Material Flow Analysis and Occupational Exposure Assessment in Additive Manufacturing End-of-Life Material Management.

Additive manufacturing (AM) offers a variety of material manufacturing techniques for a wide range of applications across many industries. Most efforts at process optimization and exposure assessment for AM are centered around the manufacturing process. However, identifying the material allocation and potentially harmful exposures in end-of-life (EoL) management is equally crucial to mitigating environmental releases and occupational health impacts within the AM supply chain. This research tracks the allocation and potential releases of AM EoL materials within the US through a material flow analysis. Of the generated AM EoL materials, 58% are incinerated, 33% are landfilled, and 9% are recycled by weight. The generated data set was then used to examine the theoretical occupational hazards during AM EoL material management practices through generic exposure scenario assessment, highlighting the importance of ventilation and personal protective equipment at all stages of AM material management. This research identifies pollution sources, offering policymakers and stakeholders insights to shape pollution prevention and worker safety strategies within the US AM EoL management pathways.

Review of generic scenario environmental release and occupational exposure models used in chemical risk assessment.

Under the Toxic Substances Control Act (TSCA), the United States Environmental Protection Agency (USEPA) is required to determine whether a new chemical substance poses an unreasonable risk to human health or the environment before the chemical is manufactured in or imported into the United States. This manuscript provides a review of the process used to evaluate the risk associated with a chemical based on the scenarios and models used in the evaluation. Specifically, the Generic Scenarios and Emission Scenario Documents developed by the USEPA were reviewed, along with background documentation prepared by USEPA to identify the core elements of the environmental release and occupational exposure scenarios used to assess the risk of the chemical being evaluated. Additionally, this contribution provides an overview of methods used to model occupational exposures and environmental releases as part of the chemical evaluation process used in other jurisdictions, along with work being performed to improve these models. Finally, the alternative methods to evaluate occupational exposures and environmental releases that may be used as part of the decision-making process regarding a chemical are identified. The contribution provides a path forward for reducing the time required and improving the chemical evaluation of the unreasonable risk determination regarding the manufacture or import of a chemical.

Ketamine: a versatile tool for anesthesia and analgesia.

PURPOSE OF REVIEW: Ketamine has been used for decades for a variety of indications. Beyond the historical benefits and effects of ketamine, newer developments have occurred worthy of an update. This review will discuss common uses and indications for ketamine in the perioperative setting, as well as highlight newer indications in recent years. RECENT FINDINGS: Multiple studies have examined the use of ketamine in a variety of environments, as ketamine has become more popular in emergency rooms and ICUs. Ketamine may be particularly beneficial in management of burn patients, who often require multiple procedures over the course of their treatment. Ketamine's role in the ongoing opioid crisis has been of particular interest, with multiple studies evaluating its potential role in managing both acute and chronic pain conditions. Ongoing studies examining the role of ketamine in treatment of depressions show promise as well. SUMMARY: Ketamine is regaining popularity in the field of anesthesia and beyond. New studies provide insight on the many indications and use that anesthesia providers may encounter during their perioperative care of patients. Ongoing research is needed to further elucidate ketamine's effects on the management of psychiatric conditions and potential indications for ketamine metabolites.

Validation of NRG oncology/RTOG-0129 risk groups for HPV-positive and HPV-negative oropharyngeal squamous cell cancer: Implications for risk-based therapeutic intensity trials.

BACKGROUND: Radiation Therapy Oncology Group (RTOG)-0129 recursive partitioning analysis was the basis for risk-based therapeutic intensification trials for oropharyngeal cancer (OPC). To the authors' knowledge, the question of whether RTOG-0129 overall survival (OS) estimates for low-risk, intermediate-risk, and high-risk groups are similar in other data sets or applicable to progression-free survival (PFS) is unknown. Therefore, the authors evaluated whether survival differences between RTOG-0129 risk groups persist at 5 years, are reproducible in an independent clinical trial, and are applicable to PFS, and whether toxicities differ across risk groups. METHODS: Prospective randomized clinical trials were analyzed retrospectively. RTOG-0129 evaluated standard versus accelerated fractionation radiotherapy concurrent with cisplatin. RTOG-0522 compared the combination of cisplatin and accelerated fractionation with or without cetuximab. Patients with OPC with available p16 status and tobacco history were eligible. RESULTS: There was a total of 260 patients and 287 patients, respectively, from RTOG-0129 and RTOG-0522, with median follow-ups for surviving patients of 7.9 years (range, 1.7-9.9 years) and 4.7 years (range, 0.1-7.0 years), respectively. Previous OS differences in RTOG-0129 persisted at 5 years. In RTOG-0522, the 5-year OS rates for the low-risk, intermediate-risk, and high-risk groups were 88.1%, 69.9%, and 45.1%, respectively (P for trend, <.001). The 5-year PFS rates for the same 3 groups were 72.9%, 56.1%, and 42.2%, respectively. In RTOG-0522 among a subgroup of patients considered to be at very good risk (p16-positive disease, smoking history of ≤10 pack-years, and classified with T1-T2 disease with ipsilateral lymph nodes measuring ≤6 cm or T3 disease without contralateral or >6 cm lymph nodes), the 5-year OS and PFS rates were 93.8% and 82.2%, respectively. Overall rates of acute and late toxicities were similar by risk group. CONCLUSIONS: RTOG-0129 risk groups persisted at 5 years and were reproducible in RTOG-0522. However, there was variability in the estimates. These data underscore the importance of long-term follow-up and appropriate patient selection in therapeutic deintensification trials.

Prospective, Randomized Study of Direct Anterior Approach vs Posterolateral Approach Total Hip Arthroplasty: A Concise 5-Year Follow-Up Evaluation.

BACKGROUND: Interest in direct anterior approach (DAA) has increased over the last decade. In our previously published study comparing DAA to posterolateral approach (PA), early 3-month benefits were noted in terms of pain and function. There was no difference noted at 6 or 12 months. This study reports average 5-year follow-up of our original study. METHODS: Originally there were 43 DAA patients and 44 PA patients. At an average 5-year follow-up, patients were evaluated clinically with a University of California at Los Angeles activity score, Harris hip score, and Hip Disability and Osteoarthritis Outcome Score Jr Survivorship analysis was calculated. Radiographs were evaluated for loosening and evidence of radiolucent lines. RESULTS: There were 2 deaths 1 in each group, neither was related to the implant or procedure. Four patients were lost to follow-up: 2 in the DAA group and 2 in the PA group. There was no statistical difference between surgical approaches in terms of Harris hip score, University of California at Los Angeles activity score, and Hip Disability and Osteoarthritis Outcome Score Jr. The 7-year survivorship was not significantly different. There were no loose implants at average 5-year follow-up. CONCLUSION: Both DAA and PA yield good results at an average 5-year follow-up in terms of survivorship, function, rate of complications, and radiographic analysis.

Response to Targeted Therapy in BRAF Mutant Anaplastic Thyroid Cancer.

Anaplastic thyroid cancer (ATC) is an aggressive uncommon malignancy with limited treatment. Traditional antineoplastic chemotherapy has not been successful in the management of metastatic ATC. As a result, the focus has shifted to the development of novel therapies for this disease. The availability of economical comprehensive genomic profiling (CGP) platforms with rapid turn-around to identify molecular aberrations in tumors that are potential therapeutic targets has increasingly changed the face of cancer therapy. Identification of targetable aberrations may help identify novel treatment options for ATC. Herein, we report our experience with a 47-year-old patient with metastatic ATC who experienced recurrent, progressive disease and rapid clinical deterioration despite surgery, radiation therapy, and treatment with 2 different chemotherapy regimens. She was found to have a BRAF V600E mutation on CGP, and was started on targeted therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib. After 2 months of treatment, she showed a clinical and radiologic response. The patient remained on this combination for 9 months until evidence of disease progression. Discontinuation of these drugs was associated with rapid tumor growth. Through this case we want to emphasize the importance of early molecular sequencing and identification of genetic aberrations in patients with ATC, and using that information to develop therapies for ATC, an aggressive malignancy with limited therapy and a poor outcome.

Mining Available Data from the United States Environmental Protection Agency to Support Rapid Life Cycle Inventory Modeling of Chemical Manufacturing.

Demands for quick and accurate life cycle assessments create a need for methods to rapidly generate reliable life cycle inventories (LCI). Data mining is a suitable tool for this purpose, especially given the large amount of available governmental data. These data are typically applied to LCIs on a case-by-case basis. As linked open data becomes more prevalent, it may be possible to automate LCI using data mining by establishing a reproducible approach for identifying, extracting, and processing the data. This work proposes a method for standardizing and eventually automating the discovery and use of publicly available data at the United States Environmental Protection Agency for chemical-manufacturing LCI. The method is developed using a case study of acetic acid. The data quality and gap analyses for the generated inventory found that the selected data sources can provide information with equal or better reliability and representativeness on air, water, hazardous waste, on-site energy usage, and production volumes but with key data gaps including material inputs, water usage, purchased electricity, and transportation requirements. A comparison of the generated LCI with existing data revealed that the data mining inventory is in reasonable agreement with existing data and may provide a more-comprehensive inventory of air emissions and water discharges. The case study highlighted challenges for current data management practices that must be overcome to successfully automate the method using semantic technology. Benefits of the method are that the openly available data can be compiled in a standardized and transparent approach that supports potential automation with flexibility to incorporate new data sources as needed.

A novel genomic signature reclassifies an oral cancer subtype.

Verrucous carcinoma of the oral cavity (OVC) is considered a subtype of classical oral squamous cell carcinoma (OSCC). Diagnosis is problematic, and additional biomarkers are needed to better stratify patients. To investigate their molecular signature, we performed low-coverage copy number (CN) sequencing on 57 OVC and exome and RNA sequencing on a subset of these and compared the data to the same OSCC parameters. CN results showed that OVC lacked any of the classical OSCC patterns such as gain of 3q and loss of 3p and demonstrated considerably fewer genomic rearrangements compared to the OSCC cohort. OVC and OSCC samples could be clearly differentiated. Exome sequencing showed that OVC samples lacked mutations in genes commonly associated with OSCC (TP53, NOTCH1, NOTCH2, CDKN2A and FAT1). RNA sequencing identified genes that were differentially expressed between the groups. In silico functional analysis showed that the mutated and differentially expressed genes in OVC samples were involved in cell adhesion and keratinocyte proliferation, while those in the OSCC cohort were enriched for cell death and apoptosis pathways. This is the largest and most detailed genomic and transcriptomic analysis yet performed on this tumour type, which, as an example of non-metastatic cancer, may shed light on the nature of metastases. These three independent investigations consistently show substantial differences between the cohorts. Taken together, they lead to the conclusion that OVC is not a subtype of OSCC, but should be classified as a distinct entity.

In-vivo alignment comparing patient specific instrumentation with both conventional and computer assisted surgery (CAS) instrumentation in total knee arthroplasty.

Patient specific instrumentation (PSI) was developed to increase total knee arthroplasty (TKA) accuracy and efficiency. The study purpose was to compare immediate post-operative mechanical alignment, achieved using PSI, with conventional and computer assisted surgery (CAS) instruments in high volume TKA practices. This prospective, multicenter, non-randomized study accrued 66 TKA patients using PSI. A computed tomography (CT) based algorithm was used to develop the surgical plan. Sixty-two percent were females, 99% were diagnosed with osteoarthritis, average age at surgery was 66 years, and 33 was the average body mass index. A historical control group was utilized that underwent TKA using conventional instruments (n=86) or CAS (n=81), by the same set of surgeons. Postoperative mechanical alignment was comparable across the groups. Operative time mean and variance were significant.

Eleven essential steps to purchasing or selling a medical practice.

Based on our experience in representing more than 100 doctors and medical specialists in practice sales and acquisitions, we have identified 11 key considerations important to a deal. There are several issues to consider while going through the process of buying or selling a practice including the implementation of a "letter of intent" as a first step rather than drafting a contract, securing a lease, and verifying the property is not in violation of the local zoning requirements. There are also considerations with regard to the patients, which range from how will the accounts receivable at the time of the closing be handled to who is responsible for the handling of continued treatment in an ongoing case after a deal is finalized. This article details these considerations and more.

Robotic-assisted total knee arthroplasty reduces soft-tissue releases which improves functional outcomes: A retrospective study.

BACKGROUND: There is increasing use of Robotic-Assisted (RA) and personalized alignment techniques in total knee arthroplasty (TKA). The hypothesis of this study was that RA TKA would result in fewer soft-tissue releases, and that fewer soft-tissue releases would be associated with improved clinical outcomes. METHODS: A retrospective review of an internal company registry was conducted for all primary TKAs performed from Jan 1, 2014, through a database extract date of Nov 4, 2022. These were grouped by whether there was an intentional soft-tissue release performed (STR) during the surgery or not (NSTR) and whether RA was utilized. The incidence of STR was compared between RA-TKAs and those performed with manual instrumentation. Knee Society Score (KSS) and Knee Society Function Scores (KSFS) were collected at 6 months, 1 year and 2 years. Kaplan-Meier survivorship was performed. RESULTS: The incidence of STR was significantly lower for RA vs. Manual (43.81% Vs 86.62%, p < 0.0001). The TKAs with NSTR had higher KSFS compared to those with STR at 6 months (84.73 Vs. 77.51, p < 0.0001), 1 year (89.87 Vs. 83.54, p < 0.0001) and 2 years (90.09 Vs. 82.65, p < 0.0001). There was no difference in survivorship, or KSS at any time point. However, the NSTR group had improved KSS pain sub score at 2 years. CONCLUSION: The results of this observational, retrospective analysis found that the incidence of soft-tissue release was lower with RA-TKA. Further, regardless of if RA was used, avoiding releases was associated with improved KSFS and KSS pain scores through 2 years post-operatively.

Five-Year Survivorship of Total Hip Arthroplasty With a Proximally Coated, Medially Collared, Triple-Tapered Femoral Stem: A Retrospective, Multicenter Registry Review.

Background The anterior approach for total hip arthroplasty (THA) has gained popularity in recent years. Some surgeons have been hesitant to adopt the approach due to concerns over increased complications such as intraoperative fracture, stem loosening, and stem revision. This study aims to evaluate the all-cause revision rate and survivorship of a collared, triple-tapered stem that was designed specifically for use with the anterior approach in THA to enhance outcomes and reduce adverse events. Methodology A retrospective outcomes review was conducted to assess survivorship and clinical outcomes for a specific proximally coated, medially collared triple-tapered (MCTT) femoral stem. Results In a cohort of 5,264 hips, Kaplan-Meier survivorship estimates (95% confidence interval [CI]; N with further follow-up), with survivorship defined as no revision of any component for any reason at five years after the index procedure, were 98.9% (97.8%-99.4%; 43) under the clinical assumption and 99.6% (99.4%-99.7%; 894) under the registry assumption. With survivorship defined as stem revision for any reason, survivorship estimates at five years postoperatively were 99.6% (99.3%-99.8%; 43) under the clinical assumption and 99.8% (99.7%-99.9%; 894) under the registry assumption. The mean follow-up time was 94.52 days (standard deviation [SD] 2.24, range 90.03-96.02). At five years postoperatively, the mean Harris Hip Score was 95.19, and the mean Hip Disability and Osteoarthritis Outcome Score Junior (HOOS JR) score was 98.66. Conclusions Our evaluation demonstrates excellent construct and stem survivorship and very low complication rates at midterm postoperative follow-up.

Advanced Multi-Layer Watertight Closure versus Conventional Closure in Total Hip and Knee Replacement Surgery.

Background: In total joint replacement procedures, surgeons have increasingly adopted advanced multi-layer, watertight closure. The objective of the study was to compare the clinical and economic outcomes for advanced multi-layer, watertight closure patients to those with conventional closure with sutures and skin staples. Methods: Patients aged ≥18 years were included in the study if they underwent total joint arthroplasty of the hip or knee as an elective, primary, inpatient procedure between January 2014 and March 2019. Cohorts having advanced multi-layer, watertight closure or conventional closure were compared using multivariable regression analysis of surgical site infections, length of stay, operating room time, procedure time, discharge status, readmissions, reoperations, and hospital emergency department visits. Results: A total of 1828 patients received at least one total hip or knee replacement, of which 434 (23.7%) had advanced multi-layer, watertight closure and 1394 (76.3%) had conventional closure. Unadjusted time to readmission, when occurring, was considerably longer following advanced multi-layer, watertight closure (89.9 vs 51.1 days, p < 0.0001), and a lower proportion of the advanced multi-layer, watertight closure cohort required reoperation within 90 days (0.0% vs 2.6%, p < 0.0001). Adjusted mean hospital length of stay was approximately half of a day shorter for advanced multi-layer, watertight closure patients (1.10 vs 1.65 days; p < 0.001), and they were also more likely to be discharged to home (Odds Ratio: 4.61; p = 0.002). Conclusion: Among patients undergoing total hip and knee arthroplasty in a highly optimized real-world clinical practice, advanced multi-layer, watertight closure was associated with significantly shorter inpatient length of stay and increased likelihood of being discharged to home compared with conventional closure. These findings suggest that advanced multi-layer, watertight closure is a valuable component of an optimal workflow for total hip or knee replacement, and may be especially valuable for high-risk patients.

Prospective randomized study of direct anterior vs postero-lateral approach for total hip arthroplasty.

Benefits of a direct anterior approach (DAA) versus a posterior-lateral (PA) approach to THA were assessed in a single-surgeon, IRB-approved, prospective, randomized clinical study. Subjects (43 DAA and 44 PA) were evaluated at 6 weeks, and 3, 6 and 12 months. The primary end point was ability to climb stairs normally and walk unlimited at each time point. Secondary end points included assessment by several outcome instruments. DAA subjects performed better during the immediate post-operative period; they had lower VAS pain scores on the first post-operative day, more subjects climbing stairs normally and walking unlimited at 6 weeks, and higher HOOS Symptoms scores at 3 months. There were no significant differences between groups at later time points. Findings confirm previous reports of benefits of DAA versus PA in early post-operative phases.

Sunrise of PFAS Replacements: A Perspective on Fluorine-Free Foams.

One type of firefighting foam, referred to as aqueous filmforming foams (AFFF), is known to contain per- and polyfluoroalkyl substances (PFAS). The concerns raised with PFAS, and their potential environmental and health impacts, have led to a surge in research on fluorine-free alternatives both in the United States and globally. Particularly, in January 2023, a new military specification (MIL-PRF-32725) for fluorine-free foam was released in accordance with Congressional requirements for the U.S. Department of Defense. This paper provides a critical analysis of the present state of the various fluorine-free options that have been developed to date. A nuanced perspective of the challenges and opportunities of more sustainable replacements is explored by examining the performance, cost, and regulatory considerations associated with these fluorine-free alternatives. Ultimately, this evaluation shows that the transition to fluorine-free replacements is likely to be complex and multifaceted, requiring careful consideration of the trade-offs involved. Yet, the ongoing work will provide valuable insights for future research on alternatives to AFFF and enhancing the safety and sustainability of fire suppression systems.

Sulforaphane Bioavailability in Healthy Subjects Fed a Single Serving of Fresh Broccoli Microgreens.

Cruciferous vegetable consumption is associated with numerous health benefits attributed to the phytochemical sulforaphane (SFN) that exerts antioxidant and chemopreventive properties, among other bioactive compounds. Broccoli sprouts, rich in SFN precursor glucoraphanin (GRN), have been investigated in numerous clinical trials. Broccoli microgreens are similarly rich in GRN but have remained largely unexplored. The goal of this study was to examine SFN bioavailability and the microbiome profile in subjects fed a single serving of fresh broccoli microgreens. Eleven subjects participated in a broccoli microgreens feeding study. Broccoli microgreens GRN and SFN contents and stability were measured. Urine and stool SFN metabolite profiles and microbiome composition were examined. Broccoli microgreens had similar GRN content to values previously reported for broccoli sprouts, which was stable over time. Urine SFN metabolite profiles in broccoli microgreens-fed subjects were similar to those reported previously in broccoli sprouts-fed subjects, including the detection of SFN-nitriles. We also reported the detection of SFN metabolites in stool samples for the first time. A single serving of broccoli microgreens did not significantly alter microbiome composition. We showed in this study that broccoli microgreens are a significant source of SFN. Our work provides the foundation for future studies to establish the health benefits of broccoli microgreens consumption.

Large-diameter modular metal-on-metal total hip arthroplasty: incidence of revision for adverse reaction to metallic debris.

Large-diameter modular metal-on-metal (MOM) total hip arthroplasty (THA) may offer reduction in wear debris and improved stability. Four studies are summarized here that used a large-diameter modular MOM system. A total of 1076 THAs were performed. This article presents data from 779 of these THAs with minimum 2-year follow-up (mean, 4.2 years) or revision since index THA (21 hips, with 1 more pending). Overall survivorship at 2 years was 98.6%; at 5 years, it was 97.0%. Seven revisions for an adverse reaction to metallic debris (ARMED), and 1 additional pending revision for ARMED, showed marked variability in presenting symptoms and intraoperative and postoperative findings. Data show good clinical performance of the modular MOM system, but suggest that surgeons must be diligent in monitoring MOM THA patients and aggressive in diagnosing and revising patients with a potential ARMED.

A phase I/II trial of concurrent immunotherapy with chemoradiation in locally advanced larynx cancer.

Objectives: Cisplatin-based chemoradiation is an established organ-preserving strategy for locally advanced laryngeal cancer, but long-term survival remains suboptimal. Immunotherapy has been studied in the metastatic and unresectable recurrent settings. However, additional data are needed to assess its role in organ preservation for locally advanced laryngeal cancer. Methods: This trial was an open-label, single-arm, multi-institutional study with a Phase I run-in portion followed by a planned Phase II component, which closed early due to low accrual. Study patients had Stage III or IV (T2-3; N0-3; M0) laryngeal squamous cell carcinoma and were candidates for larynx preservation. Pembrolizumab was given 2-3 weeks prior to chemoradiation and then, q21 days concurrently with high-dose cisplatin and radiation prescribed to a total dose of 70 Gy. The primary endpoint of the trial was organ-preservation rate (OPR) at 18 months. Results: A total of nine patients were enrolled with a median follow-up of 30.1 months. No patient required laryngectomy, resulting in 100% OPR at 18 months. The 12-month overall survival (OS) rate was 77.8% and the median duration of OS was not reached. All acute Grade 4 (n = 3) toxicities occurred in a single patient with poorly controlled diabetes at baseline. One patient had late Grade 4 laryngeal edema requiring tracheostomy 8 months after chemoradiation, which self-resolved. Conclusion: UCCI-HN-15-02 demonstrated the safety of the addition of immunotherapy to definitive chemoradiation and the patient outcomes suggest the potential for improving long-term survival while minimizing negative impact from treatment. While results from this trial were promising, a randomized study with a larger number of patients and longer follow-up is warranted to verify this treatment approach prior to wider adoption. NCT #: NCT02759575.Level of evidence: 2b.

Comparison of radiographic alignment of imageless computer-assisted surgery vs conventional instrumentation in primary total knee arthroplasty.

A total of 208 patients were enrolled in a multicenter, prospective randomized, institutional review board-approved study that compared preoperative surgical plan to postoperative 2-dimensional radiographic alignment measured by a blinded reviewer for primary total knee arthroplasty (TKA) implanted using computer-assisted surgery (CAS) compared with conventional TKA instrumentation. The results demonstrated a statistically significant improvement in the coronal tibial component alignment (P < .03) and failed to demonstrate a statistically significant improvement in the mechanical axis, femoral coronal/sagittal, and tibial sagittal alignment. Knee Society Score knee and function scores and 6-minute walk test were equivalent between the 2 treatment groups at all postoperative intervals. There was a statistically significant increase in the skin-skin time (P < .0001) and the time until first bone cut (P < .0001) for the CAS knees compared with those implanted with conventional instrumentation. The use of CAS in this randomized clinical trial conducted at high-volume centers did not offer a clinically meaningful improvement in postoperative alignment, clinical, functional, or safety outcomes compared with conventional TKA.