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2.
Am Surg ; : 31348241244647, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581578

RESUMO

BACKGROUND: From 2013 to 2020, Arizona state trauma system expanded from seven to thirteen level 1 trauma centers (L1TCs). This study utilized the state trauma registry to analyze the effect of L1TC proliferation on patient outcomes. METHODS: Adult patients age≥15 in the state trauma registry from 2007-2020 were queried for demographic, injury, and outcome variables. These variables were compared across the 2 time periods: 2007-2012 as pre-proliferation (PRE) and 2013-2020 as post-proliferation (POST). Multivariate logistic regression was performed to assess independent predictors of mortality. Subgroup analyses were done for Injury Severity Score (ISS)≥15, age≥65, and trauma mechanisms. RESULTS: A total of 482,896 trauma patients were included in this study. 40% were female, 29% were geriatric patients, and 8.6% sustained penetrating trauma. The median ISS was 4. Inpatient mortality overall was 2.7%. POST consisted of more female, geriatric, and blunt trauma patients (P < .001). Both periods had similar median ISS. POST had more interfacility transfers (14.5% vs 10.3%, P < .001). Inpatient, unadjusted mortality decreased by .5% in POST (P < .001). After adjusting for age, gender, ISS, and trauma mechanism, being in POST was predictive of death (OR: 1.4, CI:1.3-1.5, P < .001). This was consistent across all subgroups except for geriatric subgroup, which there was no significant correlation. DISCUSSION: Despite advances in trauma care and almost doubling of L1TCs, POST had minimal reduction of unadjusted mortality and was an independent predictor of death. Results suggest increasing number of L1TCs alone may not improve mortality. Alternative approaches should be sought with future regional trauma system design and implementation.

3.
Syst Rev ; 13(1): 104, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594759

RESUMO

BACKGROUND: It is uncertain if patient's characteristics are associated with complaints and claims against doctors. Additionally, evidence for the effectiveness of remedial interventions on rates of complaints and claims against doctors has not been synthesised. METHODS: We conducted a rapid review of recent literature to answer: Question 1 "What are the common characteristics and circumstances of patients who are most likely to complain or bring a claim about the care they have received from a doctor?" and Question 2 "What initiatives or interventions have been shown to be effective at reducing complaints and claims about the care patients have received from a doctor?". We used a systematic search (most recently in July 2023) of PubMed, Scopus, Web of Science and grey literature. Studies were screened against inclusion criteria and critically appraised in duplicate using standard tools. Results were summarised using narrative synthesis. RESULTS: From 8079 search results, we reviewed the full text of 250 studies. We included 25 studies: seven for Question 1 (6 comparative studies with controls and one systematic review) and 18 studies for Question 2 (14 uncontrolled pre-post studies, 2 comparative studies with controls and 2 systematic reviews). Most studies were set in hospitals across a mix of medical specialties. Other than for patients with mental health conditions (two studies), no other patient characteristics demonstrated either a strong or consistent effect on the rate of complaints or claims against their treating doctors. Risk management programs (6 studies), and communication and resolution programs (5 studies) were the most studied of 6 intervention types. Evidence for reducing complaints and medico-legal claims, costs or premiums and more timely management was apparent for both types of programs. Only 1 to 3 studies were included for peer programs, medical remediation, shared decision-making, simulation training and continuing professional development, with few generalisable results. CONCLUSION: Few patient characteristics can be reliably related to the likelihood of medico-legal complaints or claims. There is some evidence that interventions can reduce the number and costs of claims, the number of complaints, and the timeliness of claims. However, across both questions, the strength of the evidence is very weak and is based on only a few studies or study designs that are highly prone to bias.


Assuntos
Medicina , Médicos , Humanos , Comunicação
4.
Surg Open Sci ; 18: 78-84, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38435487

RESUMO

Background: In attempt to increase trauma system coverage, our state added 21 level 3 (L3TC) and level 4 trauma centers (L4TC) to the existing 7 level 1 trauma centers from 2008 to 2012. This study examined the impact of adding these lower-level trauma centers (LLTC) on patient outcomes. Methods: Patients in the state trauma registry age ≥ 15 from 2007 to 2012 were queried for demographic, injury, and outcome variables. These were compared between 2007 (PRE) and 2008-2012 (POST) cohorts. Multivariate logistic regression was performed to assess independent predictors of mortality. Subgroup analyses were performed for Injury Severity Score (ISS) ≥15, age ≥ 65, and trauma mechanisms. Results: 143,919 adults were evaluated. POST had significantly more female, geriatric, and blunt traumas (all p < 0.001). ISS was similar. Interfacility transfers increased by 10.2 %. Overall mortality decreased by 0.6 % (p < 0.001). Multivariate logistic regression analysis showed that being in POST was not associated with survival (OR: 1.07, CI: 0.96-1.18, p = 0.227). Subgroup analyses showed small reductions in mortality, except for geriatric patients. After adjusting for covariates, POST was not associated with survival in any subgroup, and trended toward being a predictor for death in penetrating traumas (OR: 1.23; 1.00-1.53, p = 0.059). Conclusions: Unregulated proliferation of LLTCs was associated with increased interfacility transfers without significant increase in trauma patients treated. LLTC proliferation was not an independent protector against mortality in the overall cohort and may worsen mortality for penetrating trauma patients. Rather than simply increasing the number of LLTCs within a region, perhaps more planned approaches are needed. Key message: This is, to our knowledge, the first work to study the effect of rapid lower level trauma center proliferation on patient outcomes. The findings of our analysis have implications for strategic planning of future trauma systems.

5.
Ann Surg Oncol ; 31(6): 3916-3925, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38472677

RESUMO

BACKGROUND: Wire localisation (WL) is the "gold standard" localisation technique for wide local excision (WLE) of non-palpable breast lesions but has disadvantages that have led to the development of wireless techniques. This study compared the cost-effectiveness of radar localisation (RL) to WL. METHODS: This was a single-institution study of 110 prospective patients with early-stage breast cancer undergoing WLE using RL with the SCOUT® Surgical Guidance System (2021-2023) compared with a cohort of 110 patients using WL. Margin status, re-excision rates, and surgery delays associated with preoperative localisation were compared. Costs from a third-party payer perspective in Australian dollars (AUD$) calculated by using microcosting, break-even point, and cost-utility analyses. RESULTS: A total of 110 WLEs using RL cost a total of AUD$402,281, in addition to the device cost of AUD$77,150. The average additional cost of a surgery delay was AUD$2318. Use of RL reduced the surgery delay rate by 10% (p = 0.029), preventing 11 delays with cost savings of AUD$25,496. No differences were identified in positive margin rates (RL: 11.8% vs. WL: 17.3%, p = 0.25) or re-excision rates (RL: 14.5% vs. WL: 21.8%, p = 0.221). In total, 290 RL cases are needed to break even. The cost of WLE using RL was greater than WL by AUD$567. There was a greater clinical benefit of 1.15 quality-adjusted life-years (QALYs) and an incremental cost-utility ratio of AUD$493 per QALY favouring RL. CONCLUSIONS: Routine use of RL was a more cost-effective intervention than WL. Close to 300 RL cases are likely needed to be performed to recover costs of the medical device. CLINICAL TRIAL REGISTRATION: ACTRN12624000068561.


Assuntos
Neoplasias da Mama , Análise Custo-Benefício , Humanos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/economia , Neoplasias da Mama/patologia , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Seguimentos , Mastectomia Segmentar/economia , Mastectomia Segmentar/métodos , Idoso , Margens de Excisão , Prognóstico , Anos de Vida Ajustados por Qualidade de Vida , Austrália , Cirurgia Assistida por Computador/economia , Cirurgia Assistida por Computador/métodos , Adulto
6.
Eur J Immunol ; 54(4): e2249800, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38334162

RESUMO

In asthma, CD4+ T-cell interaction with airway smooth muscle (ASM) may enhance its contractile properties and promote its proliferation. However, less is known about the effects of this interaction on T cells. To explore the consequences of interaction of CD4+ T cells with ASM we placed the cells in co-culture and analyzed the phenotypic and functional changes in the T cells. Effector status as well as cytokine expression was assessed by flow cytometry. An increase in CD45RA-CD45RO+ memory T cells was observed after co-culture; however, these cells were not more responsive to CD3/28 restimulation. A reduction in mitochondrial coupling and an increase in the production of mitochondrial reactive oxygen species by CD4+ T cells post-restimulation suggested altered mitochondrial metabolism after co-culture. RNA sequencing analysis of the T cells revealed characteristic downregulation of effector T-cell-associated genes, but a lack of upregulation of memory T-cell-associated genes. The results of this study demonstrate that ASM cells can induce a phenotypic shift in CD4+ T cells into memory-like T cells but with reduced capacity for activation.


Assuntos
Miócitos de Músculo Liso , Sistema Respiratório , Miócitos de Músculo Liso/metabolismo , Técnicas de Cocultura , Linfócitos T CD4-Positivos , Fenótipo
7.
Surg Endosc ; 38(3): 1239-1248, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38092973

RESUMO

BACKGROUND: Long-term durability data for radiofrequency ablation (RFA) to prevent esophageal adenocarcinoma in long-segment (LSBE) and ultralong-segment Barrett's esophagus (ULSBE) is lacking. This study aimed to determine 10-year cancer progression, eradication, and complication rates in LSBE and ULSBE patients treated with RFA. METHODS: Single-surgeon prospective database of patients with LSBE (≥ 3 to < 8 cm) and ULSBE (≥ 8 cm) who underwent RFA (2001-2021) were retrospectively analyzed. Ten-year cancer progression calculated with Kaplan-Meier analysis. Eradication rates, including complete remission of dysplasia (CR-D) and intestinal metaplasia (CR-IM), and rates of recurrence and complications, compared between LSBE and ULSBE groups. RESULTS: Ten years after starting treatment, the cancer rate was 14.3% in 56 patients. CR-D and CR-IM rates were 87.5% and 67.9%, respectively. Relapse rates from CR-D were 1.8% and 3.6% from CR-IM. Eradication rates for dysplasia in LSBE and ULSBE patients (90.6% versus 83.3%) and IM (71.9% versus 62.5%) were not significantly different. ULSBE patients required higher mean number of ablation sessions for IM eradication (4.7 versus 3.7, p = 0.032), while complication rates including strictures (4.2% versus 6.2%), perforation (0 versus 0), and bleeding (4.2% versus 3.1%), were similar between ULSBE and LSBE patients, respectively. On multivariate analysis, shorter Barrett's segment and baseline low-grade dysplasia were associated with increased likelihood for eradication of IM and dysplasia. A total number of ablation sessions or endoscopic resections ≥ 3 was associated with reduced likelihood for eradication. CONCLUSION: RFA was durable in maintaining dysplasia and IM eradication in both LSBE and ULSBE over 10 years, and with low complication rates. IM eradication was more difficult to achieve in ULSBE. Late development of cancer occurred in 14.3%.


Assuntos
Esôfago de Barrett , Ablação por Cateter , Neoplasias Esofágicas , Ablação por Radiofrequência , Humanos , Esôfago de Barrett/cirurgia , Esôfago de Barrett/patologia , Estudos Retrospectivos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Resposta Patológica Completa , Resultado do Tratamento , Esofagoscopia
8.
J Gastrointest Surg ; 27(12): 2733-2742, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37962716

RESUMO

BACKGROUND: Repair of giant paraesophageal hernia (PEH) is associated with a considerable hernia recurrence rate by objective measures. This study analyzed a large series of laparoscopic giant PEH repair to determine factors associated with anatomical recurrence. METHOD: Data was extracted from a single-surgeon prospective database of laparoscopic repair of giant PEH from 1991 to 2021. Upper endoscopy was performed within 12 months postoperatively and selectively thereafter. Any supra-diaphragmatic stomach was defined as anatomical recurrence. Patient and hernia characteristics and technical operative factors, including "composite repair" (360° fundoplication with esophagopexy and cardiopexy to right crus), were evaluated with univariate and multivariate analysis. RESULTS: Laparoscopic primary repair was performed in 862 patients. The anatomical recurrence rate was 27.3% with median follow-up of 33 months (IQR 16, 68). Recurrence was symptomatic in 45% of cases and 29% of these underwent a revision operation. Hernia recurrence was associated with younger age, adversely affected quality of life, and were associated with non-composite repair. Multivariate analysis identified age < 70 years, presence of Barrett's esophagus, absence of "composite repair", and hiatus closure under tension as independent factors associated with recurrence (HR 1.27, 95%CI 0.88-1.82, p = 0.01; HR 1.58, 95%CI 1.12-2.23, p = 0.009; HR 1.72, 95%CI 1.2-2.44, p = 0.002; HR 2.05, 95%CI 1.33-3.17, p = 0.001, respectively). CONCLUSION: Repair of giant PEH is associated with substantial anatomical recurrence associated with patient and technique factors. Patient factors included age < 70 years, Barrett's esophagus, and hiatus tension. "Composite repair" was associated with lower recurrence rate.


Assuntos
Esôfago de Barrett , Hérnia Hiatal , Laparoscopia , Humanos , Idoso , Hérnia Hiatal/cirurgia , Hérnia Hiatal/complicações , Seguimentos , Qualidade de Vida , Esôfago de Barrett/complicações , Recidiva Local de Neoplasia/cirurgia , Fundoplicatura/métodos , Laparoscopia/métodos , Herniorrafia/métodos , Recidiva , Resultado do Tratamento , Estudos Retrospectivos
9.
Ann Surg Oncol ; 30(11): 6520-6527, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37402976

RESUMO

BACKGROUND: The methods for sentinel lymph node (SLN) biopsy in breast cancer have been variable in type and number of tracers. Some units have abandoned the use of blue dye (BD) due to adverse reactions. Fluorescence-guided biopsy with indocyanine green (ICG) is a relatively novel technique. This study compared the clinical efficacy and costs between novel dual tracer ICG and radioisotope (ICG-RI) with "gold standard" BD and radioisotope (BD-RI). METHODS: Single-surgeon study of 150 prospective patients with early breast cancer undergoing SLN biopsy (2021-2022) using ICG-RI compared with a retrospective cohort of 150 consecutive previous patients using BD-RI. Number of SLNs identified, rate of failed mapping, identification of metastatic SLNs, and adverse reactions were compared between techniques. Cost-minimisation analysis performed by using Medicare item numbers and micro-costing analysis. RESULTS: Total number of SLNs identified with ICG-RI and BD-RI was 351 and 315, respectively. Mean number of SLNs identified with ICG-RI and BD-RI was 2.3 (standard deviation [SD] 1.4) and 2.1 (SD 1.1), respectively (p = 0.156). There were no cases of failed mapping with either dual technique. Metastatic SLNs were identified in 38 (25.3%) ICG-RI patients compared with 30 (20%) BD-RI patients (p = 0.641). There were no adverse reactions to ICG, whereas four cases of skin tattooing and anaphylaxis were associated with BD (p = 0.131). ICG-RI cost an additional AU$197.38 per case in addition to the initial cost for the imaging system. CLINICAL TRIAL REGISTRATION:  ACTRN12621001033831. CONCLUSIONS: Novel tracer combination, ICG-RI, provided an effective and safe alternative to "gold standard" dual tracer. The caveat was the significantly greater costs associated with ICG.


Assuntos
Neoplasias da Mama , Linfonodo Sentinela , Idoso , Feminino , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Corantes , Corantes Fluorescentes , Verde de Indocianina , Linfonodos/patologia , Medicare , Estudos Prospectivos , Radioisótopos , Estudos Retrospectivos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/métodos , Estados Unidos
12.
Neuron ; 110(13): 2183-2197.e7, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35545090

RESUMO

Social gaze interaction powerfully shapes interpersonal communication. However, compared with social perception, very little is known about the neuronal underpinnings of real-life social gaze interaction. Here, we studied a large number of neurons spanning four regions in primate prefrontal-amygdala networks and demonstrate robust single-cell foundations of interactive social gaze in the orbitofrontal, dorsomedial prefrontal, and anterior cingulate cortices, in addition to the amygdala. Many neurons in these areas exhibited high temporal heterogeneity for social discriminability, with a selectivity bias for looking at a conspecific compared with an object. Notably, a large proportion of neurons in each brain region parametrically tracked the gaze of self or other, providing substrates for social gaze monitoring. Furthermore, several neurons displayed selective encoding of mutual eye contact in an agent-specific manner. These findings provide evidence of widespread implementations of interactive social gaze neurons in the primate prefrontal-amygdala networks during social gaze interaction.


Assuntos
Tonsila do Cerebelo , Córtex Pré-Frontal , Tonsila do Cerebelo/fisiologia , Animais , Giro do Cíngulo , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Primatas
13.
Bone Res ; 10(1): 3, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34992221

RESUMO

Osteoporosis is a highly prevalent public health burden associated with an increased risk of bone fracture, particularly in aging women. Estrogen, an important medicinal component for the preventative and therapeutic treatment of postmenopausal osteoporosis, induces osteogenesis by activating the estrogen receptor signaling pathway and upregulating the expression of osteogenic genes, such as bone morphogenetic proteins (BMPs). The epigenetic regulation of estrogen-mediated osteogenesis, however, is still unclear. In this report, we found that estrogen significantly induced the expression of lysine-specific demethylase 6B (KDM6B) and that KDM6B depletion by shRNAs led to a significant reduction in the osteogenic potential of DMSCs. Mechanistically, upon estrogen stimulation, estrogen receptor-α (ERα) was recruited to the KDM6B promoter, directly enhancing KDM6B expression. Subsequently, KDM6B was recruited to the BMP2 and HOXC6 promoters, resulting in the removal of H3K27me3 marks and activating the transcription of BMP2 and HOXC6, the master genes of osteogenic differentiation. Furthermore, we found that estrogen enhanced DMSC osteogenesis during calvarial bone regeneration and that estrogen's pro-osteogenic effect was dependent on KDM6B in vivo. Taken together, our results demonstrate the vital role of the ERα/KDM6B regulatory axis in the epigenetic regulation of the estrogen-dependent osteogenic response.

14.
Int J Radiat Oncol Biol Phys ; 112(4): 880-889, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34788698

RESUMO

PURPOSE: Both oncologic outcomes and patient-reported outcomes are pivotal in prostate cancer (PCa). However, it remains unknown if there is any association between these 2 outcomes. In this secondary analysis of a randomized controlled trial, we investigated the association of short-term changes in patient-reported outcome with long-term event-free survival (EFS) and metastasis-free survival (MFS) in localized PCa. METHODS AND MATERIALS: Localized PCa patients with a Gleason score ≤7, clinical stage T1b to T3a, and prostate-specific antigen (PSA) <30 ng/mL were randomized to neoadjuvant and concurrent androgen deprivation therapy (ADT) for 6 months starting 4 months before prostate radiation therapy or concurrent and adjuvant ADT for 6 months starting simultaneously with radiation therapy. Patient-reported symptom burden was evaluated using the European Organisation for Research and Treatment of Cancer quality of life questionnaire (QLQ)-PR.25. Clinically meaningful deterioration (CMD) was defined as a ≥10-point worsening at any time within 10 months postrandomization regardless of subsequent improvement. Landmark analyses were performed to determine the association of CMD of urinary and bowel symptoms separately with EFS and MFS in patients who responded to the baseline questionnaire, were alive, and were event free at 10 months. RESULTS: Overall, 393 patients had responded to the baseline QLQ. One patient died, and 1 patient had failure within 10 months. Therefore, 391 patients were eligible for the landmark analyses. After adjusting for age, Gleason score, PSA, performance status, and treatment group, CMD of urinary symptoms was associated with worse EFS (hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.21-2.65) and MFS (HR, 1.69; 95% CI, 1.11-2.57). Considering deaths as competing events, CMD of urinary symptoms was associated with a significant increase in the relative incidence of progression (subdistribution HR, 2.42; 95% CI, 1.12-5.20). However, no association was found between CMD of bowel symptoms and EFS or MFS. CONCLUSIONS: In this study, short-term CMD of urinary symptoms was associated with significantly inferior EFS and MFS and an increase in the relative incidence of progression. Further investigations are needed to explore the biological rationale of such association in the context of ADT and radiation therapy.


Assuntos
Antagonistas de Androgênios , Neoplasias da Próstata , Antagonistas de Androgênios/uso terapêutico , Androgênios , Humanos , Masculino , Medidas de Resultados Relatados pelo Paciente , Antígeno Prostático Específico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Qualidade de Vida
15.
J Pharm Sci ; 111(7): 1911-1917, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34922927

RESUMO

The loss of active substance, both small and large molecules, from sterile liquid drug products after contact with an administration kit has been extensively reported in the literature. This loss has been reported to be caused by incompatibility of the active substances with the contact surfaces of the administration kit and adsorption or sticking of the active substance to the surfaces of the administration kit. This paper investigates the mechanism for loss of a highly potent active substance based on the type and design of the administration kit. Two administration kits (syringe/Insyte Catheter and syringe/Nexiva Catheter) of different designs were used to administer a solution formulation of an ultra-low dose (nanograms) of a model hydrophobic active substance Compound X. The Nexiva Catheter was longer with tubing and Y connectors while the Insyte Catheter was shorter with no split septum tubing. Dose recovery from both administration kits was determined using high pressure liquid chromatography. The results indicated that the full dose was recovered from the syringes and Insyte Catheter. However, there was a significant loss of active substance from the Nexiva Catheter configuration even after post administration flush, which was due to holdup volume of the formulation within dead spaces of the Nexiva Catheter. It was also demonstrated that the dose recovery from the Nexiva Catheter can be significantly increased with increase in the post administration flush volume, which further confirms that the observed loss of active substance was not due to incompatibility or surface adsorption. The significance of this work is to provide awareness to formulation scientists that closed system Catheter design with Y connectors can be the main contributor for the loss in active substance, especially at ultra-low doses, and therefore dose recovery experiments should be expanded to include proper flushing of the Y connectors to expel any holdup volume from the Catheter.


Assuntos
Seringas , Administração Intravenosa , Infusões Intravenosas
16.
Front Public Health ; 9: 752481, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616710

RESUMO

Economic shocks from COVID-19, coupled with ongoing US-China tensions, have raised debates around supply chain (or global value chain) organisation, with China at the centre of the storm. However, quantitative studies that consider the global and economy-wide impacts of rerouting supply chains are limited. This study examines the economic and emissions impacts of reorganising supply chains, using Australia-China trade as an example. It augments the Hypothetical Extraction Method by replacing traditional Input-Output analysis with a Computable General Equilibrium analysis. The estimation results demonstrate that in both exports and imports, a trade embargo between Australia and China - despite being compensated for by alternative supply chains-will cause gross domestic production losses and emissions increases for both countries and the world overall. Moreover, even though all other economies gain from the markets left by China, many of them incur overall gross domestic production losses and emission increases. The finding that the Association of Southeast Asian Nations and India may also suffer from an Australia-China trade embargo, despite a gain in trade volume, suggests that no country should add fuel to the fire. The results suggest that countries need to defend a rules-based trading regime and jointly address supply chain challenges.


Assuntos
COVID-19 , Austrália , China , Comércio , Humanos , SARS-CoV-2
17.
Clin Cancer Res ; 27(15): 4410-4421, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34031055

RESUMO

PURPOSE: Gemcitabine-based chemotherapy regimens are first-line for several advanced cancers. Because of better tolerability, gemcitabine + cisplatin is a preferred neoadjuvant, adjuvant, and/or palliative chemotherapy regimen for advanced bladder cancer. Nevertheless, predicting treatment failure and overcoming resistance remain unmet clinical needs. We discovered that splice variant (V1) of HYAL-4 is a first-in-class eukaryotic chondroitinase (Chase), and CD44 is its major substrate. V1 is upregulated in bladder cancer and drives a malignant phenotype. In this study, we investigated whether V1 drives chemotherapy resistance. EXPERIMENTAL DESIGN: V1 expression was measured in muscle-invasive bladder cancer (MIBC) specimens by qRT-PCR and IHC. HYAL-4 wild-type (Wt) and V1 were stably expressed or silenced in normal urothelial and three bladder cancer cell lines. Transfectants were analyzed for chemoresistance and associated mechanism in preclinical models. RESULTS: V1 levels in MIBC specimens of patients who developed metastasis, predicted response to gemcitabine + cisplatin adjuvant/salvage treatment and disease-specific mortality. V1-expressing bladder cells were resistant to gemcitabine but not to cisplatin. V1 expression neither affected gemcitabine influx nor the drug-efflux transporters. Instead, V1 increased gemcitabine metabolism and subsequent efflux of difluorodeoxyuridine, by upregulating cytidine deaminase (CDA) expression through increased CD44-JAK2/STAT3 signaling. CDA inhibitor tetrahydrouridine resensitized V1-expressing cells to gemcitabine. While gemcitabine (25-50 mg/kg) inhibited bladder cancer xenograft growth, V1-expressing tumors were resistant. Low-dose combination of gemcitabine and tetrahydrouridine abrogated the growth of V1 tumors with minimal toxicity. CONCLUSIONS: V1/Chase drives gemcitabine resistance and potentially predicts gemcitabine + cisplatin failure. CDA inhibition resensitizes V1-expressing tumors to gemcitabine. Because several chemotherapy regimens include gemcitabine, our study could have broad significance.


Assuntos
Antígenos de Neoplasias/fisiologia , Antimetabólitos Antineoplásicos/uso terapêutico , Condroitinases e Condroitina Liases/fisiologia , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos/fisiologia , Histona Acetiltransferases/fisiologia , Hialuronoglucosaminidase/fisiologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Desoxicitidina/uso terapêutico , Humanos , Camundongos , Prognóstico , Falha de Tratamento , Gencitabina
18.
Int J Hyg Environ Health ; 231: 113630, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33035739

RESUMO

Triphenyl phosphate (TPP or TPhP) is commonly used as an additive plasticizer or organophosphate flame retardant (OPFR) in consumer products including nail polish. We evaluated exposure to TPhP from 12 nail salon technicians working at four nail salons located in California over a period of two work days. Bulk samples of 15 nail polishes and other nail products were collected. Study participants also provided two personal air samples, two hand wipe samples (pre- and post-shift on day two), and two urine samples (pre-shift day one and post-shift day two). The geometric mean (GM) of TPhP air sampling concentrations was 7.39 ng/m3. Post-shift TPhP hand wipe concentrations (GM 1.35 µg/sample) were significantly higher (p = 0.024) than pre-shift hand wipe concentrations (GM 0.29 µg/sample). Diphenyl phosphate (DPP or DPhP), a urinary metabolite of TPhP used in this study as a biomarker of exposure, was detected in all post-shift urine samples and 75% of urine pre-shift samples. DPhP post-shift concentrations (GM 1.35 µg/g creatinine) were significantly higher than pre-shift concentrations (GM 0.84 µg/g creatinine; p = 0.012). In addition, DPhP post-shift concentrations were correlated with TPhP post-shift hand wipe concentrations, suggesting dermal contact may be a relevant exposure pathway for nail salon workers.


Assuntos
Retardadores de Chama , Organofosfatos , Humanos , Unhas , Plastificantes
19.
Ann Work Expo Health ; 64(8): 890-896, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-32747949

RESUMO

The US electronics recycling industry has introduced a novel mobile electronic waste (e-waste) shredding truck service to address increasing needs for secure data destruction of e-waste. These trucks can shred small electronics with data security concerns at remote locations for a wide variety of clients. Shredding jobs usually involve hand-feeding electronic waste (e-waste) for 4-10 h day-1, 1-5 days. Shredding of e-waste has been documented as a source of high metal exposures, especially lead and cadmium. However, no studies have been done to assess exposures on mobile e-waste shredding trucks. We conducted a pilot cross-sectional exposure assessment on a mobile e-waste shredding truck performing a 65-min shredding job (truck back door open and no local exhaust ventilation) in the Greater Boston area in 2019. We collected area air and surface wipe samples for metals along with real-time particulate measurements from different locations. The highest metal air concentrations (e.g. 2.9 µg-lead m-3) were found next and 1.8 m away from the shredder operator inside the semi-trailer. Metal surface contamination was highest near the shredder (e.g. 1190 µg-lead 100 cm-2) and extended to other parts of the truck. Near the shredder, the concentration of ultrafine particles was up to 250 000 particles cm-3 and particulate matter 2.5 mm or less in diameter (PM2.5) was up to 171 µg m-3, and neither returned to background levels after 40 min of inactivity. A diesel-electric generator was used to power the shredder and could have contributed to some of the particulate emissions. We found that mobile e-waste shredding trucks are a source of metals and particulates emissions. We recommend the industry adopts better controls for shredding inside trucks, such as local exhaust ventilation with proper filtration and use of personal protective equipment, to protect workers' health and the environment.


Assuntos
Resíduo Eletrônico , Poluentes Atmosféricos/análise , Estudos Transversais , Monitoramento Ambiental , Humanos , Veículos Automotores , Exposição Ocupacional/análise , Projetos Piloto
20.
J Surg Res ; 245: 360-366, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31425876

RESUMO

BACKGROUND: While the prevalence of HIV infection in the population is 0.5%, it is higher among trauma patients as are rates of unknown seropositivity. Routine HIV screening for all trauma evaluations was implemented at our urban level I center in 2009. We aimed to evaluate use and results of the program in our trauma population. METHODS: This was a retrospective analysis of all trauma evaluations between July 2015 and February 2018. After passage of legislation rescinding the requirement for consent to perform HIV testing, our trauma service instituted an order set which automatically tested for HIV unless the ordering physician opted out. Patients found to be infected with HIV were to be counseled and referred to specialty care. RESULTS: Of 6175 consecutive trauma evaluations during the study period, 449 (7.3%) patients had been screened within the prior year and were excluded. Of the remaining cohort, 2024 (35.3%) patients were screened with 27 (1.3%) testing positive. Among those testing positive for infection, 100% were male, 77% white, 63% non-Hispanic, and 70% lacked insurance. Twenty-five (92.6%) patients received counseling and 19 were referred to specialty care. Age, gender, race, ethnicity, Injury Severity Score, trauma activation level, and payor type were not significant predictors for positive HIV screen on logistic regression analysis. CONCLUSIONS: Despite a significantly higher rate of HIV in the trauma population, only a third of patients are screened. Such high infection rates justify the existence of this screening program but steps must be taken to increase screening rate. LEVEL OF EVIDENCE: Level 3.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Infecções por HIV/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , Provedores de Redes de Segurança/estatística & dados numéricos , Adulto , Aconselhamento/estatística & dados numéricos , Feminino , Fidelidade a Diretrizes , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Texas/epidemiologia
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