Following Mitochondrial Footprints through a Long Mucosal Path to Lung Cancer

BACKGROUND:Mitochondrial DNA (mtDNA) mutations are reported in different tumors. However, there is no information on the temporal development of the mtDNA mutations/content alteration and their extent in normal and abnormal mucosa continuously exposed to tobacco smoke in lung cancer patients. METHODOLOGY:We examined the pattern of mtDNA alteration (mtDNA mutation and content index) in 25 airway mucosal biopsies, corresponding tumors and normal lymph nodes obtained from three patients with primary lung cancers. In addition, we examined the pattern of mtDNA mutation in corresponding tumors and normal lymph nodes obtained from eight other patients with primary lung cancers. The entire 16.5 kb mitochondrial genome was sequenced on Affymetrix Mitochip v2.0 sequencing platform in every sample. To examine mtDNA content index, we performed real-time PCR analysis. PRINCIPAL FINDINGS:The airway mucosal biopsies obtained from three lung cancer patients were histopathologically negative but exhibited multiple clonal mtDNA mutations detectable in the corresponding tumors. One of the patients was operated twice for the removal of tumor from the right upper and left lower lobe respectively within a span of two years. Both of these tumors exhibited twenty identical mtDNA mutations. MtDNA content increased significantly (P<0.001) in the lung cancer and all the histologically negative mucosal biopsies except one compared to the control lymph node. CONCLUSIONS/SIGNIFICANCE:Our results document the extent of massive clonal patches that develop in lifetime smokers and ultimately give rise to clinically significant cancers. These observations shed light on the extent of disease in the airway of smokers traceable through mtDNA mutation. MtDNA mutation could be a reliable tool for molecular assessment of respiratory epithelium exposed to continuous smoke as well as disease detection and monitoring. Functional analysis of the pathogenic mtDNA mutations may be useful to understand their role in lung tumorigenesis

Performance of mitochondrial DNA mutations detecting early stage cancer

<p>Abstract</p> <p>Background</p> <p>Mutations in the mitochondrial genome (mtgenome) have been associated with cancer and many other disorders. These mutations can be point mutations or deletions, or admixtures (heteroplasmy). The detection of mtDNA mutations in body fluids using resequencing microarrays, which are more sensitive than other sequencing methods, could provide a strategy to measure mutation loads in remote anatomical sites.</p> <p>Methods</p> <p>We determined the mtDNA mutation load in the entire mitochondrial genome of 26 individuals with different early stage cancers (lung, bladder, kidney) and 12 heavy smokers without cancer. MtDNA was sequenced from three matched specimens (blood, tumor and body fluid) from each cancer patient and two matched specimens (blood and sputum) from smokers without cancer. The inherited wildtype sequence in the blood was compared to the sequences present in the tumor and body fluid, detected using the Affymetrix Genechip^®Human Mitochondrial Resequencing Array 1.0 and supplemented by capillary sequencing for noncoding region.</p> <p>Results</p> <p>Using this high-throughput method, 75% of the tumors were found to contain mtDNA mutations, higher than in our previous studies, and 36% of the body fluids from these cancer patients contained mtDNA mutations. Most of the mutations detected were heteroplasmic. A statistically significantly higher heteroplasmy rate occurred in tumor specimens when compared to both body fluid of cancer patients and sputum of controls, and in patient blood compared to blood of controls. Only 2 of the 12 sputum specimens from heavy smokers without cancer (17%) contained mtDNA mutations. Although patient mutations were spread throughout the mtDNA genome in the lung, bladder and kidney series, a statistically significant elevation of tRNA and ND complex mutations was detected in tumors.</p> <p>Conclusion</p> <p>Our findings indicate comprehensive mtDNA resequencing can be a high-throughput tool for detecting mutations in clinical samples with potential applications for cancer detection, but it is unclear the biological relevance of these detected mitochondrial mutations. Whether the detection of tumor-specific mtDNA mutations in body fluidsy this method will be useful for diagnosis and monitoring applications requires further investigation.</p

Prioritizing qualitative research in surgery: A synthesis and analysis of publication trends

Background: Over the past 2 decades, researchers have recognized the value of qualitative research. Little has been done to characterize its application to surgery. We describe characteristics and overall prevalence of qualitative surgical research.Methods: We searched PubMed and CINAHL using surgery and 7 qualitative methodology terms. Four researchers extracted information; a fifth researcher reviewed 10% of abstracts for inter-rater reliability.Results: A total of 3,112 articles were reviewed. Removing duplicates, 28% were relevant (N = 878; κ = 0.70). Common qualitative methodologies included phenomenology (34.3%) and grounded theory (30.2%). Interviews were the most common data collection method (81.9%) of patients (64%) within surgical oncology (15.4%). Postdischarge was the most commonly studied topic (30.8%). Overall, 41% of studies were published in nursing journals, while 8% were published in surgical journals. More than half of studies were published since 2011.Conclusion: Results suggest qualitative surgical research is gaining popularity. Most is published in nonsurgical journals, however, utilizing only 2 methodologies (phenomenology, grounded theory). The surgical journals that have published qualitative research had study topics restricted to a handful of surgical specialties. Additional surgical qualitative research should take advantage of a greater variety of approaches to provide insight into rare phenomena and social context

Risks, Benefits, and Importance of Collecting Sexual Orientation and Gender Identity Data in Healthcare Settings: A Multi-Method Analysis of Patient and Provider Perspectives

Purpose: Research suggests that LGBT populations experience barriers to healthcare. Organizations such as the Institute of Medicine recommend routine documentation of sexual orientation (SO) and gender identity (GI) in healthcare, to reduce LGBT disparities. We explore patient views regarding the importance of SO/GI collection, and patient and provider views on risks and benefits of routine SO/GI collection in various settings.Methods: We surveyed LGBT/non-LGBT patients and providers on their views on SO/GI collection. Weighted data were analyzed with descriptive statistics; content analysis was conducted with open-ended responses.Results: One-half of the 1516 patients and 60% of 429 providers were female; 64% of patients and 71% of providers were White. Eighty percent of providers felt that collecting SO data would offend patients, whereas only 11% of patients reported that they would be offended. Patients rated it as more important for primary care providers to know the SO of all patients compared with emergency department (ED) providers knowing the SO of all patients (41.3% vs. 31.6%; P \u3c 0.001). Patients commonly perceived individualized care as an SO/GI disclosure benefit, whereas providers perceived patient-provider interaction improvement as the main benefit. Patient comments cited bias/discrimination risk most frequently (49.7%; N = 781), whereas provider comments cited patient discomfort/offense most frequently (54.5%; N = 433).Conclusion: Patients see the importance of SO/GI more in primary care than ED settings. However, many LGBT patients seek ED care due to factors including uninsurance; therefore, the ED may represent an initial point of contact for SO/GI collection. Therefore, patient-centered approaches to collecting SO/GI are needed. Patients and providers differed in perceived risks and benefits to routine SO/GI collection. Provider training in LGBT health may address patients\u27 bias/discrimination concerns, and ultimately reduce LGBT health disparities

Risks, benefits, and importance of collecting sexual orientation and gender identity data in healthcare settings: A multi-method analysis of patient and provider perspectives

Purpose: Research suggests that LGBT populations experience barriers to healthcare. Organizations such as the Institute of Medicine recommend routine documentation of sexual orientation (SO) and gender identity (GI) in healthcare, to reduce LGBT disparities. We explore patient views regarding the importance of SO/GI collection, and patient and provider views on risks and benefits of routine SO/GI collection in various settings.Methods: We surveyed LGBT/non-LGBT patients and providers on their views on SO/GI collection. Weighted data were analyzed with descriptive statistics; content analysis was conducted with open-ended responses.Results: One-half of the 1516 patients and 60% of 429 providers were female; 64% of patients and 71% of providers were White. Eighty percent of providers felt that collecting SO data would offend patients, whereas only 11% of patients reported that they would be offended. Patients rated it as more important for primary care providers to know the SO of all patients compared with emergency department (ED) providers knowing the SO of all patients (41.3% vs. 31.6%; P \u3c 0.001). Patients commonly perceived individualized care as an SO/GI disclosure benefit, whereas providers perceived patient-provider interaction improvement as the main benefit. Patient comments cited bias/discrimination risk most frequently (49.7%; N = 781), whereas provider comments cited patient discomfort/offense most frequently (54.5%; N = 433).Conclusion: Patients see the importance of SO/GI more in primary care than ED settings. However, many LGBT patients seek ED care due to factors including uninsurance; therefore, the ED may represent an initial point of contact for SO/GI collection. Therefore, patient-centered approaches to collecting SO/GI are needed. Patients and providers differed in perceived risks and benefits to routine SO/GI collection. Provider training in LGBT health may address patients\u27 bias/discrimination concerns, and ultimately reduce LGBT health disparities

Is it okay to ask: Transgender patient perspectives on sexual orientation and gender identity collection in healthcare

Objective: The National Academy of Medicine and Joint Commission recommend routine documentation of sexual orientation (SO) and gender identity (GI) in healthcare to address lesbian, gay, bisexual, or transgender (LGBT) health disparities. We explored transgender patient-reported views on the importance on SO/GI collection, their willingness to disclose, and their perceived facilitators of SO/GI collection in primary care and emergency department (ED) settings.Methods: We recruited a national sample of self-identified transgender patients. Participants completed demographic questions, survey questions, and free-response comments regarding their views on SO/GI collection. Data were analyzed using descriptive statistics; inductive content analysis was conducted with open-ended responses.Results: Patients mostly self-identified as male gender (54.5%), white (58.4%), and SO other than heterosexual or LGB (33.7%; N = 101). Patients felt that it was more important for primary care providers to know their GI than SO (89.1% vs. 57%; p \u3c 0.001); there was no difference among reported importance for ED providers to know the patients\u27 SO versus GI. Females were more likely than males to report medical relevance to chief complaint as a facilitator to SO disclosure (89.1% vs. 80%; p = 0.02) and less likely to identify routine collection from all patients as a facilitator to GI disclosure (67.4% vs. 78.2%; p = 0.09). Qualitatively, many patients reported that medical relevance to chief complaint and an LGBT-friendly environment would increase willingness to disclose their SO/GI. Patients also reported need for educating providers in LGBT health prior to implementing routine SO/GI collection.Conclusions: Patients see the importance of providing GI more than SO to providers; nonetheless they are willing to disclose SO/GI in general.. Findings also suggest that gender differences may exist in facilitators of SO/GI disclosure. Given the underrepresentation of transgender patients in healthcare, it is crucial for providers to address their concerns with SO/GI disclosure, which include LGBT education for medical staff and provision of a safe environment

Multilevel Stigma and Its Associations with Medical Care Ratings Among Men Who Have Sex With Men in HPTN 078

Introduction: Our research assessed associations between stigma-related variables and medical care ratings among clients with HIV in HIV Prevention Trials Network (HPTN) 078 who were men who have sex with men (MSM). Methods: Logistic regression explored care ratings, stigma, socio-demographics (N = 637). Qualitative thematic coding and themes explored stigmatizing experiences in different settings (N = 111). Results: Whites were twice as likely as African-Americans to report high care ratings ( P  < .05). Clients who reported familial exclusion due to having sex with men were 40% less likely to report high medical care ratings ( P  < .05). Clients who agreed healthcare providers think people with HIV “sleep around” were half as likely to report high care ratings ( P  < .08). Stigmatization included “treating me like they’ll catch HIV from my hand,” and care avoidance so others didn’t “know I was having sex with men” . Conclusions: Providers can promote African American MSM client retention with more affirming healthcare provision, namely minimizing assumptions and addressing identities and client needs beyond just HIV care

Setting a national agenda for surgical disparities research: Recommendations from the National Institutes of Health and American College of Surgeons Summit

Health care disparities (differential access, care, and outcomes owing to factors such as race/ethnicity) are widely established. Compared with other groups, African American individuals have an increased mortality risk across multiple surgical procedures. Gender, sexual orientation, age, and geographic disparities are also well documented. Further research is needed to mitigate these inequities. To do so, the American College of Surgeons and the National Institutes of Health-National Institute of Minority Health and Disparities convened a research summit to develop a national surgical disparities research agenda and funding priorities. Sixty leading researchers and clinicians gathered in May 2015 for a 2-day summit. First, literature on surgical disparities was presented within 5 themes: (1) clinician, (2) patient, (3) systemic/access, (4) clinical quality, and (5) postoperative care and rehabilitation-related factors. These themes were identified via an exhaustive preconference literature review and guided the summit and its interactive consensus-building exercises. After individual thematic presentations, attendees contributed research priorities for each theme. Suggestions were collated, refined, and prioritized during the latter half of the summit. Breakout sessions yielded 3 to 5 top research priorities by theme. Overall priorities, regardless of theme, included improving patient-clinician communication, fostering engagement and community outreach by using technology, improving care at facilities with a higher proportion of minority patients, evaluating the longer-term effect of acute intervention and rehabilitation support, and improving patient centeredness by identifying expectations for recovery. The National Institutes of Health and American College of Surgeons Summit on Surgical Disparities Research succeeded in identifying a comprehensive research agenda. Future research and funding priorities should prioritize patients\u27 care perspectives, workforce diversification and training, and systematic evaluation of health technologies to reduce surgical disparities