Total Knee Arthroplasty With Robotic and Augmented Reality Guidance: A Hierarchical Task Analysis.

Background: Total knee arthroplasty (TKA) is a commonly performed procedure that has traditionally utilized reproducible steps using a set of mechanical instruments. The number of TKAs performed using robotic assistance is increasing, and augmented reality (AR) navigation systems are being developed. Hierarchical task analysis (HTA) aims to describe the steps of a specific task in detail to reduce errors and ensure reproducibility. The objective of this study was to develop and validate HTAs for conventional, robotic-assisted, and AR-navigated TKA. Methods: The development of HTAs for conventional TKA involved an iterative review process that incorporated the input of 4 experienced arthroplasty surgeons. The HTAs were then adapted for robotic-assisted and AR-navigated TKA by incorporating specific steps associated with the use of these systems. The accuracy and completeness of the HTAs were validated by observing 10 conventional and 10 robotic-assisted TKA procedures. Results: HTAs for conventional, robotic-assisted, and AR-navigated TKA were developed and validated. The resulting HTAs provide a comprehensive and standardized plan for each procedure and can aid in the identification of potential areas of inefficiency and risk. Robotic-assisted and AR-navigated approaches require additional steps, and there are an increased number of instances where complications may occur. Conclusions: The HTAs developed in this study can provide valuable insights into the potential pitfalls of robotic-assisted and AR-navigated TKA procedures. As AR-navigation systems are developed, they should be optimized by critical analysis using the developed HTAs to ensure maximum efficiency, reliability, accessibility, reduction of human error, and costs.

Advancements in computer vision and pathology: Unraveling the potential of artificial intelligence for precision diagnosis and beyond.

The integration of computer vision into pathology through slide digitalization represents a transformative leap in the field's evolution. Traditional pathology methods, while reliable, are often time-consuming and susceptible to intra- and interobserver variability. In contrast, computer vision, empowered by artificial intelligence (AI) and machine learning (ML), promises revolutionary changes, offering consistent, reproducible, and objective results with ever-increasing speed and scalability. The applications of advanced algorithms and deep learning architectures like CNNs and U-Nets augment pathologists' diagnostic capabilities, opening new frontiers in automated image analysis. As these technologies mature and integrate into digital pathology workflows, they are poised to provide deeper insights into disease processes, quantify and standardize biomarkers, enhance patient outcomes, and automate routine tasks, reducing pathologists' workload. However, this transformative force calls for cross-disciplinary collaboration between pathologists, computer scientists, and industry innovators to drive research and development. While acknowledging its potential, this chapter addresses the limitations of AI in pathology, encompassing technical, practical, and ethical considerations during development and implementation.

Reducing Hospitalizations and Multidrug-Resistant Organisms via Regional Decolonization in Hospitals and Nursing Homes.

Importance: Infections due to multidrug-resistant organisms (MDROs) are associated with increased morbidity, mortality, length of hospitalization, and health care costs. Regional interventions may be advantageous in mitigating MDROs and associated infections. Objective: To evaluate whether implementation of a decolonization collaborative is associated with reduced regional MDRO prevalence, incident clinical cultures, infection-related hospitalizations, costs, and deaths. Design, Setting, and Participants: This quality improvement study was conducted from July 1, 2017, to July 31, 2019, across 35 health care facilities in Orange County, California. Exposures: Chlorhexidine bathing and nasal iodophor antisepsis for residents in long-term care and hospitalized patients in contact precautions (CP). Main Outcomes and Measures: Baseline and end of intervention MDRO point prevalence among participating facilities; incident MDRO (nonscreening) clinical cultures among participating and nonparticipating facilities; and infection-related hospitalizations and associated costs and deaths among residents in participating and nonparticipating nursing homes (NHs). Results: Thirty-five facilities (16 hospitals, 16 NHs, 3 long-term acute care hospitals [LTACHs]) adopted the intervention. Comparing decolonization with baseline periods among participating facilities, the mean (SD) MDRO prevalence decreased from 63.9% (12.2%) to 49.9% (11.3%) among NHs, from 80.0% (7.2%) to 53.3% (13.3%) among LTACHs (odds ratio [OR] for NHs and LTACHs, 0.48; 95% CI, 0.40-0.57), and from 64.1% (8.5%) to 55.4% (13.8%) (OR, 0.75; 95% CI, 0.60-0.93) among hospitalized patients in CP. When comparing decolonization with baseline among NHs, the mean (SD) monthly incident MDRO clinical cultures changed from 2.7 (1.9) to 1.7 (1.1) among participating NHs, from 1.7 (1.4) to 1.5 (1.1) among nonparticipating NHs (group × period interaction reduction, 30.4%; 95% CI, 16.4%-42.1%), from 25.5 (18.6) to 25.0 (15.9) among participating hospitals, from 12.5 (10.1) to 14.3 (10.2) among nonparticipating hospitals (group × period interaction reduction, 12.9%; 95% CI, 3.3%-21.5%), and from 14.8 (8.6) to 8.2 (6.1) among LTACHs (all facilities participating; 22.5% reduction; 95% CI, 4.4%-37.1%). For NHs, the rate of infection-related hospitalizations per 1000 resident-days changed from 2.31 during baseline to 1.94 during intervention among participating NHs, and from 1.90 to 2.03 among nonparticipating NHs (group × period interaction reduction, 26.7%; 95% CI, 19.0%-34.5%). Associated hospitalization costs per 1000 resident-days changed from $64 651 to $55 149 among participating NHs and from $55 151 to $59 327 among nonparticipating NHs (group × period interaction reduction, 26.8%; 95% CI, 26.7%-26.9%). Associated hospitalization deaths per 1000 resident-days changed from 0.29 to 0.25 among participating NHs and from 0.23 to 0.24 among nonparticipating NHs (group × period interaction reduction, 23.7%; 95% CI, 4.5%-43.0%). Conclusions and Relevance: A regional collaborative involving universal decolonization in long-term care facilities and targeted decolonization among hospital patients in CP was associated with lower MDRO carriage, infections, hospitalizations, costs, and deaths.

The New WHO Category of "Molecularly Defined Renal Carcinomas": Clinical and Diagnostic Features and Management Implications.

The evolution of classification of renal tumors has been impacted since the turn of the millennium by rapid progress in histopathology, immunohistochemistry, and molecular genetics. Together, these features have enabled firm recognition of specific, classic types of renal cell carcinomas, such as clear cell renal cell carcinoma, that in current practice trigger histologic-type specific management and treatment protocols. Now, the fifth Edition World Health Classification's new category of "Molecularly defined renal carcinomas" changes the paradigm, defining a total of seven entities based specifically on their fundamental molecular underpinnings. These tumors, which include TFE3-rearranged, TFEB-altered, ELOC-mutated, fumarate hydratase-deficient, succinate dehydrogenase-deficient, ALK-rearranged, and SMARCB1-deficient renal medullary carcinoma, encompass a wide clinical and histopathologic phenotypic spectrum of tumors. Already, important management aspects are apparent for several of these entities, while emerging therapeutic angles are coming into view. A brief, clinically-oriented introduction of the entities in this new category, focusing on relevant diagnostic, molecular, and management aspects, is the subject of this review.

Pilot study of a telehealth intervention for personalized self-management for eating symptoms after gastroesophageal cancer surgery.

BACKGROUND AND OBJECTIVES: Following gastric and esophageal cancer surgery, patients often experience significant, prolonged eating-related symptoms. One promising approach to help patients improve their eating-related quality of life (QOL) is through self-management coaching to aid in diet modification. We performed a randomized pilot study of a nutritionist-led telehealth intervention for the self-management of eating after gastroesophageal cancer surgery. METHODS: Patients who were within 30 days of resuming oral intake after undergoing surgery for gastric and/or esophageal cancer were consented and then randomized to the intervention or usual care. The intervention was performed by a nutritionist trained in self-management coaching and delivered in four telehealth sessions over 4 months. The following outcomes were measured at baseline and at 6 months after baseline: QOL (EORTC QLQC30), weight, body mass index, and sarcopenia. RESULTS: Fifty-three patients were enrolled. 22/27 usual care and 21/26 intervention patients completed the study for a retention rate of 81%. Differences between the intervention and control groups were not statistically significant, but the intervention group had indications of greater improvements in overall QOL as measured by EORTC QLQC30 Summary Score (8.7 vs. 2.3, p = 0.17) as well as greater improvements in 4/5 functional domains (p > 0.3). The intervention group also had slightly more weight gain (6 kg vs. 3 kg, p = 0.3) and less sarcopenia (3/16 vs. 9/18, p = 0.07). CONCLUSIONS: This pilot study demonstrated the feasibility and acceptability of a telehealth intervention for self-management of eating symptoms after gastroesophageal cancer surgery. There were trends toward improved overall QOL in the intervention group. A larger study is needed to validate the results.

Fluoroscopy Versus Imageless Optical Navigation in Direct Anterior Approach Total Hip Arthroplasty.

BACKGROUND: Utilization of the direct anterior approach (DAA) for total hip arthroplasty (THA) has risen in popularity. Accurate implant placement is a critical factor that influences patient outcomes. The goal of this study was to compare the accuracy and precision of fluoroscopy with imageless optical navigation in DAA THA. METHODS: This was a cohort study of 640 consecutive primary DAA THAs performed with intraoperative fluoroscopy (n = 300 patients) or imageless optical navigation (n = 304 patients). Accuracy was compared by measuring acetabular cup inclination, anteversion, and leg-length discrepancy (LLD). The proportion of implants placed within the Lewinnek safe zone and those placed within a more precise target of 40 ± 5° inclination and 20 ± 5° anteversion was evaluated. RESULTS: According to the Lewinnek criteria, there was no difference in the percentage of implants placed within both inclination and anteversion targets (fluoroscopy: 90.3%; navigation: 88.8%, P = 0.519). Using the more precise targets, navigation increased the implants positioned correctly for both inclination and anteversion (fluoroscopy: 50.3%; navigation: 65.6%, P < 0.001). Navigation increased the proportion of implants positioned within the target anteversion zone (fluoroscopy: 71.3%; navigation: 83.8%, P < 0.001) but not inclination (fluoroscopy: 71.9%; navigation: 76.9%, P = 0.147). The mean LLD was higher with the use of fluoroscopy compared with navigation (5.5 mm, standard deviation: 4.1; 4.6 mm, SD: 3.4, P < 0.005). No difference in dislocation rate was observed ( P = 0.643). CONCLUSION: Both fluoroscopy and imageless optical navigation demonstrated accurate acetabular implant positioning during DAA THA. Navigation was more precise and associated with improved acetabular anteversion placement and restoration of LLD. Navigation is an accurate alternative to fluoroscopy with decreased radiation exposure.

Impact of traditional versus nontraditional initiation dosing schedule of paliperidone palmitate on 30-day readmission and safety.

Introduction: Paliperidone palmitate (PP), a second-generation long-acting injectable antipsychotic, requires 2 injections upon initiation. Due to the fast-paced nature of the inpatient setting, the second dose may be administered earlier than recommended by labeled use despite the lack of evidence that evaluates this practice. Methods: This was a retrospective chart review that investigated the outcomes associated with the timing of the second PP initiation dose with the aim of comparing patients who received the second PP dose fewer than 3 days after the first injection with those who received it between 3 and 11 days after the first injection. The primary outcomes included 30-day psychiatric readmission, index hospitalization length of stay, and time until the next psychiatric hospitalization. Secondary outcomes included 6-month readmission and the percentage of patients who experienced an adverse event after the second injection. Results: No statistically significant differences were observed between groups for 30-day readmission. There was a statistically significant shortened index length of hospitalization (median, 2 vs 4 days; P < 0.001) and a non-statistically significant trend for time until the next psychiatric hospitalization (median, 25 vs 47 days) when comparing those who received the nontraditional loading regimen to those who received the traditional labeled loading regimen. No differences were observed in the secondary outcomes or safety/tolerability. Discussion: The results of the study indicate that there are no significant differences in readmission rates and adverse drug reactions in those who received the second PP dose earlier than recommended per labeled use. Larger, controlled studies are needed to further investigate clinical and safety outcomes.

Allosteric inhibition of the T cell receptor by a designed membrane ligand.

The T cell receptor (TCR) is a complex molecular machine that directs the activation of T cells, allowing the immune system to fight pathogens and cancer cells. Despite decades of investigation, the molecular mechanism of TCR activation is still controversial. One of the leading activation hypotheses is the allosteric model. This model posits that binding of pMHC at the extracellular domain triggers a dynamic change in the transmembrane (TM) domain of the TCR subunits, which leads to signaling at the cytoplasmic side. We sought to test this hypothesis by creating a TM ligand for TCR. Previously we described a method to create a soluble peptide capable of inserting into membranes and binding to the TM domain of the receptor tyrosine kinase EphA2 (Alves et al., eLife, 2018). Here, we show that the approach is generalizable to complex membrane receptors, by designing a TM ligand for TCR. We observed that the designed peptide caused a reduction of Lck phosphorylation of TCR at the CD3ζ subunit in T cells. As a result, in the presence of this peptide inhibitor of TCR (PITCR), the proximal signaling cascade downstream of TCR activation was significantly dampened. Co-localization and co-immunoprecipitation in diisobutylene maleic acid (DIBMA) native nanodiscs confirmed that PITCR was able to bind to the TCR. AlphaFold-Multimer predicted that PITCR binds to the TM region of TCR, where it interacts with the two CD3ζ subunits. Our results additionally indicate that PITCR disrupts the allosteric changes in the compactness of the TM bundle that occur upon TCR activation, lending support to the allosteric TCR activation model. The TCR inhibition achieved by PITCR might be useful to treat inflammatory and autoimmune diseases and to prevent organ transplant rejection, as in these conditions aberrant activation of TCR contributes to disease.

Decolonization in Nursing Homes to Prevent Infection and Hospitalization.

BACKGROUND: Nursing home residents are at high risk for infection, hospitalization, and colonization with multidrug-resistant organisms. METHODS: We performed a cluster-randomized trial of universal decolonization as compared with routine-care bathing in nursing homes. The trial included an 18-month baseline period and an 18-month intervention period. Decolonization entailed the use of chlorhexidine for all routine bathing and showering and administration of nasal povidone-iodine twice daily for the first 5 days after admission and then twice daily for 5 days every other week. The primary outcome was transfer to a hospital due to infection. The secondary outcome was transfer to a hospital for any reason. An intention-to-treat (as-assigned) difference-in-differences analysis was performed for each outcome with the use of generalized linear mixed models to compare the intervention period with the baseline period across trial groups. RESULTS: Data were obtained from 28 nursing homes with a total of 28,956 residents. Among the transfers to a hospital in the routine-care group, 62.2% (the mean across facilities) were due to infection during the baseline period and 62.6% were due to infection during the intervention period (risk ratio, 1.00; 95% confidence interval [CI], 0.96 to 1.04). The corresponding values in the decolonization group were 62.9% and 52.2% (risk ratio, 0.83; 95% CI, 0.79 to 0.88), for a difference in risk ratio, as compared with routine care, of 16.6% (95% CI, 11.0 to 21.8; P<0.001). Among the discharges from the nursing home in the routine-care group, transfer to a hospital for any reason accounted for 36.6% during the baseline period and for 39.2% during the intervention period (risk ratio, 1.08; 95% CI, 1.04 to 1.12). The corresponding values in the decolonization group were 35.5% and 32.4% (risk ratio, 0.92; 95% CI, 0.88 to 0.96), for a difference in risk ratio, as compared with routine care, of 14.6% (95% CI, 9.7 to 19.2). The number needed to treat was 9.7 to prevent one infection-related hospitalization and 8.9 to prevent one hospitalization for any reason. CONCLUSIONS: In nursing homes, universal decolonization with chlorhexidine and nasal iodophor led to a significantly lower risk of transfer to a hospital due to infection than routine care. (Funded by the Agency for Healthcare Research and Quality; Protect ClinicalTrials.gov number, NCT03118232.).

exRNA-eCLIP intersection analysis reveals a map of extracellular RNA binding proteins and associated RNAs across major human biofluids and carriers.

Although the role of RNA binding proteins (RBPs) in extracellular RNA (exRNA) biology is well established, their exRNA cargo and distribution across biofluids are largely unknown. To address this gap, we extend the exRNA Atlas resource by mapping exRNAs carried by extracellular RBPs (exRBPs). This map was developed through an integrative analysis of ENCODE enhanced crosslinking and immunoprecipitation (eCLIP) data (150 RBPs) and human exRNA profiles (6,930 samples). Computational analysis and experimental validation identified exRBPs in plasma, serum, saliva, urine, cerebrospinal fluid, and cell-culture-conditioned medium. exRBPs carry exRNA transcripts from small non-coding RNA biotypes, including microRNA (miRNA), piRNA, tRNA, small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), Y RNA, and lncRNA, as well as protein-coding mRNA fragments. Computational deconvolution of exRBP RNA cargo reveals associations of exRBPs with extracellular vesicles, lipoproteins, and ribonucleoproteins across human biofluids. Overall, we mapped the distribution of exRBPs across human biofluids, presenting a resource for the community.

Use of an Artificial Intelligence Conversational Agent (Chatbot) for Hip Arthroscopy Patients Following Surgery.

Purpose: The purpose of this study was to evaluate the use of an AI conversational agent during the postoperative recovery of patients undergoing elective hip arthroscopy. Methods: Patients undergoing hip arthroscopy were enrolled in a prospective cohort for their first 6 weeks following surgery. Patients used standard SMS text messaging to interact with an artificial intelligence (AI) chatbot ("Felix") used to initiate automated conversations regarding elements of postoperative recovery. Patient satisfaction was measured at 6 weeks after surgery using a Likert scale survey. Accuracy was determined by measuring the appropriateness of chatbot responses, topic recognition, and examples of confusion. Safety was measured by evaluating the chatbot's responses to any questions with potential medical urgency. Results: Twenty-six patients were enrolled with a mean age of 36 years, and 58% (n = 15) were male. Overall, 80% of patients (n = 20) rated the helpfulness of Felix as good or excellent. In the postoperative period, 12/25 (48%) patients reported being worried about a complication but were reassured by Felix and, thus, did not seek medical attention. Of a total of 128 independent patient questions, Felix handled 101/128 questions appropriately (79%), either by addressing them independently, or facilitating contact with the care team. Felix was able to adequately answer the patient question independently 31% of the time (n = 40/128). Of 10 patient questions that were thought to potentially represent patient complications, in 3 cases Felix did not adequately address or recognize the health concern-none of these situations resulted in patient harm. Conclusion: The results of this study demonstrate that the use of a chatbot or conversational agent can enhance the postoperative experience for hip arthroscopy patients, as demonstrated by high levels of patient satisfaction. Levels of Evidence: Level IV, therapeutic case series.

The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models.

Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of 1,635 open-access datasets from four donors (∼30 tissues × âˆ¼15 assays). The datasets are mapped to matched, diploid genomes with long-read phasing and structural variants, instantiating a catalog of >1 million allele-specific loci. These loci exhibit coordinated activity along haplotypes and are less conserved than corresponding, non-allele-specific ones. Surprisingly, a deep-learning transformer model can predict the allele-specific activity based only on local nucleotide-sequence context, highlighting the importance of transcription-factor-binding motifs particularly sensitive to variants. Furthermore, combining EN-TEx with existing genome annotations reveals strong associations between allele-specific and GWAS loci. It also enables models for transferring known eQTLs to difficult-to-profile tissues (e.g., from skin to heart). Overall, EN-TEx provides rich data and generalizable models for more accurate personal functional genomics.

Chlorhexidine and Mupirocin for Clearance of Methicillin-Resistant Staphylococcus aureus Colonization After Hospital Discharge: A Secondary Analysis of the Changing Lives by Eradicating Antibiotic Resistance Trial.

BACKGROUND: The CLEAR Trial demonstrated that a multisite body decolonization regimen reduced post-discharge infection and hospitalization in methicillin-resistant Staphylococcus aureus (MRSA) carriers. Here, we describe decolonization efficacy. METHODS: We performed a large, multicenter, randomized clinical trial of MRSA decolonization among adult patients after hospital discharge with MRSA infection or colonization. Participants were randomized 1:1 to either MRSA prevention education or education plus decolonization with topical chlorhexidine, oral chlorhexidine, and nasal mupirocin. Participants were swabbed in the nares, throat, axilla/groin, and wound (if applicable) at baseline and 1, 3, 6, and 9 months after randomization. The primary outcomes of this study are follow-up colonization differences between groups. RESULTS: Among 2121 participants, 1058 were randomized to decolonization. By 1 month, MRSA colonization was lower in the decolonization group compared with the education-only group (odds ration [OR] = 0.44; 95% confidence interval [CI], .36-.54; P ≤ .001). A similar magnitude of reduction was seen in the nares (OR = 0.34; 95% CI, .27-.42; P < .001), throat (OR = 0.55; 95% CI, .42-.73; P < .001), and axilla/groin (OR = 0.57; 95% CI, .43-.75; P < .001). These differences persisted through month 9 except at the wound site, which had a relatively small sample size. Higher regimen adherence was associated with lower MRSA colonization (P ≤ .01). CONCLUSIONS: In a randomized, clinical trial, a repeated post-discharge decolonization regimen for MRSA carriers reduced MRSA colonization overall and at multiple body sites. Higher treatment adherence was associated with greater reductions in MRSA colonization.

Short term outcomes following robotic arm-assisted lateral unicompartmental knee arthroplasty.

Introduction: Robotic-arm assisted medial unicompartmental knee arthroplasty (RA-UKA) is associated with improved accuracy of implant positioning and excellent early functional outcomes. However, there is paucity of evidence regarding outcomes following RA-UKA for isolated lateral compartment osteoarthritis. The purpose of this study was to assess the short-term clinical and patient reported outcomes of lateral compartment UKA, utilising robotic-arm assistance. Methods: This was a retrospective study of prospectively collected data of 21 consecutive patients who underwent lateral RA-UKA. The study included 9 (42.9%) males and 12 (57.1%) females with a mean age of 63.4 ± 9.2 years. The Oxford Knee Score (OKS) was measured pre-operatively and at 1-year post-operatively, while range of motion (ROM) and complications were also recorded. Results: There was significant improvement of OKS at 1 year's follow up compared with the baseline score (21.8 ± 5.6 vs. 45.2 ± 2.8 respectively; p < 0.001). There was also an improvement in pre-operative ROM when compared to ROM at 1 year's follow up (123.5° ± 8° vs. 131.5° ± 6.3° respectively; p < 0.001). None of the study patients underwent revision surgery within 1 year's follow-up. Conclusion: In our study, lateral RA-UKA resulted in significant improvements in clinical and patient reported outcomes with low complications rates. Further long-term comparative studies are needed to assess the utility of lateral RA-UKA vs. conventional UKA.

Wide Variability in Return-to-Sport Criteria used by Team Physicians After Anterior Cruciate Ligament Reconstruction in Elite Athletes-A Qualitative Study.

Purpose: The purpose of this study is to explore currently used readiness to return to sport (RTS) criteria after anterior cruciate ligament reconstruction (ACLR) used in elite athletes to gain novel insights into the RTS decision-making process of professional team physicians. Methods: Eighteen qualitative semistructured interviews with professional team physicians were conducted by a single trained interviewer. The interviews were used to identify team physician concepts and themes regarding the criteria used to determine RTS after ACLR. General inductive analysis and a coding process were used to identify themes and subthemes arising from the data. A hierarchical approach in coding helped to link themes. Results: The most important RTS criteria included muscle strength, followed by satisfactory functional testing including hop tests, a satisfactory clinical examination, joint stability, psychological readiness, time since the ACLR surgery, absence of joint effusion, subjective feeling of knee stability, pain-free return to sporting movements, completion of a sport-specific rehabilitation, and at last allied team support. Conclusions: This study identified 4 main themes, including (1) objective findings, (2) informative feedback of the team members, (3) subjective findings, and (4) type of sport and time to surgery as having the most influence on RTS decision after ACLR. However, interviews showed that even among professional team physicians, the main criteria to RTS in these categories were inconsistent. A definitive set of conclusive guidelines could not be established and would be a fruitful and useful area for future research through further quantitative studies and international consensus meetings along the foundation of the presenting study. Level of Evidence: V, evidence-based practices, qualitative study.

Digital Microfluidic qPCR Cartridge for SARS-CoV-2 Detection.

Point-of-care (POC) tests capable of individual health monitoring, transmission reduction, and contact tracing are especially important in a pandemic such as the coronavirus disease 2019 (COVID-19). We develop a disposable POC cartridge that can be mass produced to detect the SARS-CoV-2 N gene through real-time quantitative polymerase chain reaction (qPCR) based on digital microfluidics (DMF). Several critical parameters are studied and improved, including droplet volume consistency, temperature uniformity, and fluorescence intensity linearity on the designed DMF cartridge. The qPCR results showed high accuracy and efficiency for two primer-probe sets of N1 and N2 target regions of the SARS-CoV-2 N gene on the DMF cartridge. Having multiple droplet tracks for qPCR, the presented DMF cartridge can perform multiple tests and controls at once.

In vitro disease modeling of oculocutaneous albinism type 1 and 2 using human induced pluripotent stem cell-derived retinal pigment epithelium.

Oculocutaneous albinism (OCA) encompasses a set of autosomal recessive genetic conditions that affect pigmentation in the eye, skin, and hair. OCA patients display reduced best-corrected visual acuity, reduced to absent ocular pigmentation, abnormalities in fovea development, and/or abnormal decussation of optic nerve fibers. It has been hypothesized that improving eye pigmentation could prevent or rescue some of the vision defects. The goal of the present study was to develop an in vitro model for studying pigmentation defects in human retinal pigment epithelium (RPE). We developed a "disease in a dish" model for OCA1A and OCA2 types using induced pluripotent stem cells to generate RPE. The RPE is a monolayer of cells that are pigmented, polarized, and polygonal in shape, located between the neural retina and choroid, with an important role in vision. Here we show that RPE tissue derived in vitro from OCA patients recapitulates the pigmentation defects seen in albinism, while retaining the apical-basal polarity and normal polygonal morphology of the constituent RPE cells.

Epithelial phenotype restoring drugs suppress macular degeneration phenotypes in an iPSC model.

Age-related Macular Degeneration (AMD), a blinding eye disease, is characterized by pathological protein- and lipid-rich drusen deposits underneath the retinal pigment epithelium (RPE) and atrophy of the RPE monolayer in advanced disease stages - leading to photoreceptor cell death and vision loss. Currently, there are no drugs that stop drusen formation or RPE atrophy in AMD. Here we provide an iPSC-RPE AMD model that recapitulates drusen and RPE atrophy. Drusen deposition is dependent on AMD-risk-allele CFH(H/H) and anaphylatoxin triggered alternate complement signaling via the activation of NF-κB and downregulation of autophagy pathways. Through high-throughput screening we identify two drugs, L-745,870, a dopamine receptor antagonist, and aminocaproic acid, a protease inhibitor that reduce drusen deposits and restore RPE epithelial phenotype in anaphylatoxin challenged iPSC-RPE with or without the CFH(H/H) genotype. This comprehensive iPSC-RPE model replicates key AMD phenotypes, provides molecular insight into the role of CFH(H/H) risk-allele in AMD, and discovers two candidate drugs to treat AMD.

Systematic Arthroscopic Treatment of Synovial Chondromatosis of the Knee.

Synovial chondromatosis is a benign metaplastic disease of the synovial joints, characterized by the development of cartilaginous nodules in the synovium. Treatment generally includes open or arthroscopic loose body removal combined with a synovectomy. An all-arthroscopic approach has been described to minimize complications and reduce morbidity while providing adequate control of local disease. The purpose of this Technical Note is to describe our techniques and technical pearls that allow for adequate excision of disease while minimizing complications and disease recurrence. The combination of patient positioning, the establishment of multiple arthroscopic portals to ensure optimal visualization and freedom of instruments, the use of a leg holder, and the use of a variety of surgical instruments to facilitate loose body removal and synovectomy is critical to optimize clinical outcomes and minimize complications. Although technically demanding, our described technique can help facilitate extensive loose body removal and complete synovectomy.

Intraoperative Spinal Cord Monitoring Does Not Decrease New Postoperative Neurological Deficits in Patients With Cervical Radiculopathy or Spondylotic Myelopathy Undergoing One or Two Level Anterior Cervical Discectomy And Fusion.

BACKGROUND: Intraoperative neurological monitoring (IONM) is commonly used in spine surgery. However, the utility of IONM in anterior cervical decompression and fusion (ACDF) remains a topic of debate. The purpose of the study was to investigate the utility and cost of IONM (both Somatosensory evoked potentials (SSEPs) and Motor Evoked Potentials (Tc-MEPs)) in reducing postoperative neurological deficits in myelopathic and non-myelopathic patients undergoing ACDF. METHODS: Retrospective chart review was performed to include only patients with cervical radiculopathy or myelopathy undergoing one or two level ACDF over a 7-year period at a busy academic center. SSEP and Tc-MEP tracings were reviewed for all monitored patients and significant changes and inconsistencies were noted. IONM billing codes (SSEP/Tc-MEP) were reviewed and summed to evaluate the average procedural cost. Medical records were reviewed for preoperative physical exam and for new postoperative neurological deficits on postoperative day one and again at six weeks and matched to the monitored tracings. RESULTS: There were 249 total patients (48 Non-monitored, 201 monitored). There was no difference in gender, age, or BMI between monitored and non-monitored groups. There was no difference in new neurological deficits in monitored compared with non-monitored patients with radiculopathy (p=0.1935) or myelopathy (p=0.1977). However, when radiculopathy and myelopathy patients were combined, there was an increased incidence of new neurologic deficits in monitored patients (8.0%) versus non-monitored patients (0%) (p=0.0830). All new neurological deficits occurred in patients with normal IONM tracings. There were no new neurologic deficits in the non-monitored radiculopathy or myelopathy groups. The average IONM procedure charge was $6500. CONCLUSION: Our results indicate that intraoperative spinal cord monitoring did not reduce new neurological deficits in our cohort of patients. The higher incidence in new neurological deficits despite no IONM changes in our monitored group suggests a lack of utility of IONM in ACDF. Furthermore, at an average of $6500 per IONM procedure, the present study underlines the importance of prudence when choosing to use IONM in the era of cost containment.Level of Evidence: III.