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Summary Introduction Testicular germ cell tumors (GCTs) are the most common solid tumor among adolescent and young adult (AYA) males. AYA patients with GCTs most typically have non-seminoma compared with seminoma, and accordingly ...
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Summary Introduction Testicular germ cell tumors (GCTs) are the most common solid tumor among adolescent and young adult (AYA) males. AYA patients with GCTs most typically have non-seminoma compared with seminoma, and accordingly there are fewer data reported on the AYA experience with testicular seminoma. Objective To evaluate national trends in postoperative treatment and overall survival (OS) outcomes in testicular seminoma by age group, specifically comparing AYAs with older adults. Study design The National Cancer Data Base (NCDB) was queried for patients with testicular seminoma diagnosed between 2004 and 2012, who underwent orchiectomy followed by observation or adjuvant therapy (chemotherapy, radiation (RT), or both). Patients were grouped by age: AYA (15–39 years), adults between 40 and 55 years, and adults >55 years. Overall survival (OS) was presented using Kaplan–Meier curves and groups compared via a log-rank test. Univariate (UVA) and multivariate (MVA) analyses were performed using Cox proportional hazards regression models. Binary multiple logistic regression identified differences in variables by age category. Results Of the total 22,361 patients the majority were AYAs (12,880, 57.6%), followed by adults 40–55 years (8,022, 35.9%), and >55 years (1,459, 6.5%). Unadjusted 5-year OS was significantly better for AYAs versus adults 40–55 years and >55 years (98.0%, 96.4%, 87.7%; p ? p ? 55 years. AYA patients were also more commonly treated at centers with greater clinical volume. Additionally, AYA patients were less likely to present with metastatic disease. Accordingly, AYA patients were less likely to undergo retroperitoneal lymph node dissection (OR 0.81; p ?=?0.001) and were less often managed with adjuvant therapy including chemotherapy (OR 0.91; p ?=?0.027), RT (OR 0.93; p ?=?0.025), or both (OR 0.68; p ?=?0.020). Discussion AYA patients with testicular seminoma present with earlier stage disease and in the clinical Stage I setting are more often are managed with active surveillance following orchiectomy when compared with older adults in this population-based analysis. Among AYA patients, OS was modestly better when compared with adults 40–55 years and significantly better when compared with adults >55 years. Conclusion Our objective to describe the patterns of care and survival outcomes for AYA patients with testicular seminoma in the USA was met by reviewing this large national dataset. These results may inform future guidelines for management of AYA seminoma. Table Cox regression for predictors of overall survival (OS) for testicular seminoma Variable Univariate Multivariate HR 95% CI p HR 95% CI p Age, years 15–39 1 1 40–55 1.81 1.53–2.14 1.80 1.52–2.13 >55 6.13 5.06–7.44 4.26 3.47–5.23 Logistic regression for variables associated with adolescent young adults (AYAs) compared with older adults Variable Univariate Multivariate OR 95% CI p OR 95% CI p Facility case volume, tertiles Low 1 1 Middle 1.13 1.06–1.21 1.14 1.07–1.21 Upper 1.18 1.10–1.26 1.17 1.09–1.25 Stage I 1 1 II 0.82 0.75–0.89 0.86 0.78–0.95 0.002 III 0.69 0.61–0.78 0.72 0.64–0.83
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Coronavirus disease (COVID) serological tests are essential to determine the overall seroprevalence of a population and to facilitate exposure estimates within that population. We performed a head-to-head assessment of enzyme immu...
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Coronavirus disease (COVID) serological tests are essential to determine the overall seroprevalence of a population and to facilitate exposure estimates within that population. We performed a head-to-head assessment of enzyme immunoassays (EIAs) and point-of-care lateral flow assays (POCTs) to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Demographics, symptoms, comorbidities, treatment, and mortality of patients whose sera were used were also reviewed. Six EIAs (Abbott, Affinity, Bio-Rad, DiaSorin, Euroimmun, and Roche) and six POCTs (BTNX, Biolidics, Deep Blue, Genrui, Getein BioTech, and Innovita) were evaluated for the detection of SARS-CoV-2 antibodies in known COVID-19-infected individuals. ABSTRACT Coronavirus disease (COVID) serological tests are essential to determine the overall seroprevalence of a population and to facilitate exposure estimates within that population. We performed a head-to-head assessment of enzyme immunoassays (EIAs) and point-of-care lateral flow assays (POCTs) to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Demographics, symptoms, comorbidities, treatment, and mortality of patients whose sera were used were also reviewed. Six EIAs (Abbott, Affinity, Bio-Rad, DiaSorin, Euroimmun, and Roche) and six POCTs (BTNX, Biolidics, Deep Blue, Genrui, Getein BioTech, and Innovita) were evaluated for the detection of SARS-CoV-2 antibodies in known COVID-19-infected individuals. Sensitivity of EIAs ranged from 50 to 100%, with only four assays having overall sensitivities of >95% after 21?days after symptom onset. Notably, cross-reactivity with other respiratory viruses (parainfluenza virus [PIV-4] [ n ?=?5], human metapneumovirus [hMPV] [ n ?=?3], rhinovirus/enterovirus [ n ?=?1], CoV-229E [ n ?=?2], CoV-NL63 [ n ?=?2], and CoV-OC43 [ n ?=?2]) was observed; however, overall specificity of EIAs was good (92 to 100%; all but one assay had specificity above 95%). POCTs were 0 to 100% sensitive >21?days after onset, with specificity ranging from 96 to 100%. However, many POCTs had faint banding and were often difficult to interpret. Serology assays can detect SARS-CoV-2 antibodies as early as 10?days after symptom onset. Serology assays vary in their sensitivity based on the marker (IgA/IgM versus IgG versus total) and by manufacturer; however, overall only 4 EIAs and 4 POCTs had sensitivities of >95% >21?days after symptom onset. Cross-reactivity with other seasonal coronaviruses is of concern. Serology assays should not be used for the diagnosis of acute infection but rather in carefully designed serosurveys to facilitate understanding of seroprevalence in a population and to identify previous exposure to SARS-CoV-2.
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Purpose In intensity‐modulated proton therapy (IMPT), protons are used to deliver highly conformal dose distributions, targeting tumors, and sparing organs‐at‐risk. However, due to uncertainties in both patient setup and relati...
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Purpose In intensity‐modulated proton therapy (IMPT), protons are used to deliver highly conformal dose distributions, targeting tumors, and sparing organs‐at‐risk. However, due to uncertainties in both patient setup and relative stopping power (RSP) calculation, margins are added to the treatment volume during treatment planning, leading to higher doses to normal tissues. Cone‐beam computed tomography (CBCT) images are taken daily before treatment; however, the poor image quality of CBCT limits the use of these images for online dose calculation. In this work, we use a deep‐learning‐based method to predict RSP maps from daily CBCT images, allowing for online dose calculation in a step toward adaptive radiation therapy. Methods Twenty‐three head‐and‐neck cancer patients were simulated using a Siemens TwinBeam dual‐energy CT (DECT) scanner. Mixed‐energy scans (equivalent to a 120?kVp single‐energy CT scan) were converted to RSP maps for treatment planning. Cone‐beam computed tomography images were taken on the first day of treatment, and the planning RSP maps were registered to these images. A deep learning network based on a cycle‐GAN architecture, relying on a compound loss function designed for structural and contrast preservation, was then trained to create an RSP map from a CBCT image. Leave‐one‐out and holdout cross validations were used for evaluation, and mean absolute error (MAE), mean error (ME), peak signal‐to‐noise ratio (PSNR), and structural similarity (SSIM) were used to quantify the differences between the CT‐based and CBCT‐based RSP maps. The proposed method was compared to a deformable image registration‐based method which was taken as the ground truth and two other deep learning methods. For one patient who underwent resimulation, the new planning RSP maps and CBCT images were used for further evaluation and validation. Results The CBCT‐based RSP generation method was evaluated on 23 head‐and‐neck cancer patients. From leave‐one‐out testing, the MAE between CT‐based and CBCT‐based RSP was 0.06?±?0.01 and the ME was ?0.01?±?0.01. The proposed method statistically outperformed the comparison DL methods in terms of MAE and ME when compared to the planning CT. In terms of dose comparison, the mean gamma passing rate at 3%/3?mm was 94% when three‐dimensional (3D) gamma index was calculated per plan and 96% when gamma index was calculated per field. Conclusions The proposed method provides sufficiently accurate RSP map generation from CBCT images, allowing for evaluation of daily dose based on CBCT and possibly allowing for CBCT‐guided adaptive treatment planning for IMPT.
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Cardiovascular disease (CVD), the leading cause of death among US adults, is more prevalent in menopausal females comparedwith age-matched males. Vasomotor symptoms of menopause (VMS; hot flashes/flushes and night sweats) are comm...
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Cardiovascular disease (CVD), the leading cause of death among US adults, is more prevalent in menopausal females comparedwith age-matched males. Vasomotor symptoms of menopause (VMS; hot flashes/flushes and night sweats) are common amongfemales undergoing menopausal transition and have been associated with elevated blood pressure (BP) and increased CVDrisk. Autonomic dysregulation of BP has been posited as a contributing factor to the elevated CVD risk in menopausal femaleswith VMS. This review includes 1) a brief overview of the relationship between VMS and CVD, 2) mechanisms of hot flushes andtheir potential impact on short- and long-term BP regulation, and 3) how the disruption of autonomic function associated withVMS might provide a mechanistic pathway to CVD development. Finally, this review will highlight knowledge gaps and futuredirections toward better understanding of hot flush physiology and VMS contributions to CVD.
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The conventional methodology for gastrointestinal pathogen detection remains time-consuming, expensive, and of limited sensitivity. The objective of this study was to evaluate the performance of the BD Max enteric viral panel (Max...
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The conventional methodology for gastrointestinal pathogen detection remains time-consuming, expensive, and of limited sensitivity. The objective of this study was to evaluate the performance of the BD Max enteric viral panel (Max EVP) assay for identification of viral pathogens in stool specimens from individuals with symptoms of acute gastroenteritis, enteritis, or colitis. ABSTRACT The conventional methodology for gastrointestinal pathogen detection remains time-consuming, expensive, and of limited sensitivity. The objective of this study was to evaluate the performance of the BD Max enteric viral panel (Max EVP) assay for identification of viral pathogens in stool specimens from individuals with symptoms of acute gastroenteritis, enteritis, or colitis. Prospective and archival stool specimens from adult and pediatric patients with diarrhea were collected in Cary-Blair medium or unpreserved containers. The results for specimens tested by the Max EVP (on the BD Max platform) were compared to those obtained by the reference method (alternate PCR assays, followed by bidirectional sequencing). Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated. A total of 2,239 specimens were collected, with 2,148 being included for analysis. In this population, 39.6% of specimens were from outpatients, 42.1% were from patients <21?years old, and 49.7% were from females. Prevalence rates for prospective specimens were 7.3%, 4.5%, 3.5%, 2.4%, and 1.2% for norovirus, sapovirus, astrovirus, rotavirus, and adenovirus, respectively. PPA was 92.8%, 84.9%, 93.0%, 100%, and 95.6%, for norovirus, sapovirus, astrovirus, rotavirus, and adenovirus, respectively. NPA was ≥99.4% for all targets. In conjunction with the clinical presentation, laboratory findings, and epidemiological information, the Max EVP assay is effective for the differential diagnosis of enteric disease caused by norovirus, sapovirus, astrovirus, rotavirus, and adenovirus. This assay can be used individually for patients at high risk for a viral enteropathogen (e.g., in outbreak settings) or as an adjunct to other enteric bacterial panels.
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Regulatory authorities require safety and potency testing prior to the release of each production lot of acellular pertussis (aP)-containing vaccines. Currently, the murine histamine sensitization test (HIST) is used to evaluate t...
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Regulatory authorities require safety and potency testing prior to the release of each production lot of acellular pertussis (aP)-containing vaccines. Currently, the murine histamine sensitization test (HIST) is used to evaluate the presence of residual pertussis toxin in aP containing vaccines. However, the testing requires the use of a significant number of mice and results in unrelieved pain and distress. NICEATM, ICCVAM, their partners in the International Cooperation on Alternative Test Methods, and the International Working Group for Alternatives to HIST organized a workshop to discuss recent developments in alternative assays to the HIST, review data from an international collaborative study on non-animal alternative tests that might replace the HIST, and address the path toward global acceptance of this type of method. Currently, there are three potential alternative methods to HIST. Participants agreed that no single in?vitro method was sufficiently developed for harmonized validation studies at this time. It is unlikely that any single in?vitro method would be applicable to all aP vaccines without modification, due to differences between vaccines. Workshop participants recommended further optimization of cell-based assays under development. Participants agreed that the next international collaborative studies should commence in 2013 based on discussions during this workshop.
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BackgroundTherapeutic strategies for traumatic brain injury (TBI) in the last three decades have failed to show significant benefit in large scale studies. Given the multitude of pathological mechanisms involved in TBI, strategies...
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BackgroundTherapeutic strategies for traumatic brain injury (TBI) in the last three decades have failed to show significant benefit in large scale studies. Given the multitude of pathological mechanisms involved in TBI, strategies focusing on multimodality regimen have gained interest as promising future interventions. HypothesisWe hypothesized that combining noninvasive transcranial magnetic stimulation (TMS) with rehabilitative training in an environmental enrichment (EE) can facilitate post-TBI recovery in rats via cortical excitability and reorganization. MethodsWe subjected rats to controlled cortical impact, and then assigned them to one of four groups: 1. No treatments (TBI), 2. EE after injury (TBI?+?EE), 3. TMS for one week (TBI?+?TMS), and 4. TMS for one week combined with EE (TBI?+?TMS/EE). For TMS, a 10?Hz repetitive TMS protocol was used. ResultsAt 7 days, TBI?+?TMS and TBI?+?TMS/EE groups had significantly increased primary somatosensory cortex local field potential (LFP) compared to TBI and TBI?+?EE groups (P?0.05). Also, TBI?+?TMS/EE group had significantly improved performance on beam walk test compared to TBI group (P?0.005). At 6 weeks, there was significantly higher response in TBI?+?TMS/EE group compared to TBI?+?TMS for somatosensory cortex LFP (P?0.05), bicep motor evoked potentials (MEP) (P?0.05), challenge ladder test performance (P?0.01), and fMRI responses to tactile forepaw stimulation. ConclusionsWe demonstrate here for the first time the mechanism by which combined therapy using TMS and EE after TBI leads to functional improvement, possibly via cortical excitability and reorganization.
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Background. The recommended therapy for patients with chronic hepatitis C (CHC), genotype 1, who have cirrhosis and have failed prior therapy is 12 weeks of sofosbuvir (SOF), ledipasvir (LDV), and ribavirin (RBV). This recommendat...
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Background. The recommended therapy for patients with chronic hepatitis C (CHC), genotype 1, who have cirrhosis and have failed prior therapy is 12 weeks of sofosbuvir (SOF), ledipasvir (LDV), and ribavirin (RBV). This recommendation is based on expert opinion, and the efficacy of 12 weeks of SOF/LDV compared to SOF/LDV/RBV in this patient population has not yet been established. Methods. We conducted a systematic review and meta-analysis. Two investigators independently searched electronic databases and relevant conference proceedings for randomized controlled trials comparing rates of sustained virologic response 12 weeks after therapy (SVR12) when using 12 weeks of SOF/LDV versus 12 weeks of SOF/LDV/RBV in patients with CHC, genotype 1, who have cirrhosis and failed previous therapy. Results. Our search strategy yielded 596 studies of which four met criteria for inclusion. The pooled RR of not achieving SVR12 with SOF/LDV versus SOF/LDV/RBV was 1.21 (95% CI: 0.42–3.48). Adverse events were lower in the SOF/LDV compared to the SOF/LDV/RBV arms (pooled RR: 0.11, 95% CI: 0.04–0.29). Conclusions. Our findings suggest that 12 weeks of SOF/LDV cannot be considered noninferior to 12 weeks of SOF/LDV/RBV to achieve SVR12 in patients with CHC who have cirrhosis and failed prior therapy.
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Sports-related concussions (SRC) have been associated with emotional, cognitive, and affective symptoms including a negative impact on motor-based learning. However, no study has assessed the impact of SRC on cerebellar-based moto...
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Sports-related concussions (SRC) have been associated with emotional, cognitive, and affective symptoms including a negative impact on motor-based learning. However, no study has assessed the impact of SRC on cerebellar-based motor learning. Cerebellar-based motor learning was assessed in three different groups of athletes with different SRC history: athletes with no history of SRC: athletes in the acute stage of SRC (within two weeks of injury), and athletes in the chronic stage of SRC (over one year after injury). We used a visuomotor adaptation task (VAT) to measure both explicit strategy-based learning and implicit error-based learning. We found that there was no difference in cerebellar dependent motor learning in SRC and non-SRC athletes. These findings suggest that the cerebellum may be more resilient to damage from SRCs than the motor cortex.
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Introduction The ID NOW is FDA approved for the detection of SARS-CoV-2 in symptomatic individuals within the first 7?days of symptom onset for COVID-19 if tested within 1?h of specimen collection. Gap statement Clinical data on t...
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Introduction The ID NOW is FDA approved for the detection of SARS-CoV-2 in symptomatic individuals within the first 7?days of symptom onset for COVID-19 if tested within 1?h of specimen collection. Gap statement Clinical data on the performance of the ID NOW are limited, with many studies varying in their study design and/or having small sample size. Aim In this study we aimed to determine the clinical performance of the ID NOW compared to conventional RT-PCR testing. Methodology Adults with COVID-19 in the community or hospital were recruited into the study. Paired throat swabs were collected, with one throat swab transported immediately in an empty sterile tube to the laboratory for ID NOW testing, and the other transported in universal transport media and tested by an in-house SARS-CoV-2 RT-PCR assay targeting the E gene. Results In total, 133 individuals were included in the study; 129 samples were positive on either the ID NOW and/or RT-PCR. Assuming any positive result on either assay represents a true positive, positive per cent agreement (PPA) of the ID NOW compared to RT-PCR with 95?% confidence intervals was 89.1?% (82.0–94.1%) and 91.6?% (85.1–95.9%), respectively. When analysing individuals with symptom duration ≤7?days and who had the ID NOW performed within 1?h ( n =62), ID NOW PPA increased to 98.2?%. Conclusion Results from the ID NOW were reliable, especially when adhering to the manufacturer’s recommendations for testing.
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