential cartilage incongruities in the transplantation of a large femoral osteochondral allograft. The anterior-posterior length (APL) of a condyle is used as a criterion for donor-graft acceptance. We hypothesized that there would be a linear correlation between the ROC and APL of a condyle, that the ROC and APL would differ significantly between the medial femoral condyle (MFC) and the lateral femoral condyle (LFC), and that a donor graft from the LFC would be suitable for an MFC defect. METHODS: Knee magnetic resonance imaging scans of 147 patients with no cartilage defects were analyzed. Best-fit circles in the sagittal plane were determined at standardized locations on each condyle. Assuming the use of a 20-mm graft that was flush to the edges of the native cartilage, the central graft prominence was calculated for potential donor-host differences in the ROC. RESULTS: There was a linear correlation between the ROC and APL. There were significant differences in the mean ROC and APL between the MFC and LFC. Based on calculations of the central graft prominence among all ROC combinations within the patient group, 100% of potential medial-to-medial, 97.8% of lateral-to-lateral, and 92.5% of lateral-to-medial transplantations would produce a central graft prominence of <1 mm. On average, an allograft harvested from an LFC (mean ROC, 25.7 mm; mean APL, 69.8 mm) implanted into an MFC defect site (mean ROC, 31.9 mm; mean APL, 66.6 mm) would have a central graft prominence of 0.4 ± 0.3 mm. CONCLUSIONS: Assuming a maximum central graft prominence tolerance of +1 mm, our findings demonstrate that matching the ROC or APL would not be necessary for potential medial-to-medial or lateral-to-lateral allograft transplants within this patient group. Implantation of an LFC donor allograft into an MFC defect is also supported by our findings.

Targeting MEK in a Translational Model of Histiocytic Sarcoma.

Histiocytic sarcoma in humans is an aggressive orphan disease with a poor prognosis as treatment options are limited. Dogs are the only species that spontaneously develops histiocytic sarcoma with an appreciable frequency, and may have value as a translational model system. In the current study, high-throughput drug screening utilizing histiocytic sarcoma cells isolated from canine neoplasms identified these cells as particularly sensitive to a MEK inhibitor, trametinib. One of the canine cell lines carries a mutation in PTPN11 (E76K), and another one in KRAS (Q61H), which are associated with the activation of oncogenic MAPK signaling. Both mutations were previously reported in human histiocytic sarcoma. Trametinib inhibited sensitive cell lines by promoting cell apoptosis, indicated by a significant increase in caspase 3/7. Furthermore, in vitro findings were successfully recapitulated in an intrasplenic orthotopic xenograft mouse model, which represents a disseminated aggressive form of histiocytic sarcoma. Mice with histiocytic sarcoma xenograft neoplasms that were treated with trametinib had significantly longer survival times. Target engagement was validated as activity of ERK, downstream of MEK, was significantly downregulated in neoplasms of treated mice. Additionally, trametinib was found in plasma and neoplastic tissues within projected therapeutic levels. These findings demonstrate that in dogs, histiocytic sarcoma may be associated with a dysfunctional MAPK pathway, at least in some cases, and may be effectively targeted through MEK inhibition. Clinical trials to test safety and efficacy of trametinib in dogs with histiocytic sarcoma are warranted, and may provide valuable translational information to similar diseases in humans. Mol Cancer Ther; 17(11); 2439-50. ©2018 AACR.

Inherent differences in keratinocyte function in hidradenitis suppurativa: Evidence for the role of IL-22 in disease pathogenesis.

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease of apocrine gland-bearing skin which affects approximately 1-4% of the population. Defective keratinocyte function has been postulated to play a role in HS pathogenesis. Using an in vitro scratch assay, differences between normal, HS, and chronic wound (CW) keratinocytes were evaluated. Normal keratinocytes exhibited faster scratch closure than HS or CW, with normal samples showing 93.8% closure at 96 hours compared to 80.8% in HS (p = 0.016) and 71.5% in CW (p = 0.0012). The keratinocyte viability was similar in normal and HS (91.12 ± 6.03% and 86.55 ± 3.28%, respectively, p = 0.1583), but reduced in CW (72.34 ± 13.12%, p = 0.0138). Furthermore, apoptosis measured by annexin V/propidium iodide, was higher in CW keratinocytes (32.10 ± 7.29% double negative cells compared to 68.67 ± 10.37% in normal and 55.10 ± 9.46% in HS, p = 0.0075). Normal keratinocytes exhibited a significantly higher level of IL-1α (352.83 ± 42.79 pg/ml) compared to HS (169.96 ± 61.62 pg/ml) and CW (128.23 ± 96.61 pg/ml, p = 0.004). HS keratinocytes exhibited significantly lower amounts of IL-22 (8.01 pg/ml) compared to normal (30.24 ± 10.09 pg/ml) and CW (22.20 ± 4.33 pg/ml, p = 0.0008), suggesting that defects in IL-22 signaling may play a role in HS pathogenesis. These findings support intrinsic differences in keratinocyte function in HS which cannot be attributed to reduced keratinocyte viability or increased apoptosis.

Post-discharge adherence with venous thromboembolism prophylaxis after orthopedic trauma: Results from a randomized controlled trial of aspirin versus low molecular weight heparin.

BACKGROUND: Orthopedic trauma patients are often treated with venous thromboembolism (VTE) chemoprophylaxis with aspirin or low molecular weight heparin (LMWH) after discharge from their index admission, but adherence patterns are not known. We hypothesized that overall adherence would be moderate and greater with aspirin compared to LMWH. METHODS: We conducted a randomized controlled trial of adult trauma patients with an operative extremity fracture or any pelvic/acetabular fracture requiring VTE prophylaxis. Patients were randomized to receive either LMWH 30 mg BID or aspirin 81 mg BID. Patients prescribed outpatient prophylaxis were contacted between 10 and 21 days after discharge to assess adherence measured by the validated Morisky Medication Adherence Scale (MMAS-8). Adherence scores were compared between the two treatment arms with similar results for intention-to-treat and as-treated analyses. As-treated multivariable logistic regression was performed to determine factors associated with low-medium adherence scores. RESULTS: One hundred fifty patients (64 on LMWH, 86 on aspirin) on chemoprophylaxis at time of follow-up completed the questionnaire. As-treated analysis showed that adherence was high overall (mean MMAS 7.2 out of 8, SD 1.5) and similar for the two regimens (LMWH: 7.4 vs. aspirin: 7.0, p = 0.13). However, patients on LMWH were more likely to feel hassled by their regimen (23% vs. 9%, p = 0.02). In a multivariable model, low-medium adherence was associated with taking LMWH as the prophylaxis medication (aOR 2.34, CI 1.06-5.18, p = 0.04), having to self-administer the prophylaxis (aOR 4.44, CI 1.45-13.61, p < 0.01), being of male sex (aOR 2.46, CI 1.10-5.49, p = 0.03), and of younger age (aOR 0.72 per additional 10 years of age, CI 0.57-0.91, p < 0.01). CONCLUSIONS: Overall post-discharge adherence with VTE prophylaxis was high. Several factors, including prophylaxis by LMWH, were associated with decreased adherence. These factors should be considered when managing patients and designing efficacy trials. LEVEL OF EVIDENCE: Therapeutic, level II.