POU4F3 is a Sensitive and Specific Marker of Merkel Cell Carcinoma.

Although of therapeutic importance, a single sensitive and specific immunostain to distinguish Merkel cell carcinoma (MCC) from mimics is not currently available. In addition, single tumor cells are difficult to detect in sentinel lymph node biopsy. Leveraging publicly available data sets of 9264 solid tumors and over 600,000 single-cell transcriptomes, we identified POU4F3 to be a specific marker of MCC. Analyses of Pan-Cancer RNA bulk sequencing data of 24 tumor types from Tumor Cancer Genomic Atlas (TCGA) datasets as well as non-TCGA SCLC and MCC datasets confirmed POU4F3 specificity for MCC. Single-cell RNA sequencing analyses also confirmed lack of POU4F3 expression in lung small cell carcinoma as well as a variety of normal tissues. Nuclear POU4F3 immunohistochemical expression was noted in 98.7% of 153 MCCs and in only 1.7% of mimics (3 of 180 cases, including 95 small cell carcinomas of which 55 from lung and the remainder from other sites). Three POU4F3-positive non-MCC cases were from lung (2 cases) and vagina (1 case). All 153 tested MCC cases were negative for ASCL1, a key transcriptional regulator highly expressed in SCLC. NeuroD1 was seen in a subset of MCC cases (20.9%, 32/153). POU4F3 immunostain was performed on 29 sentinel lymph nodes and strong POU4F3 nuclear expression facilitated ease of metastasis detection, even single tumor cells. Our study built on prior works shows that POU4F3 to be a sensitive and specific clinical marker of MCC.

Gene expression differences associated with intrinsic hindfoot muscle loss in the jerboa, Jaculus jaculus.

Vertebrate animals that run or jump across sparsely vegetated habitats, such as horses and jerboas, have reduced the number of distal limb bones, and many have lost most or all distal limb muscle. We previously showed that nascent muscles are present in the jerboa hindfoot at birth and that these myofibers are rapidly and completely lost soon after by a process that shares features with pathological skeletal muscle atrophy. Here, we apply an intra- and interspecies differential RNA-Seq approach, comparing jerboa and mouse muscles, to identify gene expression differences associated with the initiation and progression of jerboa hindfoot muscle loss. We show evidence for reduced hepatocyte growth factor and fibroblast growth factor signaling and an imbalance in nitric oxide signaling; all are pathways that are necessary for skeletal muscle development and regeneration. We also find evidence for phagosome formation, which hints at how myofibers may be removed by autophagy or by nonprofessional phagocytes without evidence for cell death or immune cell activation. Last, we show significant overlap between genes associated with jerboa hindfoot muscle loss and genes that are differentially expressed in a variety of human muscle pathologies and rodent models of muscle loss disorders. All together, these data provide molecular insight into the process of evolutionary and developmental muscle loss in jerboa hindfeet.

Preventing Static Biofilm Formation of Staphylococcus aureus on Different Types of Surfaces Using Microbubbles.

Bacterial fouling and biofilm formation on surfaces have been ongoing problems in real life as well as in the medical field. Different approaches have been taken to tackle the issues, from costly surface modification to antibiotic-delivering strategies. In this study, we examined the potential of using stabilized microbubbles (MBs) to shield against bacterial adhesion. Three types of surfaces were tested: hydrophilic glass (hydrophilic surface), neutral hydrophobic polystyrene (PS)-coated surfaces, and negatively charged hydrophobic octadecyltrichlorosilane (OTS)-coated surfaces. By evaluating the colony-forming unit (CFU) values from each surface, MBs stabilized by 0.05 mM SDS were shown to only produce significant reduction of Staphylococcus aureus adhesion on PS surfaces, up to 60.29 and 82.32% compared to no-MB PS surfaces, and no-MB uncoated surfaces, correspondingly, due to the appropriate size, stability, and negative charges of the MB shielding layer. On the other hand, OTS coatings had an intrinsic antiadhesion effect (69.83% compared to uncoated surface), given that the negatively charged OTS-aqueous interface or surface porosity nature of the coating prohibited the attachment of MBs, leading to the elimination of the antifouling effect of MBs. Ultimately, MBs gave better shielding results than surface modification when compared to uncoated surfaces and hence can be applied more widely.

Modular air-liquid interface aerosol exposure system (MALIES) to study toxicity of nanoparticle aerosols in 3D-cultured A549 cells in vitro.

We present a novel lung aerosol exposure system named MALIES (modular air-liquid interface exposure system), which allows three-dimensional cultivation of lung epithelial cells in alveolar-like scaffolds (MatriGrids®) and exposure to nanoparticle aerosols. MALIES consists of multiple modular units for aerosol generation, and can be rapidly assembled and commissioned. The MALIES system was proven for its ability to reliably produce a dose-dependent toxicity in A549 cells using CuSO4 aerosol. Cytotoxic effects of BaSO4- and TiO2-nanoparticles were investigated using MALIES with the human lung tumor cell line A549 cultured at the air-liquid interface. Experiments with concentrations of up to 5.93 × 105 (BaSO4) and 1.49 × 106 (TiO2) particles/cm3, resulting in deposited masses of up to 26.6 and 74.0 µg/cm2 were performed using two identical aerosol exposure systems in two different laboratories. LDH, resazurin reduction and total glutathione were measured. A549 cells grown on MatriGrids® form a ZO-1- and E-Cadherin-positive epithelial barrier and produce mucin and surfactant protein. BaSO4-NP in a deposited mass of up to 26.6 µg/cm2 resulted in mild, reversible damage (~ 10% decrease in viability) to lung epithelium 24 h after exposure. TiO2-NP in a deposited mass of up to 74.0 µg/cm2 did not induce any cytotoxicity in A549 cells 24 h and 72 h after exposure, with the exception of a 1.7 fold increase in the low exposure group in laboratory 1. These results are consistent with previous studies showing no significant damage to lung epithelium by short-term treatment with low concentrations of nanoscale BaSO4 and TiO2 in in vitro experiments.

Pertussis seasonal variation in Northern Vietnam: the evidence from a tertiary hospital.

BACKGROUND: Pertussis is a highly contagious and dangerous respiratory disease that threatens children's health in many countries, including Vietnam, despite vaccine coverage. From 2015 to 2018, Vietnam experienced an increasing number of pertussis patients. Therefore, this study aimed to investigate the trend and examine the seasonal variations of pertussis in North Vietnam. METHODS: Data were collected from medical records of all under-5-year-old inpatients admitted to the National Children's Hospital in Hanoi, Vietnam (VNCH) 2015-2018. A descriptive analysis was performed to describe the distribution of incident cases by year and season. Linear multivariable regression was conducted to investigate the association between the incidence of cases and seasonality adjusted by age and vaccination status. RESULTS: We identified 1063 laboratory-confirmed patients during 2015-2018, including 247 (23.2%) severe patients. The number of pertussis patients admitted to VNCH per 1000 hospitalizations was 3.2 in 2015, compared to 1.9, 3.1, and 2.1 in 2016, 2017, and 2018, respectively. Outbreaks occurred biennially; however, there was no significant difference in the number of severe patients over this period. Most cases occurred in the hot season (509 patients, or nearly half of the study population). With the adjustment of the vaccination rate and average age, the risk of pertussis-associated hospitalization in the mild season and the hot season was 21% (95% CI [0.12; 0.3]) and 15% (95% CI [0.05; 0.25]) higher than that in the warm season, respectively. The rate of hospitalizations was high in the mild season (28.9%) and the warm season (30.8%), nearly twice as much as that in the hot season; nevertheless, the death rate was only striking high in the mild season, about 5-6 times as much as those in the other seasons. CONCLUSION: The pertussis incidence in Northern Vietnam varied between seasons, peaking in the hot season (April-July). However, severe patients and deaths increased in the mild season (December-March). Interventions, for example, communication activities on pertussis and vaccination, are of immense importance in lowering the prevalence of pertussis. In addition, early diagnoses and early warnings performed by health professionals should be encouraged.

Malignant Proliferating Pilar Tumor With Sarcomatous Transformation ("Carcinosarcoma"): Case Report With Molecular Profile.

ABSTRACT: Malignant proliferating pilar tumors (MPPTs) are rare, unique cutaneous adnexal tumors. Sarcomatous transformation in MPPTs is even rarer (4 previous cases reported). Here, we report an extraordinary case of a MPPT with sarcomatous transformation occurring on the scalp of a 63-year-old man with an in-depth molecular profile along with histologic, immunohistochemical, and follow-up data. Shared mutations in the epithelial and sarcomatous components included a loss-of-function TP53 mutation. An inactivating TP53 mutation was only identified in the epithelial component, and an inactivating CDKN2A mutation was only identified in the sarcomatous component. Copy number variations previously reported in MPPT were also identified, including 6p21.1 loss, 6q arm loss, and 15q21.1-q26.3 gain [epithelial], and 6p22.2-p22.3 loss [sarcoma]. Histologically, the tumor demonstrated juxtaposed areas of proliferating pilar tumor, carcinoma with clear cell change, and sarcomatous areas that did not stain for AE1/AE3, p40, CD34, S100 protein, and smooth muscle actin  by immunohistochemistry. The patient is alive at 2 years without evidence of recurrence or metastasis.

The Histopathology of Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic Syndrome: Report of 12 Skin Biopsies From 6 Patients.

ABSTRACT: We present the histopathology of 12 skin biopsies from 6 patients with vacuoles, enzyme E1, X-linked, autoinflammatory, somatic syndrome and review the literature. The age of these 6 men ranges from 62 to 83 years (median of 70 years). UBA1 mutation was documented in all 6 patients. Multiple organ systems were involved with constitutional symptoms noted in 4 of 6 patients (67%), cutaneous involvement in 6 of 6 patients (100%), hematologic abnormalities in 6 of 6 patients (100%), pulmonary involvement in 4 of 6 patients (67%), musculoskeletal abnormalities in 3 of 6 patients (50%), vascular thrombosis in 2 of 6 patients (33%), ocular involvement in 2 of 6 patients (33%), and gastrointestinal involvement in 5 of 6 patients (83%). Of the 6 presented patients, neutrophilic dermatosis was seen in 3 biopsies, histiocytoid neutrophilic dermatosis in 1 biopsy, neutrophilic dermatosis with vasculitis in 1 biopsy, neutrophilic and granulomatous dermatitis in 2 biopsies, septal panniculitis consistent with erythema nodosum in 2 biopsies, and nonspecific patterns in 3 biopsies. In summary, neutrophilic dermatosis, small-vessel vasculitis, and panniculitis are frequent histopathologic patterns noted in decreasing frequency in skin biopsies of the patients with vacuoles, enzyme E1, X-linked, autoinflammatory, somatic syndrome. However, the histopathologic findings can be diverse, nonspecific in some instances, and varied among different biopsies obtained from the same patient.

Amphiphiles Formed from Synthetic DNA-Nanomotifs Mimic the Stepwise Dispersal of Transcriptional Clusters in the Cell Nucleus.

Stem cells exhibit prominent clusters controlling the transcription of genes into RNA. These clusters form by a phase-separation mechanism, and their size and shape are controlled via an amphiphilic effect of transcribed genes. Here, we construct amphiphile-nanomotifs purely from DNA, and we achieve similar size and shape control for phase-separated droplets formed from fully synthetic, self-interacting DNA-nanomotifs. Increasing amphiphile concentrations induce rounding of droplets, prevent droplet fusion, and, at high concentrations, cause full dispersal of droplets. Super-resolution microscopy data obtained from zebrafish embryo stem cells reveal a comparable transition for transcriptional clusters with increasing transcription levels. Brownian dynamics and lattice simulations further confirm that the addition of amphiphilic particles is sufficient to explain the observed changes in shape and size. Our work reproduces key aspects of transcriptional cluster formation in biological cells using relatively simple DNA sequence-programmable nanostructures, opening novel ways to control the mesoscopic organization of synthetic nanomaterials.

Effect of single versus grouped culture of human cumulus-oocyte complexes in PCOS women treated with biphasic in vitro maturation: A sibling oocyte pilot study.

Purpose: This study investigated the differences in the maturation rate of single versus grouped cumulus-oocyte complexes (COCs) culture methods for capacitation in vitro maturation (CAPA-IVM) in women with polycystic ovary syndrome (PCOS). Methods: This study was performed at My Duc Phu Nhuan Hospital, Vietnam from October 1, 2020 to October 24, 2021. Women aged 18-37 years with a diagnosis of PCOS were recruited. COCs from each woman were randomly divided into two groups: single or grouped culture during CAPA-IVM culture. The primary outcome was the maturation rate. Results: A total of 322 COCs from 15 eligible women included were randomly assigned to the two study groups. The maturation rate was comparable between the single and grouped culture groups (61.3% vs. 64.8%; p = 0.56). There were no significant differences in the number of 2-pronuclei fertilized oocytes, number of day-3 embryos, and number of good-quality embryos in the two culture method groups. In the single culture group, COCs morphology was associated with the day-3 embryo formation rate but not the maturation rate. Conclusions: Comparable oocyte maturation and embryology outcomes between single and grouped COCs culture utilizing sibling COCs derived from women with PCOS suggest the feasibility of both methods for CAPA-IVM culture.

Combinations of EGFR and MET inhibitors reduce proliferation and invasiveness of mucosal melanoma cells.

Mucosal melanoma (MM) is a very rare and aggressive type of cancer for which immunotherapy or targeted therapy such as BRAF/MEK inhibitors, used in cutaneous melanoma, usually fail. Due to our earlier experience showing the high effectiveness of epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (MET) inhibitors in reducing the activation of the MAPK and PI3K/AKT signalling pathways, we aim to test whether these drugs would also be effective for mucosal melanoma. Cells representing two commercially available mucosal melanoma cell lines (GAK and HMVII) and one cell line obtained from a patient's vaginal melanoma were treated with MET or EGFR inhibitors, or combinations of these agents. The dual-inhibitor treatment strategy resulted in a decrease of cell proliferation, migration and invasion. Moreover, combinations of inhibitors led to reduction of pEGFR/EGFR and pMET/MET ratio and downregulation of PI3K/AKT and MEK/ERK1/2-based signalling pathways. Our findings indicate a potential therapeutic strategy based on EGFR and MET inhibitors in mucosal melanoma, which should be further evaluated in vivo and in clinical experiments. They also suggest that targeting multiple receptor tyrosine kinases may block signalling crosstalk and possibly delay the appearance of resistance to kinase inhibitors in mucosal melanoma cells.

Expression of Genes Associated With Epithelial-Mesenchymal Transition in Merkel Cell Polyomavirus-Negative Merkel Cell Carcinoma.

Two accepted possible pathways for Merkel cell carcinoma (MCC) pathogenesis include the clonal integration of the Merkel cell polyomavirus (MCPyV) into the neoplastic cells and by UV irradiation. We hypothesize that, in UV etiology, the expression of genes associated with epithelial-mesenchymal transition (EMT) would be higher in MCPyV-negative MCCs. We compared RNA expression in 16 MCPyV-negative with that in 14 MCPyV-positive MCCs in 30 patients using NanoString panel of 760 gene targets as an exploratory method. Subsequently, we confirmed the findings with a publicly available RNA sequencing data set. The NanoString method showed that 29 of 760 genes exhibited significant deregulation. Ten genes (CD44, COL6A3, COL11A1, CXCL8, INHBA, MMP1, NID2, SPP1, THBS1, and THY1) were part of the EMT pathway. The expression of CDH1/E-cadherin, a key EMT gene, and TWIST1, regulator gene of EMT, was higher in MCPyV-negative tumors. To further investigate the expression of EMT genes in MCPyV-negative MCCs, we analyzed publicly available RNA sequencing data of 111 primary MCCs. Differential expression and gene set enrichment analysis of 35 MCPyV-negative versus 76 MCPyV-positive MCCs demonstrated significantly higher expression of EMT-related genes and associated pathways such as Notch signaling, TGF-ß signaling, and Hedgehog signaling, and UV response pathway in MCPyV-negative MCCs. The significance of the EMT pathway in MCPyV-negative MCCs was confirmed independently by a coexpression module analysis. One of the modules (M3) was specifically activated in MCPyV-negative MCCs and showed significant enrichment for genes involved in EMT. A network analysis of module M3 revealed that CDH1/E-cadherin was among the most connected genes (hubs). E-cadherin and LEF1 immunostains demonstrated significantly more frequent expression in MCPvV-negative versus MCPyV-positive tumors (P < .0001). In summary, our study showed that the expression of EMT-associated genes is higher in MCPyV-negative MCC. Because EMT-related proteins can be targeted, the identification of EMT pathways in MCPyV-negative MCCs is of potential therapeutic relevance.

A DNA Segregation Module for Synthetic Cells.

The bottom-up construction of an artificial cell requires the realization of synthetic cell division. Significant progress has been made toward reliable compartment division, yet mechanisms to segregate the DNA-encoded informational content are still in their infancy. Herein, droplets of DNA Y-motifs are formed by liquid-liquid phase separation. DNA droplet segregation is obtained by cleaving the linking component between two populations of DNA Y-motifs. In addition to enzymatic cleavage, photolabile sites are introduced for spatio-temporally controlled DNA segregation in bulk as well as in cell-sized water-in-oil droplets and giant unilamellar lipid vesicles (GUVs). Notably, the segregation process is slower in confinement than in bulk. The ionic strength of the solution and the nucleobase sequences are employed to regulate the segregation dynamics. The experimental results are corroborated in a lattice-based theoretical model which mimics the interactions between the DNA Y-motif populations. Altogether, engineered DNA droplets, reconstituted in GUVs, can represent a strategy toward a DNA segregation module within bottom-up assembled synthetic cells.

Histologic margin status is a predictor of relapse in lentigo maligna melanoma.

BACKGROUND: Most surgical margins for lentigo maligna melanomas reported in the literature are clinical and not histologic. OBJECTIVES: We sought to determine whether histologic margin status is an independent predictor of progression. METHODS: Clinicopathologic information of 268 invasive lentigo maligna melanomas diagnosed from 1990-2019 were analyzed. Statistical analyses were performed using Cox proportional hazards model and Boruta method. RESULTS: A total of 75% of the lesions were located on the head and neck. The range of follow-up for all patients was 0 to 31.8 years (median, 10.2 years). Time to local recurrence ranges from 0 to 20 years (median, 3 years). Progression developed in 54 (20.1%) of 268 patients. Local recurrence was seen only in 36 (13.4%), both local recurrence and subsequent metastasis in 7 (2.6%), and only metastasis in 11 (4.1%) of 268 patients. Histologic margin status (positive and close/<3 mm) and tumor site (head and neck location) significantly correlated with worse progression-free survival. LIMITATIONS: Single institution and retrospective study. CONCLUSIONS: Histologic margin status is the strongest predictor of progression for lentigo maligna melanoma. Patients with positive or close/<3 mm histologic margins should consider a re-excision due to the increased risk of relapse.

How public health insurance expansion affects healthcare utilizations in middle and low-income households: an observational study from national cross-section surveys in Vietnam.

Public health insurance (PHI) has been implemented with different levels of participation in many countries, from voluntary to mandatory. In Vietnam, a law amendment made PHI compulsory nationwide in 2015 with a tolerance phase allowing people a flexible time to enroll. This study aims to examine mechanisms under which the amendment affected the enrollment, healthcare utilization, and out-of-pocket (OOP) expenditures by middle- and low-income households in this transitioning process.Using the biennial Vietnam Household Living Standard Surveys, the study applied the doubly robust difference-in-differences approach to compare outcomes in the post-amendment period from the 2016 survey with those in the pre-amendment period from the 2014 survey. The approach inheriting advantages from its predecessors, i.e., the difference-in-differences and the augmented inverse-probability weighting methods, can mitigate possible biases in policy evaluations due to the changes within the group and between groups over time in the cross-section observational study.The results showed health insurance expansion with extensive subsidies in premiums and medical coverage for persons other than the full-time employed, young children or elderly members in the family, significantly increased enrollments in the middle- and low-income groups by 9% and 8%, respectively. The number of visits for PHI-eligible services also increased, approximately 0.5 more visit per person in the middle-income and 1 more visit per person in the low-income. The amendment, however, so far did not show any significant effect on reducing OOP payments, neither for the low nor the middle-income groups. To further expand PHI coverage and financial protections, policymakers should focus on improving public health facilities, contracting PHI to more accredited private health providers, and motivating the high-income group's enrollments.

Why do consumers choose private over public health services? Reflective accounts of health providers in Vietnam.

BACKGROUND: In Vietnam and many developing countries, private healthcare is increasingly being leveraged by governments to complement public services and increase health service access and utilisation. Extensive understanding of patterns of utilisation of private over public health services, and the rationale for such consumer decisions, is important to ensure and promote safe, affordable and patient-centred care in the two sectors. Few studies within the Southeast Asian Region have explored how private and public providers interact (via social networks, marketing, and direct contact) with consumers to affect their service choices. This study investigates providers' views on social factors associated with the use of private over public health services in Vietnam. METHOD: A thematic analysis was undertaken of 30 semi-structured interviews with experienced health system stakeholders from the Vietnam national assembly, government ministries, private health associations, health economic association, as well as public and private hospitals and clinics. RESULTS: Multiple social factors were found to influence the choice of private over public services, including word-of-mouth, the patient-doctor relationship and relationships between healthcare providers, healthcare staff attitudes and behaviour, and marketing. While private providers maximise their use of these social factors, most public providers seem to ignore or show only limited interest in using marketing and other forms of social interaction to improve services to meet patients' needs, especially those needs beyond strictly medical intervention. However, private providers faced their own particular challenges related to over-advertisement, over-servicing, excessive focus on patients' demands rather than medical needs, as well as the significant technical requirements for quality and safety. CONCLUSIONS: This study has important implications for policy and practice in Vietnam. First, public providers must embrace social interaction with consumers as an effective strategy to improve their service quality. Second, appropriate regulations of private providers are required to protect patients from unnecessary treatments, costs and potential harm. Finally, the insights from this study have direct relevance to many developing countries facing a similar challenge of appropriately managing the growth of the private health sector.

Contribution of private health services to universal health coverage in low and middle-income countries: Factors affecting the use of private over public health services in Vietnam.

The private sector's contribution to Universal health coverage (UHC) has been increasingly recognised by policymakers in low- and middle-income countries. This study aimed to identify service-provider and consumer-level factors affecting choice of private over public health services in Vietnam. A concurrent mixed-method design was adopted. A quantitative phase explored consumers' health service choice by analysing data from a random national sample of 10,354 individuals aged 16 and over. The qualitative phase investigated how private and public providers organise their services to influence consumer choices by conducting interviews with policymakers, hospital and clinic managers, and health practitioners. The combined results demonstrate that at the individual level, absence of any type of health insurance was the factor most closely associated with the use of private services. Private health services were more likely to be used by people from ethnic majority groups compared to ethnic minorities (odds ratio [OR]: 1.6, 95% CI: 1.4-2.0), and by people living in urban compared to rural areas (OR: 1.1, 95% CI: 1.0-1.3). The service providers suggested that consumers opted for private services that were perceived to have poorer quality in the public sector, such as counselling, physical therapy and rehabilitative care. Additional motivational factors include the private sector's more flexible working hours, shorter waiting times, flexible pricing of services, personalised care and better staff behaviour. The findings can inform national health system planning and coordination activities in Vietnam and other countries that aim to harness the attributes of both the public and private sectors to achieve UHC.

Comparison of clinical and radiographic outcomes of arthroscopic-assisted percutaneous fixation versus open reduction internal fixation of lateral tibial plateau fractures.

PURPOSE: Treatment for tibial plateau fractures continues to evolve but maintains primary objectives of anatomic reduction of the joint line and a rapid recovery course. Arthroscopic-assisted percutaneous fixation (AAPF) has been introduced as an alternative to traditional open reduction internal fixation (ORIF). The purpose of the study is to compare clinical and radiographic outcomes in patients with low-energy Schatzker type I-III tibial plateau fractures treated with AAPF versus ORIF. METHODS: A retrospective chart review was performed at a level 1 trauma centre to compare outcomes of 120 patients (57 AAPF, 63 ORIF) with low-energy lateral Schatzker type I-III tibial plateau fractures who underwent tibial plateau fixation between 2009 and 2018. Demographic information, injury characteristics, and surgical treatment were recorded. The main outcome measurements included reduction step-off, joint space narrowing, time to weight bearing, and implant removal. RESULTS: There was no difference in age, gender distribution, BMI, ASA, Schatzker classification distribution, initial displacement, blood loss, and reduction step-off between the two groups (p > 0.05). Shorter tourniquet time (74.1 ± 21.7 vs 100.0 ± 21.0 min; p < 0.001), shorter time to full weight bearing (47.8 ± 15.2 vs. 69.1 ± 17.2 days; p < 0.001), and lower rate of joint space narrowing (3.5% vs. 28.6% with more than 1 mm, p < 0.001) were associated with the AAPF cohort, with no difference in pain, knee range of motion, or implant removal rate between the two cohorts. CONCLUSION: AAPF may be a viable alternative to ORIF for the management of low-energy tibial plateau fractures with outcomes not inferior compared to the traditional ORIF method.

Outcomes of arthroscopic-assisted lateral tibial plateau fixation: a systematic review.

PURPOSE: The purpose of this study is to evaluate and summarize the current literature on outcomes of arthroscopic-assisted tibial plateau fixation (AATPF) when applied for only lateral tibial plateau fractures. METHODS: A comprehensive search of nine databases was conducted: ClinicalTrials.gov, Cochrane Library via Wiley, Embase and MEDLINE via Ovid, Global Index Medicus, PubMed, Scopus, SPORTDiscus via EBSCO, and Web of Science Core Collection. The study was performed in concordance with PRISMA guidelines. Studies eligible for inclusions included Schatzker I-III lateral tibial plateau fractures with a minimum of 6-month follow-up. Data extraction was performed by two authors independently using a predesigned form. RESULTS: A total of 17 studies, 7 prospective and 10 retrospective, including 565 patients (age 15-82 years old) treated with AATPF were included in this review with follow-up ranging from 6 to 138 months. All 10 studies that used categorical functional outcomes demonstrated excellent/very good or good outcomes in > 90% of patients. When compared to patients managed with the traditional open reduction internal fixation (ORIF), patients treated with AATPF had statistically significantly better range of motion mean difference [5.21° (95% CI - 2.50 to 12.92, p < 0.0001)], lower blood loss [66.19 mL (95% confidence interval (CI) 32.54-99.84 mL, p < 0.0001)], shorter hospital stay [- 1.41 days (95% CI - 3.39 to 0.58 days, p < 0.0001)], better Hospital Special Surgery score [11.31 (95% CI 6.49-16.12, p < 0.0001)], and higher Rasmussen radiographic score [1.26 (95% CI - 0.72 to 3.23, p < 0.0001)]. CONCLUSION: AATPF is a promising treatment of lateral tibial plateau fractures with some advantages over the traditional ORIF. LEVEL OF EVIDENCE: Therapeutic Level III.

Implementation and Clinical Adoption of Precision Oncology Workflows Across a Healthcare Network.

BACKGROUND: Precision oncology relies on molecular diagnostics, and the value-proposition of modern healthcare networks promises a higher standard of care across partner sites. We present the results of a clinical pilot to standardize precision oncology workflows. METHODS: Workflows are defined as the development, roll-out, and updating of disease-specific molecular order sets. We tracked the timeline, composition, and effort of consensus meetings to define the combination of molecular tests. To assess clinical impact, we examined order set adoption over a two-year period (before and after roll-out) across all gastrointestinal and hepatopancreatobiliary (GI) malignancies, and by provider location within the network. RESULTS: Development of 12 disease center-specific order sets took ~9 months, and the average number of tests per indication changed from 2.9 to 2.8 (P = .74). After roll-out, we identified significant increases in requests for GI patients (17%; P < .001), compliance with testing recommendations (9%; P < .001), and the fraction of "abnormal" results (6%; P < .001). Of 1088 GI patients, only 3 received targeted agents based on findings derived from non-recommended orders (1 before and 2 after roll-out); indicating that our practice did not negatively affect patient treatments. Preliminary analysis showed 99% compliance by providers in network sites, confirming the adoption of the order sets across the network. CONCLUSION: Our study details the effort of establishing precision oncology workflows, the adoption pattern, and the absence of harm from the reduction of non-recommended orders. Establishing a modifiable communication tool for molecular testing is an essential component to optimize patient care via precision oncology.