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Walid Ayoub, MD, Hepatology Fellow, Center for Liver Diseases and Transplantation, Cedars-Sinai Medical Center, Los Angeles, California

Paul Martin, MD, Medical Director, Liver Transplant Program, Center for Liver Diseases and Transplantation, Cedars-Sinai Medical Center, Los Angeles, California; Professor of Medicine, UCLA School of Medicine, Los Angeles, California

Tram Tran, MD, Assistant Medical Director, Hepatology and Liver Transplant Program, Cedars-Sinai Medical Center, Los Angeles, California; Assistant Professor, Department of Medicine, UCLA School of Medicine, Los Angeles, California

Dr. Ayoub has no significant financial interests to disclose. Dr. Ayoub reported that he does not discuss any investigational or unlabeled uses of commercial products in this activity.

Dr. Martin has disclosed that he is a Speaker, has served as an advisor or consultant, and has served as an investigator for Roche and Gilead. Dr. Martin reported that he does not discuss any investigational or unlabeled uses of commercial products in this activity.

Dr. Tran has disclosed that she has served as an advisor or consultant for Roche, Schering Plough, and Gilead Sciences. She has received grants for educational activities from Roche and Schering Plough. Dr. Tran reported that she does not discuss any investigational or unlabeled uses of commercial products in this activity.

Fri, 05 Aug 2022 12:00:00 -0500 en text/html
Killexams : Using Circulating Tumor DNA in Colorectal Cancer: Current and Evolving Practices

Despite the fact that ctDNA has increasingly become a part of the paradigm for molecular profiling and that high concordance is observed between baseline plasma and tissue testing, tissue biopsy remains the gold standard in general for solid tumors. There are advantages to a tissue-based approach. To date, from a technical standpoint, tissue biopsy is more sensitive in detecting fusions since these are large gene rearrangements.7 Although ctDNA can detect copy-number variations, the efficacy is limited to patients with high tumor content or extreme copy-number amplifications, whereas copy losses are very difficult to detect in plasma. Even for coding variants, sufficient ctDNA may not be detectable in approximately 15% of the patients with metastatic cancers on the basis of tumor type and burden.52

From a clinical standpoint, blood-based ctDNA testing can also have less utility in CRC patients with peritoneal carcinomatosis or brain metastases because of the respective blood-based barriers. Creative strategies to use ctDNA detection in other body fluids (cerebrospinal fluid, ascites, pleural effusion etc) are under investigation.53-57

Steps are needed to standardize ctDNA profiling across platforms and to describe how ctDNA tests relate to a tissue result, as other biomarkers such as plasma tumor mutational burden are being reported. Plasma tumor mutational burden scores trended higher compared with tissue TMB and it is unclear how or whether these should be compared with tissue-based results.58 It is important keep these technical and clinical applications in mind when applying any of the ctDNA platforms for patients with CRC.

In conclusion, ctDNA is emerging as a powerful tool for various applications including molecular profiling, MRD detection, early recurrence monitoring, and treatment response prediction. ctDNA can potentially be used to guide adjuvant therapy, and/or considering additional imaging techniques (magnetic resonance imaging and/or positron emission tomography-computed tomography) to identify sites of occult metastasis potentially amenable to a locoregional therapy approach in the surveillance setting.

ctDNA is highly prognostic and ctDNA clearance is emerging as a biomarker that could help with early assessment of therapeutic efficacy. Whether it can be a surrogate end point for recurrence or DFS is yet to be determined. This approach could expedite clinical trial read out, reduce the cost of trials, and allow us to bring advances to the patients sooner. ctDNA will enhance recruitment to clinical trials and increase the number of patients eligible for a precision medicine approach. It may also allow us to abort approved but ineffective therapies in patients who do not respond to targeted or immunotherapies. With the completion of ongoing clinical trials, we anticipate patients with stage III and high-risk stage II CRC with no evidence of MRD postoperatively can perhaps be monitored under active surveillance without adjuvant chemotherapy and potentially treated at the time of MRD detection.

Keeping in mind the limitations, CRC as a disease is particularly suited to a liquid biopsy–based approach since there is a great deal of shedding of circulating tumor fragments (cells, DNA, methylation markers, etc). The utility of ctDNA has broadened from its initial use in the advanced/metastatic setting for molecular profiling and detection of acquired resistance mechanisms, toward identifying MRD as well as early detection. We are also seeing hints of ctDNA being more than just a prognostic marker in the MRD setting. It is important to reiterate that there are different types of ctDNA liquid biopsy platforms, each with advantages and disadvantages and different clinical indications. Interpretation and application of ctDNA results cannot be done in isolation, and the clinical context needs to be kept in mind besides the assay/technical issues. Enrollment in ongoing clinical trials that use ctDNA as an integral biomarker and harmonizing of reporting across platforms will be key to further advance the field.

1. Ashworth TR: A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Australas Med J 14:146-147, 1869 Google Scholar 2. Bettegowda C, Sausen M, Leary RJ, et al: Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 6:224ra24, 2014 Crossref, MedlineGoogle Scholar 3. Manca P, Corallo S, Lonardi S, et al: SO-24 Circulating tumor DNA variant allelic fraction as a surrogate for disease burden estimation in patients with RAS wild-type metastatic colorectal cancer: A secondary endpoint of the VALENTINO study. Ann Oncol 32:S212, 2021 CrossrefGoogle Scholar 4. Vidal J, Muinelo L, Dalmases A, et al: Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients. Ann Oncol 28:1325-1332, 2017 Crossref, MedlineGoogle Scholar 5. Osumi H, Shinozaki E, Takeda Y, et al: Clinical relevance of circulating tumor DNA assessed through deep sequencing in patients with metastatic colorectal cancer. Cancer Med 8:408-417, 2018 Crossref, MedlineGoogle Scholar 6. Kagawa Y, Elez E, García-Foncillas J, et al: Combined analysis of concordance between liquid and tumor tissue biopsies for RAS mutations in colorectal cancer with a single metastasis site: The METABEAM study. Clin Cancer Res 27:2515-2522, 2021 Crossref, MedlineGoogle Scholar 7. Parikh AR, Leshchiner I, Elagina L, et al: Liquid versus tissue biopsy for detecting acquired resistance and tumor heterogeneity in gastrointestinal cancers. Nat Med 25:1415-1421, 2019 Crossref, MedlineGoogle Scholar 8. Yoshino T: SCRUM-Japan GI-SCREEN: The nationwide cancer genome screening projects for gastrointestinal cancer in Japan. Ann Oncol 26:vii5, 2015 CrossrefGoogle Scholar 9. 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J Clin Oncol 39, 2021 (suppl 15; abstr 3565) LinkGoogle Scholar 22. Loupakis F, Sharma S, Derouazi M, et al: Detection of molecular residual disease using personalized circulating tumor DNA assay in patients with colorectal cancer undergoing resection of metastases. JCO Precis Oncol 5:1166-1177, 2021 LinkGoogle Scholar 23. Nimeiri H, Young A, Madison R, et al: Comprehensive genomic profiling (CGP)-informed personalized molecular residual disease (MRD) detection: An exploratory analysis from the PREDATOR study of metastatic colorectal cancer (mCRC) patients undergoing surgical resection. J Clin Oncol 40, 2022 (suppl 4; abstr 187) LinkGoogle Scholar 24. Kotaka M, Shirasu H, Watanabe J, et al: Association of circulating tumor DNA dynamics with clinical outcomes in the adjuvant setting for patients with colorectal cancer from an observational GALAXY study in CIRCULATE-Japan. J Clin Oncol 40, 2022 (suppl 4; abstr9) LinkGoogle Scholar 25. Reinert T, Henriksen TV, Christensen E, et al: Analysis of plasma cell-free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer. JAMA Oncol 5:1124-1131, 2019 Crossref, MedlineGoogle Scholar 26. Wilkinson NW, Yothers G, Lopa S, et al: Long-term survival results of surgery alone versus surgery plus 5-fluorouracil and leucovorin for stage II and stage III colon cancer: Pooled analysis of NSABP C-01 through C-05. A baseline from which to compare modern adjuvant trials. Ann Surg Oncol 17:959-966, 2010 Crossref, MedlineGoogle Scholar 27. André T, Boni C, Navarro M, et al: Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 27:3109-3116, 2009 LinkGoogle Scholar 28. Osterman E, Glimelius B: Recurrence risk after up-to-date colon cancer staging, surgery, and pathology: Analysis of the entire Swedish population. Dis Colon Rectum 61:1016-1025, 2018 Crossref, MedlineGoogle Scholar 29. Chakrabarti S, Peterson CY, Sriram D, et al: Early stage colon cancer: Current treatment standards, evolving paradigms, and future directions. World J Gastrointest Oncol 12:808-832, 2020 Crossref, MedlineGoogle Scholar 30. Wan JCM, Massie C, Garcia-Corbacho J, et al: Liquid biopsies come of age: Towards implementation of circulating tumour DNA. Nat Rev Cancer 17:223-238, 2017 Crossref, MedlineGoogle Scholar 31. Siravegna G, Marsoni S, Siena S, et al: Integrating liquid biopsies into the management of cancer. Nat Rev Clin Oncol 14:531-548, 2017 Crossref, MedlineGoogle Scholar 32. Biagi JJ, Raphael MJ, Mackillop WJ, et al: Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: A systematic review and meta-analysis. JAMA 305:2335-2342, 2011 Crossref, MedlineGoogle Scholar 33. Henriksen TV, Reinert T, Christensen E, et al: The effect of surgical trauma on circulating free DNA levels in cancer patients—implications for studies of circulating tumor DNA. Mol Oncol 14:1670-1679, 2020. Crossref, MedlineGoogle Scholar 34. Dasari A, Morris VK, Allegra CJ, et al: CtDNA applications and integration in colorectal cancer: An NCI Colon and Rectal–Anal Task Forces whitepaper. Nat Rev Clin Oncol 17:757-770, 2020 Crossref, MedlineGoogle Scholar 35. Henriksen TV, Tarazona N, Frydendahl A, et al: Circulating tumor DNA in stage III colorectal cancer, beyond minimal residual disease detection, towards assessment of adjuvant therapy efficacy and clinical behavior of recurrences. Clin Cancer Res 14:1748-1753, 2021 Google Scholar 36. Taieb J, Taly V, Vernerey D, et al: Analysis of circulating tumour DNA (ctDNA) from patients enrolled in the IDEA-FRANCE phase III trial: Prognostic and predictive value for adjuvant treatment duration. Ann Oncol 30:v867, 2019 CrossrefGoogle Scholar 37. Dawson SJ, Tsui DW, Murtaza M, et al: Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 368:1199-1209, 2013 Crossref, MedlineGoogle Scholar 38. Diaz LA Jr, Williams RT, Wu J, et al: The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 486:537-540, 2012 Crossref, MedlineGoogle Scholar 39. Siravegna G, Mussolin B, Buscarino M, et al: Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients. Nat Med 21:795-801, 2015 Crossref, MedlineGoogle Scholar 40. Parikh AR, Mojtahed A, Schneider JL, et al: Serial CtDNA monitoring to predict response to systemic therapy in metastatic gastrointestinal cancers. Clin Cancer Res 26:1877-1885, 2020 Crossref, MedlineGoogle Scholar 41. Tin A, Aushev V, Kalashnikova E, et al: Correlation of variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors. Mol Oncol 15:57-66, 2021 MedlineGoogle Scholar 42. Andre T, Shiu KK, Kim TW, et al: Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 Study. J Clin Oncol 38, 2020 (suppl 18; abstr LBA4) LinkGoogle Scholar 43. Kasi PM, Budde G, Krainock M, et al: Circulating tumor DNA (ctDNA) serial analysis during progression on PD-1 blockade and later CTLA4 rescue in patients with mismatch repair deficient metastatic colorectal cancer. J Immunother Cancer 10:e003312, 2022 Crossref, MedlineGoogle Scholar 44. Bratman SV, Yang SC, Iafolla MA, et al: Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nat Cancer 1:873-881, 2020 Crossref, MedlineGoogle Scholar 45. Zhang Q, Luo J, Wu S, et al: Prognostic and predictive impact of circulating tumor DNA in patients with advanced cancers treated with immune checkpoint blockade. Cancer Discov 10:1842-1853, 2020 Crossref, MedlineGoogle Scholar 46. Parseghian CM, Loree JM, Morris VK, et al: Anti-EGFR-resistant clones decay exponentially after progression: Implications for anti-EGFR re-challenge. Ann Oncol 30:243-249, 2019 Crossref, MedlineGoogle Scholar 47. Murtaza M, Dawson SJ, Tsui DW, et al: Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 497:108-112, 2013 Crossref, MedlineGoogle Scholar 48. Loree JM, Henry J, Raghav KPS, et al: Serial circulating tumor DNA (CtDNA) monitoring in metastatic colorectal cancer (mCRC) reveals dynamic profile of actionable alterations. J Clin Oncol 39, 2021 (suppl 15; abstr 3572) LinkGoogle Scholar 49. Sartore-Bianchi A, Pietrantonio F, Lonardi S, et al: Phase II study of anti-EGFR rechallenge therapy with panitumumab driven by circulating tumor DNA molecular selection in metastatic colorectal cancer: The CHRONOS trial. J Clin Oncol 39, 2021 (suppl 15; abstr 3506) LinkGoogle Scholar 50. Morelli MP, Overman MJ, Dasari A, et al: Characterizing the patterns of clonal selection in circulating tumor DNA from patients with colorectal cancer refractory to anti-EGFR treatment. Ann Oncol 26:731-736, 2015 Crossref, MedlineGoogle Scholar 51. Cremolini C, Rossini D, Dell’Aquila E, et al: Rechallenge for patients with RAS and BRAF wild-type metastatic colorectal cancer with acquired resistance to first-line cetuximab and irinotecan: A phase 2 single-arm clinical trial. JAMA Oncol 5:343-350, 2019 Crossref, MedlineGoogle Scholar 52. Ma M, Zhu H, Zhang C, et al: “Liquid biopsy”—CtDNA detection with great potential and challenges. Ann translational Med 3:235, 2015 MedlineGoogle Scholar 53. Diehl F, Schmidt K, Durkee KH, et al: Analysis of mutations in DNA isolated from plasma and stool of colorectal cancer patients. Gastroenterology 135:489-498, 2008 Crossref, MedlineGoogle Scholar 54. De Mattos-Arruda L, Mayor R, Ng CKY, et al: Cerebrospinal fluid- derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Nat Commun 6:8839, 2015 Crossref, MedlineGoogle Scholar 55. Kimura H, Fujiwara Y, Sone T, et al: EGFR mutation status in tumour-derived DNA from pleural effusion fluid is a practical basis for predicting the response to gefitinib. Br J Cancer 95:1390-1395, 2006 Crossref, MedlineGoogle Scholar 56. Wang Y, Springer S, Mulvey CL, et al: Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas. Sci Transl Med 7:293ra104, 2015 Crossref, MedlineGoogle Scholar 57. Reckamp KL, Melnikova VO, Karlovich C, et al: A highly sensitive and Quantitative test platform for detection of NSCLC EGFR mutations in urine and plasma. J Thorac Oncol 11:1690-1700, 2016 Crossref, MedlineGoogle Scholar 58. Drusbosky L, Bilen MA, Azzi G, et al: Blood-based tumor mutational burden from circulating tumor DNA (ctDNA) across advanced solid malignancies using a commercially available liquid biopsy assay. J Clin Oncol 39, 2021 (suppl 15; abstr 3040) LinkGoogle Scholar 59. Cohen S, Hook N, Krinshpun S, et al: SO-34 Clinical experience of a personalized and tumor-informed circulating tumor DNA assay for minimal residual disease detection in oligometastatic colorectal cancer patients. Ann Oncol 31:S229, 2020 CrossrefGoogle Scholar 60. Kasi PM, Dayyani F, Morris V, et al: Tumor-informed assessment of molecular residual disease and its incorporation into practice for patients with early and advanced stage colorectal cancer (CRC-MRD Consortia). J Clin Oncol 38, 2020 (suppl 15; abstr 4108) LinkGoogle Scholar 61. Tarazona N, Henriksen TV, Carbonell-Asins JA, et al: Circulating tumor DNA to detect minimal residual disease, response to adjuvant therapy, and identify patients at high risk of recurrence in patients with stage I-III CRC. J Clin Oncol 38, 2020 (suppl 15; abstr 4009) LinkGoogle Scholar 62. Anandappa G, Starling N, Begum R, et al: Minimal residual disease (MRD) detection with circulating tumor DNA (CtDNA) from personalized assays in stage II-III colorectal cancer patients in a UK multicenter prospective study (TRACC). J Clin Oncol 39, 2021 (suppl 3; abstr 102) LinkGoogle Scholar 63. Shirasu H, Taniguchi H, Watanabe J, et al: O-11 Monitoring molecular residual disease by circulating tumor DNA in resectable colorectal cancer: Molecular subgroup analyses of a prospective observational study GALAXY in CIRCULATE-Japan. Ann Oncol 32:S222-S223, 2021 CrossrefGoogle Scholar 64. 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Killexams : Hemochromatosis Case Definition: Out of Focus?

Although hemochromatosis was first described in the 19th century, John Sheldon's 1934 description of 300 cases remains a landmark publication in defining the clinical characteristics of the disease. Since that time there have been many advances, including the discovery of the hemochromatosis (HFE) gene in 1996, mutations of which (e.g. 845G·A [C282Y]) are found in the majority of patients with typical hemochromatosis. Expert opinion is, however, varied regarding what constitutes the ideal case definition for hemochromatosis. This has led to confusion amongst clinicians and patients.

Why do we need a case definition for any medical condition? Has the subclassification of any group of clinically similar diseases improved life for the patient with a single subclass of those diseases? A precise case definition is useful to study the natural history of a disease, direct appropriate treatment, and judge response to therapy. Furthermore, a consistent case definition is particularly important when studies are compared and outcomes are combined, such as in a meta-analysis.

Most of the debate regarding hemochromatosis centers on its phenotypic or genotypic diagnosis. Whether a clinically asymptomatic patient with elevated iron levels should be classified as having hemochromatosis is currently an issue of debate. Some investigators have proposed a case definition for hemochromatosis comprising a sustained elevation in serum ferritin levels (>200 µg/l in women and >300 µg/l in men) and transferrin saturation (>45% in women and >50% in men) in the absence of any other risk factors for iron overload. This approach has the advantage of simplicity, but it would probably identify a number of patients who do not have iron overload. A screening study demonstrated that a transferrin saturation of >55% had a positive predictive value of only 4.4% for identifying male 845G·A (C282Y) homozygotes.[1]

Other researchers insist that iron overload should be documented and quantified by liver biopsy. The pattern of iron distribution might be helpful in defining the cause of disease. The hepatic iron index (hepatic iron concentration divided by patient age) was devised before genetic testing, and originally used to differentiate patients with alcoholic siderosis from those with genetic hemochromatosis. Later it was extrapolated for use in the case definition of hemochromatosis. This introduced the concept that a quantitative measure of iron overload should be used to define the disease. Subsequent studies using genetic testing, however, have shown that many patients with early hemochromatosis do not have an elevated hepatic iron index (>1.9), and that patients with other types of iron overload do have an elevated hepatic iron index.[2] Liver biopsy is unappealing to patients with mild abnormalities (serum ferritin levels <1,000 µg/l), and MRI has a poor sensitivity for the detection of mild iron overload.

Quantitative phlebotomy is another method to measure iron overload. The removal of 5 g of mobilizable iron by phlebotomy (approximately 20 × 500 ml phlebotomies) followed by a fall in serum ferritin levels to under 50 µg/l has been considered as a case definition.

The creation of arbitrary quantitative thresholds for any of these variables (serum ferritin levels, transferrin saturation, liver iron, iron removed) in order to define hemochromatosis has obvious limitations. A patient just below a threshold might have a clinical diagnosis as strong as another patient just above a threshold.

Another perspective on the case definition for hemochromatosis is that patients should have a constellation of clinical signs and symptoms. The association of any symptoms of hemochromatosis with elevated iron levels or 845G·A (C282Y) homozygosity has, however, come under increased scrutiny.[3,4,5] Patients with bronze diabetes (a type of diabetes associated with hemochromatosis) probably represent <1% of all hemochromatosis patients, and studies have shown that the prevalence of diabetes is similar in both 845G·A (C282Y) homozygous and control populations. Other symptoms associated with hemochromatosis, such as fatigue and arthralgia, are nonspecific and very common in the general population. Of all of the putative symptoms of hemochromatosis, liver disease is the most consistently identified abnormality. Many patients with liver disease are, however, asymptomatic-even those with hepatic fibrosis.

A purely phenotypic case definition of hemochromatosis seems to combine apples and oranges (HFE-related and nonHFE-related iron overload) and it defeats the original purpose of having a case definition: to characterize the disease prognosis and natural history and, most importantly, guide its management.

Following the discovery of the HFE gene, a simple genetic test became available for the diagnosis of hemochromatosis. In tertiary referral centers for hemochromatosis in Canada, Australia and France, over 95% of typical hemochromatosis patients were homozygous for 845G·A (C282Y). By contrast, reports continue to be published that suggest only 60–80% of patients with hemochromatosis are homozygous for 845G·A (C282Y);[6] however, the phenotypic case definition for hemochromatosis in these studies might not have been as stringent, and family studies are not often performed. The use of the genetic test as a 'gold standard' test for hemochromatosis has not, therefore, been widely accepted. Furthermore, it has been recognized that approximately 20% of male and 50% of female 845G·A (C282Y) homozygotes have normal serum ferritin levels, making iron overload in these individuals an unlikely possibility.[5] If iron overload is the cornerstone of the diagnosis, how can these patients be classified as having hemochromatosis? There was also concern that the identification of a nonexpressing 845G·A (C282Y) homozygote could lead to anxiety and genetic discrimination, but this has not been Verified in large international studies.[7,8,9]

Previous studies have suggested that the classification of hemochromatosis should be based on genetic testing for HFE, ferroportin, transferrin receptor 2, hemojuvelin and hepcidin. Genetic testing for nonHFE-related iron overload might never be broadly available clinically because of the rarity of these diseases. Furthermore, genetic sequencing will often be required for diagnosis in many cases because of the heterogeneity of the mutations involved. For most clinicians there are only two types of hemochromatosis: typical 845G·A-related (C282Y-related) and atypical. The term nonHFE-related iron overload is preferred to the term nonHFE hemochromatosis.

I favor the case definition for hemochromatosis as being 845G·A (C282Y) homozygosity with an elevated serum ferritin level. An 845G·A (C282Y) homozygote with normal iron tests has a genetic predisposition to develop iron overload-related symptoms. A compound heterozygote (845G·A [C282Y]/187C·G [H63D]) or 187C·G (H63D) homozygote with elevated serum ferritin and no other risk factors probably has HFE-related iron overload. As patients with these genotypes usually have much milder degrees of iron overload, they should be considered separately in clinical studies. A disadvantage of a mixed genotypic/phenotypic case definition is that it will not be suitable for studies comparing the effect of genotype on phenotype. Until rapid total genome sequencing is introduced into clinical practice, a small category of patients will remain with nonHFE-related familial iron overload that cannot be classified without substantial genetic sequencing efforts. Most experts in the area agree to disagree on a case definition for hemochromatosis. It is most important for individual studies to have precise case definitions. Will a standard case definition be developed by the 100th anniversary of John Sheldon's landmark monograph, in 2034? Definitely maybe.

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Mon, 11 Jul 2022 12:01:00 -0500 en text/html
Killexams : Research shows low patient comprehension of terms commonly found in electronic health information

When the 21st Century Cures Act went into effect in April 2021, health care organizations began releasing electronic health information (EHI) to patients immediately.

An aim of the act is to reduce barriers to patients' timely access to EHI, and previous research has shown that patients sometimes access reports even before clinicians. An ongoing concern, however, is that pathology and radiology reports are written with the clinician, rather than the patient, as the intended audience.

Based on surveys of patients to assess comprehension of breast pathology report terminology, recently published research demonstrates poor patient understanding of terminology and a pressing need to develop and integrate educational tools to support patients.

"Our aims were to get a clearer picture of what patients were understanding and not understanding, and to learn more about what educational tools patients would find most helpful," says Alexandra Verosky, a third-year medical student in the University of Colorado School of Medicine and lead author of the study. "We're seeing this need not just in breast oncology and surgery, but across all areas of health care."

Defining frequently used terms

Verosky and her co-researchers, including research mentor and CU Cancer Center member Sarah Tevis, MD, an assistant professor of surgical oncology, designed a survey to assess patient understanding of eight terms common in breast pathology reports: malignant, benign, metastatic, neoplasm, negative, mass, carcinoma, and high grade.

The 527 study participants who completed the electronic survey were asked to provide free-text definitions of the eight terms, as well as interpret whether the terms are "good ," "bad news," or "could be good news or bad news."

About 80% of patients correctly defined malignant and 73% currently defined benign, but the other terms were correctly defined at much lower rates. While partially correct definitions were tabulated—and 82% of respondents were partially correct in defining carcinoma—more than 40% of respondents didn't know or didn't provide a definition for neoplasm.

"One of the things that was really surprising was we asked on the survey whether the respondent is a health care worker, but the data showed that being one didn't correlate with better understanding of medical terms," Verosky says.

These findings demonstrate "that we need to use definitions and terminology that patients will understand in the clinic and not make assumptions about what they may or may not know based on demographics or their field of work or education level," Tevis says. "This helps us better understand what patients are taking in when they read these reports and that should guide how we talk with patients in general."

Good news or bad news

In identifying whether the eight terms were "good news," "bad news," or "could be good news or bad news," more than 95% of respondents correctly identified malignant as bad news. The most commonly misidentified term was high grade, though 10% of respondents identified carcinoma as "could be good news or ."

Verosky noted that the study was limited in those who responded—a majority were white and college educated—and added that the survey currently is being translated to Spanish so that further research can help broaden understanding of patient comprehension of terms.

In a separate, ongoing study, Tevis and her co-researchers are giving participants a trial medical report and internet access to understand which terms they are looking up and which sites they are using to get that information.

"Another issue we're seeing is if you have a pathology report, you'll see a diagnosis at the top with supporting information, then pages of legalese underneath that," Tevis says. "I've had instances when I've called patients to discuss reports and they're on page five of the small print that even I don't read. So, it's really important that we're gaining a deeper understanding of how are seeing and understanding these reports and what educational tools we can develop to support them."

Of the participants in the breast pathology research, a majority indicated that tools including a brief summary paragraph at the top of pathology reports, as well as an integrated electronic tool that would allow users to hover over phrases for clear definitions, would be the most useful.

"We've developed a Chrome plug-in that will provide the definitions and guide users to a website that we've vetted for both practicing level and reliable information," Tevis says. "We're going to pilot that as a next step, and continue expanding our research to understand how broader populations are receiving this information."

Definitions for eight common cancer :

Mass: An abnormal collection of tissue or cells that may or may not be cancerous.

High Grade: A term used to describe cells that look abnormal under a microscope.

Benign: Not cancerous/non-malignant.

Malignant: Cancerous; abnormal cells that can invade and destroy normal tissue or spread to other parts of the body.

Negative: The abnormality being looked for is not found/not present.

Neoplasm: New growth/abnormal growth which may or may not be cancer/ tumor.

Carcinoma: Cancer originating from the lining layer (epithelial cells) of organs (or skin).

Metastatic: Cancer that has spread from the primary (original) site to other structures or organs.

More information: Alexandra Verosky et al, Patient comprehension of breast pathology report terminology: The need for patient-centered resources, Surgery (2022). DOI: 10.1016/j.surg.2022.05.007

Citation: Research shows low patient comprehension of terms commonly found in electronic health information (2022, August 4) retrieved 9 August 2022 from

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Thu, 04 Aug 2022 09:01:00 -0500 en text/html
Killexams : Documents to have in one place in case of medical emergency

It may seem like there’s plenty of time to get things done — time to write a will, pay off debts, consider retirement, create end-of-life plans, select a health care proxy, and so on. In reality, waiting until later may create major problems.

That’s why, along with the many benefits that aging brings, such as perspective, knowledge, descendants, and experience, it’s important to face another part of it: health issues. In fact, people 65 and older visit the emergency room at higher rates than any other age group, according to research published by the Healthcare Cost and Utilization Project.

Knowing you’re at higher risk of health problems with advanced age doesn’t have to scare you. But it can help you see the necessity of being prepared. That’s why you should create and file these documents and pieces of information in case of emergency, according to the National Institute on Aging:

  • Social Security card
  • Birth and death certificates of household members
  • Education and military records
  • Names and contact information for close friends and relatives
  • List of medications you take regularly
  • Location of living will with original signature
  • Sources of income, including pension, IRA, 401(k), and so on
  • Insurance information, including life, health, car, and home
  • Names of banks and account numbers
  • Mortgage and debt information and how they’re paid
  • Location of original deed of trust for home

Find a single place to keep all this information, and then tell trusted family members where it is.

Digital file saving

You may put originals or hard copies together in a folder or binder, but you can also use an electronic storage location.

“Important documents can exist in digital form on our smart phones, flash drives and cloud-based servers,” according to the Centers for Disease Control and Prevention. “Digital documents are convenient, but with convenience, comes risk. It’s imperative that we secure our digital files with passwords and/or two-factor authentication.”

You can save electronic copies of paperwork in a password-protected format on an external hard drive, flash drive, or secure cloud-based service, according to the CDC. Family members will still need to be aware of where your drives are stored and what your passwords are to access devices and accounts.

Legally binding paperwork

Preparation for the future also includes recording health and financial decisions and ensuring any directives are legally witnessed or notarized. These forms should answer the following questions, according to Five Wishes advance care planning:

Relevant legal documents may include a living will, health care proxy document, a Do Not Resuscitate form if applicable, and a Health Insurance Portability and Accountability Act form that gives permission for information about your hospitalization or condition to be released to loved ones, according to Forbes.

“It is crucial that you have them in place before you have an emergency,” according to Forbes. “Of course none of us believe that we will ever need to use any of them but life can often surprise us.”

Preparing for life’s curveballs has the benefit of ensuring you and your loved ones are on the same page and know what to expect as much as possible when emergencies arise.

Wed, 27 Jul 2022 00:00:00 -0500 en text/html
Killexams : An ORR student spent 10 days at Tufts. Now see what he thinks about biomedical engineering. cannot provide a good user experience to your browser. To use this site and continue to benefit from our journalism and site features, please upgrade to the latest version of Chrome, Edge, Firefox or Safari.

Fri, 29 Jul 2022 07:17:00 -0500 en-US text/html
Killexams : Personal health records may be useful for patient self-management and communication in colorectal cancer networks

JMIR Publications recently published "Uses of Personal Health Records for Communication Among Colorectal Cancer Survivors, Caregivers, and Providers: Interview and Observational Study in a Human-Computer Interaction Laboratory" in JMIR Human Factors which reported that personal health records (PHRs) may be useful for patient self-management and participation in communication with their caregivers and health care providers.

All groups noted the added value of linking the PHR to an electronic health record, self-tracking, self-management, and secure messaging. Patients and caregivers also saw information in the PHR as a useful memory tool given their visits to multiple doctors.

Providers had reservations about patients viewing raw data, which they were not prepared to interpret or might be inaccurate; patients and caregivers did not express any reservations about having access to more information.

Patients saw PHR communication functions as a potential tool for relationship building. Patients and caregivers valued the journal as a tool for reflection and delivery of emotional support.

PHR perceptions differed by role, with providers seeing the PHR as informational, while patients and caregivers viewed the tool as more relational.

Dr. Thomas Carr from The Roudebush Veterans Affairs Medical Center said, "Personal Health Records (PHRs) have grown in popularity and functionality over time."

In the United States, patients with chronic disease represented the first target populations for PHRs; while their adoption rate is only slightly higher than that in the general population, patients with chronic diseases make greater use of PHR capabilities.

Providers have previously described secure messaging as having particular value for both themselves and their patients; however, providers also expressed concern about the inability of patients to share other types of information with their health care team and the impact on workflow.

In this study, the perspectives of patients, caregivers, and health care providers were all evaluated concurrently in relation to a PHR developed for colorectal cancer survivors.

Patient and caregiver engagement is important for the adoption of PHRs, whereas provider buy-in is critical to the implementation of these technologies in health care settings.

Across stakeholders, these authors explored several questions, including "Who should be provided access to, share information, and communicate with the PHR?" and "What type of patient-generated information should be incorporated into the PHR?" Finally, they asked how the PHR impacts workflow and what best practices may guide the future design and implementation of PHRs for patients with cancer.

JMIR HumanFactors: Uses of Personal Health Records for Communication Among Colorectal Cancer Survivors, Caregivers, and Providers: Interview and Observational Study in a Human-Computer Interaction Laboratory

-; JMIR Publications (@jmirpub) January 25, 2022

Dr. Cartmell and the research team concluded in their JMIR Publications Research Output that PHR perceptions are role-dependent, but there is marked consensus on many aspects of PHR design among stakeholders.

This suggests that a single, integrated tool can be designed to meet several identified patient needs, including self-tracking and self-management, as well as more informed and shared medical decisions.

Providers have unique concerns about the increased time burden and the accuracy of patient-entered data, and more fundamentally, how web-based communication tools may change the nature of the physician's professional role.

Patients perceive these tools as a potential pathway to personal understanding that can deepen their relationships with doctors.

Nonetheless, to realize this promise, patients and caregivers may need to search for and encourage health care providers to partner with them in exploring how emerging patient-centered technologies can be successfully implemented in modern medical practice to Boost the relational quality of care.


Journal reference:

Haggstrom, D.A & Carr, T., (2022) Uses of Personal Health Records for Communication Among Colorectal Cancer Survivors, Caregivers, and Providers: Interview and Observational Study in a Human-Computer Interaction Laboratory. JMIR Human Factors.

Tue, 02 Aug 2022 01:34:00 -0500 en text/html
Killexams : specialists in Gastroenterology

Specialists in Gastroenterology is a well-established gastroenterology group in Saint Louis. The physicians combine new technology with compassionate patient care. Patients can trust more than 100 combined years of clinical experience. Compassionate patient care and passion for the practice of medicine sets specialists in Gastroenterology apart from others. 

The Total GI Healthcare Approach includes:

- Colonoscopy, upper endoscopy, and small bowel endoscopy at its state-of-the-art outpatient endoscopy center–Advanced Endoscopy Center

- Treatments for bacterial imbalance and inflammation causing IBS and SIBO

- Evaluation of acid reflux using the 96-hour Bravo pH acid monitor

- Treatment of hepatitis C and fatty liver disease

- Evaluation and treatment of Crohn's disease and ulcerative colitis

- Evaluation of GI motility disorders using Smart-Pill GI motility test

- Endoscopic treatment of hemorrhoids

- Advanced endoscopic procedures including ERCP and endoscopic ultrasound

- Infusion center for biological therapy of inflammatory bowel disease and phlebotomy for hemochromatosis.

- Opportunity to be involved in research of new medication and medical devices

Call or go online today to learn more about specialists in Gastroenterology and its compassionate, knowledgeable, experienced physicians and staff. 


Thu, 28 Jul 2022 14:11:00 -0500 en-us text/html
Killexams : NHS patients and healthcare staff share passive aggressive signs spotted in UK hospitals

Sick of your attitude! People share the passive aggressive signs spotted in NHS hospitals and GP surgeries - from a request not to use the lift to RULES on using the toilet

  • Medical student @juliaisobela shared an image of a sign posted in an NHS department where patients had blood tests - asking them not to sit down
  • Others responded that a phlebotomy department is exactly the kind of place where patients might need to take a seat after having their blood drawn 
  • Flurry of similarly passive aggressive signs were then shared, including one that told workers they could only urinate in a staff toilet - with number twos banned 

Healthcare professionals and patients have been sharing some of the passive aggressive signage they've spotted in NHS hospitals across the country. 

After Twitter user and medical student @juliaisobela, from Leamington Spa, Warwickshire, posted an image of a note in a phlebotomy department that requested patients having blood drawn should only 'sit down if you really need to', others stepped in with sightings of makeshift signs - often grumpy - they'd seen. 

She wrote: 'Passive aggressive NHS signs back at it again (pls let me sit down I just want to sit down)… ' 

People responded that a blood test department might be exactly the kind of place where patients might need to sit down. @JulianBurton15 quipped: 'Please only faint and lacerate your scalp if you really need to.'

@MsPassmore agreed it was a harsh missive, saying: 'Gees... forget sit down, I have to lie down when having blood drawn! Very strange sign.'

The post sparked a slew of photos of signs that have made an appearance in overstretched hospitals and GP surgeries, all showing similarly unforgiving requests - including a staff toilet where only urinating is allowed. 

Here, FEMAIL rounds up notes that come with barely hidden discontent: 

Blood tests can occasionally make patients feel faint... but there's no mercy in this phlebotomy department, shared on Twitter by @juliaisobela from Leamington Spa, Warwickshire

It's a lift, but we don't want you to use it...this sign advises people to put one foot in front of the other to reach the next floor. It was shared on Twitter by a user from Great Yarmouth 

No number twos! This hospital staff toilet relies on employees only needing a we. The photo was spotted by a Twitter user from St Albans

When a sign contradicts a sign... the blood test department at this hospital has apparently shut up shop. It was spotted by a Cardiff University medical student

An GP surgery from Devon is clearly creaking under the weight of appointments makes it clear 'urgent' cases only are encouraged  

And if you've really got to go, this hospital would rather you let some fresh air breeze through and leave the door open, even if it might be embarrassing

Respectfully, but very firmly put - this red plastic chair is going nowhere. It left British Twitter users brainstorming about what pranks they might pull with it

Staff must find other ways to warm their lunch according to this note, which was left in the kitchen area of an NHS facility

A British woman was left baffled by this sign in a local GP's surgery, arguing it might put people off visiting 

Sarcasm and apostrophe blunders unite in this grumpy missive posted on social media by a baffled passerby

Thu, 14 Jul 2022 03:39:00 -0500 text/html
Killexams : OCTC, OHRH offering phlebotomy career fair

Owensboro Community & Technical College has partnered with Owensboro Health Regional Hospital to hold a phlebotomy career fair on Wednesday, July 27.

Session times are at 9:30 a.m., 11:30 a.m. and 4:30 p.m. and will be identical. The fair will be held in conference room 8 at OCTC’s downtown campus at 1501 Frederica St.

OHRH recruiters will share information about employment and the fast-track training partnership with OCTC, where hired applicants can earn wages while training to become a certified phlebotomist.

Phlebotomists are trained to draw blood from a patient for clinical or medical testing, transfusions, donations or research.

“Phlebotomists are a vital part of solving health care riddles,” said Allyson Sanders, director of sales and marketing for OCTC Workforce Solutions.

Applicants hired for the Phlebotomy Work & Learn program will train Mondays and Wednesdays from 4 to 7 p.m. for a 10-week period. Regular work hours will be based on the employer’s schedule. Tuition and other course costs may be paid by a healthcare facility.

Sanders said OCTC has partnered with OHRH for years, stating they’re an “excellent industry partner” and that OHRH is always seeking to “skill up” its potential employees.

Cindy Fiorella, vice president of Workforce Solutions, said the fair is a “proven opportunity” and OCTC is grateful to OHRH to be able to offer it again.

“Students can not only start a career with one of the top employers in our area, but also get their training completely paid for,” Fiorella said.

The event is open to the public and assistance will be provided with the employment application process. Initial interviews will also be conducted.

Sun, 24 Jul 2022 17:15:00 -0500 en text/html
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