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RATIONALE: Gamma knife stereotactic radiosurgery (GKRS) is a recognized safe and effective treatment for brain metastasis; however, some complications can present significant clinical challenges. This case report highlights a rare occurrence of cerebrospinal fluid (CSF) leakage and pneumocranium following GKRS, emphasizing the need for awareness and prompt management of these complications. PATIENT CONCERNS: A 35-year-old male with a history of malignant neoplasm of the lip in 2015 and perineural spread of malignancy into the left cavernous sinus was treated with GKRS in 2017. The patient was admitted emergently 39 days after discharge due to persistent headache and dizziness. DIAGNOSES: Brain computed tomography (CT) revealed diffuse bilateral pneumocranium alongside an observation of CSF leakage. INTERVENTIONS: A surgical procedure involving a left frontal-temporal craniotomy was performed to excise a residual skull base tumor and repair the dura, guided by a navigator system. The conclusive pathological assessment revealed the presence of squamous cell carcinoma markers. OUTCOMES: The patient exhibited excellent tolerance to the entire procedure and experienced a prompt and uneventful recovery process. After surgery, the symptoms alleviated and CSF leak stopped. The follow-up image showed the pneumocranium resolved. LESSONS: Pneumocranium due to early-stage post-GKRS is uncommon. The rapid tumor shrinkage and timing of brain metastasis spreading through the dura can lead to CSF leak and pneumocranium. We reviewed current treatment options and presented a successful craniotomy-based dura repair case.
Subject(s)
Brain Neoplasms , Radiosurgery , Adult , Humans , Male , Brain Neoplasms/secondary , Brain Neoplasms/radiotherapy , Brain Neoplasms/surgery , Cerebrospinal Fluid Leak/etiology , Pneumocephalus/etiology , Postoperative Complications/etiology , Radiosurgery/adverse effects , Radiosurgery/methods , Tomography, X-Ray ComputedABSTRACT
Multifocal papillary thyroid carcinomas (PTCs) are common and the majority of the tumors harbor mutual BRAF p.V600E mutation. This study aimed to investigate a contemporary series of multifocal PTCs with discordant molecular drivers. Consecutive thyroidectomies diagnosed with multifocal PTCs ≥0.5 cm between 2019 and 2023 were reviewed. Immunohistochemistry (IHC) for BRAF VE1 was performed for all tumors. Cases with discordant BRAF IHC results or morphologic discrepancy were identified, and BRAF IHC-negative tumors were subjected to RAS Q61R IHC and/or targeted RNA next-generation sequencing. A total of 770 patients with a main PTC ≥0.5 cm were identified; 255 (33.1%) had multifocal disease, and 142 (18.4%) had at least another PTC ≥0.5 cm. Among them, 13 cases (9.2%, 13/142) had discordant molecular drivers. Twelve cases had one or more BRAF-positive PTCs accompanied by a BRAF-negative PTC (3 with CCDC6::RET fusion, 1 with NCOA4::RET fusion, 1 with ACBD5::RET fusion, 2 with ETV6::NTRK3 fusion, 1 with TG::FGFR1 fusion, 1 with LMTK2::BRAF fusion, 1 with AGK::BRAF fusion and RAS p.Q61R mutation, 1 with RAS p.Q61R mutation, and 1 without detectable molecular drivers). The last case had tumors with discordant fusion drivers (VIM::NTRK3 and TNS1::BRAF). Most cases showed tumors that were morphologically distinct (92.3%, 12/13) and occurred in the contralateral lobes (76.9%, 10/13). Notably, we identified 4 cases (30.8%) that presented as collision tumors and 6 cases (46.2%) that showed lymph node metastases, including 2 with simultaneous involvement by tumors with discordant molecular drivers, as novel findings. In summary, a subset (9.2%) of multifocal PTCs had discordant molecular drivers and 84.6% of them were a combination of BRAF-positive and kinase gene fusion-associated PTCs, most with distinct morphologies. Almost half of the cases had nodal metastasis and a third of them showed simultaneous involvement by tumors with discordant molecular drivers. The results highlight the clinical importance of identifying such cases, given the potentially different treatments.
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Socket wall resorption leading to a loss of surrounding bone following tooth extraction has been documented in the dental literature. The use of various socket-shield techniques has been suggested as a solution to this issue. In these approaches, the tooth root is sectioned in two, and the coronal two-thirds of the buccal root is preserved in the socket. This allows the periodontium along with the bundle and buccal bone to remain intact, thus preventing or minimizing bone remodeling. According to the literature, this procedure is highly technique sensitive, especially when it comes to sectioning the root. Additionally, the procedure requires significant time, and several complications may occur, such as fenestration or luxation of the remaining root, requiring its complete extraction. This case report presents a modified socket-shield technique using a trephine bur guided by a computer-designed surgical guide to simplify root sectioning, thus reducing surgical time while increasing predictability of the outcome.
Subject(s)
Dental Implants, Single-Tooth , Immediate Dental Implant Loading , Humans , Tooth Socket/surgery , Immediate Dental Implant Loading/methods , Tooth Extraction/methods , Tooth Root/surgeryABSTRACT
Prime editing enables precise installation of genomic substitutions, insertions and deletions in living systems. Efficient in vitro and in vivo delivery of prime editing components, however, remains a challenge. Here we report prime editor engineered virus-like particles (PE-eVLPs) that deliver prime editor proteins, prime editing guide RNAs and nicking single guide RNAs as transient ribonucleoprotein complexes. We systematically engineered v3 and v3b PE-eVLPs with 65- to 170-fold higher editing efficiency in human cells compared to a PE-eVLP construct based on our previously reported base editor eVLP architecture. In two mouse models of genetic blindness, single injections of v3 PE-eVLPs resulted in therapeutically relevant levels of prime editing in the retina, protein expression restoration and partial visual function rescue. Optimized PE-eVLPs support transient in vivo delivery of prime editor ribonucleoproteins, enhancing the potential safety of prime editing by reducing off-target editing and obviating the possibility of oncogenic transgene integration.
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INTRODUCTION: Restraint use in the emergency department (ED) can pose significant risks to patients and health care workers. We evaluate the effectiveness of Code De-escalation- a standardized, team-based approach for management and assessment of threatening behaviors- in reducing physical restraint use and workplace violence in a community ED. METHODS: A retrospective observational study of a pathway on physical restraint use among patients placed on an involuntary psychiatric hold in a community ED. This pathway includes a built-in step for the team members to systematically assess perceptions of threats from the patient behavior and threats perceived by the patient. Our primary outcome was the change in the rate of physical restraint use among patients on an involuntary psychiatric hold. Our secondary outcome was the change in the rate of workplace violence events involving all ED encounters. We evaluated our outcomes by comparing all encounters in a ten-month period before and after implementation, and compared our results to rates at neighboring community hospitals within the same hospital network. RESULTS: Pre intervention there were 434 ED encounters involving a psychiatric hold, post-intervention there were 535. We observed a significant decrease in physical restraint use, from 7.4% to 3.7% (ARR 0.028 [95% CI 0.002-0.055], p < 0.05). This was not seen at the control sites. CONCLUSIONS: A standardized de-escalation algorithm can be effective in helping ED's decrease their use of physical restraints in management of psychiatric patients experiencing agitation.
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Restraint, Physical , Workplace Violence , Humans , Restraint, Physical/methods , Hospitals, Community , Emergency Service, Hospital , AggressionABSTRACT
BACKGROUND: Many academic medical centers (AMC) transfer patients who require admission but not tertiary care to partner community hospitals from their emergency departments (ED). These transfers alleviate ED boarding but may worsen existing healthcare disparities. We assessed whether disparities exist in the transfer of patients from one AMC ED to a community hospital General Medical Service. METHODS: We performed a retrospective cohort study on all patients screened for transfer between April 1 and December 31, 2021. During the screening process, the treating ED physician determines whether the patient meets standardized clinical criteria and a patient coordinator requests patient consent. We collected patient demographics data from the electronic health record and performed logistic regression at each stage of the transfer process to analyze how individual characteristics impact the odds of proceeding with transfer. RESULTS: 5558 patients were screened and 596 (11%) ultimately transferred. 1999 (36%) patients were Black or Hispanic, 698 (12%) had a preferred language other than English, and 956 (17%) were on Medicaid or uninsured. A greater proportion of Black and Hispanic patients were deemed eligible for interhospital transfer compared to White patients and a greater proportion of Hispanic patients completed transfer to the community hospital (p < 0.017 after Bonferroni correction). After accounting for other demographic variables, patients older than 50 (OR 1.21, 95% CI 1.04-1.40), with a preferred language other than English (OR 1.27, 95% CI 1.00-1.62), and from a priority neighborhood (OR 1.38, 95% CI 1.18-1.61) were more likely to be eligible for transfer, while patients who were male (OR 1.50, 95% CI 1.10-2.05) and younger than 50 (OR 1.85, 95% CI 1.20-2.78) were more likely to consent to transfer (p < 0.05). CONCLUSION: Health disparities exist in the screening process for our interfacility transfer program. Further investigation into why these disparities exist and mitigation strategies should be undertaken.
Subject(s)
Hospitals, Community , Patient Transfer , United States , Humans , Male , Female , Retrospective Studies , Emergency Service, Hospital , Health InequitiesABSTRACT
BACKGROUND: Systemic therapy is the standard treatment for unresectable colorectal cancer with liver metastasis (CRCLM). Transarterial chemoembolization with drug-eluting beads (DEB-TACE) is considered an effective treatment option for CRCLM. Few studies have investigated the combination of DEB-TACE, chemotherapy, and targeted therapy for CRCLM. In the present study, we evaluated the disease control rate (DCR), adverse events, and survival among patients with CRCLM who underwent the combination of DEB-TACE and chemotherapy/targeted therapy. MATERIALS: We retrospectively reviewed 35 patients with CRCLM who were treated between January 2015 and January 2021. Standard systemic chemotherapy, targeted therapy, and 66 DEB-TACE procedures were administered. Data were collected on each DEB-TACE procedure, including chemotherapy agents, tumor burden of liver metastasis, number of DEB-TACE courses, and adverse events. Patients who received DEB-TACE after failure of first-line systemic therapy were categorized into the first-line failure group. Patients who received DEB-TACE after the failure of second-line, third-line, or fourth-line therapy were categorized into the other group. Subgroup analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between the two groups. RESULTS: In total, 35 patients with CRCLM (34 patients with adenocarcinoma and 1 patient with neuroendocrine carcinoma) were enrolled. In total, 13 patients (37.1%) had extrahepatic metastases at initial diagnosis. In this study, 66 DEB-TACE procedures were performed. The DCR was 54.3%. The median OS period was 47.4 months, and the estimated 3-year OS rate was 59.5%. The median PFS period was 6.3 months, and the estimated 1-year PFS rate was 20.6%. The PFS period was longer in the first-line failure group than in the other group (7.2 vs. 6.3 months). No significant difference was observed in OS between the two groups. Four episodes (6.1%) of grade 3 intra-abdominal infection were observed. CONCLUSION: The combination of chemotherapy, targeted therapy, and DEB-TACE can lead to a favorable DCR and survival outcomes in patients with CRCLM. Early intervention with DEB-TACE (i.e., after the failure of first-line therapy) has the potential to extend the PFS period in patients with CRCLM. Severe adverse events were rare and manageable. Further prospective, randomized controlled studies are warranted to obtain more conclusive findings.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Colorectal Neoplasms , Liver Neoplasms , Humans , Liver Neoplasms/pathology , Carcinoma, Hepatocellular/pathology , Retrospective Studies , Chemoembolization, Therapeutic/methods , Treatment Outcome , Colorectal Neoplasms/pathologyABSTRACT
Importance: Emergency department (ED) triage substantially affects how long patients wait for care but triage scoring relies on few objective criteria. Prior studies suggest that Black and Hispanic patients receive unequal triage scores, paralleled by disparities in the depth of physician evaluations. Objectives: To examine whether racial disparities in triage scores and physician evaluations are present across a multicenter network of academic and community hospitals and evaluate whether patients who do not speak English face similar disparities. Design, Setting, and Participants: This was a cross-sectional, multicenter study examining adults presenting between February 28, 2019, and January 1, 2023, across the Mass General Brigham Integrated Health Care System, encompassing 7 EDs: 2 urban academic hospitals and 5 community hospitals. Analysis included all patients presenting with 1 of 5 common chief symptoms. Exposures: Emergency department nurse-led triage and physician evaluation. Main Outcomes and Measures: Average Triage Emergency Severity Index [ESI] score and average visit work relative value units [wRVUs] were compared across symptoms and between individual minority racial and ethnic groups and White patients. Results: There were 249â¯829 visits (149â¯861 female [60%], American Indian or Alaska Native 0.2%, Asian 3.3%, Black 11.8%, Hispanic 18.8%, Native Hawaiian or Other Pacific Islander <0.1%, White 60.8%, and patients identifying as Other race or ethnicity 5.1%). Median age was 48 (IQR, 29-66) years. White patients had more acute ESI scores than Hispanic or Other patients across all symptoms (eg, chest pain: Hispanic, 2.68 [95% CI, 2.67-2.69]; White, 2.55 [95% CI, 2.55-2.56]; Other, 2.66 [95% CI, 2.64-2.68]; P < .001) and Black patients across most symptoms (nausea/vomiting: Black, 2.97 [95% CI, 2.96-2.99]; White: 2.90 [95% CI, 2.89-2.91]; P < .001). These differences were reversed for wRVUs (chest pain: Black, 4.32 [95% CI, 4.25-4.39]; Hispanic, 4.13 [95% CI, 4.08-4.18]; White 3.55 [95% CI, 3.52-3.58]; Other 3.96 [95% CI, 3.84-4.08]; P < .001). Similar patterns were seen for patients whose primary language was not English. Conclusions and Relevance: In this cross-sectional study, patients who identified as Black, Hispanic, and Other race and ethnicity were assigned less acute ESI scores than their White peers despite having received more involved physician workups, suggesting some degree of mistriage. Clinical decision support systems might reduce these disparities but would require careful calibration to avoid replicating bias.
Subject(s)
Ethnicity , Triage , Adult , Humans , Female , Middle Aged , Cross-Sectional Studies , Emergency Service, Hospital , Chest PainABSTRACT
Phosphaturic mesenchymal tumors (PMT) are uncommon neoplasms that cause hypophosphatemia/osteomalacia mainly by secreting fibroblast growth factor 23. We previously identified FN1::FGFR1/FGF1 fusions in nearly half of the PMTs and frequent KL (Klotho or α-Klotho) overexpression in only those with no known fusion. Here, we studied a larger cohort of PMTs for KL expression and alterations. By FN1 break-apart fluorescence in situ hybridization (FISH) and reappraisal of previous RNA sequencing data, 6 tumors previously considered "fusion-negative" (defined by negative results of FISH for FN1::FGFR1 fusion and FGF1 break-apart and/or of RNA sequencing) were reclassified as fusion-positive PMTs, including 1 containing a novel FN1::ZACN fusion. The final cohort of fusion-negative PMTs included 33 tumors from 32 patients, which occurred in the bone (n = 18), soft tissue (n = 10), sinonasal tract (n = 4), and brain (n = 1). In combination with previous work, RNA sequencing, RNA in situ hybridization, and immunohistochemistry showed largely concordant results and demonstrated KL/α-Klotho overexpression in 17 of the 28 fusion-negative and none of the 10 fusion-positive PMTs studied. Prompted by a patient in this cohort harboring germline KL upstream translocation with systemic α-Klotho overexpression and multifocal PMTs, FISH was performed and revealed KL rearrangement in 16 of the 33 fusion-negative PMTs (one also with amplification), including 14 of the 17 cases with KL/α-Klotho overexpression and none of the 11 KL/α-Klotho-low fusion-negative and 11 fusion-positive cases studied. Whole genomic sequencing confirmed translocation and inversion in 2 FISH-positive cases involving the KL upstream region, warranting further investigation into the mechanism whereby these rearrangements may lead to KL upregulation. Methylated DNA immunoprecipitation and sequencing suggested no major role of promoter methylation in KL regulation in PMT. Interestingly, KL-high/-rearranged cases seemed to form a clinicopathologically homogeneous group, showing a predilection for skeletal/sinonasal locations and typically matrix-poor, cellular solitary fibrous tumor-like morphology. Importantly, FGFR1 signaling pathways were upregulated in fusion-negative PMTs regardless of the KL status compared with non-PMT mesenchymal tumors by gene set enrichment analysis, perhaps justifying FGFR1 inhibition in treating this subset of PMTs.
Subject(s)
Mesenchymoma , Paranasal Sinuses , Soft Tissue Neoplasms , Humans , In Situ Hybridization, Fluorescence , Fibroblast Growth Factor 1/genetics , Soft Tissue Neoplasms/genetics , Mesenchymoma/genetics , Mesenchymoma/pathology , Translocation, Genetic , Paranasal Sinuses/pathologyABSTRACT
INTRODUCTION: Emergency departments (ED) employ many strategies to address crowding and prolonged wait times. They include front-end Care Initiation and clinician-in-triage models that start the diagnostic and therapeutic process while the patient waits for a care space in the ED. The objective of this study was to quantify the impact of a Care Initiation model on resource utilization and operational metrics in the ED. METHODS: We performed a retrospective analysis of ED visits at our institution during October 2021. Baseline characteristics were compared with Chi-square and quantile regression. We used t-tests to calculate unadjusted difference in outcome measures, including number of laboratory tests ordered and average time patients spent in the waiting room and the ED treatment room, and the time from arrival until ED disposition. We performed propensity score analysis using matching and inverse probability weighting to quantify the direct impact of Care Initiation on outcome measures. RESULTS: There were 2,407 ED patient encounters, 1,191 (49%) of whom arrived during the hours when Care Initiation was active. A total of 811 (68%) of these patients underwent Care Initiation, while the remainder proceeded directly to the main treatment area. Patients were more likely to undergo Care Initiation if they had lower acuity and lower risk of admission, and if the ED was busier as measured by the number of recent arrivals and percentage of occupied ED beds. After adjusting for patient-specific and department-level covariates, Care Initiation did not increase the number of diagnostic laboratory tests ordered. Care Initiation was associated with increased waiting room time by 1.8 hours and longer time from arrival until disposition by 1.3 hours, but with decreased time in the main treatment area by 0.6 hours, which represents a 15% reduction. CONCLUSION: Care Initiation was associated with a 15% reduction in time spent in the main ED treatment area but longer waiting room time and longer time until ED disposition without significantly increasing the number of laboratory studies ordered. While previous studies produced similar results with Care Initiation models accessing all diagnostic modalities including imaging, our study demonstrates that a more limited Care Initiation model can still result in operational benefits for EDs.
Subject(s)
Benchmarking , Emergency Service, Hospital , Humans , Cohort Studies , Retrospective Studies , Time Factors , Triage , CrowdingABSTRACT
Patients with gastrointestinal (GI) bleeding present to the emergency department (ED) with a wide spectrum of illness severity. Among the most critically ill patients, comorbidities and other risk factors, such as liver disease and anticoagulation, can complicate their management. These patients are resource-intensive to stabilize and resuscitate, often requiring the continuous attention of multiple ED staff members along with rapid mobilization of specialty care. At a tertiary care hospital with the ability to provide definitive care for the most critically ill patients with GI bleeding, we introduced a multi-disciplinary team activation pathway to bring together specialists to immediately respond to the ED. We designed a Code GI Bleed pathway to expedite hemodynamic stabilization, diagnostics, source control, and timely disposition out of the ED to the intensive care unit or relevant procedural area of the hospital.
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BACKGROUND: Electronic paper (E-paper) screens use electrophoretic ink to provide paper-like low-power displays with advanced networking capabilities that may potentially serve as an alternative to traditional whiteboards and television display screens in hospital settings. E-paper may be leveraged in the emergency department (ED) to facilitate communication. Providing ED patient status updates on E-paper screens could improve patient satisfaction and overall experience and provide more equitable access to their health information. OBJECTIVE: We aimed to pilot a patient-facing digital whiteboard using E-paper to display relevant orienting and clinical information in real time to ED patients. We also sought to assess patients' satisfaction after our intervention and understand our patients' overall perception of the impact of the digital whiteboards on their stay. METHODS: We deployed a 41-inch E-paper digital whiteboard in 4 rooms in an urban, tertiary care, and academic ED and enrolled 110 patients to understand and evaluate their experience. Participants completed a modified Hospital Consumer Assessment of Health Care Provider and Systems satisfaction questionnaire about their ED stay. We compared responses to a matched control group of patients triaged to ED rooms without digital whiteboards. We designed the digital whiteboard based on iterative feedback from various departmental stakeholders. After establishing IT infrastructure to support the project, we enrolled patients on a convenience basis into a control and an intervention (digital whiteboard) group. Enrollees were given a baseline survey to evaluate their comfort with technology and an exit survey to evaluate their opinions of the digital whiteboard and overall ED satisfaction. Statistical analysis was performed to compare baseline characteristics as well as satisfaction. RESULTS: After the successful prototyping and implementation of 4 digital whiteboards, we screened 471 patients for inclusion. We enrolled 110 patients, and 50 patients in each group (control and intervention) completed the study protocol. Age, gender, and racial and ethnic composition were similar between groups. We saw significant increases in satisfaction on postvisit surveys when patients were asked about communication regarding delays (P=.03) and what to do after discharge (P=.02). We found that patients in the intervention group were more likely to recommend the facility to family and friends (P=.04). Additionally, 96% (48/50) stated that they preferred a room with a digital whiteboard, and 70% (35/50) found the intervention "quite a bit" or "extremely" helpful in understanding their ED stay. CONCLUSIONS: Digital whiteboards are a feasible and acceptable method of displaying patient-facing data in the ED. Our pilot suggested that E-paper screens coupled with relevant, real-time clinical data and packaged together as a digital whiteboard may positively impact patient satisfaction and the perception of the facility during ED visits. Further study is needed to fully understand the impact on patient satisfaction and experience. TRIAL REGISTRATION: ClinicalTrials.gov NCT04497922; https://clinicaltrials.gov/ct2/show/NCT04497922.
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Extraskeletal myxoid chondrosarcoma (EMC) is an ultrarare sarcoma typically exhibiting myxoid/reticular histology and NR4A3 translocation. However, morphologic variants and the relevance of non-EWSR1::NR4A3 fusions remain underexplored. Three challenging pan-Trk-expressing cases, featuring cellular to solid histology, were subjected to RNA exome sequencing (RES), unveiling different NR4A3-associated fusions. Alongside RES-analyzed cases, fluorescence in situ hybridization was performed to confirm 58 EMCs, with 48 available for pan-Trk immunostaining and KIT sequencing. Except for 1 (2%) NR4A3-rearranged EMC without identifiable partners, 46 (79%), 9 (16%), and 2 (3%) cases harbored EWSR1::NR4A3, TAF15::NR4A3, and TCF12::NR4A3 fusions, respectively. Five EWSR1::NR4A3-positive EMCs occurred in the subcutis (3) and bone (2). Besides 43 classical cases, there were 8 cellular, 4 rhabdoid/anaplastic, 2 solid, and 1 mixed tumor-like variants. Tumor cells were oval/spindle to pleomorphic and formed loose myxoid/reticular to compact sheet-like or fascicular patterns, imparting broad diagnostic considerations. RES showed upregulation of NTRK2/3, KIT, and INSM1. Moderate-to-strong immunoreactivities of pan-Trk, CD117, and INSM1 were present in 35.4%, 52.6%, and 54.6% of EMCs, respectively. KIT p. E554K mutation was detected in 2/48 cases. TAF15::NR4A3 was significantly associated with size >10 cm (78%, P = .025). Size >10 cm, moderate-to-severe nuclear pleomorphism, metastasis at presentation, TAF15::NR4A3 fusion, and the administration of chemotherapy portended shorter univariate disease-specific survival, whereas only size >10 cm (P = .004) and metastasis at presentation (P = .032) remained prognostically independent. Conclusively, EMC may manifest superficial or osseous lesions harboring EWSR1::NR4A3, underrecognized solid or anaplastic histology, and pan-Trk expression, posing tremendous challenges. Most TAF15::NR4A3-positive cases were >10 cm in size, ie, a crucial independent prognosticator, whereas pathogenic KIT mutation rarely occurred.
Subject(s)
Chondrosarcoma , Receptors, Steroid , Sarcoma , TATA-Binding Protein Associated Factors , Humans , In Situ Hybridization, Fluorescence , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , Chondrosarcoma/genetics , Chondrosarcoma/diagnosis , Sarcoma/genetics , TATA-Binding Protein Associated Factors/genetics , Repressor Proteins/genetics , DNA-Binding Proteins/genetics , Receptors, Steroid/genetics , Receptors, Thyroid Hormone/geneticsABSTRACT
Bizarre parosteal osteochondromatous proliferation (BPOP) (Nora lesion) is a benign bone surface lesion, which most commonly occurs in the digits of young patients and has a high rate of recurrence. Histologically, it is composed of a mixture of disorganized bone, cartilage, and spindle cells in variable proportions and characterized by amorphous "blue bone" mineralization. Recurrent chromosomal abnormalities, including t(1;17)(q32-42;q21-23) and inv(7)(q21.1-22q31.3-32), have been reported in BPOP. However, the exact genes involved in the rearrangements remain unknown. In this study, we analyzed 8 BPOP cases affecting the fingers, toe, ulna, radius, and fibula of 5 female and 3 male patients, aged 5 to 68 years. RNA sequencing of 5 cases identified genetic fusions between COL1A2 and LINC-PINT in 3 cases and COL1A1::MIR29B2CHG fusion in 1, both validated using fluorescence in situ hybridization and reverse transcription (RT)-PCR. The remaining fusion-negative case harbored 3 COL1A1 mutations as revealed by whole-exome sequencing and confirmed using Sanger sequencing. All these genetic alterations were predicted to cause frameshift and/or truncation of COL1A1/2. The chromosomal locations of COL1A2 (7q21.3), LINC-PINT (7q32.3), COL1A1 (17q21.33), and MIR29B2CHG (1q32.2) were consistent with the breakpoints identified in the previous cytogenetic studies. Subsequent screening of 3 BPOPs using fluorescence in situ hybridization identified 1 additional case each with COL1A1 or COL1A2 rearrangement. Our findings are consistent with reported chromosomal abnormalities and implicate the disruption of type I collagen, and perhaps of either noncoding RNA gene as a tumor suppressor, in the tumorigenesis of BPOP. The prevalence and tumorigenic mechanisms of these COL1A1/2 alterations in BPOP require further investigation.
Subject(s)
Bone Neoplasms , Neoplasms, Connective Tissue , Soft Tissue Neoplasms , Female , Humans , Male , Cell Proliferation , Chromosome Aberrations , In Situ Hybridization, Fluorescence , Mutation , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , AgedABSTRACT
Many countries and regions have set their schedules to achieve the carbon neutrality between 2030 and 2070. Microalgae are capable of efficiently fixing CO2 and simultaneously producing biomass for multiple applications, which is considered one of the most promising pathways for carbon capture and utilization. This work reviews the current research on microalgae CO2 fixation technologies and the challenges faced by the related industries and government agencies. The technoeconomic analysis indicates that cultivation is the major cost factor. Use of waste resources such as wastewater and flue gas can significantly reduce the costs and carbon footprints. The life cycle assessment has identified fossil-based electricity use as the major contributor to the global warming potential of microalgae-based CO2 fixation approach. Substantial efforts and investments are needed to identify and bridge the gaps among the microalgae strain development, cultivation conditions and systems, and use of renewable resources and energy.
Subject(s)
Carbon Dioxide , Microalgae , Carbon Dioxide/metabolism , Microalgae/metabolism , Carbon/metabolism , Wastewater , BiomassABSTRACT
In the era of the coronavirus disease 2019 (COVID-19) pandemic, surgeons and medical staff are often at a high risk of infection in the operating room, especially when the patient is spontaneously breathing. In this study, we examined the minimum requirements for personal protective equipment with double surgical masks to potentially reduce unnecessary waste of supplies. Methods: Two mannequins were each connected to a test lung machine simulating a surgeon and patient with spontaneous breathing. An aerosol generator containing severe acute respiratory syndrome coronavirus 2 virion particle substitutes was connected to the patient mannequin. The sampling points for the target molecules were set at different distances from the patient mannequin and sent for multiplex quantitative polymerase chain reaction analysis. Three clinical scenarios were designed, which differed in terms of the operating room pressure and whether a fabric curtain barrier was installed between the mannequins. Results: Analysis of the multiplex quantitative polymerase chain reaction results showed that the cycle threshold (Ct) value of the target molecule increased as the distance from the aerosol source increased. In the negative-pressure operating room, the Ct values were significantly increased at all sample points compared with the normal pressure room setting. The Ct value sampled at the surgeon mannequin wearing double face masks was significantly increased when a cloth curtain barrier was set up between the two mannequins. Conclusion: Double surgical masks provide elementary surgeon protection against COVID-19 in a negative pressure operating room, with a physical barrier in place between the surgeon and patient who is spontaneously breathing during local anesthesia or sedated surgery.
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BACKGROUND: Work Relative Value Units (wRVUs) are a component of many compensation models, and a proxy for the effort required to care for a patient. Accurate prediction of wRVUs generated per patient at triage could facilitate real-time load balancing between physicians and provide many practical operational and clinical benefits. OBJECTIVE: We examined whether deep-learning approaches could predict the wRVUs generated by a patient's visit using data commonly available at triage. METHODS: Adult patients presenting to an urban, academic emergency department from July 1, 2016-March 1, 2020 were included. Deidentified triage information included structured data (age, sex, vital signs, Emergency Severity Index score, language, race, standardized chief complaint) and unstructured data (free-text chief complaint) with wRVUs as outcome. Five models were examined: average wRVUs per chief complaint, linear regression, neural network and gradient-boosted tree on structured data, and neural network on unstructured textual data. Models were evaluated using mean absolute error. RESULTS: We analyzed 204,064 visits between July 1, 2016 and March 1, 2020. The median wRVUs were 3.80 (interquartile range 2.56-4.21), with significant effects of age, gender, and race. Models demonstrated lower error as complexity increased. Predictions using averages from chief complaints alone demonstrated a mean error of 2.17 predicted wRVUs per visit (95% confidence interval [CI] 2.07-2.27), the linear regression model: 1.00 wRVUs (95% CI 0.97-1.04), gradient-boosted tree: 0.85 wRVUs (95% CI 0.84-0.86), neural network with structured data: 0.86 wRVUs (95% CI 0.85-0.87), and neural network with unstructured data: 0.78 wRVUs (95% CI 0.76-0.80). CONCLUSIONS: Chief complaints are a poor predictor of the effort needed to evaluate a patient; however, deep-learning techniques show promise. These algorithms have the potential to provide many practical applications, including balancing workloads and compensation between emergency physicians, quantify crowding and mobilizing resources, and reducing bias in the triage process.
Subject(s)
Emergency Service, Hospital , Workload , Adult , Humans , Triage/methods , Algorithms , Machine LearningABSTRACT
Microalgae have been shown to have a promising potential for CO2 utilization and wastewater treatment which still faces the challenges of high resource and energy requirements. The implementation of the circular economy concept is able to address the issues that limit the application of microalgae-based technologies. In this review, a comprehensive discussion on microalgae-based CO2 utilization and wastewater treatment was provided, and the integration of this technology with the circular economy concept, for long-term economic and environmental benefits, was described. Furthermore, technological challenges and feasible strategies towards the improvement of microalgae cultivation were discussed. Finally, necessary regulations and effective policies favoring the implementation of microalgae cultivation into the circular economy were proposed. These are discussed to support sustainable development of microalgae-based bioremediation and bioproduction. This work provides new insights into the implementation of the circular economy concept into microalgae-based CO2 utilization and wastewater treatment to enhance sustainable production.
Subject(s)
Microalgae , Water Purification , Carbon Dioxide , Biomass , Biodegradation, Environmental , Wastewater , BiofuelsABSTRACT
Crystals are known to grow nonclassically or via four classical modes (the layer-by-layer, dislocation-driven, dendritic, and normal modes, which generally involve minimal interfacet surface diffusion). The field of nanoscience considers this framework to interpret how nanocrystals grow; yet, the growth of many anisotropic nanocrystals remains enigmatic, suggesting that the framework may be incomplete. Here, we study the solution-phase growth of pentatwinned Au nanorods without Br, Ag, or surfactants. Lower supersaturation conditions favored anisotropic growth, which appeared at variance with the known modes. Temporal electron microscopy revealed kinetically limited adatom funneling, as adatoms diffused asymmetrically along the vicinal facets (situated inbetween the {100} side-facets and {111} end-facets) of our nanorods. These vicinal facets were perpetuated throughout the synthesis and, especially at lower supersaturation, facilitated {100}-to-vicinal-to-{111} adatom diffusion. We derived a growth model from classical theory in view of our findings, which showed that our experimental growth kinetics were consistent with nanorods growing via two modes simultaneously: radial growth occurred via the layer-by-layer mode on {100} side-facets, whereas the asymmetric interfacet diffusion of adatoms to {111} end-facets mediated longitudinal growth. Thus, shape anisotropy was not driven by modulating the relative rates of monomer deposition on different facets, as conventionally thought, but rather by modulating the relative rates of monomer integration via interfacet diffusion. This work shows how controlling supersaturation, a thermodynamic parameter, can uncover distinct kinetic phenomena on nanocrystals, such as asymmetric interfacet surface diffusion and a fundamental growth mode for which monomer deposition and integration occur on different facets.