Cachexia is a multisystem syndrome characterized by weight loss, anorexia, loss of muscle mass, systemic inflammation, insulin resistance, and functional decline. Management of cachexia involves ...addressing multiple underlying biological mechanisms. Previous review on pharmacological management of cancer cachexia identified progestins and corticosteroids as effective agents for treatment of cachexia. However, to date no consensus exists on a single effective or standard treatment for management of cachexia. The aim of this systematic review is to determine the effectiveness of pharmacological treatments used to manage cachexia among adult cancer patients.
We performed literature searches of PubMed (NLM), Embase (Ovid), and Medline(Ovid) to identify clinical trials focused on pharmacological management of cancer cachexia among adult cancer patients from 2004 to 2018. Three reviewers screened a random selection of abstracts to measure for interrater reliability. After this step, each screener screened two-thirds of all abstracts and 177 studies were identified for full text review. The primary outcome was impact of pharmacological management on change in either weight or lean body mass in cancer patients.
We identified 19 articles (representing 20 RCTs) that focused on pharmacological management of cancer cachexia. Agents showing promising results included Anamorelin and Enobosarm. Anamorelin at 50 or 100 mg per day for 12 weeks showed a consistent benefit across all studies and resulted in significant improvement in weight as compared to baseline among cancer patients. Enobosarm at 1 and 3 mg per day was also effective in improving lean body mass and QOL symptoms among advancer stage cancer patients. Finally, use of combination agents provide evidence for targeting multiple pathways underlying cachexia mechanism to achieve maximum benefit. No agents showed functional improvement in cancer patients.
Anamorelin as a single agent shows promising results in improving cachexia related weight loss among cancer patients. Further research on combination therapies may be helpful to address critical gaps in cachexia management.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Data suggest that the effects of coronavirus disease 2019 (COVID-19) differ among U.S. racial/ethnic groups.
To evaluate racial/ethnic disparities in severe acute respiratory syndrome coronavirus 2 ...(SARS-CoV-2) infection rates and COVID-19 outcomes, factors contributing to disparities, and interventions to reduce them.
English-language articles in MEDLINE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, searched from inception through 31 August 2020. Gray literature sources were searched through 2 November 2020.
Observational studies examining SARS-CoV-2 infections, hospitalizations, or deaths by race/ethnicity in U.S. settings.
Single-reviewer abstraction confirmed by a second reviewer; independent dual-reviewer assessment of quality and strength of evidence.
37 mostly fair-quality cohort and cross-sectional studies, 15 mostly good-quality ecological studies, and data from the Centers for Disease Control and Prevention and APM Research Lab were included. African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection, hospitalization, and COVID-19-related mortality compared with non-Hispanic White populations, but not higher case-fatality rates (mostly reported as in-hospital mortality) (moderate- to high-strength evidence). Asian populations experience similar outcomes to non-Hispanic White populations (low-strength evidence). Outcomes for other racial/ethnic groups have been insufficiently studied. Health care access and exposure factors may underlie the observed disparities more than susceptibility due to comorbid conditions (low-strength evidence).
Selection bias, missing race/ethnicity data, and incomplete outcome assessments in cohort and cross-sectional studies must be considered. In addition, adjustment for key demographic covariates was lacking in ecological studies.
African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection and COVID-19-related mortality but similar rates of case fatality. Differences in health care access and exposure risk may be driving higher infection and mortality rates.
Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development. (PROSPERO: CRD42020187078).
BACKGROUND: CpG island methylator phenotype (CIMP) tumors, comprising 20% of colorectal cancers, are associated with female sex, age, right-sided location, and BRAF mutations. However, other factors ...potentially associated with CIMP have not been robustly examined. This meta-analysis provides a comprehensive assessment of the clinical, pathologic, and molecular characteristics that define CIMP tumors. METHODS: We conducted a comprehensive search of the literature from January 1999 through April 2018 and identified 122 articles, on which comprehensive data abstraction was performed on the clinical, pathologic, molecular, and mutational characteristics of CIMP subgroups, classified based on the extent of DNA methylation of tumor suppressor genes assessed using a variety of laboratory methods. Associations of CIMP with outcome parameters were estimated using pooled odds ratio or standardized mean differences using random-effects model. RESULTS: We confirmed prior associations including female sex, older age, right-sided tumor location, poor differentiation, and microsatellite instability. In addition to the recognized association with BRAF mutations, CIMP was also associated with PIK3CA mutations and lack of mutations in KRAS and TP53. Evidence of an activated immune response was seen with high rates of tumor-infiltrating lymphocytes (but not peritumoral lymphocytes), Crohn-like infiltrates, and infiltration with Fusobacterium nucleatum bacteria. Additionally, CIMP tumors were associated with advance T-stage and presence of perineural and lymphovascular invasion. CONCLUSION: The meta-analysis highlights key features distinguishing CIMP in colorectal cancer, including molecular characteristics of an active immune response. Improved understanding of this unique molecular subtype of colorectal cancer may provide insights into prevention and treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Data suggest that there were disparities in H1N1 vaccine uptake, and these may inform COVID-19 vaccination efforts. We conducted a systematic review to evaluate disparities in H1N1 vaccine ...uptake, factors contributing to disparities, and interventions to reduce them.
Methods
We searched English-language articles in MEDLINE ALL, PsycINFO, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from database inception through May 8, 2020. Observational studies examining H1N1 vaccine uptake by race/ethnicity, socioeconomic status, rurality, and disability status in US settings were included. Two reviewers independently assessed study eligibility. Single-reviewer data abstraction was confirmed by a second reviewer. We conducted independent dual quality assessment, and collective strength of evidence assessment.
Results
We included 21 studies. African American/Black, Latino, and low-socioeconomic status participants had disproportionately lower H1N1 vaccination rates (
low- to moderate-strength evidence
). However, Latinos were more likely than Whites to
intend
to be vaccinated, and African American/Blacks and participants with lower-socioeconomic status were just as likely to intend to be vaccinated as their White and higher-socioeconomic status counterparts (
low-strength evidence
). Vaccine uptake for other groups has been insufficiently studied. Factors potentially contributing to disparities in vaccine uptake included barriers to vaccine access, inadequate information, and concerns about vaccine safety and efficacy. Studies were largely cross-sectional. Many of the studies are a decade old and were conducted in the context of a different pandemic. The categorization of racial and ethnic groups was not consistent across studies and not all groups were well-studied.
Discussion
Efforts to avoid disparities in COVID-19 vaccination uptake should prioritize vaccine accessibility and convenience in African American/Black, Latino, and low-SES communities; engage trusted stakeholders to share vaccine information; and address concerns about vaccine safety and efficacy.
Primary Funding Source
Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development.
Protocol Registration
PROSPERO CRD42020187078
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
AT-rich interactive domain 1A (
) is commonly mutated in colorectal cancer, frequently resulting in truncation and loss of protein expression. ARID1A recruits MSH2 for mismatch repair during DNA ...replication. ARID1A deficiency promotes hypermutability and immune activation in preclinical models, but its role in patients with colorectal cancer is being explored.
The DNA sequencing and gene expression profiling of patients with colorectal cancer were extracted from The Cancer Genome Atlas and MD Anderson Cancer Center databases, with validation utilizing external databases, and correlation between ARID1A and immunologic features. IHC for T-cell markers was performed on a separate cohort of patients.
Twenty-eight of 417 patients with microsatellite stable (MSS) colorectal cancer (6.7%) had
mutation. Among 58 genes most commonly mutated in colorectal cancer,
mutation had the highest increase with frameshift mutation rates in MSS cases (8-fold,
< 0.001). In MSS,
mutation was enriched in immune subtype (CMS1) and had a strong correlation with IFNγ expression (Δ
score +1.91,
< 0.001). Compared with
wild-type, statistically significant higher expression for key checkpoint genes (e.g., PD-L1, CTLA4, and PDCD1) and gene sets (e.g., antigen presentation, cytotoxic T-cell function, and immune checkpoints) was observed in mutant cases. This was validated by unsupervised differential expression of genes related to immune response and further confirmed by higher infiltration of T cells in IHC of tumors with
mutation (
= 0.01).
The immunogenicity of
-mutant cases is likely due to an increased level of neoantigens resulting from increased tumor mutational burden and frameshift mutations. Tumors with
mutation may be more susceptible to immune therapy-based treatment strategies and should be recognized as a unique molecular subgroup in future immune therapy trials.
COVID-19 infections are seen across all age groups, but they have shown to have a predisposition for the elderly and those with underlying comorbidities. Patients with severe COVID-19 infections and ...comorbidities are more prone to respiratory distress syndrome, mechanical ventilator use, and ultimately succumb to these complications. Little evidence exists of the prevalence of underlying lung comorbidities among COVID-19 patients and associated mortality. We performed a systematic review of the literature including PubMed (Medline), Embase (Ovid), Google Scholar, and Cochrane Library. The last date for our search was April 29, 2020. We included all original research articles on COVID-19 and calculated prevalence of chronic lung disease patients among COVID-19 patients using random effects model. Further, we assessed for mortality rates among COVID-19 patients associated with these lung comorbidities. The authors identified 29 articles that reported prevalence of chronic lung conditions among COVID-19 patients. Among those, 26 were from China and 3 from the United States. The pooled prevalence of lung comorbidities including asthma, chronic obstructive pulmonary disease (COPD), and lung cancer was 3% (95% confidence interval CI = 0%-14%), 2.2% (95% CI = 0.02%-0.03%), and 2.1% (95% CI = 0.00%-0.21%), respectively. Mortality rates associated with these comorbidities was 30% (41/137) for COPD and 19% (7/37) for lung cancer respectively. No mortality rates were reported for patients with asthma. This study offers latest evidence of prevalence of chronic lung conditions among patients with COVID-19. Asthma, followed by COPD and lung cancer, was the most common lung comorbidity associated with COVID-19, while the higher mortality rate was found in COPD. Future studies are needed to assess other lung comorbidities and associated mortality among patients diagnosed with COVID-19.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Many efficacious interventions exist that could be implemented by screening sites.•Cessation estimates are lower than the general population.•Multi-modality interventions appear to be most ...efficacious.•Cessation persists at 12-months in two intervention categories.
Current guidelines recommend delivery of smoking cessation interventions with lung cancer screening (LCS). Unfortunately, there are limited data to guide clinicians and policy-makers in choosing cessation interventions in this setting. Several trials are underway to fill this evidence gap, but results are not expected for several years.
We conducted a systematic review and meta-analysis of current literature on the efficacy of smoking cessation interventions among populations eligible for LCS. We searched PubMed, Medline, and PsycINFO for randomized controlled trials of smoking cessation interventions published from 2010–2017. Trials were eligible for inclusion if they sampled individuals likely to be eligible for LCS based on age and smoking history, had sample sizes >100, follow-up of 6- or 12-months, and were based in North America, Western Europe, Australia, or New Zealand.
Three investigators independently screened 3,813 abstracts and identified 332 for full-text review. Of these, 85 trials were included and grouped into categories based on the primary intervention: electronic/web-based, in-person counseling, pharmacotherapy, and telephone counseling. At 6-month follow-up, electronic/web-based (odds ratio OR 1.14, 95% CI 1.03–1.25), in-person counseling (OR 1.46, 95% CI 1.25–1.70), and pharmacotherapy (OR 1.53, 95% CI 1.33–1.77) interventions significantly increased the odds of abstinence. Telephone counseling increased the odds but did not reach statistical significance (OR 1.21, 95% CI 0.98–1.50). At 12-months, in-person counseling (OR 1.28 95% CI 1.10–1.50) and pharmacotherapy (OR 1.46, 95% CI 1.17–1.84) remained efficacious, although the decrement in efficacy was of similar magnitude across all intervention categories.
Several categories of cessation interventions are promising for implementation in the LCS setting.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ObjectiveAspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) are preventive against cardiovascular disease (CVD) and several cancer types, but long-term use has been associated ...with significant health risks, resulting in conflicting recommendations on NSAID use for prevention of CVD and cancer. Previous research indicates that aspirin use increases with age and CVD risk factors and that a large percentage of the US population regularly use analgesics, including NSAIDs, but there has not been a recent, in-depth assessment of NSAID use prevalence, changes in use over time or predictors of NSAID use in the USA.MethodsWe used the cross-sectional, National Health And Nutrition Examination Survey (NHANES) from 1988 to 1994 and three continuous cycles (1999–2004) to assess regular NSAID use prevalence, changes over time and predictors of regular NSAID use.ResultsOverall, regular NSAID use increased over time and varied by demographic features. Participants over 60 years of age, women, participants with high body mass index, increased waist circumference or heart disease were significantly more likely to be regular NSAID users. By contrast, non-Hispanic African American and Mexican American participants were significantly less likely to regularly use NSAIDs.ConclusionsThis study uses a nationally representative data set (NHANES) to provide an exploration of regular NSAID use patterns over time, highlighting several demographic, lifestyle and clinical conditions associated with regular NSAID use. Understanding who is likely to regularly use NSAIDs enables more targeted messaging both for increasing the preventive benefits and for limiting the toxicities associated with regular use of NSAIDs.
Mucinous colorectal cancer (CRC) is a unique histologic subtype that remains poorly defined. We aimed to better characterize this subtype of CRC and identified an increased frequency of mutations in ...GNAS, ERBB2, BRAF, KRAS, and SMAD4 with the mucinous histologic subtype, in addition to increased consensus molecular subtype (CMS) 1 (microsatellite instability immune) and decreased CMS2 (canonical) prevalence. Adverse clinical features included microsatellite instability and synchronous metastatic disease at presentation. Even after controlling for clinical and mutation differences, the mucinous histologic subtype was associated with worse overall survival.
The mucinous histologic subtype accounts for 5% to 20% of colorectal cancer (CRC) cases but remains poorly characterized. The present study characterized the baseline characteristics, mutational profile, and clinical outcomes of patients diagnosed with mucinous CRC.
We identified 1877 patients with metastatic CRC with available histologic findings and molecular profiling and summarized the baseline clinical and pathologic characteristics and overall survival (OS) stratified by the histologic type. The data from separate cohorts with consensus molecular subtype (CMS) and CpG island methylator information were also summarized.
The mucinous histologic type was found in 277 of the 1877 patients (14.8%) and was associated with an increased prevalence of microsatellite instability (P < .001) and a right-sided primary (P < .001). An increased frequency of CMS1 (microsatellite instability immune) and lower rates of CMS2 (canonical) were identified, with mucinous compared with nonmucinous adenocarcinoma (P < .0001). Mutations in SMAD4 (P < .001), GNAS (P < .001), ERBB2 (P = .02), BRAF (P < .001), and KRAS (P < .001) occurred at greater frequencies in the mucinous CRC cases, and TP53 (P < .001), APC (P < .001), and NRAS mutations (P = .03) were less common. Univariate (hazard ratio HR, 1.38; 95% confidence interval CI, 1.17-1.63; P < .001) and multivariate analysis (HR, 1.36; 95% CI, 1.12-1.64; P = .002) demonstrated that the mucinous histologic type is associated with worse OS. The features associated with the mucinous histologic subtype were independent predictors for shorter OS, including BRAF (HR, 1.74; 95% CI, 1.35-2.25; P < .001) and KRAS (HR, 1.42; 95% CI, 1.22-1.65; P < .001) mutations, right-sided location (HR, 1.20; 95% CI, 1.04-1.39; P = .01), and synchronous metastases (HR, 2.92; 95% CI, 2.49-3.42; P < .001).
Compared with nonmucinous adenocarcinoma, the mucinous histologic type is associated with a worse prognosis, even when controlling for known prognostic features. This unique biologic behavior should be considered in the treatment and prognostic assessment of patients with CRC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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