•This is the first systematic review and meta-analysis to assess CBI use in RM-NPC.•EBV-specific CTL and DC second/subsequent line monotherapy have good safety profiles.•CBI combination ...therapy/first-line monotherapy may be evaluated with more studies.
Recurrent/Metastatic Nasopharyngeal Carcinoma (RM-NPC) remains difficult to treat and contributes to considerable mortality. The first-line treatment for RM-NPC is Gemcitabine and Cisplatin and second-line treatment options differ. The endemic variant of NPC is associated with Epstein-Barr Virus (EBV). Therefore, Cell-based Immunotherapy (CBI) targeting EBV-specific RM-NPC may be effective.
We systematically searched PubMed, Embase and the Cochrane Library for randomised or observational studies investigating the efficacy and safety of CBI in the treatment of RM-NPC. We performed all meta-analyses using the random-effects model. Studies were further stratified by endemicity, nature of disease and drug type to investigate for potential between-study heterogeneity and additional pre-specified tests were employed to assess for publication bias.
We screened 1,671 studies and included 13 studies with 403 participants in the systematic review, of which nine studies were eligible for meta-analysis. The use of CBI monotherapy as second or subsequent line treatment for EBV-positive RM-NPC revealed an ORR of 10 % (95 %CI = 3 %–29 %), median PFS of 2.37 months (95 %CI = 1.23–3.51) and median OS of 10.16 months (95 %CI = 0.67–19.65). For EBV-specific Cytotoxic T-Lymphocyte monotherapy, the pooled PD rate was 54 % (95 %CI = 9 %–93 %), SD rate was 22 % (95 %CI = 2 %–75 %) and incidence rate of any grade adverse events was 45 %. For Dendritic Cell monotherapy, a PD rate of 80 % (95 % CI = 29 %–98 %), SD rate of 11 % (95 % CI = 0 %–82 %) and incidence rate of any grade adverse events of 29 % was achieved.
CBI monotherapy demonstrates some activity in pre-treated RM-NPC. More trials are needed to better understand how to integrate CBI into RM-NPC care.
Freshwater habitats are of high conservation value and provide a wide range of ecosystem services. Effective management requires regular monitoring. However, conventional methods based on direct ...observation or specimen collection are so invasive, expensive and labour-intensive that frequent monitoring is uncommon. Here, we test whether the evaluation of environmental DNA (eDNA) from water based on a simple protocol can be used for assessing biodiversity. We use universal metazoan primers for characterizing water eDNA across horizontal and vertical spatial dimensions in two reservoirs with known species diversity for two key taxa. eDNA obtained directly from 42 samples × 15 ml water (total = 630 ml) per reservoir yielded DNA signatures for more than 500 metazoan species, of which 105 could be identified to species/genus based on DNA barcodes. We show that eDNA can be used to assign each water sample to its reservoir of origin, and that eDNA outperforms conventional survey methods in single-sample richness comparisons, while revealing evidence for hundreds of unknown species that are undetected by conventional bioassessment methods. eDNA also confirms the presence of a recently discovered invasive snail species and provides evidence for the continued survival of a rare native species of goby not sighted in that habitat since 2007. eDNA thus promises to be a useful addition to the bioassessment toolbox for freshwater systems.
Introduction: In patients with acute ischemic stroke, the location and volume of an irreversible infarct core determine prognosis and treatment. We aimed to determine if automated CT perfusion (CTP) ...is non-inferior to diffusion-weighted imaging (DWI) or fluid-attenuated inversion recovery (FLAIR) in predicting the acute infarct core. Methods: In this systematic review and meta-analysis, we searched MEDLINE and EMBASE from 1960 to December 2020. Five outcome measures were examined: volumetric difference, volumetric correlation, sensitivity and specificity at the patient level, Dice coefficient, and sensitivity and specificity at the voxel level. A random-effects meta-analysis was performed for volumetric difference and correlation. Results: From 3,986 studies retrieved, 48 studies met our inclusion criteria with 46 studies on anterior circulation, one study on posterior circulation, and one study on lacunar infarct strokes. In anterior circulation stroke, there were no significant mean volumetric differences between CTP and acute DWI (cerebral blood flow CBF 0.52 mL, 95% CI −0.07, 1.11, I 2 0.0%; relative CBF rCBF 3.01 mL, 95% CI −0.46, 6.48, I 2 82.6%; relative cerebral blood volume rCBV −12.84 mL, 95% CI −38.56, 12.88, I 2 96.2%) and between CTP and delayed DWI or FLAIR (rCBF −1.29 mL, 95% CI −6.49, 3.92, I 2 91.8%; rCBV −5.80 mL, 95% CI −16.20, 4.60, I 2 84.2%). Mean correlation between CTP and acute DWI was 0.90 (95% CI 0.80, 0.95, I 2 60.0%) for rCBF and 0.84 (95% CI 0.58, 0.94, I 2 93.5%) for rCBV. Mean correlation between CTP and delayed DWI or FLAIR was 0.74 (95% CI 0.57, 0.85, I 2 94.6%) for rCBF and 0.90 (95% CI 0.69, 0.97, I 2 93.1%) for rCBV. Sensitivity and specificity at the patient level were reported by three studies and Dice coefficient by four studies. Statistical analysis could not be performed for sensitivity and specificity at the voxel level. Limited evidence was available for posterior circulation or lacunar infarct strokes. Conclusion: Due to significant heterogeneity and insufficient high-quality studies reporting each outcome, there is insufficient evidence to reliably determine the accuracy of CTP prediction of the infarct core compared to DWI or FLAIR.
Macrophage activation syndrome is a rare disorder leading to unregulated immune activity manifesting with nonspecific constitutional symptoms, laboratory abnormalities, and multiorgan involvement. We ...report the case of a patient who presented with acute hepatitis secondary to macrophage activation syndrome diagnosed by liver biopsy and successfully treated with intravenous immune globulin, anakinra, and rituximab.
A 42-year-old Laotian woman with adult-onset immunodeficiency with anti-interferon gamma antibodies presented with a fever, headache, generalized myalgia, dark urine, and reduced appetite in the setting of family members at home with similar symptoms. Her laboratory workup was notable for evidence of acute hepatitis without acute liver failure. After an unrevealing comprehensive infectious and noninvasive rheumatologic workup was completed, a liver biopsy was performed ultimately revealing the diagnosis of macrophage activation syndrome. She was successfully treated with intravenous immune globulin, anakinra, and rituximab.
This case highlights the importance of maintaining macrophage activation syndrome on the differential of a patient with acute hepatitis of unknown etiology in the correct clinical context and the value of a liver biopsy in making a diagnosis when noninvasive testing is unrevealing.
Dental fluorosis is caused by ingestion of excessive fluoride during tooth development resulting in hypomineralization of the enamel and can present as white or brown intrinsic lesions. This case ...report describes a combination of minimally invasive techniques: microabrasion, bleaching, and resin infiltration to address brown enamel fluorosis present on the maxillary anterior teeth of a young patient. Before resin infiltration, air microabrasion was targeted at subsurface lesions located on the maxillary central and lateral incisors, and chairside bleaching was done with 37% hydrogen peroxide (Opalescence). After which, hypoplastic lesions on the buccal surfaces were etched before being treated with two sessions of resin infiltration (ICON and DMG). Following treatment, satisfactory esthetic outcomes were achieved. Accurate diagnosis, depth of lesions, and understanding the effectiveness and limitations of each technique are essential to select the appropriate type of treatment to obtain the best esthetic outcome. In conclusion, the conservative management of varying severity of dental fluorosis may require the appropriate use of combination treatment modalities, such as microabrasion, bleaching and resin infiltration, when clinically indicated, to address the treatment needs and achieve a desired outcome.
Iron deficiency anemia (IDA) is a major health burden among women in Asia. Key issues in IDA management in Asia are under-diagnosis and under-treatment. The lack of Asia-specific guidelines, and ...suboptimal utilization of treatment compounds the management of IDA. To address these gaps, a panel of 12 experts in obstetrics, gynecology, and hematology from six regions in Asia convened to review current practices and clinical evidence and provide practical guidance on IDA diagnosis and management in Asian women. The Delphi approach was used to obtain objective opinions and attain consensus on statements pertaining to awareness, diagnosis, and management of IDA. In total, 79 statements attained consensus and are summarized to provide guidance on raising awareness of IDA and approaches for improved diagnosis and treatment of IDA among women in various settings: pregnancy, postpartum, heavy menstrual bleeding, gynecologic cancers, and perioperative care. This clinician-led consensus integrates appropriate recommendations based on clinical evidence and best practices and is intended to guide decision making in the management of iron deficiency/IDA in women. The expert panel raises a call for timely diagnosis and utilization of appropriate treatment, including use of high-dose intravenous iron, stringent blood management, and interdisciplinary collaboration, for optimization of IDA management among women in Asia.
Decompensated cirrhosis is a common precipitant for hospitalization, and there is limited information concerning factors that influence the delivery of quality care in cirrhotic inpatients. We sought ...to determine the relation between physician specialty and inpatient quality care for decompensated cirrhosis.
We reviewed 247 hospital admissions for decompensated cirrhosis, managed by hospitalists or intensivists, between 2009 and 2013. The primary outcome was quality care delivery, defined as adherence to all evidence-based specialty society practice guidelines pertaining to each specific complication of cirrhosis. Secondary outcomes included new complications, length-of-stay, and in-hospital death.
Overall, 147 admissions (59.5%) received quality care. Quality care was given more commonly by intensivists, compared with hospitalists (71.7% vs. 53.1%, P = .006), and specifically for gastrointestinal bleeding (72% vs. 45.8%, P = .03) and hepatic encephalopathy (100% vs. 63%, P = .005). Involvement of gastroenterology consultation was also more common in admissions in which quality care was administered (68.7% vs. 54.0%, P = .023). Timely diagnostic paracentesis was associated with reduced new complications in admissions for refractory ascites (9.5% vs. 46.6%, P = .02), and reduced length-of-stay in admissions for spontaneous bacterial peritonitis (5 days vs. 13 days, P = .02).
Adherence to quality indicators for decompensated cirrhosis is suboptimal among hospitalized patients. Although quality care adherence appears to be higher among cirrhotic patients managed by intensivists than by hospitalists, opportunities for improvement exist in both groups. Rational and cost-effective strategies should be sought to achieve this end.
WD40-repeat protein 62 (WDR62) is a spindle pole protein required for normal cell division and neuroprogenitor differentiation during brain development. Microcephaly-associated mutations in WDR62 ...lead to mitotic mislocalization, highlighting a crucial requirement for precise WDR62 spatiotemporal distribution, although the regulatory mechanisms are unknown. Here, we demonstrate that the WD40-repeat region of WDR62 is required for microtubule association, whereas the disordered C-terminal region regulates cell-cycle-dependent compartmentalization. In agreement with a functional requirement for the WDR62–JNK1 complex during neurogenesis, WDR62 specifically recruits JNK1 (also known as MAPK8), but not JNK2 (also known as MAPK9), to the spindle pole. However, JNK-mediated phosphorylation of WDR62 T1053 negatively regulated microtubule association, and loss of JNK signaling resulted in constitutive WDR62 localization to microtubules irrespective of cell cycle stage. In contrast, we identified that Aurora A kinase (AURKA) and WDR62 were in complex and that AURKA-mediated phosphorylation was required for the spindle localization of WDR62 during mitosis. Our studies highlight complex regulation of WDR62 localization, with opposing roles for JNK and AURKA in determining its spindle association.
The key to understanding the COVID-19 correlates of protection is assessing vaccine-induced immunity in different demographic groups. Young people are at a lower risk of COVID-19 mortality, females ...are at a lower risk than males, and females often generate stronger immune responses to vaccination.
We studied immune responses to two doses of BNT162b2 Pfizer COVID-19 vaccine in an adolescent cohort (n = 34, ages 12-16), an age group previously shown to elicit significantly greater immune responses to the same vaccine than young adults. Adolescents were studied with the aim of comparing their response to BNT162b2 to that of adults; and to assess the impacts of other factors such as sex, ongoing SARS-CoV-2 infection in schools, and prior exposure to endemic coronaviruses that circulate at high levels in young people. At the same time, we were able to evaluate immune responses to the co-administered live attenuated influenza vaccine. Blood samples from 34 adolescents taken before and after vaccination with COVID-19 and influenza vaccines were assayed for SARS-CoV-2-specific IgG and neutralising antibodies and cellular immunity specific for SARS-CoV-2 and endemic betacoronaviruses. The IgG targeting influenza lineages contained in the influenza vaccine were also assessed.
Robust neutralising responses were identified in previously infected adolescents after one dose, and two doses were required in infection-naïve adolescents. As previously demonstrated, total IgG responses to SARS-CoV-2 Spike were significantly higher among vaccinated adolescents than among adults (aged 32-52) who received the BNT162b2 vaccine (comparing infection-naïve, 49,696 vs. 33,339; p = 0.03; comparing SARS-CoV-2 previously infected, 743,691 vs. 269,985; p <0.0001) by the MSD v-plex assay. There was no evidence of a stronger vaccine-induced immunity in females compared than in males.
These findings may result from the introduction of novel mRNA vaccination platforms, generating patterns of immunity divergent from established trends and providing new insights into what might be protective following COVID-19 vaccination.
This study examined the effects of computer anxiety and computer knowledge on self-efficacy and life satisfaction within the retired older adult computer users. Participants consisted of older adults ...(aged 53–88) recruited from computer clubs in Florida. Path analysis revealed that computer use helped to increase self-efficacy and lower computer anxiety thereby increasing overall life satisfaction. Gender differences in computer use were also examined. Males and females used computers at about the same rate but females reported more anxiety and less computer knowledge. Furthermore, more males reported using the Internet. Of those who reported using the Internet, more females reported browsing for health- and hobby-related information. The implications of these findings were discussed.
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