Current Clinical Standard Of Care Research Articles

Fiberscopic pattern removal for optimal coverage in 3D bladder reconstructions of fiberscope cystoscopy videos.

In the current clinical standard of care, cystoscopic video is not routinely saved because it is cumbersome to review. Instead, clinicians rely on brief procedure notes and still frames to manage bladder pathology. Preserving discarded data via 3D reconstructions, which are convenient to review, has the potential to improve patient care. However, many clinical videos are collected by fiberscopes, which are lower cost but induce a pattern on frames that inhibit 3D reconstruction. The aim of our study is to remove the honeycomb-like pattern present in fiberscope-based cystoscopy videos to improve the quality of 3D bladder reconstructions. Our study introduces an algorithm that applies a notch filtering mask in the Fourier domain to remove the honeycomb-like pattern from clinical cystoscopy videos collected by fiberscope as a preprocessing step to 3D reconstruction. We produce 3D reconstructions with the video before and after removing the pattern, which we compare with a metric termed the area of reconstruction coverage (), defined as the surface area (in pixels) of the reconstructed bladder. All statistical analyses use paired -tests. Preprocessing using our method for pattern removal enabled reconstruction for all () cystoscopy videos included in the study and produced a statistically significant increase in bladder coverage (). This algorithm for pattern removal increases bladder coverage in 3D reconstructions and automates mask generation and application, which could aid implementation in time-starved clinical environments. The creation and use of 3D reconstructions can improve documentation of cystoscopic findings for future surgical navigation, thus improving patient treatment and outcomes.

Abstract A035: Genome-wide CRISPRi screening reveals determinants of platinum sensitivity and resistance in high-grade serous ovarian cancer

Abstract A035: Genome-wide CRISPRi screening reveals determinants of platinum sensitivity and resistance in high-grade serous ovarian cancer

CD117 Antibody-Drug Conjugate Conditioning Allows Efficient Engraftment of Gene-Modified CD34+ Cells with Fertility Preservation in a Rhesus Gene Therapy Model

Hematopoietic stem cell (HSC) gene therapy is curative for multiple genetic diseases; however, it is limited due to toxicities from chemotherapy-based conditioning. To target HSCs directly, we developed an anti-human CD117 ( c-KIT)-targeted antibody-drug conjugate (CD117-ADC) conjugated to a DNA-binding payload that cross-reacted with non-human primates. To investigate the activity of CD117-ADC in non-human primates, we administered a single injection of ADC without HSC infusion, resulting in a >99% depletion of CD34+CD90+ bone marrow cells in cynomolgus macaques (n=2 of 3 in 0.1 mg/kg and n=3 in 0.3 mg/kg); similar to the ablation observed with 4 doses of myeloablative busulfan (Bu) (n=3). With escalating ADC doses (0.2-0.6 mg/kg), the optimal timing of HSC infusion (6 days in 0.2 or 0.3 mg/kg and 10 days in 0.4mg/kg) was determined in rhesus macaques (n=1 each). The animal dosed 0.6 mg/kg required euthanasia on day 14 due to irreversible hematopoietic suppression and severe liver toxicity. In our preliminary transplantation study, dosing 0.2 mg/kg ADC to rhesus macaques (n=2) resulted in bone marrow depletion and modest-level engraftment of gene-modified cells (vector copy number per cell (VCN) 0.05±0.01) (ASH 2019). Therefore, we evaluated higher single doses of CD117-ADC in rhesus macaques (0.3 mg/kg for ZL13 and ZJ62, and 0.4 mg/kg for H635 and H96G, n=4) and directly compared to Bu conditioning (5.5 mg/kg x 4 days, n=2). Mobilized rhesus CD34+ cells (ADC 6.4±2.9e6/kg vs. Bu 4.1±0.1e6/kg, n.s.) were transduced with a lentiviral vector for stable fetal hemoglobin (HbF) induction (Sci Transl Med. 2021). These cells ( in vitro VCN 10.1±3.8 vs. 10.2±7.3, n.s.) were transplanted into autologous animals after ADC or Bu conditioning. The time course of blood cell count suppression and recovery was similar between ADC and Bu animals, except for a strong reduction of platelet counts observed only with ADC (ASH 2021). Two months post-transplant, substantial levels of vector-containing granulocytes were observed long-term in 1 of 2 animals receiving 0.3 mg/kg ADC (ZJ62, VCN 0.16) and in both animals receiving 0.4 mg/kg (H635, VCN 0.46 and H96G, VCN 0.21) at a similar range to the two Bu animals (0.44±0.17, n.s.). Robust HbF induction was detected in three ADC animals with substantial VCN as measured by both HbF-positive cells (F-cells 8.5±1.8% vs. 13.7±5.8%, n.s.) and HPLC measurement of total HbF (8.0±2.9% vs. 11.1±5.2%, n.s.). In ZL13 (0.3 mg/kg ADC), lower gene marking (VCN 0.02) was observed, along with lower HbF induction (F-cells 1.0% and HbF amounts 0.9%). Importantly, ADC resulted in minimal off-target toxicity, unlike those associated with Bu (such as infertility, veno-occlusive disease, pulmonary dysfunction, mucositis, or seizures). High diversity of gene-modified cells (Simpson's diversity index >0.99) without any large clone (maximal integration site 0.3-3.7%) was observed by integration site analysis 1-year post-transplant with both ADC (0.3-0.4 mg/kg) and Bu. Infertility is a major complication of conventional myeloablative conditioning that limits the uptake of curative therapies; therefore, we investigated fertility in CD117-ADC animals. When monitored daily for menstrual bleeding, the menstrual cycles of all 4 female macaques (ZL13, ZJ62, H635, and H96G) were maintained post-ADC conditioning (0.92±0.11 per month) in contrast to our previously transplanted animals following myeloablative Bu (0.23±0.11, n=4, p<0.01) and total body irradiation (0.33±0.3, n=6, p<0.05). To confirm fertility, all transplanted animals post-ADC including females (n=4) and males (n=2) were housed for mating at a rhesus breeding colony. Two ADC females (ZL13 and H635) gave birth, and an ADC male (12U032) was paired with a pregnant female. Importantly, an ADC female (H635) was paired with an ADC male (13U047). In summary, a single-injection CD117-ADC allows for efficient engraftment of gene-modified CD34+ HSCs in a rhesus gene therapy model, achieving similar levels as the current clinical standard of care, myeloablative Bu conditioning. Robust HbF induction was also confirmed at the protein level in our rhesus gene therapy model with ADC conditioning. The transplanted animals with ADC maintained their fertility. Overall, these data indicate that an ADC-based targeted approach offers safer conditioning and could improve the risk-benefit profile in HSC gene therapy.

Evaluation of pain-alleviating strategies during allergy shots (subcutaneous immunotherapy): a randomized controlled pilot study.

Background. Subcutaneous immunotherapy (SCIT) is a potential disease-modifying therapy effective for treatment of various allergic disorders. Pain and fear are common concerns of children, which can pose stress and result in negative experiences. The purpose of this study was to evaluate and compare the effectiveness of three marketed distraction devices and ethyl chloride spray (a routinely used topical anesthetic agent for painful procedures), the current clinical standard of care in reducing the perception of needle pain during SCIT administration in children. Methods. 40 children, aged 4-17 years, receiving SCIT with use of one of three alternative pain therapies or with standard practice were enrolled. Participants were randomly assigned to one of the pain-modifying interventions. The three interventional groups were ShotBlocker® (Bionix, Toledo, OH, USA), Buzzy® I (Pain Care Labs, Atlanta, GA, USA) (vibration only), and Buzzy® II (vibration with ice). Control group was ethyl chloride spray. The study consisted of two visits during SCIT administration process. Results. Of these 40 children, 12 received the ShotBlocker, 8 received the Buzzy I, 11 received the Buzzy II, and 9 received ethyl chloride spray (control group). Conclusions. There were no significant differences found between each of the distraction devices and between the control group. Type II error/false negative finding cannot be ruled out because of a small sample. Therefore, we cannot conclude that no true difference exists between each distraction device and the control group simply because of occurrence of a non-significant P-value in our study.

Discrepancies between Cystatin C-Based and Creatinine-Based eGFR.

Recent guidance suggests clinicians increase use of cystatin C for the estimation of GFR. Discrepant levels of creatinine- versus cystatin C-based eGFR (eGFRcr versus eGFRcys) can occur and might signify inaccurate estimation of GFR using creatinine alone. This study sought to enhance the knowledge of the risk factors and clinical implications of having a large eGFR discrepancy. Participants in the Atherosclerosis Risk in Communities Study, a prospective cohort study of US adults, were followed over 25 years. eGFR discrepancy was measured at five clinical visits and defined as eGFRcys either 30% lower or higher than eGFRcr, the current clinical standard of care. The associations between eGFR discrepancies and kidney-related laboratory parameters were assessed using linear and logistic regression and long-term adverse outcomes, including kidney failure, AKI, heart failure, and death, using Cox proportional hazards models. Among 13,197 individuals (mean age 57 [SD 6] years, 56% women, 25% Black race), 7% had eGFRcys 30% lower than eGFRcr at visit 2 (1990-1992), and this proportion increased over time to 23% by visit 6 (2016-2017). By contrast, the percent with eGFRcys 30% higher than eGFRcr was relatively stable (3%-1%). Independent risk factors for having eGFRcys 30% lower than eGFRcr included older age, female sex, non-Black race, higher eGFRcr, higher body mass index, weight loss, and current smoking. Those with eGFRcys 30% lower than eGFRcr had more anemia and higher uric acid, fibroblast growth factor 23, and phosphate levels as well as higher risk of subsequent mortality, kidney failure, AKI, and heart failure compared with those with similar eGFRcr and eGFRcys values. Having eGFRcys lower than eGFRcr was associated with worse kidney-related laboratory derangements and a higher risk of adverse health outcomes. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_09_08_CJN0000000000000217.mp3.

Evaluation of a connexin-based peptide for the treatment of age-related macular degeneration

A critical target in age-related macular degeneration (AMD) is the retinal pigment epithelium (RPE), which forms the outer blood-retina barrier (BRB). RPE-barrier dysfunction might result from the disruption of intercellular tight junctions (TJs). A Connexin43 (Cx43)-based peptide, aCT1, has been shown to prevent VEGF-induced loss of transepithelial resistance, choroidal neovascularization (CNV) and RPE-cell damage via the stabilization of TJs. Here, we probe the relative efficacies of aCT1 alone, anti-VEGF alone, and aCT1 with anti-VEGF in treating AMD pathologies. aCT1 monotherapy administered as topical eye drops with and without a VEGF blocking antibody administered systemically was tested in a mouse model of laser-induced CNV. The CNV mouse is the standard neovascular AMD model, reproducing hallmarks of its pathology. CNV lesion size and fluid accumulation were assessed using optical coherence tomography. During the angiogenesis phase of CNV lesion development, single applications of anti-VEGF or aCT1 reduced lesion and fluid dome size equally. The combinatorial aCT1/anti-VEGF strategy demonstrated lack of additive effects in this model. These data suggest that TJ stabilization by aCT1 is effective in ameliorating RPE dysfunction in a model of AMD-like angiogenesis, and that this strategy is as effective as the current clinical standard of care, anti-VEGF therapy. Critically, aCT1 holds potential as a new neovascular AMD treatment that can be administered using eye drops, which is preferable to the intravitreal injections required for standard anti-VEGF therapy.

Therapeutic Potential of Small Molecule Inhibitors of TBK1 in Glioma

<h3>Purpose/Objective(s)</h3> Previously, we identified TBK1 as a therapeutic target in glioma using a high-throughput molecular approach. TBK1 has been shown to play a critical role in both the inflammatory response and tumor progression through multiple signaling pathways, including interferon, NF-κB, PI3K-AKT, and Ras-ERK pathways. The goal of this study was to assess the therapeutic potential of targeting TBK1. We hypothesize that the use of small molecule inhibitors of TBK1 alone or in combination with temozolomide (TMZ) and/or radiation may be a promising novel therapeutic strategy in glioma. <h3>Materials/Methods</h3> TBK1 siRNAs and commercially available small molecule inhibitors of TBK1, Amlexanox (AML) and GSK-8612, were purchased for <i>in vitro</i> characterization. Cell survival and colony formation assays were performed using glioma cell lines (LN18, U87, GBM30). Radiation was delivered one hour post GSK-8612/AML/TMZ treatment. pTBK1, pIRF3, pIkBa, pp65, and pAKT expression were evaluated using Western blot. Cleaved PARP (Western blot) and Annexin –V staining (flow cytometry) were used to evaluate the effect on cell apoptosis. <h3>Results</h3> Knockdown of TBK1 via siRNAs or small molecular inhibitor (AML and GSK-8612) resulted in decreased cell viability and colony formation and increased apoptosis in LN18 and GBM30 cells in a dose- and time-dependent manner. Importantly, a synergistic effect was observed when cell lines were treated with AML or GSK-8612 in combination with TMZ and/or radiation. Further molecular analysis of interferon signaling pathway or the NF-κB signaling pathway revealed that GSK-8612 decreased phosphorylation of IRF3, p65, IkBa, and AKT <h3>Conclusion</h3> In conclusion, these results suggest that TBK1 may be a promising therapeutic target in gliomas by regulating the interferon and/or NF-κB signaling pathways. Importantly, these TBK1 inhibitors were found to enhance the efficacy of the current clinical standard of care (TMZ and radiation) <i>in vitro</i>. Due to the critical need for better therapeutic strategies for glioma patients, it is our hope that further evaluation and optimization of these inhibitors will result in an improved treatment option with enhanced patient outcomes. Future work will focus on <i>in vivo</i> studies with AML or GSK-8612 alone and in combination with TMZ and radiation, as well as characterizing the toxicity profile of this combination therapy.

Management of Non-Small Cell Lung Cancer: Updates from the European Lung Cancer Congress 2022

The recently concluded European Lung Cancer Congress 2022 (ELCC22) showcased some very exciting data, with more than 200 abstracts presented during the meeting. Through this review, we focus on selected clinically relevant abstracts that in our opinion represent significant updates in the current management of non-small cell lung cancer (NSCLC). Here, we summarize the updates in surgical management, adjuvant therapy and therapy for advanced stage NSCLC and put these advances in the context of the current clinical standard of care.

Supervised Autonomous Electrosurgery for Soft Tissue Resection.

Surgical resection is the current clinical standard of care for treating squamous cell carcinoma. Maintaining an adequate tumor resection margin is the key to a good surgical outcome, but tumor edge delineation errors are inevitable with manual surgery due to difficulty in visualization and hand-eye coordination. Surgical automation is a growing field of robotics to relieve surgeon burdens and to achieve a consistent and potentially better surgical outcome. This paper reports a novel robotic supervised autonomous electrosurgery technique for soft tissue resection achieving millimeter accuracy. The tumor resection procedure is decomposed to the subtask level for a more direct understanding and automation. A 4-DOF suction system is developed, and integrated with a 6-DOF electrocautery robot to perform resection experiments. A novel near-infrared fluorescent marker is manually dispensed on cadaver samples to define a pseudotumor, and intraoperatively tracked using a dual-camera system. The autonomous dual-robot resection cooperation workflow is proposed and evaluated in this study. The integrated system achieves autonomous localization of the pseudotumor by tracking the near-infrared marker, and performs supervised autonomous resection in cadaver porcine tongues (N=3). The three pseudotumors were successfully removed from porcine samples. The evaluated average surface and depth resection errors are 1.19 and 1.83mm, respectively. This work is an essential step towards autonomous tumor resections.

Improved Clinical Assessment of Myeloid Malignancies By Transcriptome Profiling

Clinical genetic testing for myeloid malignancies including acute myeloid leukemia (AML) and myelodysplatic syndromes (MDS) currently relies on cytogenetic assays and targeted sequencing of clinically relevant genes. As more genes with diagnostic and prognostic relevance to these diseases are discovered, traditional testing methods will not be able to scale to effectively meet clinical needs. Next-generation sequencing platforms offer a potential way around this bottle-neck, but the analytic and clinical validity of these methods must be firmly established. To determine whether RNA-Seq, whole-genome sequencing (WGS), or whole-exome sequencing (WES) could meet or exceed the current clinical standard of care, we used these platforms to study retrospective and prospective cohorts of patients with myeloid malignancies.From a retrospective cohort of 176 patients, we generated RNA-Seq, WES, WGS libraries (176, 92, and 18, respectively). The patient cohort spanned a broad range of myeloid malignancies, including AML, MDS, and therapy-related AML and MDS. We observed that, for similar sequencing efforts, RNA-Seq libraries provided the highest coverage depth over clinically relevant genes, while WGS and WES platforms suffered from recurrent coverage dropouts, particularly in the GC-rich CEBPA gene (median coverage depths of 406x, 115x, and 33x for RNA-Seq, WES, and WGS libraries). We used de novo assembly to assess gene fusions from the RNA-Seq libraries, and demonstrated that all gene fusions previously detected by karyotyping were detectable (41 distinct patients, including 13 inv(16), 9 t(15;17), 8 t(8;21), 3 t(9;11), and 2 t(9;11)). Additionally, we identified five patients with novel rearrangements in the MLL gene family, with potential therapy-altering relevance. We observed complete sensitivity (30 cases) for FLT3 -ITD detection, and detected nine novel low-frequency events undetectable by the previous assay, which were validated using a targeted sequencing panel. We generated SNV and short indel calls for all platforms, and observed that most variants were concordant between platforms (2,079 matched variants aross 92 patients for the RNA-Seq/WES comparison). Missed variant calls (102) in WES libraries were generally due to poor sequencing coverage, while missing calls (44) in RNA-Seq libraries were generally due to allele-specific expression. We generated HLA genotypes for all patients using the RNA-Seq patients, and observed near-total concordance with previous clinical results, increasing the clinical utility of RNA-Seq based testing (of 621 called alleles, only two mismatches were observed at two-digit resolution).To determine whether gene expression information could be used to identify distinct risk groups within normal-karyotype AMLs, we performed unsupervised clustering analysis and network-based clustering analysis, identifying distinct clusters using both approaches. We demonstrate distinct co-occurrence of two expression clusters with NPM1 - and FLT3 alterations, and distinct survival outcomes for these novel clusters. Additionally, we observed distinct pathway enrichments associated with these clusters, linking molecular subtypes with gene expression signatures.Altogether, we observed that RNA-Seq offered substantial clinical benefits, due to the ability to recover expressed gene fusions and whole-transcriptome expression information, SNV and short indel variants, and HLA genotype information. Additionally, we observed gene expression heterogeneity which can be used to better stratify intermediate-risk patients. WGS and WES platforms showed recurrent weaknesses in coverage for clinically-relevant genes, and provided less actionable information overall. This work provides crucial analytic validation for the incorporation of RNA-Seq based testing for patients with myeloid malignancies, which may lead to substantial clinical benefits for those patients. DisclosuresNo relevant conflicts of interest to declare.

Examination of a first-in-class bis-dialkylnorspermidine-terphenyl antibiotic in topical formulation against mono and polymicrobial biofilms.

Biofilm-impaired tissue is a significant factor in chronic wounds such as diabetic foot ulcers. Most, if not all, anti-biotics in clinical use have been optimized against planktonic phenotypes. In this study, an in vitro assessment was performed to determine the potential efficacy of a first-in-class series of antibiofilm antibiotics and compare outcomes to current clinical standards of care. The agent, CZ-01179, was formulated into a hydrogel and tested against mature biofilms of a clinical isolate of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa ATCC 27853 using two separate methods. In the first method, biofilms were grown on cellulose discs on an agar surface. Topical agents were spread on gauze and placed over the biofilms for 24 h. Biofilms were quantified and imaged with confocal and scanning electron microscopy. In the second method, biofilms were grown on bioabsorbable collagen coupons in a modified CDC biofilm reactor. Coupons were immersed in treatment for 24 h. The first method was limited in its ability to assess efficacy. Efficacy profiles against biofilms grown on collagen were more definitive, with CZ-01179 gel eradicating well-established biofilms to a greater degree compared to clinical standards. In conclusion, CZ-01179 may be a promising topical agent that targets the biofilm phenotype. Pre-clinical work is currently being performed to determine the translatable potential of CZ-01179 gel.

Correction

Correction

GoPerio - impact of a personalized video and an automated two-way text-messaging system in oral hygiene motivation: study protocol for a randomized controlled trial

BackgroundOral hygiene is of paramount importance for the preservation of oral health, and for patients affected by periodontal disease establishing an effective oral hygiene routine is the first step of therapy. Several clinical frameworks have been developed to foster behavior change, such as motivational interviewing. However, two obstacles can be identified. First, patients tend to forget the advice they were given during the consultation. Second, it is hard to maintain motivation in the long term, thus leading to relapse. An innovative eHealth solution was designed with the aim to tackle both obstacles and supplement the current clinical standard of care. The primary objective is to compare the full mouth plaque scores of study groups (eHealth plus standard of care versus standard of care only) at 8 weeks of follow up. The main secondary objective is to compare the full mouth bleeding score at 8 weeks of follow up.Methods/designThe “GoPerio” study is a multicenter, randomized, controlled trial assessing the impact of a novel eHealth concept for oral hygiene motivation (personalized video of oral hygiene routine available for the patient via a cloud server plus interactive text messages) in addition to the current standard of care (motivational interviewing plus tooth scaling and polishing). The minimum sample size required is 86 patients. Participants will be randomized (allocation ratio 1:1): test group (eHealth plus standard of care) versus control group (standard of care only). The primary outcome is oral hygiene as measured by the full mouth (six sites per tooth) plaque control record (PCR) index. The main secondary outcome is gingival inflammation as measured by the full mouth (six sites per tooth) bleeding on probing (BOP) index. Both the primary and the main secondary outcomes are evaluated by blinded and calibrated examiners at 8 weeks of follow up. The other secondary outcomes are patient satisfaction and patient behavior change and motivation.DiscussionThe study will investigate the value of an innovative eHealth approach to strengthen patient motivation for oral hygiene. If proven effective, such an approach would supplement the current clinical standard of care, resulting in improved clinical outcomes with negligible impact on productivity in a dental practice.Trial registrationClinicalTrials.gov, NCT03109808. Registered on 12 April 2017.Sponsor: Hospices Civils de Lyon. BP 2251, 3 quai des Célestins, 69,229 Lyon cedex 02.Protocol version: 1.0 as of 21 September 2016.

Intraoperative monitoring of neuromuscular function with soft, skin-mounted wireless devices

Peripheral nerves are often vulnerable to damage during surgeries, with risks of significant pain, loss of motor function, and reduced quality of life for the patient. Intraoperative methods for monitoring nerve activity are effective, but conventional systems rely on bench-top data acquisition tools with hard–wired connections to electrode leads that must be placed percutaneously inside target muscle tissue. These approaches are time and skill intensive and therefore costly to an extent that precludes their use in many important scenarios. Here we report a soft, skin-mounted monitoring system that measures, stores, and wirelessly transmits electrical signals and physical movement associated with muscle activity, continuously and in real-time during neurosurgical procedures on the peripheral, spinal, and cranial nerves. Surface electromyography and motion measurements can be performed non-invasively in this manner on nearly any muscle location, thereby offering many important advantages in usability and cost, with signal fidelity that matches that of the current clinical standard of care for decision making. These results could significantly improve accessibility of intraoperative monitoring across a broad range of neurosurgical procedures, with associated enhancements in patient outcomes.

Evaluation of a model-based poroelastography algorithm for edema quantification

A critical component of end stage renal disease treatment is optimal fluid management. Patients with reduced kidney function risk developing fluid overload, and many dialysis patients exceed recommended levels of fluid retention, leading to frequent clinical intervention and higher mortality. Despite this, current clinical standards of care rely on reactive semi-quantitative tests to grade fluid overload and peripheral edema. Poroelastography has been proposed as a quantitative means of estimating fluid overload in peripheral edema, but clinical studies have met limited success, in part because of measurement noise. We developed a new poroelastography method based on an inverse problem formulation to address the shortcomings of current methods. Our technique iteratively minimizes the error between ultrasound displacement measurements and the solution of a Biot poroelastic model. This formulation does not depend on noise-amplifying derivatives and ratios. We tested our algorithm in a simulation study using synthetic displacement data with Gaussian noise and speckle tracking measurements from simulated sonograms. Our algorithm accurately estimated the Poisson’s ratio at all noise levels tested. Reconstruction errors for all cases were less than 10% and outperformed traditional methods. Although our method required 4-12 hours to run, it is easily parallelized. Future work will focus on benchtop validation.

Meniscal Root Repairs.

Meniscal root tears are substantial injuries that usually require surgical management. If left untreated, meniscal root tears can lead to the rapid onset of osteoarthritis similar to that seen after a total meniscectomy. Meniscal root tears often go unnoticed on magnetic resonance imaging and arthroscopy, in large part because meniscal root anatomy and its biomechanical importance have been defined only recently. In a transtibial meniscal root repair, the current clinical standard of care, the root is reattached to its native attachment site on the tibial plateau, restoring tibiofemoral contact mechanics. While this video article shows a posterior medial root repair technique, the same anatomic, biomechanical, and surgical principles apply to a posterior lateral meniscal root attachment. The principal steps in this procedure include (1) verifying the presence of a posterior medial meniscal root tear with arthroscopic visualization and probing, (2) inspecting the root tear and debriding the root attachment site to bone with a curet, (3) arthroscopic release of any adhesions that cause retraction of the meniscal root to a nonanatomic position, (4) drilling of two separate transtibial tunnels that extend down to the anteromedial portion of the tibia, (5) placing an accessory portal to pass the sutures, (6) placing two simple sutures through the torn meniscal root and shuttling them down the tibial tunnels, and (7) tying the sutures over a surgical button on the anteroproximal portion of the tibia with the knee flexed 90°. Postoperatively, patients remain non-weight-bearing for six weeks. Passive knee flexion from 0° to 90° is allowed for the first two weeks. After two weeks, motion is increased as tolerated. Patients initiate weight-bearing at postoperative week six and commence the use of a stationary bicycle. Resistive exercises are slowly progressed, and the patient should avoid squatting as well as squatting and lifting for four months. Patients are expected to return to normal physical activity within four to six months postoperatively.

Next-generation vision testing: the quick CSF

Abstract The Contrast Sensitivity Function relates the spatial frequency and contrast of a spatial pattern to its visibility and thus provides a fundamental description of visual function. However, the current clinical standard of care typically restricts assessment to visual acuity, i.e. the smallest stimulus size that can be resolved at full contrast; alternatively, tests of contrast sensitivity are typically restricted to assessment of the lowest visible contrast for a fixed letter size. This restriction to one-dimensional subspaces of a two-dimensional space was necessary when stimuli were printed on paper charts and simple scoring rules were applied manually. More recently, however, computerized testing and electronic screens have enabled more flexible stimulus displays and more complex test algorithms. For example, the quick CSF method uses a Bayesian adaptive procedure and an information maximization criterion to select only informative stimuli; testing times to precisely estimate the whole contrast sensitivity function are reduced to 2-5 minutes. Here, we describe the implementation of the quick CSF method in a medical device. We make several usability enhancements to make it suitable for use in clinical settings. A first usability study shows excellent results, with a mean System Usability Scale score of 86.5.

Detecting Infection in Neonates: Promises and Challenges of a Salivary Approach

Premature newborns present unique challenges for the caregiver. Their clinical fragility and immature immune system places them at increased risk for bacterial and viral infections. Current clinical standard of care mandates invasive phlebotomy to assess an infant for an infection. However, serial blood draws can lead to blood transfusions and the infliction of noxious stimuli to this vulnerable population. Salivary screening for common neonatal morbidities, such as infections, could vastly improve the care for these infants and positively affect their long-term clinical outcomes. Recent technological advancements have improved our ability to detect thousands of proteins and/or microbes from a single salivary sample, making noninvasive assessment in neonates a possibility. This article reviews the clinical applications and challenges associated with integrating salivary analysis for infectious surveillance into the neonatal population.

Electrospun Tropoelastin for Delivery of Therapeutic Adipose-Derived Stem Cells to Full-Thickness Dermal Wounds.

Objective: To evaluate the physiological effects of electrospun tropoelastin scaffolds as therapeutic adipose-derived stem cell (ADSC) delivery vehicles for the treatment of full-thickness dermal wounds. Approach: Using the process of electrospinning, several prototype microfiber scaffolds were created with tropoelastin. Initial testing of scaffold biocompatibility was performed in vitro through ADSC culture, followed by scanning electron microscopy (SEM) for assessment of ADSC attachment, morphology, and new extracellular matrix (ECM) deposition. The wound healing effects of ADSC-seeded scaffolds were then evaluated in a murine dermal excisional wound model. Results: For the in vitro study, SEM revealed exceptional biocompatibility of electrospun tropoelastin for ADSCs. In the wound-healing study, ADSC-treated groups demonstrated significantly enhanced wound closure and epithelial thickness compared to controls. Innovation: This is the first report on the use of tropoelastin-based biomaterials as delivery vehicles for therapeutic ADSCs. Conclusion: We have demonstrated that tropoelastin-based ADSC delivery vehicles significantly accelerate wound healing compared to controls that represent the current clinical standard of care. Furthermore, the unique mechanical and biochemical characteristics of tropoelastin may favor its use over other biological or synthetic scaffolds for the treatment of certain pathologies due to its unique intrinsic mechanical properties.

Translational research to improve the treatment of severe extremity injuries

ObjectivesSevere extremity injuries are the most significant injury sustained in combat wounds. Despite optimal clinical management, non-union and infection remain common complications. In a concerted effort to dovetail research efforts,...