...one of the concerns surrounding tocilizumab use in patients with COVID-19 is the risk of secondary infection, and although tocilizumab did not result in any deaths from secondary infection, the ...investigators did not collect data on non-fatal infections or other adverse events. ...important physiological data regarding hypoxaemia, such as longitudinal assessment of the partial pressure of arterial oxygen to the fraction of inspired oxygen, were not collected. ...given that patients with COVID-19 often have a prolonged hospital course, it is unclear whether a reduction in 28-day mortality will translate into longer-term mortality benefit, and we look forward to the preplanned analyses at 6 months.
Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels. Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but ...data are limited. This multicenter retrospective study describes the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation. Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications. Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death. The radiographically confirmed VTE rate was 4.8% (95% confidence interval CI, 2.9-7.3), and the overall thrombotic complication rate was 9.5% (95% CI, 6.8-12.8). The overall and major bleeding rates were 4.8% (95% CI, 2.9-7.3) and 2.3% (95% CI, 1.0-4.2), respectively. In the critically ill, radiographically confirmed VTE and major bleeding rates were 7.6% (95% CI, 3.9-13.3) and 5.6% (95% CI, 2.4-10.7), respectively. Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization (D-dimer >2500 ng/mL, adjusted odds ratio OR for thrombosis, 6.79 95% CI, 2.39-19.30; adjusted OR for bleeding, 3.56 95% CI, 1.01-12.66), critical illness, and death. Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450 × 109/L (adjusted OR, 3.56 95% CI, 1.27-9.97), C-reactive protein (CRP) >100 mg/L (adjusted OR, 2.71 95% CI, 1.26-5.86), and erythrocyte sedimentation rate (ESR) >40 mm/h (adjusted OR, 2.64 95% CI, 1.07-6.51). ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than in those without. DIC, clinically relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations. Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.
Despite increasing recognition of the importance of immune checkpoint inhibitor-associated AKI, data on this complication of immunotherapy are sparse.
We conducted a multicenter study of 138 patients ...with immune checkpoint inhibitor-associated AKI, defined as a ≥2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI.
Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor-associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6-37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis-causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis-causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor-associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI.
This multicenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.
Purpose - Cause-related marketing activities are increasingly becoming a meaningful part of corporate marketing plans. This paper aims to examine the relationship between the company, cause and ...customer, and how fit between these three groups influences consumer response via generating a positive attitude toward the company-cause alliance and purchase intent for the sponsored product.Design methodology approach - Two studies are carried out, first among students and second among consumers.Findings - Two studies (study 1=232 students, study 2=531 consumers) demonstrate that company-cause fit improves attitude toward the company-cause alliance and increases purchase intent. Additionally, this effect is enhanced under conditions of customer-company and customer-cause congruence, and the consumer's overall attitude toward the sponsoring company. Skepticism about the company's motivation for participating in a cause-related marketing initiative was not relevant to consumer purchase decisions.Research limitations implications - Results from these studies suggest that consumers may in fact make two different assessments of the sponsoring company in a cause-related marketing campaign. One assessment may be more cognitive where the consumer compares his or her own identity to that of the company: "Is this company like me? Are our identities alike?" The second assessment is more affective or emotional: "Do I like this company? Do I feel positively about this company?" The strength of the consumer sample suggests that when building a cause-related marketing program, marketing managers should select a cause that makes sense to the consumer to be a partner in the alliance, build a general positive feeling toward their brand, and limit any self-serving promotion of the cause-related marketing alliance to the target consumer population.Originality value - The paper provides useful information on the relationship between the company, cause and customer, and how the fit between these three groups influences consumer response.
J. Neurochem. (2012) 120, 1060–1071.
This study describes the effects of long‐chain fatty acids on inflammatory signaling in cultured astrocytes. Data show that the saturated fatty acid palmitic ...acid, as well as lauric acid and stearic acid, trigger the release of TNFα and IL‐6 from astrocytes. Unsaturated fatty acids were unable to induce cytokine release from cultured astrocytes. Furthermore, the effects of palmitic acid on cytokine release require Toll‐like receptor 4 rather than CD36 or Toll‐like receptor 2, and do not depend on palmitic acid metabolism to palmitoyl‐CoA. Inhibitor studies revealed that pharmacologic inhibition of p38 or p42/44 MAPK pathways prevents the pro‐inflammatory effects of palmitic acid, whereas JNK and PI3K inhibition does not affect cytokine release. Depletion of microglia from primary astrocyte cultures using the lysosomotropic agent l‐leucine methyl ester revealed that the ability of palmitic acid to trigger cytokine release is not dependent on the presence of microglia. Finally, data show that the essential ω‐3 fatty acid docosahexaenoic acid acts in a dose‐dependent manner to prevent the actions of palmitic acid on inflammatory signaling in astrocytes. Collectively, these data demonstrate the ability of saturated fatty acids to induce astrocyte inflammation in vitro. These data thus raise the possibility that high levels of circulating saturated fatty acids could cause reactive gliosis and brain inflammation in vivo, and could potentially participate in the reported adverse neurologic consequences of obesity and metabolic syndrome.
The good fat, the bad fat, and the brain Obesity and metabolic syndrome detrimentally affect the brain through unknown mechanisms. This paper demonstrates the ability of saturated fatty acids to trigger cytokine release from cultured astrocytes, and the ability of ω‐3 unsaturated fatty acids to block cytokine release. These data suggest that circulating saturated fatty acids could cause brain inflammation and thus participate in the adverse neurologic consequences of metabolic syndrome
Aims/hypothesis
Type 2 diabetes mellitus has been implicated as a risk factor for hearing loss, with possible mechanisms including microvascular disease, acoustic neuropathy or oxidative stress. A ...few small studies have examined the longitudinal association between type 2 diabetes and hearing loss, but larger studies are needed. Our objective was to examine whether type 2 diabetes (including diabetes duration) is associated with incident hearing loss in two prospective cohorts: Nurses’ Health Studies (NHS) I and II.
Methods
We conducted a longitudinal study of 139,909 women to examine the relationship between type 2 diabetes and the risk of self-reported incident hearing loss. A physician-diagnosis of diabetes was ascertained from biennial questionnaires. The primary outcome was hearing loss reported as moderate or worse in severity (categorised as a ‘moderate or severe’ hearing problem, or ‘moderate hearing trouble or deaf’) on questionnaires administered in 2012 in NHS I and 2009 or 2013 in NHS II. Cox proportional hazards regression was used to adjust for potential confounders.
Results
During >2.4 million person-years of follow-up, 664 cases of moderate or worse hearing loss were reported among those with type 2 diabetes and 10,022 cases among those without type 2 diabetes. Compared with women who did not have type 2 diabetes, those with type 2 diabetes were at higher risk for incident moderate or worse hearing loss (pooled multivariable-adjusted HR 1.16 95% CI 1.07, 1.27). Participants who had type 2 diabetes for ≥8 years had a higher risk of moderate or worse hearing loss compared with those without type 2 diabetes (pooled multivariable-adjusted HR 1.24 95% CI 1.10, 1.40).
Conclusions/interpretation
In this large longitudinal study, type 2 diabetes was associated with a modestly higher risk of moderate or worse hearing loss. Furthermore, longer duration diabetes was associated with a higher risk of moderate or worse hearing loss.
The specific family of device-to-device (D2D) communication underlying downlink cellular networks eliminates the reliance on base stations for its transmission by allowing direct transmission between ...two devices in each other's close proximity that reuse the cellular resource blocks for enhancing the attainable network capacity and spectrum efficiency. By considering downlink resource reuse and energy harvesting (EH), our goal is to maximize the sum-rate of the D2D links, without degrading the quality-of-service requirement of the cellular users. We formulated a sum-rate maximization problem of joint resource block and power allocation for the D2D links, which resulted in a non-convex problem that was then transformed into a more tractable convex optimization problem. Based on the results of our Lagrangian constrained optimization, we propose joint resource block and power allocation algorithms for the D2D links, when there is non-causal (offline) and causal (online) knowledge of the EH profiles at the D2D transmitters. The performance of the algorithms is quantified using simulation results for different network parameters settings, where our online algorithm performs close to the upper bound provided by our offline algorithm.
To investigate if the timing of initiation of invasive mechanical ventilation (IMV) for critically ill patients with COVID-19 is associated with mortality.
The data for this study were derived from a ...multicenter cohort study of critically ill adults with COVID-19 admitted to ICUs at 68 hospitals across the US from March 1 to July 1, 2020. We examined the association between early (ICU days 1-2) versus late (ICU days 3-7) initiation of IMV and time-to-death. Patients were followed until the first of hospital discharge, death, or 90 days. We adjusted for confounding using a multivariable Cox model.
Among the 1879 patients included in this analysis (1199 male 63.8%; median age, 63 IQR, 53-72 years), 1526 (81.2%) initiated IMV early and 353 (18.8%) initiated IMV late. A total of 644 of the 1526 patients (42.2%) in the early IMV group died, and 180 of the 353 (51.0%) in the late IMV group died (adjusted HR 0.77 95% CI, 0.65-0.93).
In critically ill adults with respiratory failure from COVID-19, early compared to late initiation of IMV is associated with reduced mortality.
Research under the topic of "Bottom of Pyramid" (BoP) has emphasized how marketing to the world's poor is a profitable endeavor for companies. It is argued that the poor don't only seek to fulfill ...their basic needs but also spend their discretionary income on aspirational goods. Motivated to investigate the validity of this claim, we study the meaning and nature of aspirational consumption of the poor. The data for this article come from a qualitative study conducted with 58 urban poor consumers in India. Findings show that in order to market profitably, companies should target the poor with products and services focused on strengthening the capabilities of the poor and therefore the capacity to aspire. The findings from this research shed light on the meaning of aspirational consumption as interpreted by the poor consumers and more importantly identifies the source of motivation and categories of aspiration.
PDF
