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来源期刊:PubMed 发表时间:2020-09-10 01:44:26
作者列表: Turcotte EL,Rahme RJ,Merrill SA,Hess RA,Lettieri SC,Bendok BR
Abstract: :Fluorescence-guided resection of brain tumors using 5-aminolevulinic acid (5-ALA) has been established for high-grade gliomas. Recently, its application for the resection of low grade tumors and benign lesions including meningioma has been suggested in the literature.1 Achieving a Simpson grade I resection in meningioma surgery is associated with a lower rate of recurrence.2,3 Although meningiomas are mostly benign and well-circumscribed lesions, they can be locally aggressive, invading brain parenchyma and other critical structures. In these cases, 5-ALA-guided resection may help maximize the extent of tumor resection and limit disruption of normal structures. In this video, we present 3 cases demonstrating the use of 5-ALA-induced fluorescence to alleviate 3 specific challenges in meningioma resection: 1) to aid visualization with a minimally invasive approach, 2) to distinguish recurrent tumor from scar tissue from prior treatments, and 3) to ensure that no viable tumor cells remain on the surface of a critical artery. The first patient is a 60-year-old woman who was found to have an incidental left sphenoid wing meningioma on magnetic resonance imaging. We elected for an extended lateral orbital craniotomy through a transpalpebral approach. The second patient is a 72-year-old man with recurrent left occipital parietal meningioma who underwent a parietal craniotomy. The third case was a 62-year-old woman with a foramen magnum meningioma encircling the left vertebral artery. These cases demonstrate the utility of 5-ALA in a variety of challenges associated with resection of meningiomas (Video 1).
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来源期刊:PubMed 发表时间:2020-09-10 01:42:39
作者列表: Gupta T,Singh VP,Balasubramian A,Menon H,Kurkure PA,Kumar S,Jalali R
Abstract: :The entire world including India is currently fighting the coronavirus disease 19 (COVID-19) pandemic that threatens to disrupt healthcare systems globally in terms of capacity and resources. This outbreak necessitates an urgent review of existing management guidelines for commonly encountered tumors of the brain and central nervous system (CNS). Such a review should include a reassessment of benefit-risk ratio to align with local, national, and international priorities without compromising on delivery of care in terms of safety, compassion, efficiency, and effectiveness. Towards this end, the Indian Society of Neuro-Oncology (ISNO) constituted an online expert panel with adequate representation from all major treatment modalities (neuro-surgery, radiation oncology, and pediatric/medical oncology) to formulate a "COVID-19 context" position statement to guide the care of neuro-oncology patients during the ongoing crisis. The ISNO position statement suggests graded prioritization (based on clinical presentation, type of tumor, expected prognosis, and relevance of immediate therapy) for efficient utilization of resources and provides a framework through a set of general considerations, treatment modality-based considerations, and disease-specific considerations for the guidance of healthcare professionals involved in the delivery of care and services to patients with CNS tumors. The views expressed herein represent the current consensus of key opinion leaders from within the Indian neuro-oncology community and should not be in any case considered binding medically or legally to individual physicians and/or hospitals who may formulate their guidelines based on local setup and health-environment and update them periodically based on emerging evidence through the COVID-19 pandemic.
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来源期刊:PubMed 发表时间:2020-09-10 01:41:12
作者列表: Lv J,Chen FK,Liu C,Liu PJ,Feng ZP,Jia L,Yang ZX,Hou F,Deng ZY
Abstract: AIMS:This study aims to explore the effect and underlying mechanism of zoledronic acid (ZA) on the incidence of thyroid cancer (TC) tumorigenesis. MATERIALS AND METHODS:Human mononuclear cells THP-1 were differentiated into M2-like tumor associated macrophages (TAMs) by incubation with PMA followed by additional incubation of IL-4 and IL-13. TC cells TPC-1 and IHH4 were co-cultured with M2-like TAMs. Identification of M2-like TAMs markers were determined by immunohistochemistry or flow cytometry. Cell proliferation, stemness and migration/invasion ability were measured by colony, sphere formation assay and transwell assay, respectively. The expression levels of cell stemness, EMT and Wnt/β-catenin pathway-related factors were verified by qRT-PCR, Western blotting, and immunofluorescence. A subcutaneous tumor model was established in nude mice to examine the in vivo effects of ZA. KEY FINDINGS:M2-like TAMs were enriched in TC tissues, and they promoted the colony/sphere formation, accompanied with a down-regulated expression in E-cadherin and an up-regulated expression in N-cadherin, Vimentin and other stemness-associated markers (CD133, Oct4, c-Myc) in TC cells. The effects were suppressed when ZA co-treatment was given, because ZA inhibited the polarization of M2-like TAMs and β-catenin entry into the nucleus. Moreover, in agreement with in vitro data, ZA also limited subcutaneous tumor formation and macrophage enrichment in nude mice. SIGNIFICANCE:ZA suppressed M2-like TAMs induced TC cell proliferation, stemness and metastasis through inhibiting M2-like TAMs polarization and Wnt/β-catenin pathway, which sheds light on the mechanisms of TC and provides avenues for the development of clinical therapy to TC.
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来源期刊:PubMed 发表时间:2020-09-09 01:49:44
作者列表: Kłosiński K,Girek M,Czarnecka K,Pasieka Z,Skibiński R,Szymański P
Abstract: :A new series of tetrahydroacridine derivatives with the fluorobenzoyl moiety was synthesized and evaluated for cytotoxic activity against lung cancer cell lines A549 and colorectal cancer HT29. The cytotoxic activity of the compounds was compared on the somatic cell line-EAhy926. Compounds showed high cytotoxic activity on A549 cells (IC50 183.26-68.07 μM) and HT29 cells (IC50 68.41-19.70 μM), higher than controls-etoposide (IC50 451.47 μM) toward A549 and 5-fluorouracil (IC50 1626.85 μM) against HT29. Derivative 4 was the most cytotoxic to A549, whereas for the cell lines HT29 compound 6. Selected compounds showed similar cytotoxicity to the EAhy926 cell line (IC50 about 50 μM). In the hyaluronidase inhibition assay, all compounds exhibited anti-inflammatory activity, including 4 exhibiting the best inhibitory activity-IC50 of 52.27 μM when the IC50 heparin was 56.41 μM. Mathematical modeling was performed to determine LD50 after intraperitoneal, oral, intravenous and subcutaneous administration and to predict potential mutagenicity and carcinogenicity of the compounds analyzed. Obtained results showed that tested derivatives are slightly toxic compounds, and LD50 values (mg/kg) ranged from 680 to 1200 (oral rat model), the analyzed compounds have low mutagenic potential, and differences between derivatives are insignificant and very low probability of carcinogenicity. To confirm mathematical calculations, an in vivo test was carried out on a laboratory mouse model for two selected compounds. It allowed to qualify compounds: 6 to category 4 of the GHS scale, and 4 to category 3 of the GHS scale.
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来源期刊:PubMed 发表时间:2020-09-09 00:26:27
作者列表: Goyal N,Hoit D,DiNitto J,Elijovich L,Fiorella D,Pierot L,Lamin S,Spelle L,Saatci I,Cekirge S,Arthur AS
Abstract: :Wide-necked bifurcation aneurysms (WNBAs) make up 26-36% of all brain aneurysms. Treatments for WNBAs pose unique challenges due to the need to preserve major bifurcation vessels while achieving a durable occlusion of the aneurysm. Intrasaccular flow disruption is an innovative technique for the treatment of WNBAs. The Woven EndoBridge (WEB) device is the only United States Food and Drug Administration approved intrasaccular flow disruption device. In this review article we discuss various aspects of treating WNBAs with the WEB device, including indications for use, aneurysm/device selection strategies, antiplatelet therapy requirement, procedural technique, potential complications and bailouts, and management strategies for residual/recurrent aneurysms after initial WEB treatment.
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来源期刊:PubMed 发表时间:2020-09-09 00:18:16
作者列表: van den Hoogen IJ,van Rosendael AR,Lin FY,Lu Y,Dimitriu-Leen AC,Smit JM,Scholte AJHA,Achenbach S,Al-Mallah MH,Andreini D,Berman DS,Budoff MJ,Cademartiri F,Callister TQ,Chang HJ,Chinnaiyan K,Chow BJW,Cury RC,DeLago A,Feuchtner G,Hadamitzky M,Hausleiter J,Kaufmann PA,Kim YJ,Leipsic JA,Maffei E,Marques H,de Araújo Gonçalves P,Pontone G,Raff GL,Rubinshtein R,Villines TC,Gransar H,Jones EC,Peña JM,Shaw LJ,Min JK,Bax JJ
Abstract: AIMS:We aimed to compare semiquantitative coronary computed tomography angiography (CCTA) risk scores - which score presence, extent, composition, stenosis and/or location of coronary artery disease (CAD) - and their prognostic value between patients with and without diabetes mellitus (DM). Risk scores derived from general chest-pain populations are often challenging to apply in DM patients, because of numerous confounders. METHODS:Out of a combined cohort from the Leiden University Medical Center and the CONFIRM registry with 5-year follow-up data, we performed a secondary analysis in diabetic patients with suspected CAD who were clinically referred for CCTA. A total of 732 DM patients was 1:1 propensity-matched with 732 non-DM patients by age, sex and cardiovascular risk factors. A subset of 7 semiquantitative CCTA risk scores was compared between groups: 1) any stenosis ≥50%, 2) any stenosis ≥70%, 3) stenosis-severity component of the coronary artery disease-reporting and data system (CAD-RADS), 4) segment involvement score (SIS), 5) segment stenosis score (SSS), 6) CT-adapted Leaman score (CT-LeSc), and 7) Leiden CCTA risk score. Cox-regression analysis was performed to assess the association between the scores and the primary endpoint of all-cause death and non-fatal myocardial infarction. Also, area under the receiver-operating characteristics curves were compared to evaluate discriminatory ability. RESULTS:A total of 1,464 DM and non-DM patients (mean age 58 ± 12 years, 40% women) underwent CCTA and 155 (11%) events were documented after median follow-up of 5.1 years. In DM patients, the 7 semiquantitative CCTA risk scores were significantly more prevalent or higher as compared to non-DM patients (p ≤ 0.022). All scores were independently associated with the primary endpoint in both patients with and without DM (p ≤ 0.020), with non-significant interaction between the scores and diabetes (interaction p ≥ 0.109). Discriminatory ability of the Leiden CCTA risk score in DM patients was significantly better than any stenosis ≥50% and ≥70% (p = 0.003 and p = 0.007, respectively), but comparable to the CAD-RADS, SIS, SSS and CT-LeSc that also focus on the extent of CAD (p ≥ 0.265). CONCLUSION:Coronary atherosclerosis scoring with semiquantitative CCTA risk scores incorporating the total extent of CAD discriminate major adverse cardiac events well, and might be useful for risk stratification of patients with DM beyond the binary evaluation of obstructive stenosis alone.
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来源期刊:PubMed 发表时间:2020-08-31 00:56:35
作者列表: Rees CA,Pineros DB,Amour M,Munseri P,Said J,Magohe A,Matee M,Pallangyo K,von Reyn CF
Abstract: BACKGROUND:Ratios of different immune cell populations (i.e., monocyte-to-lymphocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte ratios) have been studied as a means of predicting future tuberculosis (TB) disease risk or to assist in the diagnosis of incident TB disease. No studies to-date, however, have evaluated the potential of these ratios to predict or assist in the diagnosis of incident TB infection - the first step in the natural history of TB disease. METHODS:In this prospective study, we evaluated the complete blood count (CBC)-derived metrics of monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) as predictors of future TB infection risk or aids in the diagnosis of TB infection among 145 Tanzanian adolescents enrolled in the DAR-901 vaccine trial, using paired CBCs and interferon-gamma release assays (IGRAs) obtained at 0, 60 and 720 days after study enrollment. RESULTS:At baseline, there were no significant differences between study participants who remained persistently IGRA negative throughout the study period and those who subsequently converted to IGRA positive with respect to MLR (0.18 vs 0.17, p = 0.10), NLR (0.88 vs 1.02, p = 0.08), or PLR (115 vs 120, p = 0.28). Similarly, no significant differences were noted with respect to MLR, NLR, and PLR between IGRA converters and time-matched negative controls at the time of IGRA conversion. With respect to other blood cell measures, however, there were modest but significant differences between IGRA negatives and IGRA converters with respect to red blood cell count (4.8 vs 4.6 ×  106 cells/mcL, p = 0.008), hemoglobin (12.6 vs 12.3 g/dL, p = 0.01), and hematocrit (38.8 vs 37.8%, p = 0.005). CONCLUSIONS:In contrast to prior studies that have suggested that the ratios of different immune cell populations are associated with development of TB disease, our present findings do not demonstrate an association between these ratios and the development of TB infection. However, decreased red blood cell measures were associated with the subsequent development of TB infection, suggesting either that dysregulation of iron metabolism may play a role in TB pathogenesis or that following TB infection, iron dysregulation may precede IGRA positivity. TRIAL REGISTRATION:Clinicaltrials.gov NCT02712424 . Date of registration: March 14, 2016.
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来源期刊:PubMed 发表时间:2020-08-31 00:54:14
作者列表: Cavalheiro S,Serrato-Avila JL,Párraga RG,Da Costa MDS,Nicácio JM,Rocha PR,Chaddad-Neto F
Abstract: OBJECTIVE:In this article, we describe a new safe entry point for the posterolateral pons. METHODS:To show the adjacent anatomy and measure the part of the interpeduncular sulcus that can be safely accessed, we first performed a review of the literature regarding the pons anatomy and its surgical approaches. Thereafter, 1 human cadaveric head and 15 (30 sides) human brainstems with attached cerebellums were bilaterally dissected with the fiber microdissection technique. A clinical correlation was made with an illustrative case of a dorsolateral pontine World Health Organization grade I astrocytoma. RESULTS:The safe distance for accessing the interpeduncular sulcus was found to extend from the caudal end of the lateral mesencephalic sulcus to the point at which the intrapontine segment of the trigeminal nerve crosses the interpeduncular sulcus. The mean distance was 8.2 mm (range, 7.15-8.85 mm). Our interpeduncular sulcus safe entry zone can be exposed through a paramedian infratentorial supracerebellar approach. When additional exposure is required, the superior portion of the quadrangular lobule of the cerebellar hemispheric tentorial surface can be removed. In the presented case, surgical resection of the tumor was performed achieving a gross total resection, and the patient was discharged without neurologic deficit. CONCLUSIONS:The interpeduncular sulcus safe entry zone provides an alternative direct route for treating intrinsic pathologic entities situated in the posterolateral tegmen of the pons between the superior and middle cerebellar peduncles. The surgical corridor provided by this entry point avoids most eloquent neural structures, thereby preventing surgical complications.
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来源期刊:PubMed 发表时间:2020-08-30 11:56:14
作者列表: Ma LJ,Wu TM,Feng IJ,Hsu CC,Su SB,Wang JJ,Huang CC
Abstract: BACKGROUND:Physicians have better medical knowledge, which may decrease the risk of dementia; however, this issue remains unclear. This study was performed to clarify it. METHODS:We conducted a nationwide population-based study that recruited 29,388 physicians, 50,000 participants from the general population, and 30,446 other healthcare professionals (HCPs; excluding physicians) for this study. The prevalence of dementia was compared among the three groups and physician subgroups by tracing their medical histories from 2006 to 2012. RESULTS:Physicians had a lower prevalence of dementia than the general population after adjusting for age, sex, head trauma, hypothyroidism, hypertension, diabetes mellitus, stroke, vascular disease, atrial fibrillation, hypercholesterolemia, depression, and alcoholism [adjusted odds ratio (AOR) 0.56; 95% confidence interval (CI) 0.47-0.67]. Other HCPs also had a lower prevalence for dementia than the general population (AOR 0.46; 95% CI 0.36-0.60). Compared with other HCPs, physicians had no difference in the prevalence for dementia (AOR 0.98 95% CI 0.71-1.36). Physicians who were older, specialized in pediatrics and worked at local hospitals and clinics had a higher prevalence for dementia than their counterparts did. CONCLUSIONS:Physicians had a lower prevalence for dementia than the general population. The prevalence for dementia in specific subgroups of physicians was higher, which needs to be clarified by further studies.
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来源期刊:PubMed 发表时间:2020-08-29 11:14:55
作者列表: Barr DA,Lewis JM,Feasey N,Schutz C,Kerkhoff AD,Jacob ST,Andrews B,Kelly P,Lakhi S,Muchemwa L,Bacha HA,Hadad DJ,Bedell R,van Lettow M,Zachariah R,Crump JA,Alland D,Corbett EL,Gopinath K,Singh S,Griesel R,Maartens G,Mendelson M,Ward AM,Parry CM,Talbot EA,Munseri P,Dorman SE,Martinson N,Shah M,Cain K,Heilig CM,Varma JK,von Gottberg A,Sacks L,Wilson D,Squire SB,Lalloo DG,Davies G,Meintjes G
Abstract: BACKGROUND:The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI. METHODS:We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022. FINDINGS:We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96·2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per μL (the median for the cohort) was 45% (95% CI 38-52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63-87), increasing to 89% (80-94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2·48, 95% CI 2·05-3·08) but not after 30 days (1·25, 0·84-2·49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3·15, 95% CI 1·16-8·84). INTERPRETATION:In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients. FUNDING:This study was supported by Wellcome fellowships 109105Z/15/A and 105165/Z/14/A.
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来源期刊:PubMed 发表时间:2020-08-29 10:55:52
作者列表: Bai HX,Wang R,Xiong Z,Hsieh B,Chang K,Halsey K,Tran TML,Choi JW,Wang DC,Shi LB,Mei J,Jiang XL,Pan I,Zeng QH,Hu PF,Li YH,Fu FX,Huang RY,Sebro R,Yu QZ,Atalay MK,Liao WH
Abstract: :Background Coronavirus disease 2019 (COVID-19) and pneumonia of other diseases share similar CT characteristics, which contributes to the challenges in differentiating them with high accuracy. Purpose To establish and evaluate an artificial intelligence (AI) system for differentiating COVID-19 and other pneumonia at chest CT and assessing radiologist performance without and with AI assistance. Materials and Methods A total of 521 patients with positive reverse transcription polymerase chain reaction results for COVID-19 and abnormal chest CT findings were retrospectively identified from 10 hospitals from January 2020 to April 2020. A total of 665 patients with non-COVID-19 pneumonia and definite evidence of pneumonia at chest CT were retrospectively selected from three hospitals between 2017 and 2019. To classify COVID-19 versus other pneumonia for each patient, abnormal CT slices were input into the EfficientNet B4 deep neural network architecture after lung segmentation, followed by a two-layer fully connected neural network to pool slices together. The final cohort of 1186 patients (132 583 CT slices) was divided into training, validation, and test sets in a 7:2:1 and equal ratio. Independent testing was performed by evaluating model performance in separate hospitals. Studies were blindly reviewed by six radiologists without and then with AI assistance. Results The final model achieved a test accuracy of 96% (95% confidence interval [CI]: 90%, 98%), a sensitivity of 95% (95% CI: 83%, 100%), and a specificity of 96% (95% CI: 88%, 99%) with area under the receiver operating characteristic curve of 0.95 and area under the precision-recall curve of 0.90. On independent testing, this model achieved an accuracy of 87% (95% CI: 82%, 90%), a sensitivity of 89% (95% CI: 81%, 94%), and a specificity of 86% (95% CI: 80%, 90%) with area under the receiver operating characteristic curve of 0.90 and area under the precision-recall curve of 0.87. Assisted by the probabilities of the model, the radiologists achieved a higher average test accuracy (90% vs 85%, Δ = 5, P < .001), sensitivity (88% vs 79%, Δ = 9, P < .001), and specificity (91% vs 88%, Δ = 3, P = .001). Conclusion Artificial intelligence assistance improved radiologists' performance in distinguishing coronavirus disease 2019 pneumonia from non-coronavirus disease 2019 pneumonia at chest CT. © RSNA, 2020 Online supplemental material is available for this article.
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来源期刊:PubMed 发表时间:2020-08-29 10:54:52
作者列表: Yang MC,Hung PP,Wu YK,Peng MY,Chao YC,Su WL
Abstract: OBJECTIVES:Families are a transmission route for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of the close contact. Monitoring of the viral load will be a valuable method to reduce the optimal number of quarantine days, especially in presymptomatic and symptomatic carriers of their households. The traditional three-generation families living together are seen frequently in East Asia, including in Taiwan. STUDY DESIGN:We report on a family cluster with six individuals infected with coronavirus disease in Taiwan. METHODS:The current public policy in Taiwan is quarantine for at least 14 days, based on the incubation period, or until the patient has tested negative three days in a row using the SARS-CoV-2 reverse transcription polymerase chain reaction. Details on the onset date of clinical symptoms, throat swab conversion, and course of disease were collected from medical records retrospectively. RESULTS:In the household of this three-generation Taiwanese family, the infection rate was 60%. The ratio of males to females was 4:2, and the age range was 11-85 years. The prevalence of asymptomatic disease was 33.3% (2/6). The longest throat swab conversion time was 37 days, and the estimated course of disease from symptoms to first conversion of throat swab was 59 days. CONCLUSIONS:Large families, including three-generation families in a single dwelling, should be monitored when the index case is found. Presymptomatic and symptomatic family members could be quarantined for an appropriate duration which, in our experience, is 2 months.
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来源期刊:PubMed 发表时间:2020-08-29 00:53:23
作者列表: Yu J,Tostanoski LH,Peter L,Mercado NB,McMahan K,Mahrokhian SH,Nkolola JP,Liu J,Li Z,Chandrashekar A,Martinez DR,Loos C,Atyeo C,Fischinger S,Burke JS,Slein MD,Chen Y,Zuiani A,Lelis FJN,Travers M,Habibi S,Pessaint L,Van Ry A,Blade K,Brown R,Cook A,Finneyfrock B,Dodson A,Teow E,Velasco J,Zahn R,Wegmann F,Bondzie EA,Dagotto G,Gebre MS,He X,Jacob-Dolan C,Kirilova M,Kordana N,Lin Z,Maxfield LF,Nampanya F,Nityanandam R,Ventura JD,Wan H,Cai Y,Chen B,Schmidt AG,Wesemann DR,Baric RS,Alter G,Andersen H,Lewis MG,Barouch DH
Abstract: :The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers at levels comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. After vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with viral loads in sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.
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来源期刊:PubMed 发表时间:2020-08-28 09:44:31
作者列表: Langan SM,Irvine AD,Weidinger S
Abstract: :Atopic dermatitis is a common inflammatory skin disorder characterised by recurrent eczematous lesions and intense itch. The disorder affects people of all ages and ethnicities, has a substantial psychosocial impact on patients and relatives, and is the leading cause of the global burden from skin disease. Atopic dermatitis is associated with increased risk of multiple comorbidities, including food allergy, asthma, allergic rhinitis, and mental health disorders. The pathophysiology is complex and involves a strong genetic predisposition, epidermal dysfunction, and T-cell driven inflammation. Although type-2 mechanisms are dominant, there is increasing evidence that the disorder involves multiple immune pathways. Currently, there is no cure, but increasing numbers of innovative and targeted therapies hold promise for achieving disease control, including in patients with recalcitrant disease. We summarise and discuss advances in our understanding of the disease and their implications for prevention, management, and future research.
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来源期刊:PubMed 发表时间:2020-08-28 09:33:55
作者列表: Cohn LN,Pechlivanoglou P,Lee Y,Mahant S,Orkin J,Marson A,Cohen E
Abstract: OBJECTIVE:To assess health outcomes of parents caring for children with chronic illnesses compared with parents of healthy children. STUDY DESIGN:We searched OvidSP MEDLINE, EBM Reviews-Cochrane Central Register of Controlled Trials, EMBASE, and EBSCOHost CINAHL through September 2019. Included were English-language studies reporting health conditions or mortality of parents of affected children compared with healthy controls. RESULTS:Of 12 181 screened publications, 26 met inclusion criteria. Eight studies reported on anxiety, 23 on depression, 1 on mortality, and 1 on cardiovascular disease. Parents of chronically ill children had greater anxiety (standardized mean difference 0.42; 95% CI 0.24-0.60; P < .001) and depression scores (standardized mean difference 0.35; 95% CI 0.26-0.45; P < .001) than parents of healthy children. Thirty-five percent of parents of affected children met cut-offs for clinical depression, compared with 19% in the control (relative risk 1.75; 95% CI 1.55-1.97). Fifty-seven percent of such parents met cut-offs for anxiety, compared with 38% in the control (relative risk 1.40; 95% CI 1.18-1.67). One study of mothers of children with congenital anomalies reported a greater mortality risk than a comparison (adjusted hazard ratio 1.22; 95% CI 1.15-1.29), and another reported that these mothers experience an increased risk of cardiovascular disease (adjusted hazard ratio 1.15; 95% CI 1.07-1.23). CONCLUSIONS:Parents of chronically ill children experience poorer mental health (more anxiety and depression), and mothers of those with congenital anomalies may have greater risk of cardiovascular disease and mortality than parents of unaffected children. Our findings suggest a need for targeted interventions to attenuate adverse parental caregiver health outcomes. PRIOR REGISTRATION:PROSPERO CRD42018094657 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=94657).
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来源期刊:PubMed 发表时间:2020-08-28 09:33:55
作者列表: Charous SJ,Westfall E
Abstract: BACKGROUND:Silicone stents are commonly employed to treat subglottic stenosis. A frequent complication is the tendency of stents to migrate. As such, various techniques to secure stents have been developed over the years, none of which have gained large popularity. We present a novel, low-cost, and easy-to-perform technique herein. OBJECTIVES:To describe a novel surgical technique to secure silicone stents and prevent migration for management of subglottic stenosis. MATERIALS AND METHODS:After standard excision and dilation of stenotic portions in the subglottic or trachea. A silicone stent is introduced in a standard fashion. To secure the stent, an 18-G needle loaded with braided suture is inserted through skin, trachea, and stent. Endoscopic visualization then permits the surgeon to grasp the suture with forceps. A separate transcutaneous puncture site is performed with an 18-G needle attached to a 10-cc syringe (plunger removed) and blue tip suction within the empty syringe, creating an airtight suctioning tool. The grasped suture is gently introduced into the eye of the needle and quickly travels into the 10-cc syringe with suction assist, leaving both extracorporeal ends of the suture to tie. RESULTS:This stitch has been employed on seven occasions on four patients. There have been no episodes of stent migration. A laboratory model found the 18-G needle and braided 3-0 suture performed optimally. CONCLUSIONS:We present a novel surgical technique to secure silicone stents in management subglottic or tracheal stenosis. LEVEL OF EVIDENCE:Level 4 Laryngoscope, 130:E346-E348, 2020.
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来源期刊:PubMed 发表时间:2020-08-28 09:14:22
作者列表: Harada S,Inatomi Y,Nakajima M,Yonehara T
Abstract: :A 51-year-old man with a past history of hypothyroidism suddenly became comatose after a few days of general malaise and headache. On admission to our hospital, his consciousness level was Japan Coma Scale III-200, but no focal neurological deficits were evident. Serum anti-thyroglobulin antibody was >4,000 IU/ml and anti-thyroid peroxidase antibody was 265 IU/ml. Well characterized neuronal antibodies were not fully examined in this case, but based on high titers of serum thyroid antibodies, methylprednisolone pulse therapy was started under diagnosis of suspected Hashimoto encephalopathy. Although methylprednisolone pulse therapy was effective, every time the dose of oral prednisolone was reduced, relapse attacks similar to the first episode occurred, a total of seven times. At each relapse, cerebrospinal fluid findings and MRI findings were normal. Plasmapheresis and azathioprine were added, until two years after onset, when further acute neurological attacks no longer occurred, but attention and memory impairments persisted. Relapse in Hashimoto encephalopathy is not rare; careful, long-term follow-up is needed.
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来源期刊:PubMed 发表时间:2020-08-28 09:04:37
作者列表: Fukuda Y,Matsuo A,Hirayama K,Sato K,Ozono K,Soejima K,Moritsuka T,Honda K,Hiu T,Kawahara I,Ono T,Haraguchi W,Ushijima R,Tsutsumi K
Abstract: :We report two rare cases of late-onset brain edema after craniotomy for clipping or coating of unruptured intracranial aneurysms, possibly due to an allergic reaction to topically applied fibrin glue or gelatin sponge used for arachnoid plasty to cover the opened sylvian cistern. Both patients were women in their 60s with an allergic predisposition and both followed a similar clinical course. A slight fever and headache persisted during the postoperative period. Five to six weeks after surgery without complications, MR images showed an extensive T2 prolongated region in the white matter around the operative field, indicative of vasogenic edema, with mass effect and meningeal enhancement around the sylvian fissure that had been covered with gelatin sponge and sprayed fibrin glue. Swelling of the cerebral cortex around the sylvian fissure subjected to arachnoid plasty was also observed. Blood tests showed the absence of an inflammatory reaction and cerebrospinal fluid examination showed lymphocytosis that was considered to be due to an aseptic meningeal reaction or meningitis. Clinical symptoms and imaging findings steadily improved with the administration of steroids and antiallergic agents. Delayed brain edema may occur around the arachnoid plasty area despite an uneventful chronic postoperative period, which could be due to an allergic reaction to locally administered fibrin glue or gelatin sponge. Thus, the application of arachnoid plasty using fibrin glue and gelatin sponge in patients with a predisposition to allergies needs to be carefully considered.
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来源期刊:PubMed 发表时间:2020-08-28 08:54:51
作者列表: Chugh S,Pietropaolo A,Montanari E,Sarica K,Somani BK
Abstract: PURPOSE OF REVIEW:To present the latest evidence related to the predictors of urinary tract infections (UTIs) and urosepsis after ureteroscopy (URS) for stone disease. RECENT FINDINGS:Our review suggests that almost half of all post-URS complications are related to infectious complications although reported rates of urosepsis were low. The use of antibiotic prophylaxis, treatment of pre-operative UTI, and low procedural time seem to reduce this risk. However, the risk is higher in patients with higher Charlson comorbidity index, elderly patients, female gender, long duration of pre-procedural indwelling ureteric stents and patients with a neurogenic bladder and with high BMI. Infectious complications following ureteroscopy can be a source of morbidity and potential mortality. Although majority of these are minor, efforts must be taken to minimise them especially in high-risk patients. This includes the use of prophylactic antibiotics, limiting stent dwell and procedural time, prompt identification and treatment of UTI and urosepsis, and careful planning in patients with large stone burden and multiple comorbidities.
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来源期刊:PubMed 发表时间:2020-08-28 08:20:26
作者列表: Bollino M,Geppert B,Lönnerfors C,Falconer H,Salehi S,Persson J
Abstract: OBJECTIVE:To achieve the full potential of sentinel lymph node (SLN) detection in endometrial cancer, both presumed low- and high-risk groups should be included. Perioperative resource use and complications should be minimized. Knowledge on distribution and common anatomical sites for metastatic SLNs may contribute to optimizing the concept while maintaining sensitivity. Proceeding from previous studies, simplified algorithms based on histology and lymphatic anatomy are proposed. METHODS:Data on mapping rates and locations of pelvic SLNs (metastatic and non-metastatic) from two previous prospective SLN studies in women with endometrial cancer were retrieved. Cervically injected indocyanine green was used as a tracer and an ipsilateral re-injection was performed in case of non-display of the upper and/or lower paracervical pathways. A systematic surgical algorithm was followed with clearly defined SLNs depicted on an anatomical chart. In high-risk endometrial cancer patients, removal of SLNs was followed by a pelvic and para-aortic lymphadenectomy. RESULTS:423 study records were analyzed. The bilateral mapping rates of the upper and lower paracervical pathways were 88.9% and 39.7%, respectively. 72% of all SLNs were typically positioned along the upper paracervical pathway (interiliac and/or proximal obturator fossa) and 71 of 75 (94.6%) of pelvic node positive women had at least one metastatic SLN at either of these positions. Women with grade 1-2 endometroid cancers (n=275) had no isolated metastases along the lower paracervical pathway compared with two women with high-risk histologies (n=148). CONCLUSION:SLNs along the upper paracervical pathway should be identified in all endometrial cancer histological subtypes; removal of nodes at defined typical positions along the upper paracervical pathway may replace a site-specific lymphadenectomy in case of non-mapping despite tracer re-injection. Detection of SLNs along the lower paracervical pathway can be restricted to high-risk histologies and a full pre-sacral lymphadenectomy should be performed in case of non-display.
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