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INTRODUCTION: Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) commonly presents as a peri-implant effusion (seroma). CD30 (TNFRSF8) is a consistent marker of tumor cells but also can be expressed by activated lymphocytes in benign seromas. Diagnosis of BIA-ALCL currently includes cytology and detection of CD30 by immunohistochemistry or flow cytometry, but these studies require specialized equipment and pathologists' interpretation. We hypothesized that a CD30 lateral flow assay (LFA) could provide a less costly rapid test for soluble CD30 that eventually could be used by non-specialized personnel for point-of-care diagnosis of BIA-ALCL. METHODS: We performed LFA for CD30 and enzyme-linked immunosorbent assay (ELISA) for 15 patients with pathologically confirmed BIA-ALCL and 10 patients with benign seromas. To determine the dynamic range of CD30 detection by LFA, we added recombinant CD30 protein to universal buffer at seven different concentrations ranging from 125 pg/mL to 10,000 pg/mL. We then performed LFA for CD30 on cryopreserved seromas of 10 patients with pathologically confirmed BIA-ALCL and 10 patients with benign seromas. RESULTS: Recombinant CD30 protein added to universal buffer produced a distinct test line at concentrations higher than 1000 pg/mL and faint test lines at 250-500 pg/mL. LFA produced a positive test line for all BIA-ALCL seromas undiluted and for 8 of 10 malignant seromas at 1:10 dilution, whereas 3 of 10 benign seromas were positive undiluted but all were negative at 1:10 dilution. Undiluted CD30 LFA had a sensitivity of 100.00%, specificity of 70.00%, positive predictive value of 76.92%, and negative predictive value of 100.00% for BIA-ALCL. When specimens were diluted 1:10, sensitivity was reduced to 80.00% but specificity and positive predictive values increased to 100.00%, while negative predictive value was reduced to 88.33%. When measured by ELISA, CD30 was below 1200 pg/mL in each of six benign seromas, whereas seven BIA-ALCL seromas contained CD30 levels > 2300 pg/mL, in all but one case calculated from dilutions of 1:10 or 1:50. CONCLUSIONS: BIA-ALCL seromas can be distinguished from benign seromas by CD30 ELISA and LFA, but LFA requires less time (<20 min) and can be performed without special equipment by non-specialized personnel, suggesting future point-of-care testing for BIA-ALCL may be feasible.
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INTRODUCTION: Unrealistic patient expectations for wait times can lead to poor satisfaction. This study's dual purpose was: (1) to address disparities between patients' perceived priority level and the Emergency Severity Index (ESI) assigned by emergency room triage nurses; and (2) to evaluate validity and reliability of using the Patient Perception of Priority to be Seen Survey (PPPSS) to investigate patient expectations for emergency department urgency. METHODS: A two-group pretest-posttest quasi-experimental approach compared patient urgency opinions to nurse urgency ratings with and without a scripted educational intervention. This tested how closely patient perceptions were related to triage nurse ratings. RESULTS: Reliability for the PPPSS was acceptable (reliability = 0.75). Patients who were rated lower urgency on the ESI by triage nurses tended to self-report higher urgency (rho = -0.44, P < .01). Attitudes were more consistent in the posttest patient group who were exposed to the scripted verbal description of emergency department procedures (χ2 (1, N = 352) = 8.09, P < .01). Patients who disagreed with emergency nurse scores tended to be younger on average (eg, < 40 years old; rho = 0.69, P < .01). Male identified patients tended to be rated both by nurses and themselves as higher urgency (beta = 0.18, P = .02). DISCUSSION: We recommend the PPPSS for nurses and researchers to quickly assess patient expectations. Additionally, promoting patient understanding through a scripted educational strategy about the ESI system may also result in improvements in communication between patients and nurses.
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Enfermagem em Emergência , Triagem , Humanos , Masculino , Adulto , Triagem/métodos , Reprodutibilidade dos Testes , Psicometria , Serviço Hospitalar de Emergência , Inquéritos e QuestionáriosRESUMO
COVID-19 is caused by SARS-CoV-2 (SC2) and is more prevalent and severe in elderly and patients with comorbid diseases (CM). Because chitinase 3-like-1 (CHI3L1) is induced during aging and CM, the relationships between CHI3L1 and SC2 were investigated. Here, we demonstrate that CHI3L1 is a potent stimulator of the SC2 receptor angiotensin converting enzyme 2 (ACE2) and viral spike protein priming proteases (SPP), that ACE2 and SPP are induced during aging, and that anti-CHI3L1, kasugamycin, and inhibitors of phosphorylation abrogate these ACE2- and SPP-inductive events. Human studies also demonstrate that the levels of circulating CHI3L1 are increased in the elderly and patients with CM, where they correlate with COVID-19 severity. These studies demonstrate that CHI3L1 is a potent stimulator of ACE2 and SPP, that this induction is a major mechanism contributing to the effects of aging during SC2 infection, and that CHI3L1 co-opts the CHI3L1 axis to augment SC2 infection. CHI3L1 plays a critical role in the pathogenesis of and is an attractive therapeutic target in COVID-19.
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Envelhecimento , COVID-19/metabolismo , Proteína 1 Semelhante à Quitinase-3/metabolismo , Envelhecimento/efeitos dos fármacos , Aminoglicosídeos/farmacologia , Aminoglicosídeos/uso terapêutico , Enzima de Conversão de Angiotensina 2/metabolismo , Linhagem Celular Tumoral , Proteína 1 Semelhante à Quitinase-3/antagonistas & inibidores , Células HEK293 , Humanos , SARS-CoV-2/fisiologia , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND: Determination of sedation type during gastrointestinal procedures is generally based on risk assessment via the American Society of Anesthesiologists (ASA) classification system, but the reliance of anesthesia risk on clinical factors remains largely uninvestigated. We aim to determine the association between various clinical factors and choice of sedation type during gastrointestinal procedures. METHODS: This single-center, retrospective cohort study used electronic medical records to identify patients receiving colonoscopy or endoscopy at Rhode Island Hospital. The electronic medical record was queried for history of alcohol abuse, opioid abuse, polysubstance abuse, prescriptions for psychotropic or opioid medications and ASA classification. Logistic regression was used to measure how patient characteristics correlated with sedation type. RESULTS: Totally, 2,033 patients were included in the study; 1,080 patients received moderate sedation and 853 received monitored anesthesia care (MAC). Three hundred fifty-four (60.2%) MAC patients had a history of alcohol abuse compared to 234 (39.8%) moderate sedation patients (P < 0.2334); 178 (62.9%) MAC and 105 (37.1%) moderate sedation patients had a history of opioid abuse (P < 0.001); 203 (73.6%) MAC and 73 (26.4%) moderate sedation patients had a history of polysubstance abuse (P < 0.001); and 815 (75.1%) MAC patients had psychiatric comorbidities versus 270 (24.9%) in the moderate sedation group (P < 0.001). In the MAC cohort, alcohol, opioid, polysubstance abuse and psychiatric history were associated with previous failure of moderate sedation (P < 0.0001). CONCLUSIONS: For a subset of patients, clinical factors including alcohol, opioid, polysubstance abuse and psychiatric history, in addition to ASA classification, play an important role in sedation management.
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Mutagenesis is integral for bacterial evolution and the development of antibiotic resistance. Environmental toxins and stressors are known to elevate the rate of mutagenesis through direct DNA toxicity, known as stress-associated mutagenesis, or via a more general stress-induced process that relies on intrinsic bacterial pathways. Here, we characterize the spectra of mutations induced by an array of different stressors using high-throughput sequencing to profile thousands of spectinomycin-resistant colonies of Bacillus subtilis. We found 69 unique mutations in the rpsE and rpsB genes, and that each stressor leads to a unique and specific spectrum of antibiotic-resistance mutations. While some mutations clearly reflected the DNA damage mechanism of the stress, others were likely the result of a more general stress-induced mechanism. To determine the relative fitness of these mutants under a range of antibiotic selection pressures, we used multistrain competitive fitness experiments and found an additional landscape of fitness and resistance. The data presented here support the idea that the environment in which the selection is applied (mutagenic stressors that are present), as well as changes in local drug concentration, can significantly alter the path to spectinomycin resistance in B. subtilis.
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Bacillus subtilis , Espectinomicina , Antibacterianos/farmacologia , Bacillus subtilis/genética , Dano ao DNA/genética , Resistência Microbiana a Medicamentos , Mutação , Espectinomicina/farmacologiaRESUMO
This study tested whether a new training tool, the Exposure Guide (EG), improved in-session therapist behaviors (i.e., indicators of quality) that have been associated with youth outcomes in prior clinical trials of exposure therapy. Six therapists at a community mental health agency (CMHA) provided exposure therapy for 8 youth with obsessive-compulsive disorder (OCD). Using a nonconcurrent multiple baseline design with random assignment to baseline lengths of 6 to 16â¯weeks, therapists received gold-standard exposure therapy training with weekly consultation (baseline phase) followed by addition of EG training and feedback (intervention phase). The primary outcome was therapist behavior during in-session exposures, observed weekly using a validated coding system. Therapist behavior was evaluated in relation to a priori benchmarks derived from clinical trials. Additional outcomes included training feasibility/acceptability, therapist response to case vignettes and beliefs about exposure, and independent evaluator-rated clinical outcomes. Three therapists reached behavior benchmarks only during the EG (intervention) phase. Two therapists met benchmarks during the baseline phase; one of these subsequently moved away from benchmarks but met them again after starting the EG phase. Across all therapists, the percentage of weeks meeting benchmarks was significantly higher during the EG phase (86.4%) vs. the baseline phase (53.2%). Youth participants experienced significant improvement in OCD symptoms and global illness severity from pre- to posttreatment. Results provide initial evidence that adding the EG to gold-standard training can change in-session therapist behaviors in a CMHA setting.
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Terapia Cognitivo-Comportamental , Terapia Implosiva , Transtorno Obsessivo-Compulsivo , Adolescente , Benchmarking , Criança , Humanos , Transtorno Obsessivo-Compulsivo/terapia , Projetos de Pesquisa , Resultado do TratamentoRESUMO
This study measured therapist behaviors in relation to subsequent habituation within exposure tasks, and also tested their direct and indirect relationships (via habituation) with clinical outcomes of exposure therapy. We observed 459 videotaped exposure tasks with 111 participants in three clinical trials for pediatric obsessive-compulsive disorder (POTS trials). Within exposure tasks, therapist behaviors and patient fear were coded continuously. Outcomes were habituation and posttreatment change in symptom severity, global improvement, and treatment response. More therapist behaviors that encourage approach-and less use of accommodation, unrelated talk, and externalizing language-predicted greater subsequent habituation during individual exposure tasks (exposure-level), and also predicted improved patient clinical outcomes via higher "total dose" of habituation across treatment (patient-level indirect effect). For six of seven therapist behaviors analyzed, the relationship with subsequent habituation within exposure differed by patient fear (low, moderate, or high) at the time the behavior was used. Two therapist behaviors had direct effects in the opposite direction expected; more unrelated talk and less intensifying were associated with greater patient symptom reduction. Results shed light on the "black box" of in-session exposure activities and point to specific therapist behaviors that may be important for clinical outcomes. These behaviors might be best understood in the context of changing patient fear during exposure tasks. Future studies should test whether therapist behaviors can be experimentally manipulated to produce improvement in clinical outcomes.
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Terapia Cognitivo-Comportamental , Terapia Implosiva , Transtorno Obsessivo-Compulsivo , Criança , Habituação Psicofisiológica , Humanos , Transtorno Obsessivo-Compulsivo/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Background Mesenchymal stem cell-derived extracellular vesicles (EVs) promote angiogenesis in the ischemic myocardium. This study examines the difference in vascular density, myocardial perfusion, molecular signaling, and gene expression between normal diet (ND) and high fat diet (HFD) groups at baseline and following intramyocardial injection of EVs. Methods and Results Intact male Yorkshire swine fed either an ND (n=17) or HFD (n=14) underwent placement of an ameroid constrictor on the left circumflex coronary artery. Subsequently, animals received either intramyocardial injection of vehicle-saline as controls; (ND-controls n=7, HFD-controls, n=6) or EVs; (ND-EVs n=10, HFD-EVs n=8) into the ischemic territory. Five weeks later, myocardial function, perfusion, vascular density, cell signaling, and gene expression were examined. EVs improved indices of myocardial contractile function, myocardial perfusion, and arteriogenesis in both dietary cohorts. Interestingly, quantification of alpha smooth muscle actin demonstrated higher basal arteriolar density in HFD swine compared with their ND counterparts; whereas EVs were associated with increased CD31-labeled endothelial cell density only in the ND tissue, which approached significance. Levels of total endothelial nitric oxide synthase, FOXO1 (forkhead box protein O1) , transforming growth factor-ß, phosphorylated VEGFR2 (vascular endothelial growth factor receptor 2), and phosphorylated MAPK ERK1/ERK2 (mitogen-activated protein kinase) were higher in ischemic myocardial lysates from ND-controls compared with HFD-controls. Conversely, HFD-control tissue showed increased expression of phosphorylated endothelial nitric oxide synthase, phosphorylated FOXO1, VEGFR2, and MAPK ERK1/ERK2 with respect to ND-controls. Preliminary gene expression studies indicate differential modulation of transcriptional activity by EVs between the 2 dietary cohorts. Conclusions HFD produces a profound metabolic disorder that dysregulates the molecular mechanisms of collateral vessel formation in the ischemic myocardium, which may hinder the therapeutic angiogenic effects of EVs.
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Indutores da Angiogênese/farmacologia , Circulação Coronária/fisiologia , Vasos Coronários/diagnóstico por imagem , Dieta Hiperlipídica/efeitos adversos , Vesículas Extracelulares/patologia , Isquemia Miocárdica/etiologia , Miocárdio/metabolismo , Animais , Doença Crônica , Circulação Coronária/efeitos dos fármacos , Vasos Coronários/fisiopatologia , Modelos Animais de Doenças , Masculino , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/metabolismo , Miocárdio/patologia , Neovascularização Patológica/diagnóstico , Neovascularização Patológica/etiologia , Neovascularização Patológica/metabolismo , Fosforilação , SuínosRESUMO
COVID-19 is caused by the SARS-CoV-2 (SC2) virus and is more prevalent and severe in the elderly and patients with comorbid diseases (CM). Because chitinase 3-like-1 (CHI3L1) is induced during aging and CM, the relationships between CHI3L1 and SC2 were investigated. Here we demonstrate that CHI3L1 is a potent stimulator of the SC2 receptor ACE2 and viral spike protein priming proteases (SPP), that ACE2 and SPP are induced during aging and that anti-CHI3L1, kasugamycin and inhibitors of phosphorylation, abrogate these ACE2- and SPP- inductive events. Human studies also demonstrated that the levels of circulating CHI3L1 are increased in the elderly and patients with CM where they correlate with COVID-19 severity. These studies demonstrate that CHI3L1 is a potent stimulator of ACE2 and SPP; that this induction is a major mechanism contributing to the effects of aging during SC2 infection and that CHI3L1 coopts the CHI3L1 axis to augment SC2 infection. CHI3L1 plays a critical role in the pathogenesis of and is an attractive therapeutic target in COVID-19.
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Hemorrhagic shock induces an aberrant immune response characterized by simultaneous induction of a proinflammatory state and impaired host defenses. The objective of this study was to evaluate the impact of conditionally immortalized neutrophil progenitors (NPs) on this aberrant immune response. We employed a mouse model of hemorrhagic shock, followed by the adoptive transfer of NPs and subsequent inoculation of Staphylococcus aureus to induce pneumonia. We observed that transplant of NPs decreases the proportion of host neutrophils that express programmed death ligand 1 and intercellular adhesion molecule 1 in the context of prior hemorrhage. Following hemorrhage, NP transplant decreased proinflammatory cytokines in the lungs, increased neutrophil migration into the airspaces, and enhanced bacterial clearance. Further, hemorrhagic shock improved NP engraftment in the bone marrow. These results suggest that NPs hold the potential for use as a cellular therapy in the treatment and prevention of secondary infection following hemorrhagic shock.
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Células Progenitoras Mieloides/imunologia , Células Progenitoras Mieloides/metabolismo , Neutrófilos/imunologia , Pneumonia/imunologia , Choque Hemorrágico/imunologia , Choque Hemorrágico/metabolismo , Staphylococcus aureus/imunologia , Animais , Antígeno B7-H1/metabolismo , Medula Óssea/imunologia , Linhagem Celular , Movimento Celular , Terapia Baseada em Transplante de Células e Tecidos , Citocinas/metabolismo , Modelos Animais de Doenças , Imunidade , Molécula 1 de Adesão Intercelular/metabolismo , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/transplante , Pneumonia/microbiologia , Choque Hemorrágico/complicaçõesRESUMO
BACKGROUND: Patient-reported outcome (PRO) measures often address quality of life (QOL) and help improve communication and shared decision-making. The home parenteral nutrition patient-reported outcome questionnaire (HPN-PROQ) was developed for patients to self-assess factors that influence QOL. The aim of this study was to establish construct validity. METHOD: Responses were analyzed for 77 HPN-dependent patients with chronic and prolonged acute intestinal failure. General linear modeling was conducted to describe patterns of interactions and association between items included in the HPN-PROQ. RESULTS: Most patients (78%) had chronic intestinal failure. Mean HPN duration was 3.3 ± 0.6 years. Underlying illness had a moderate or major effect on QOL for 88%; 59% reported their QOL had been negatively impacted by HPN. There was no difference in QOL among chronic patients, depending on how important they rated "being able to do what I want to do" (P = .1), whereas prolonged acute intestinal failure patients had significantly lower QOL if they rated "being able to do what I want to do" extremely vs very important (adjusted P = .02). Confidence with ability to perform HPN procedures was associated with understanding the need for HPN (P < .01). As ratings increased for emotional difficulty in coping with HPN so did HPN impact on QOL (linear trend P < .01). CONCLUSION: Construct validity of the HPN-PROQ was evident. The HPN-PROQ considers the unique experience of living with a complex nutrition therapy.
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Enteropatias , Nutrição Parenteral no Domicílio , Humanos , Enteropatias/terapia , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Severe bronchopulmonary dysplasia (sBPD) can lead to long term morbidity. We created a sBPD multidisciplinary team in 2011 to optimize care and improve outcomes. STUDY DESIGN: Retrospective chart review of three groups between 2008 and 2016: patients with sBPD born before 2011, patients with sBPD born after 2011, and patients with moderate BPD born after 2011. RESULTS: Infants with sBPD after 2011 had a shorter NICU length of stay compared with children born before 2011 (mean 140 days vs 170 days p < 0.007), weighed more at discharge (z-score -0.8 vs -1.35 p = 0.01), had less failure to thrive post discharge (32% vs 51% p = 0.05) and had more well visits in the first six months of life (mean 6.7 vs 5.3 p = 0.04). No difference was observed in the rate of readmissions in the first two years of life. CONCLUSION: Our multidisciplinary team has improved the inpatient management of patients with sBPD.
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Displasia Broncopulmonar , Assistência ao Convalescente , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/terapia , Criança , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Pacientes Internados , Equipe de Assistência ao Paciente , Alta do Paciente , Estudos RetrospectivosRESUMO
BACKGROUND: Online portals have been shown to be a valuable tool for patients to improve compliance with medical treatment in numerous studies across medical specialties. Our aim was to study the effects of the use of web-based applications that allow patients to track their appointments, labs, and provider visit notes on achievement of renal transplantation. STUDY DESIGN: This is a retrospective chart review of patients in 2 outpatient dialysis centers associated with a 719-bed tertiary care academic medical center. RESULTS: Nine percent of portal users at 3 years after initiation of hemodialysis were the recipients of kidney transplants vs 9% of nonusers. At 4 years, 23% of users were transplant recipients vs 13% of nonusers. At 5 years, 40% of users were transplant recipients vs 14% of nonusers. There was statistically significant divergence of the curves, with the greatest difference observed at 5 years (p = 0.047). In addition, increased number of logins per month was associated with shortened time to renal transplantation (p = 0.0067). CONCLUSIONS: Online portal use is associated with a higher likelihood of being approved as a transplantation candidate and increased number of logins is associated with shortened time to renal transplantation.
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Transplante de Rim , Portais do Paciente/estatística & dados numéricos , Diálise Renal , Insuficiência Renal/cirurgia , Tempo para o Tratamento , Utilização de Instalações e Serviços , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/mortalidade , Estudos RetrospectivosRESUMO
BACKGROUND: Among patients undergoing colonoscopy, anticoagulants are usually stopped and are sometimes substituted by a heparin bridge (hep-bridge). We aimed to assess adverse events associated with hep-bridge compared to temporary cessation of anticoagulants (no-bridge). METHODS: This was a single-center, retrospective cohort study that included anticoagulated patients undergoing colonoscopy between 2013 and 2016 at a Veterans Affairs Medical Center. In the no-bridge cohort, warfarin was stopped for 5 days and novel anticoagulants for 2 days pre-procedure. In the hep-bridge cohort, anticoagulants were stopped and were substituted by subcutaneous enoxaparin. The primary outcome was post-polypectomy bleeding. Secondary outcomes included cardiovascular events, all-cause adverse events and emergency department or unscheduled ambulatory office visits within 30 days. The predictive values of the HAS-BLED and CHADS2 scores were evaluated. RESULTS: A total of 662 patients were included, of whom 551 underwent polypectomy (mean age 68.6 years; 97.6% male). Four hundred seventy colonoscopies were performed with no-bridge and 192 with hep-bridge. Post-polypectomy bleeding occurred in 6.0% of procedures: 5.7% in the no-bridge cohort compared to 13.0% of hep-bridge procedures (P=0.0038). Cardiovascular or thrombotic events occurred after 2.6% of the no-bridge and 5.2% of the hep-bridge procedures (P=0.1176). Emergency department or unscheduled office visits within 30 days were reported after 18.7% of the no-bridge procedures and 29.7% of the hep-bridge procedures (P<0.0001). Neither CHADS2 nor HASBLED scores predicted bleeding. CONCLUSION: The use of hep-bridge was associated with a greater incidence of post-polypectomy bleeding and more emergency department and unscheduled office visits compared with cessation of all anticoagulants.
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BACKGROUND: Lymphocytes have become the target of cancer interventions through engineering or immune checkpoint antibodies. We previously found decreased lymphocyte counts to be a predictor of mortality and complications in trauma and cardiac surgery patients. We hypothesized lack of lymphocyte count recovery postoperatively would predict outcomes in esophagectomy patients. METHODS: A retrospective review of all patients undergoing esophagectomy for adenocarcinoma performed over 13 y at our center by a single surgeon after institutional review board approval was performed. Patients were grouped by postoperative lymphocytes counts: never low, low with recovery, and low without recovery. Resolution of lymphopenia was assessed by day 4. Primary end points were overall and recurrence-free survival. RESULTS: In total, 198 patients were included with a minimum 6-mo follow-up. Collectively the 5-y recurrence and overall survival rates were 36% and 50%, respectively. Recurrence was significantly higher at 5 y in patients with persistent lymphopenia (43%) compared with those who recovered (14% P = 0.0017) and those who never dropped (0% P = 0.0009). The persistent lymphopenia group had significantly lower survival (45%) compared with the two other groups (67% P = 0.0232). CONCLUSIONS: There is a significant decrease in the overall and recurrence-free survival in those patients whose lymphocyte count drops without recovery after their esophagectomy. These data imply differences in immune responses to the stress of surgery that can be measured with routine postoperative laboratory values and are indicative of overall outcomes.
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Neoplasias Esofágicas/mortalidade , Esofagectomia/efeitos adversos , Linfócitos , Linfopenia/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Intervalo Livre de Doença , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/cirurgia , Feminino , Seguimentos , Humanos , Contagem de Linfócitos , Linfopenia/sangue , Linfopenia/etiologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/epidemiologia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Chondrosarcoma is a highly aggressive primary malignant bone tumor mostly occurring in adults. There are no effective systemic treatments, and patients with this disease have poor survival. miR-181a is an oncomiR that is overexpressed in high-grade chondrosarcoma and promotes tumor progression. Regulator of G-protein signaling 16 (RGS16) is a target of miR-181a. Inhibition of RGS16 expression by miR-181a enhances CXC chemokine receptor 4 signaling, which in turn increases MMP1 and VEGF expression, angiogenesis, and metastasis. Here, we report the results of systemic treatment with anti-miRNA oligonucleotides (AMO) directed against miR-181a utilizing a nanopiece delivery platform (NPs). NPs were combined with a molecular beacon or anti-miR-181a oligonucleotides and are shown to transfect chondrosarcoma cells in vitro and in vivo Intratumoral injection and systemic delivery had similar effects on miR-181a expression in nude mice bearing chondrosarcoma xenografts. Systemic delivery of NPs carrying anti-miR-181a also restored RGS16 expression, decreased expression of VEGF and MMP1, MMP activity, and tumor volume by 32% at day 38, and prolonged survival from 23% to 45%. In conclusion, these data support that systemic delivery of AMO shows promise for chondrosarcoma treatment.
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Antagomirs/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Condrossarcoma/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , MicroRNAs/genética , Animais , Antagomirs/farmacologia , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Condrossarcoma/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Camundongos Nus , MicroRNAs/antagonistas & inibidores , Nanopartículas , Proteínas RGS/genética , Regulação para Cima/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Transcranial motor-evoked potentials (TcMEPs) are used to monitor the descending motor pathway during scoliosis surgery. By comparing potentials before and after correction, surgeons may prevent postoperative functional loss in distal muscles. There is currently no consensus as to which muscles should be monitored. The purpose of this study is to determine the least invasive monitoring protocol with the best localization of potential neurologic deficit. A retrospective review of 125 patients with TcMEP monitoring during surgery for thoracolumbar scoliosis between 2008 and 2015 was conducted. 18 patients had postoperative neurologic consult due to deficit. The remaining 107 patients were a consecutive cohort without postoperative neurologic consult. TcMEPs were recorded from vastus lateralis (VL), tibialis anterior (TA), peroneus longus (PL), adductor hallucis (AH) and abductor pollicis brevis (APB) bilaterally. The effectiveness of each muscle combination was evaluated independently and then compared to other combinations using Akaike Information Criterion (AIC). Monitoring of VL, TA, PL, and AH yielded sensitivity of 77.8% and specificity of 92.5% (AIC=66.7). Monitoring of TA, PL and AH yielded sensitivity of 77.8% and specificity of 94.4% (AIC=62.4). Monitoring of VL, TA and PL yielded sensitivity of 72.2% and specificity of 93.5% (AIC=70.1). Monitoring of TA and PL yielded sensitivity of 72.2% and specificity of 96.3% (AIC=63.9). TcMEP monitoring of TA, PL, and AH provided the highest sensitivity and specificity and best predictive power for postoperative lower extremity weakness.
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BACKGROUND: Achilles tendon tears are potentially career-ending injuries for professional athletes. For players in the National Football League (NFL), return requires not only surgery and extensive rehabilitation but also the ability to compete in a market with limited positions that annually introduces new recruits. PURPOSE/HYPOTHESIS: We authors sought to evaluate factors related to return to play (RTP) and changes in performance following a primary Achilles tear. Our hypothesis was that "skilled" position players and those drafted in later rounds would return at a lower rate as compared with "unskilled" position players and higher draft-round players. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: From a previously established database, 80 NFL players were identified as having primary Achilles tendon tears between the 2009 and 2014 seasons. RTP was defined as playing in a regular season or postseason game following injury. Probability of RTP was modeled as a function of time after injury in Kaplan-Meier analysis with demographic variables assessed via generalized linear models. Twelve players (15%) experienced a subsequent Achilles tendon tear during or after the study period and were included in the overall RTP rate but were excluded from performance analyses owing to the confounding effects of an ipsilateral retear or contralateral tear. RESULTS: The overall RTP rate was 61.3%. Age, number of prior seasons, position type, or draft round status did not significantly affect RTP when evaluated with Kaplan-Meier analysis. In the season before their injury, players who did RTP played in a significantly greater number of regular season games (13.7) compared with players who did not RTP (8.71) (P = .011). Players who did not RTP exhibited a significant decrease in performance in the season preceding injury (12.7 regular season games played 2 seasons preinjury vs 8.71 regular season games played 1 season prior preinjury;, P = .019). Players who returned did not display a significant change in the number of games played or started in seasons following injury when >1 season after return was evaluated. CONCLUSION: Rate of RTP following primary Achilles tendon tears may be lower than previously published. However, for those able to return, performance only in the season immediately following injury appears to be affected; players return to preinjury levels if given the opportunity to play >1 season after injury.
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Analyzing the reading grade level of online mental health information is an important first step in ensuring that information is largely accessible by the general public, so as not to perpetuate existing health disparities across socioeconomic groups. The present study systematically examined grade-level readability of mental health information related to various psychiatric diagnoses, obtained from 6 highly utilized mental health websites, using a generalized estimating equations approach. Results suggest that, in general, the readability of mental health information is largely well above the 6th-to-8th grade level recommended by several national health organizations, including the CDC and NIH (Kutner, Greenberg, Jin, & Paulsen, 2006; National Institutes of Health, 2001, 2017), with reading-grade-level estimates from the model ranging from 5.62 to 17.9. Further efforts are required to ensure that writers of online health information do not exacerbate existing health disparities by ignoring these guidelines. (PsycINFO Database Record (c) 2019 APA, all rights reserved).