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OBJECTIVE: To synthesize the evidence for incidence, pathophysiology, etiology, and protocol-based management of hyperammonemia in lung transplant patients. BACKGROUND: Elevated ammonia levels are toxic to the brain, and hyperammonemia results in a potentially fatal complication for lung transplant recipients. The hallmark of this condition is ammonia production being way out of proportion to the degree of liver derangement. While there are many hypotheses, the cause remains obscure. METHODS: A retrospective review of patients with hyperammonemia following lung transplantation was done to understand the pathophysiology, various treatment modalities, and its impact on patient mortality and morbidity. Studies in the English literature were identified through an electronic database search from PubMed/MEDLINE, Ovid Embase, Google Scholar, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Web of Science, and ClinicalTrials.gov until June 2020. No restriction of dates were used, and the search was up until June 2020. DISCUSSION: Mortality among patients with hyperammonemia following lung transplantation is high. Multi-modal treatment approaches include avoiding nephrotoxic drugs, use of bowel decontamination, nitrogen scavengers, branched-chain amino acids, adjustment of immunosuppression, antibiotics like fluoroquinolones or azithromycin, and renal replacement therapy. However, there remains a scarcity of preoperative screening protocol for patients at risk of hyperammonemia as well evidence-based post-operative management guidelines. Intermittent hemodialysis, compared to continuous venovenous hemodialysis, provides better patient outcomes. CONCLUSION: Early detection of patients at risk by appropriate screening, along with maintaining a high degree of suspicion for hyperammonemia and multi-modal treatment approach, is the key to successful patient outcomes. Further prospective observational studies would facilitate development of protocol-based treatment of this potentially fatal condition.

Background: Early studies have reported various electrolyte abnormalities at admission in patients with severe coronavirus disease (COVID-19). 64 out of 112 patients admitted to our institution presented with hypermagnesemia at presentation. It is believed this may be important in the evaluation of severe SARS-CoV-2 infections. This study evaluated the outcomes of hypermagnesemia in patients with COVID-19. Methods: A retrospective chart review of patients admitted to the hospital with confirmed SARS-CoV-2 infection. A review of the medical literature regarding hypermagnesemia, magnesium levels in critical care illness and electrolyte abnormalities in COVID-19 patients was performed. Differences in demographic and clinical characteristics of patients with hypermagnesemia and normomagnesemia were evaluated using descriptive statistics. Other known variables of disease severity were analyzed. Results: 64 patients (57%) were identified with hypermagnesemia (≥ 2.5mg/dl). 30 of those patients were admitted to the ICU (47% p < 0.001). 21 patients required ventilator support (33% p < 0.0001). With age adjusted logistic regression analysis hypermagnesemia was associated with mortality (p = 0.037). Conclusion: Potential pathogenetic mechanisms were explored and discussed for hypermagnesemia and its relation to severe SARS-CoV-2. This study demonstrates that hypermagnesemia is a significant marker of disease severity and adverse outcome in SARS-CoV-2 infections. We recommend serum magnesium be added to the panel of tests routinely ordered in evaluation of severe SARS-CoV-2 infections. Funding Statement: The author(s) received no financial support for the research, authorship, and/or publication of this article. Declaration of Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethics Approval Statement: The Institutional Review Board of Kern Medical approved this study as minimal risk research.

Patients with B-lymphoid malignancies have been consistently identified as a population at high risk of severe COVID-19. Whether this is exclusively due to cancer-related deficits in humoral and cellular immunity, or whether risk of severe COVID-19 is increased by anticancer therapy, is uncertain. Using data derived from the COVID-19 and Cancer Consortium (CCC19), we show that patients treated for B-lymphoid malignancies have an increased risk of severe COVID-19 compared with control populations of patients with non–B-lymphoid malignancies. Among patients with B-lymphoid malignancies, those who received anticancer therapy within 12 months of COVID-19 diagnosis experienced increased COVID-19 severity compared with patients with non–recently treated B-lymphoid malignancies, after adjustment for cancer status and several other prognostic factors. Our findings suggest that patients recently treated for a B-lymphoid malignancy are at uniquely high risk for severe COVID-19.Significance:Our study suggests that recent therapy for a B-lymphoid malignancy is an independent risk factor for COVID-19 severity. These findings provide rationale to develop mitigation strategies targeted at the uniquely high-risk population of patients with recently treated B-lymphoid malignancies.This article is highlighted in the In This Issue feature, p. 171

Supplementary Figure from Patients Recently Treated for B-lymphoid Malignancies Show Increased Risk of Severe COVID-19

Table S1 show survival analysis for patients with metastatic OS. Table S2 shows LC3B+ puncta in paired specimens. Table S3 shows expression of HMBG1 and SQSTM1 in OS specimens. Table S4 shows the association between biomarkers and histologic treatment response. Table S5 shows pHSP27 expression in OS specimens. Figure S1 shows representative staining of SQSTM1 and HMGB1 in OS. Figures S2-S3 show relapse-free survival based upon biomarker expression. Figure S4 shows survival analysis by LC3B+ amongst patients with poor response to chemotherapy. Figure S5 shows representative staining for pHSP27 in OS.

Why celecoxib exerts chemopreventive activity in only some familial adenomatous polyposis (FAP) patients remains poorly understood. We conducted a phase II clinical study to identify potential predictive biomarkers for celecoxib chemopreventive activity in FAP. Twenty-seven patients with FAP completed a 6-month oral course of 400 mg of celecoxib twice a day; they underwent colonoscopies before and after celecoxib treatment to assess colorectal polyp tumor burden and to obtain normal and polyp colorectal biopsies to measure celecoxib, 13-S-hydroxyoctadecadienoic acid (13-HODE), 15-HETE, 12-HETE, and LTB4 levels by LC/MS-MS. Celecoxib levels in sera from those patients were also measured before treatment and after 2, 4, and 6 months of treatment. Nineteen of the 27 patients experienced a response to celecoxib, with a ≥ 28% reduction of colonic polyp burden on the basis of a reproducible quantitative assessment of colonoscopy results. Celecoxib levels were significantly lower in polyp tissues than in normal colorectal tissues. Celecoxib levels in sera and normal colorectal tissues were correlated in patients who experienced a response to celecoxib but not in those who did not. Among the measured lipoxygenase products, only 13-HODE levels were significantly lower in polyp tissues than in normal tissues. Our findings demonstrate the differential bioavailability of celecoxib between normal and polyp tissues and its potential effects on clinical response in patients with FAP.Prevention Relevance:This study evaluated potential predictive biomarkers for celecoxib chemopreventive activity in patients with FAP. Our findings demonstrated the differential bioavailability of celecoxib between normal and polyp tissues and its potential effects on clinical chemopreventive response in patients with FAP.See related Spotlight, p. 205

Supplementary Data from Celecoxib Colorectal Bioavailability and Chemopreventive Response in Patients with Familial Adenomatous Polyposis

Summary of the relative prognostic and mutational impact of tumor location in metastatic colorectal cancer. Sub-caption: Relative prevalence of mutations at each site was compared to the median prevalence across all sites and used to calculate relative font size for each gene name. Hazard ratios displayed in the figure utilize rectal location as the reference category.

Comparison of overall survival based on primary tumor side using a multivariate proportional hazards model controlling for co-variates that differed based on tumor location.

Sensitivity analysis comparing mutation prevalence estimates by site of biopsy of tissue used for next generation sequencing panel in metastatic colorectal cancer.

Supplemental legend

Sensitivity analysis demonstrating optimal left vs right cut-point to maximize prognostic differences based on side in metastatic colorectal cancer. Sub-caption: Numbers in figure represent the hazard ratio followed by the 95% confidence interval within square brackets. The hazard ratio estimate occurs at the location used to divide left from right in each sensitivity analysis. For example, if the division between right and left occurs between the hepatic flexure and transverse colon, the hazard ratio estimate will be placed on the graph half way between the hepatic flexure and transverse colon (ie. 1.66).

Purpose: Colorectal cancers are classified as right/left-sided based on whether they occur before/after the splenic flexure, with established differences in molecular subtypes and outcomes. However, it is unclear if this division is optimal and whether precise tumor location provides further information.Experimental Design: In 1,876 patients with colorectal cancer, we compared mutation prevalence and overall survival (OS) according to side and location. Consensus molecular subtype (CMS) was compared in a separate cohort of 608 patients.Results: Mutation prevalence differed by side and location for TP53, KRAS, BRAFV600, PIK3CA, SMAD4, CTNNB1, GNAS, and PTEN. Within left- and right-sided tumors, there remained substantial variations in mutation rates. For example, within right-sided tumors, RAS mutations decreased from 70% for cecal, to 43% for hepatic flexure location (P = 0.0001), while BRAFV600 mutations increased from 10% to 22% between the same locations (P < 0.0001). Within left-sided tumors, the sigmoid and rectal region had more TP53 mutations (P = 0.027), less PIK3CA (P = 0.0009), BRAF (P = 0.0033), or CTNNB1 mutations (P < 0.0001), and less MSI (P < 0.0001) than other left-sided locations. Despite this, a left/right division preceding the transverse colon maximized prognostic differences by side and transverse colon tumors had K-modes mutation clustering that appeared more left than right sided. CMS profiles showed a decline in CMS1 and CMS3 and rise in CMS2 prevalence moving distally.Conclusions: Current right/left classifications may not fully recapitulate regional variations in tumor biology. Specifically, the sigmoid-rectal region appears unique and the transverse colon is distinct from other right-sided locations. Clin Cancer Res; 24(5); 1062–72. ©2017 AACR.See related commentary by Dienstmann, p. 989

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused the coronavirus diseases 2019 (COVID-19) pandemic, continues to spread rapidly worldwide and is associated with high rates of mortality among older adults, those with comorbidities, and those in poor physiological states. This paper aimed to systematically identify the impact of frailty on overall mortality among older adults with COVID-19. We conducted a systematic review of the literature indexed in 4 databases. A random-effects model with inverse variance-weighted meta-analysis using the odds ratio was used to study the association of frailty levels with clinical outcomes among older adults with COVID-19. Heterogeneity was measured using the I2 statistic and Egger's test. We identified 22 studies that met our inclusion criteria, including 924,520 total patients. Overall, frailty among older adults was associated with high rates of COVID-19-related mortality compared with non-frail older adults (OR [odds ratio]:5.76; 95% confidence interval [95% CI]: 3.85–8.61, I2: 40.5%). Our results show that physical limitations, such as those associated with frailty among older adults, are associated with higher rates of COVID-19-related mortality.

Healthy sleep behaviors are a cornerstone to mental wellness and sports performance among athletes. Disturbances in sleep timing, quantity, and quality may impact an athlete's performance in the short and long term. Sleep disturbances may contribute to overall health, risk of injury, and career duration. This review discusses the prevalence of sleep disorders among athletes and its impact on mental health problems. A strategic approach is provided and highlights the importance of proactively identifying sleep disorders versus waiting for the problem to express itself. A summary of available therapeutic interventions to improve sleep in the athlete population is presented.

Summary Background Prevention, control, and treatment of respiratory tract cancers are important steps towards achieving target 3.4 of the UN Sustainable Development Goals (SDGs)—a one-third reduction in premature mortality due to non-communicable diseases by 2030. We aimed to provide global, regional, and national estimates of the burden of tracheal, bronchus, and lung cancer and larynx cancer and their attributable risks from 1990 to 2019. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 methodology, we evaluated the incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs) of respiratory tract cancers (ie, tracheal, bronchus, and lung cancer and larynx cancer). Deaths from tracheal, bronchus, and lung cancer and larynx cancer attributable to each risk factor were estimated on the basis of risk exposure, relative risks, and the theoretical minimum risk exposure level input from 204 countries and territories, stratified by sex and Socio-demographic Index (SDI). Trends were estimated from 1990 to 2019, with an emphasis on the 2010–19 period. Findings Globally, there were 2·26 million (95% uncertainty interval 2·07 to 2·45) new cases of tracheal, bronchus, and lung cancer, and 2·04 million (1·88 to 2·19) deaths and 45·9 million (42·3 to 49·3) DALYs due to tracheal, bronchus, and lung cancer in 2019. There were 209 000 (194 000 to 225 000) new cases of larynx cancer, and 123 000 (115 000 to 133 000) deaths and 3·26 million (3·03 to 3·51) DALYs due to larynx cancer globally in 2019. From 2010 to 2019, the number of new tracheal, bronchus, and lung cancer cases increased by 23·3% (12·9 to 33·6) globally and the number of larynx cancer cases increased by 24·7% (16·0 to 34·1) globally. Global age-standardised incidence rates of tracheal, bronchus, and lung cancer decreased by 7·4% (−16·8 to 1·6) and age-standardised incidence rates of larynx cancer decreased by 3·0% (−10·5 to 5·0) in males over the past decade; however, during the same period, age-standardised incidence rates in females increased by 0·9% (−8·2 to 10·2) for tracheal, bronchus, and lung cancer and decreased by 0·5% (−8·4 to 8·1) for larynx cancer. Furthermore, although age-standardised incidence and death rates declined in both sexes combined from 2010 to 2019 at the global level for tracheal, bronchus, lung and larynx cancers, some locations had rising rates, particularly those on the lower end of the SDI range. Smoking contributed to an estimated 64·2% (61·9–66·4) of all deaths from tracheal, bronchus, and lung cancer and 63·4% (56·3–69·3) of all deaths from larynx cancer in 2019. For males and for both sexes combined, smoking was the leading specific risk factor for age-standardised deaths from tracheal, bronchus, and lung cancer per 100 000 in all SDI quintiles and GBD regions in 2019. However, among females, household air pollution from solid fuels was the leading specific risk factor in the low SDI quintile and in three GBD regions (central, eastern, and western sub-Saharan Africa) in 2019. Interpretation The numbers of incident cases and deaths from tracheal, bronchus, and lung cancer and larynx cancer increased globally during the past decade. Even more concerning, age-standardised incidence and death rates due to tracheal, bronchus, lung cancer and larynx cancer increased in some populations—namely, in the lower SDI quintiles and among females. Preventive measures such as smoking control interventions, air quality management programmes focused on major air pollution sources, and widespread access to clean energy should be prioritised in these settings. Funding Bill & Melinda Gates Foundation.

PURPOSE South Asian Association for Regional Cooperation (SAARC) nations are a group of eight countries with low to medium Human Development Index values. They lack trained human resources in primary health care to achieve the WHO-stated goal of Universal Health Coverage. An unregulated service sector of informal health care providers (IPs) has been serving these underserved communities. The aim is to summarize the role of IPs in primary cancer care, compare quality with formal providers, quantify distribution in urban and rural settings, and present the socioeconomic milieu that sustains their existence. METHODS A narrative review of the published literature in English from January 2000 to December 2021 was performed using MeSH Terms Informal Health Care Provider/Informal Provider and Primary Health Care across databases such as Medline (PubMed), Google Scholar, and Cochrane database of systematic reviews, as well as World Bank, Center for Global Development, American Economic Review, Journal Storage, and Web of Science. In addition, citation lists from the primary articles, gray literature in English, and policy blogs were included. We present a descriptive overview of our findings as applicable to SAARC. RESULTS IPs across the rural landscape often comprise more than 75% of primary caregivers. They provide accessible and affordable, but often substandard quality of care. However, their network would be suitable for prompt cancer referrals. Care delivery and accountability correlate with prevalent standards of formal health care. CONCLUSION Acknowledgment and upskilling of IPs could be a cost-effective bridge toward universal health coverage and early cancer diagnosis in SAARC nations, whereas state capacity for training formal health care providers is ramped up simultaneously. This must be achieved without compromising investment in the critical resource of qualified doctors and allied health professionals who form the core of the rural public primary health care system.

Background The clinical utility of a blood-based biomarker in squamous cell carcinoma of the anus (SCCA) is unknown. We analyzed carcinoembryonic antigen (CEA), a commonly employed assay for patients with colorectal adenocarcinoma, as a serum biomarker for patients with biopsy-proven SCCA. Materials and methods Medical records from 219 patients with biopsy-proven SCCA at the University of Texas MD Anderson Cancer Center were reviewed under an IRB-approved protocol from 2013 to 2020 to assess for correlations between CEA levels and corresponding clinical and pathologic characteristics. Results The mean CEA among subgroups by clinical status at the time of presentation to our institution was highest among those patients with metastatic SCCA to visceral organs (M-V, 20.7 ng/mL), however this finding was not statistically significant by ANOVA (p = .74). By clinical subgroup, the percentage of patients with an abnormally elevated CEA was highest in those patients with metastatic disease to lymph nodes (M-L, 41.2%) followed by recurrent/unresectable SCCA (36.8%), and metastatic SCCA to visceral organs (M-V, 35.2%), and was statistically significant between groups (Fisher's exact test p = .02). Using RECIST criteria for tumor progression and disease response, the mean change in CEA for patients with progression was an increase in 19 ng/mL, compared to a change of -7.3 ng/mL in those with disease response (p = .004). We likewise assessed whether CEA levels were associated with survival outcomes for all patients with metastatic SCCA, and found no correlation between CEA and likelihood for survival in a ROC analysis (multivariate, age-adjusted analysis for CEA cutoff of 8, HR = 1.01, 95% CI 0.52-1.96). Conclusions Despite interesting patterns of abnormally high CEA in SCCA patients with advanced disease, and correlation of increased CEA with disease progression (and conversely decreased CEA with disease response), CEA is not associated with survival outcomes in SCCA, and is not a clinically relevant biomarker in this disease.

Increasing number of breast cancer survivors in the USA have led to greater focus on the long-term health outcomes and surveillance care among these women. However limited evidence exists of use of surveillance mammography among breast cancer survivors and how it varies across racial/ethnic groups. We conducted a systematic review of the literature to explore disparities in use of surveillance mammogram among women breast cancer survivors by searching for relevant studies published between 2000 and 2020 from Medline (Ovid), PubMed (National Library of Medicine), and PsycINFO (Ovid) bibliographic databases. Two authors independently screened titles, abstracts, and full texts of all articles that reported surveillance mammography use across racial/ethnic groups. Data on study design, screening eligibility, sample size, operational definition, and/or measure of the use of a surveillance mammogram among breast cancer survivors and the association between race/ethnicity and use of a surveillance mammogram were summarized in the evidence tables. We identified 1544 records from the three databases, and 30 studies examined the use of surveillance mammograms among breast cancer survivors across race/ethnic groups. Of these, 21 provided adjusted estimates of racial/ethnic disparities in use of surveillance mammograms, and 15 of these reported statistically significant disparities. In summary, most studies reported that non-white women (mainly Blacks and Hispanics) were less likely to receive a timely surveillance mammogram compared to White. This study extends the evidence of racial/ethnic disparities beyond completion of initial treatment by finding similar disparities in receipt of surveillance mammograms among breast cancer survivors. Our findings identify a need to improve efforts to increase post-treatment use of surveillance mammography among racial/ethnic minority women to reduce these gaps and improve overall clinical and quality of life outcomes.

Purpose We examined if childhood socioeconomic status (SES) was related to adult leucocyte telomere length (TL) using the data of 361 African American (AA) participants from the GENE-FORECAST Study. We also assessed the mediating role of behavioral and psychosocial factors in the association between childhood SES and adult TL. Methods Childhood SES was assessed individually by using participant’s mother’s education and occupation, father’s education and occupation, parental home ownership, and family structure. TL was assessed using the quantitative polymerase chain reaction method. Information on potential confounders and mediators were collected. The associations of childhood SES with TL were assessed using multivariable linear regression models. We used path analysis to quantify and test the share of these associations that was statistically explained by each of the mediators (participant’s educational attainment, smoking status, physical activity, dietary habit, perceived stress, and depressive symptoms). Results Mother’s education was associated with longer average TL (β: 0.021; 95% CI: 0.001, 0.04, p=0.038) in confounder adjusted models. Once mediators were introduced in the model, the estimates were reduced and remained marginally significant (β: 0.017; 95% CI: −0.003, 0.038, p=0.061). According to path model, approximately 19% of the effect of mother’s education on TL (β: 0.004; 95% CI: −0.001, 0.01, p < 0.10) was mediated through participant’s own education level. No significant mediation effect was observed for any other mediators. Conclusions These data provide evidence that participant’s mother’s education was positively linked to adult TL in AA population. Participant’s own educational level partially explained this association.

Since December 2019, the global burden of the COVID-19 pandemic has increased rapidly and has impacted nearly every country in the world, affecting those who are elderly or with underlying comorbidities or immunocompromised states. Aim of this systematic review is to summarize lung histopathological characteristics of COVID-19, not only for diagnostic purpose but also to evaluate changes that can reflect pathophysiological pathways that can inform clinicians of useful treatment strategies. We identified following histopathological changes among our patients:: hyaline membranes; endothelial cells/ interstitial cells involvement; alveolar cells, type I pneumocytes/ type II pneumocytes involvement; interstitial and/ or alveolar edema; evidence of hemorrhage, of inflammatory cells, evidence of microthrombi; evidence of fibrin deposition and of viral infection in the tissue samples. The scenario with proliferative cell desquamation is typical of Acute Respiratory Distress Syndrome (ARDS) that can be classified as diffuse alveolar damage (DAD) and not DAD-ARDS. The proposed pathological mechanism concerns the role of both innate and adaptive components of the immune system. COVID-19 lethal cases present themselves as a heterogeneous disease, characterized by the different simultaneous presence of different histological findings, which reflect histological phases with corresponding different pathological pathways (epithelial, vascular and fibrotic changes), in the same patient. Supplementary Information The online version contains supplementary material available at 10.1186/s13027-021-00369-0.

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 Supplementary Information The online version contains supplementary material available at 10.1007/s11606-021-06715-7.

Purpose The US Preventive Services Task Force recommends lung cancer screening with Low-Dose Computed Tomography (LDCT) in high-risk individuals. Our objective was to identify demographic, health, and financial factors associated with screening uptake, with a focus on urban-rural differences. Methods We analyzed data from the 2018 and 2019 Behavioral Risk Factor Surveillance System and its optional Lung Cancer Screening Module to examine factors associated with screening uptake among 20 states that administered the optional module. We compared differences in factors associated with uptake overall and by geographical regions and conducted multivariable logistic mixed-effects regression, accounting for participant clustering by state to assess the impact of these factors on uptake. Findings Overall 1,268 participants underwent LDCT screening with no significant differences observed between rural (16.3%) and urban residents (17.7%, p = 0.67). In multivariable models, rural residents did not differ significantly in their LDCT screening uptake (OR = 0.85; 95% CI: 0.67-1.09, p = 0.20), but uptake was significantly higher for participants with underlying chronic respiratory conditions, veterans, those with higher pack-year history, and those with poor/fair general health and prior history of cancer. Uptake declined with age, higher education level, concerns about paying for medical care, and lack of primary care. Conclusions Modifiable targets can be leveraged to increase LDCT screening. Based on significant predictors of screening uptake, clinicians should prioritize interventions that effectively consider smoking history as well as those identified as effective in veterans' health settings. Additionally, reducing structural barriers to care related to insurance and income will be key to reducing disparities.

Susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the risk of mortality among people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLWHA) is largely unknown. PLWHA are unique due to their altered immune system from their history of chronic HIV infection and their use of antiretroviral therapy, some of which have been used experimentally to treat coronavirus disease 2019 (COVID-19). Therefore, we conducted a systematic review and meta-analysis to assess the epidemiology of SARS-COV-2/HIV coinfection and estimate associated mortality from COVID-19 (Prospero Registration ID: CRD42020187980). PubMed, SCOPUS, OVID and Cochrane Library databases, and medRxiv preprint repositories were searched from January 1, 2020, to December 12, 2020. Data were extracted from studies reporting COVID-19 attack and mortality rates in PLWHA compared to their HIV-negative counterparts. Pooled attack and mortality risks were quantified using random-effects models. We identified 22 studies that included 20,982,498 participants across North America, Africa, Europe, and Asia. The median age was 56 years, and 50% were male. HIV-positive persons had a significantly higher risk of SARS-CoV-2 infection [risk ratio (RR) 1.24, 95% CI 1.05–1.46)] and mortality from COVID-19 (RR 1.78, 95% CI 1.21–2.60) than HIV-negative individuals. The beneficial effects of tenofovir and protease-inhibitors in reducing the risk of SARS-CoV-2 infection and death from COVID-19 in PLWHA remain inconclusive. HIV remains a significant risk factor for acquiring SARS-CoV-2 infection and is associated with a higher risk of mortality from COVID-19. In support of the current Centers for Disease Control and Prevention (CDC) guidelines, persons with HIV need priority consideration for the SARS-CoV-2 vaccine.

BACKGROUND: Data suggest that the effects of coronavirus disease 2019 (COVID-19) differ among U.S. racial/ethnic groups. PURPOSE: 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. (PROSPERO: CRD42020187078). DATA SOURCES: 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. STUDY SELECTION: Observational studies examining SARS-CoV-2 infections, hospitalizations, or deaths by race/ethnicity in U.S. settings. DATA EXTRACTION: Single-reviewer abstraction confirmed by a second reviewer; independent dual-reviewer assessment of quality and strength of evidence. DATA SYNTHESIS: 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). LIMITATIONS: 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. CONCLUSION: 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. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development.

Background Cancer patients are particularly vulnerable to COVID-19, partially owing to their compromised immune systems and curbed or cut cancer healthcare services caused by the pandemic. As a result, cancer caregivers may have to shoulder triple crises: the COVID-19 pandemic, pronounced healthcare needs from the patient, and elevated need for care from within. While technology-based health interventions have the potential to address unique challenges cancer caregivers face amid COVID-19, limited insights are available. Thus, to bridge this gap, we aim to identify technology-based interventions designed for cancer caregivers and report the characteristics and effects of these interventions concerning the distinctive challenges cancer caregivers face amid COVID-19. Additionally, this paper will present practical insights into the diverse intervention approaches that can assist in the delivery of digital health solutions for cancer caregivers amid and beyond COVID-19.Methods A systematic review of the literature will be conducted in PubMed, PsycINFO, CINAHL, and Scopus in September, 2020. Articles that center on technology-based interventions for cancer caregivers will be included in the review. The search strategy was developed in consultation with an academic librarian who is experienced in systematic review studies. Titles, abstracts, and full-text articles will be screened against eligibility criteria developed a priori. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses procedures will be followed for the reporting process.Results NA—This is a protocol study.Conclusions COVID-19 has uprooted cancer care as we know it. Due to barriers introduced by the COVID-19 pandemic, such as medical resources rationing, cancer caregivers often have to step up to address patients' healthcare needs and wants. This, in turn, will exert substantial stress on informal caregivers, above and beyond COVID-19-related burdens the general public shoulders on a daily basis. Findings of this study can shed light on evidence-based and practical solutions cancer caregivers can utilize to mitigate the unique challenges they face amid COVID-19. Furthermore, results of this study will also offer valuable insights for researchers who aim to develop interventions for cancer caregivers in the context of COVID-19. In addition, we also expect to be able to identify areas for improvement that need to be addressed in order for health experts to more adequately help cancer caregivers weather the storm of global health crises like COVID-19 and beyond.Study Protocol Registration: PROSPERO CRD42020196301

BackgroundCpG Island Methylator Phenotype (CIMP) is an epigenetic phenotype in CRC characterized by hypermethylation of CpG islands in promoter regions of tumor suppressor genes, leading to their transcriptional silencing and loss of function. While the prevalence of CRC differs across geographical regions, no studies have compared prevalence of CIMP-High phenotype across regions. The purpose of this project was to compare the prevalence of CIMP across geographical regions after adjusting for variations in methodologies to measure CIMP in a meta-analysis.MethodsWe searched PubMed, Medline, and Embase for articles focusing on CIMP published from 2000 to 2018. Two reviewers independently identified 111 articles to be included in final meta-analysis. We classified methods used to quantify CIMP into 4 categories: a) Classical (MINT marker) Panel group b) Weisenberg-Ogino (W-O) group c) Human Methylation Arrays group and d) Miscellaneous group. We compared the prevalence of CIMP across geographical regions after correcting for methodological variations using meta-regression techniques.ResultsThe pooled prevalence of CIMP-High across all studies was 22% (95% confidence interval:21–24%; I2 = 94.75%). Pooled prevalence of CIMP-H across Asia, Australia, Europe, North America and South America was 22, 21, 21, 27 and 25%, respectively. Meta-regression analysis identified no significant differences in the prevalence of CIMP-H across geographical regions after correction for methodological variations. In exploratory analysis, we observed variations in CIMP-H prevalence across countries.ConclusionAlthough no differences were found for CIMP-H prevalence across countries, further studies are needed to compare the influence of demographic, lifestyle and environmental factors in relation to the prevalence of CIMP across geographical regions.

Background The evidence has shown that SARS CoV-2 infected patients with comorbidities are more likely to have severe disease sequel and mortality. In SARS-CoV-2 infected cancer patients risks associated with other underlying comorbidities might vary from those in non-cancer SARS CoV-2 infected patients. The relative impact of different underlying health conditions among patients with cancer and SARS CoV-2 infection remains yet to be explored. This systematic review aims to explore the prevalence of comorbidities among cancer patients with SARS CoV-2 infection and their impact on mortality. Methods Online databases PubMed, Embase, Scopus and Web of science were searched for articles published between 9th July 2019 to July 8th 2020.Studies of cancer patients (>18 years) with diagnosis of SARS CoV-2 infection, published in English were included. A random-effects modelling for the meta-analyses was applied to assess the pooled prevalence and odds ratio for mortality due to comorbidities in SARS CoV-2 infected cancer patients. Results Total 31studies with 4086 SARS-CoV-2 infectedcancer patientsmet the inclusion criteria. Most prevalent co-morbidities in cancer patients with SARS CoV-2 infection were hypertension [42.3% (95%CI:37.5- 47.0)], diabetes [17.8% (95% CI: 15.3-20.4)] and cardiovascular diseases [16.7% (95%CI:12.9-20.4)].The risk of mortality (pOR) was significantly higher in individuals with hypertension[1.6(95%CI 1.24-2.00)], cardiovascular diseases [2.2 (95%CI 1.49- 3.27)], chronic obstructive pulmonary diseases [1.4(95% CI 1.05-2.00)] and diabetes [1.35(95%CI 1.06-1.73)]. Conclusion Our results indicates that the mortality in SARS-CoV-2 infected cancer patients is affected by preexisting non-cancer comorbidities. By identifying the comorbidities predictive for mortality, clinicians can better stratify the risk of cancer patients presenting with SARS-COV-2, on their initial contact with health services. .

Background: African Americans (AA) are disproportionally affected by cardiovascular disease as compared to other racial-ethnic groups. Exposure to adverse socioeconomic conditions may partially explain disparities in risk factors and prevalence and cardiovascular diseases for AA. We aim to study the impact of poverty status on metabolic syndrome (MetS) and its components among African Americans. Methods: We used data from the National Health and Nutritional Examination Survey (NHANES) cycles 2001-2006. We defined MetS using the Joint Scientific Definition as the presence of any 3/5 components: elevated blood pressure (BP), elevated triglycerides (TGL), lower high-density lipoprotein cholesterol (LDL), elevated fasting plasma glucose (FPG), and elevated waist circumference (WC). Poverty to income ratio (PIR) was categorized as below poverty ( 3) groups. We used multivariable survey-weighted logistic regression models to study the impact of poverty status of prevalence of MetS and its components among AA men and women. Results: Overall, the average aggregate prevalence of MetS among AA sample was 22% in our study with prevalence being 25% for women and 18% among men (p 3) (OR = 1.57, 95%CI = 1.00 - 2.46, p = 0.05) with no association observed among men (OR (PIR = 1) = 0.70, 95%CI = 0.43 - 1.19, p = 0.13). Further, similar associations were observed for individual components among women including: elevated waist circumference (OR = 2.04, 95%CI = 1.37, 3.01, p 3). No association of poverty status with MetS and its components were observed among AA men. Clustering of factors identified key groups that define MetS among women included WC. Conclusion: African American women living below poverty have a higher likelihood of having MetS and 4 of 5 individual components. Clustering of these factors differ across men and women and should be further explored as tools for clinical management. Main Points: 1) Metabolic syndrome remains an important public health burden among African Americans and shows disparities by socioeconomic status; 2) Women living below poverty were more likely to have MetS and associated components as compared to women living above poverty; 3) Clustering of components gave us snapshot of factors that should be considered to develop gender specific targeted health interventions for MetS among African Americans.

PURPOSE Cervical cancer screening is not well implemented in many low- and middle-income countries (LMICs). Mobile health (mHealth) refers to utilization of mobile technologies in health promotion and disease management. We aimed to qualitatively synthesize published articles reporting the impact of mHealth on cervical cancer screening–related health behaviors. METHODS Three reviewers independently reviewed articles with the following criteria: the exposure or intervention of interest was mHealth, including messages or educational information sent via mobile telephone or e-mail; the comparison was people not using mHealth technology to receive screening-related information, and studies comparing multiple different mHealth interventional strategies were also eligible; the primary outcome was cervical cancer screening uptake, and secondary outcomes included awareness, intention, and knowledge of screening; appropriate research designs included randomized controlled trials and quasi-experimental or observational research; and the study was conducted in an LMIC. RESULTS Of the 8 selected studies, 5 treated mobile telephone or message reminders as the exposure or intervention, and 3 compared the effects of different messages on screening uptake. The outcomes were diverse, including screening uptake (n = 4); health beliefs regarding the Papanicolaou (Pap) test (n = 1); knowledge of, attitude toward, and adherence to colpocytologic examination (n = 1); interest in receiving messages about Pap test results or appointment (n = 1); and return for Pap test reports (n = 1). CONCLUSION Overall, our systematic review suggests that mobile technologies, particularly telephone reminders or messages, lead to increased Pap test uptake; additional work is needed to unequivocally verify whether mhealth interventions can improve knowledge regarding cervical cancer. Our study will inform mHealth-based interventions for cervical cancer screening promotion in LMICs.