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We sought to identify the general health of college students. A total of 4402 university freshmen and sophomores were recruited to report their general health through an online questionnaire. Respo...

To revise the FIGO staging for carcinoma of the vulva using a new approach that involves analyses of prospectively collected data. The FIGO Committee for Gynecologic Oncology reviewed the recent literature to gain an insight into the impact of the 2009 vulvar cancer staging revision. The Committee resolved to revise the staging with a goal of simplification and actively collaborated with the United States National Cancer Database to analyze prospectively collected data on carcinoma of the vulva. Many tumor characteristics were collected for all stages of vulvar cancer treated between 2010 and 2017. Statistical analysis was performed with SAS software. Overall survival was estimated based on tumor characteristics. Log-rank and Wilcoxon tests were used to analyze overall survival similarities between and within groups of tumor characteristics. Characteristics with similar survivals were then grouped into the same stages and substages. Kaplan-Meier overall survival curves were generated for the resulting stages and substages. There were 12 063 cases with available data. The resulting new staging for carcinoma of the vulva has two substages in Stage I, no substage in Stage II, three substages in Stage III, and two substages in Stage IV. The Kaplan-Meier overall survival curves showed clear separation between stages and substages. The 2021 vulvar cancer staging is the first from the FIGO Committee for Gynecologic Oncology to be derived from data analyses. This revision has a new definition for depth of invasion, uses the same definition for lymph node metastases utilized in cervical cancer, and allows findings from cross-sectional imaging to be incorporated into vulvar cancer staging. The 2021 FIGO staging for carcinoma of the vulva is data-derived, validated, and much simpler than earlier revisions.

BACKGROUND: Past research has found high rates of hyperventilation in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), but hyperventilation can be influenced by psychological factors. Clinical respiratory rates have been less frequently assessed. AIM: This study aimed to identify the predictors of rapid respiratory rates in patients referred to an outpatient clinic specializing in ME/CFS. METHODS: Adults (n = 216) referred to an outpatient clinic specializing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) participated in a two-day cardiopulmonary exercise test. As part of that evaluation, subjects had resting respiratory rates measured on two consecutive days. The current study used questionnaires to assess the relationship between tachypnea (rapid respiratory rates) and a variety of domains including post-exertional malaise (PEM), a common complaint in patients with ME/CFS, and psychiatric/somatic symptoms, using hierarchical logistic regression analysis. RESULTS: PEM was a significant predictor of tachypnea, while psychological/somatic assessments and sedentary behaviors were not significantly predictive of tachypnea. CONCLUSIONS: These findings suggest that respiratory rate may be useful as an objective clinical metric of PEM, and potentially ME/CFS.

We followed college students before, during, and after infectious mononucleosis (IM) for the development of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).We used network analysis to s...

Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) involves severe fatigue, unrefreshing sleep, and cognitive impairment, leading to functional difficulties; prior studies have not evaluated risk factors with behavioral and immune data collected before developing ME/CFS. Up to 5% of university students develop infectious mononucleosis (IM) annually, and 9–12% meet criteria for ME/CFS 6 months later. We sought to determine predictors of ME/CFS. Methods We enrolled college students at the start of the school year (time 1), identified those who developed IM (time 2), and followed them for 6 months (time 3), identifying 3 groups: those who developed ME/CFS, severe ME/CFS (meeting >1 set of criteria), and who were asymptomatic. We conducted 8 behavioral and psychological surveys and analyzed cytokines at 3 time points. Results 238 of the 4501 students (5.3%) developed IM; 6 months later, 55 of the 238 (23%) met criteria for ME/CFS and 157 (66%) were asymptomatic. 67 of the 157 asymptomatic students served as controls. Students with severe ME/CFS were compared with students who were asymptomatic at 3 time points. The former group was not different from the latter group at time 1 (prior to developing IM) in stress, coping, anxiety, or depression but were different in several behavioral measures and had significantly lower levels of IL-6 and IL-13. At time 2 (when they developed IM), the 2 ME/CFS groups tended to have more autonomic complaints and behavioral symptoms while the severe-ME/CFS group had higher levels of IL-12 and lower levels of IL-13 than the recovered group. Conclusions At baseline, those who developed ME/CFS had more physical symptoms and immune irregularities, but not more psychological symptoms, than those who recovered.

Background: About 10% of individuals who contract infectious mononucleosis (IM) have symptoms 6 months later that meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Our study for the first time examined whether it is possible to predict who will develop ME/CFS following IM. Methods: We have reported on a prospectively recruited cohort of 4,501 college students, of which 238 (5.3%) developed IM. Those who developed IM were followed-up at six months to determine whether they recovered or met criteria for ME/CFS. The present study focuses on 48 students who after six months had a diagnosis of ME/CFS, and a matched control group of 58 students who had no further symptoms after their IM. All of these 106 students had data at baseline (at least 6 weeks prior to the development of IM), when experiencing IM, and 6 months following IM. Of those who did not recover from IM, there were two groups: 30 were classified as ME/CFS and 18 were classified as severe ME/CFS. We measured the results of 7 questionnaires, physical examination findings, the severity of mononucleosis and cytokine analyses at baseline (pre-illness) and at the time of IM. We examined predictors (e.g., pre-illness variables as well as variables at onset of IM) of those who developed ME/CFS and severe ME/CFS following IM. Results: From analyses using receiver operating characteristic statistics, the students who had had severe gastrointestinal symptoms of stomach pain, bloating, and an irritable bowel at baseline and who also had abnormally low levels of the immune markers IL-13 and/or IL-5 at baseline, as well as severe gastrointestinal symptoms when then contracted IM, were found to have a nearly 80% chance of having severe ME/CFS persisting six months following IM. Conclusions: Our findings are consistent with emerging literature that gastrointestinal distress and autonomic symptoms, along with several immune markers, may be implicated in the development of severe ME/CFS. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness affecting over a million people in the US1. Six months after having had Infectious Mononucleosis (IM), about 9-12% of individuals are diagnosed with this syndrome. For example, Hickie et al.2 showed an 11% rate of ME/CFS six months following acute infection with Epstein-Barr virus as well as following two other similar systemic infections. Katz et al.3 found similar outcomes following IM in youth. In a recent prospective, longitudinal study, university students were assessed prior to IM, at the time of IM, and at a six-month follow-up. Those who developed severe ME/CFS had differences in several pre-illness domains compared to those who recovered from IM without further symptoms4. In addition, Katz et al.5 found that the severity of IM was predictive of severe ME/CFS 6 months following IM. We have used these baseline pre-illness behavioral and immune data along with severity of IM data to predict who will develop severe ME/CFS six months following IM.

Objectives The Institute of Medicine (IOM 2015. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington: The National Academies Press) suggested new criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), which requires an endorsement of either neurocognitive impairment or orthostatic intolerance (OI) in addition to other core symptoms. While some research supports the inclusion of OI as a core symptom, others argue that overlap with neurocognitive impairment does not justify the either/or option. The current study assessed methods of operationalizing OI using items from the DePaul Symptom Questionnaire (DSQ-1 and -2) as a part of the IOM criteria. Evaluating the relationship between OI and neurocognitive symptoms may lead to a better understanding of diagnostic criteria for ME/CFS. Methods Two-hundred and forty-two participants completed the DSQ. We examined how many participants met the IOM criteria while endorsing different frequencies and severities of various OI symptoms. Results Neurocognitive impairment was reported by 93.4% of respondents. OI without concurrent neurocognitive symptoms only allowed for an additional 1.7–4.5% of participants to meet IOM criteria. Conclusions Neurocognitive symptoms and OI overlap in ME/CFS, and our results do not support the IOM’s inclusion of neurocognitive impairment and OI as interchangeable symptoms. Furthermore, our findings highlight the need for a uniform method of defining and measuring OI via self-report in order to accurately study OI as a symptom of ME/CFS.

256 Background: Current staging for colon cancer utilizing the American Joint Committee on Cancer TNM framework stratifies disease into groups according to how advanced the disease is and provides important standardized, individual prognostic information. Ideally, staging systems should exhibit hierarchical logic, with increasing stage reflecting worse prognosis. We sought to evaluate hierarchy within the 8th edition AJCC staging system for colon cancer. Methods: All patients with primary colon (including rectosigmoid) cancer diagnosed 2010-2017 were identified from the National Cancer Database (NCDB). Patients were only included if they carried a histologic diagnosis of invasive primary (non-recurrent) cancer, underwent radical surgery, and had complete pathologic staging data (T, N, M category data). Patients with missing follow-up data were excluded. Kaplan-Meier curves were used to assess overall survival by AJCC 8th edition pathologic summary stage group to determine whether staging was hierarchical for colon cancer. Multivariable modeling and log likelihood ratio test was then used to identify relative contributions of T and N variables to overall survival. Results: Among 270,584 colon cancer patients, pathologic staging was noted to be hierarchical by T category alone and by N category alone. However, summary staging was non-hierarchical in both instances. Multivariable modeling confirmed the AJCC non-hierarchy issue (colon HRs: 1, 1.54, 2.62, 2.60, 1.02, 2.15, and 4.38 for stage 1 as reference, 2a, 2b, 2c, 3a, 3b, 3c respectively). Multivariable modeling demonstrated that high T category (T4a, T4b) conferred the greatest risk of mortality based on hazard ratio (T4a HR 2.76, T4b HR 3.04), while high T category as well as high N category (N2a, N2b) contributed substantially to the survival model based on z-score. Further modeling assessing the predictive power of T and N category with respect to overall survival demonstrated that T category more strongly predicted overall survival than N category in colon cancer (likelihood chi-square test statistic pT:7009 vs pN:3586). Conclusions: Hierarchy in survival based on AJCC summary stage was not observed for patients with stage II-III colon cancer resulting in a paradoxical better observed survival with some stage III cancer subgroups compared to stage II cancer subgroups. High T category appears to more significantly impact survival than N category for patients with N0-N1 disease, while high N category appears more important for patients with T1-3 disease. Future revisions of the AJCC staging system should account for the differential impact of T and N category identified herein to more accurately confer prognostic information.

INTRODUCTION: Our objective was to determine which symptoms among long-hauler COVID-19 patients change over time, and how their symptoms compare to another chronic illness group. 278 long-haulers completed two symptom questionnaires at one time point, with one recounting experiences from an average of 21.7 weeks prior. METHODS: We used a comparison group of 502 patients diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Participants completed a standardized symptom questionnaire and a list of additional CDC COVID-19 symptoms. RESULTS: Over time, the long-haulers reported an overall reduction of most symptoms including unrefreshing sleep and post-exertional malaise, but an intensification of neurocognitive symptoms. When compared to ME/CFS, the COVID-19 sample was initially more symptomatic for the immune and orthostatic domains but over time, the long-haulers evidenced significantly less severe symptoms than those with ME/CFS, except in the orthostatic domain. Among the COVID-19 long haulers, several neurocognitive symptoms got worse over time, whereas improvements occurred in most other areas. CONCLUSIONS: These types of differential patterns of symptoms over time might contribute to helping better understand the pathophysiology of those reporting prolonged illness following COVID-19.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic disease with the hallmark symptom of post-exertional malaise. Evidence for physiological causes is converging, however, currently no diagnostic test or biomarker is available. People with ME/CFS experience stigmatization, including the perception that the disease is psychosomatic. In a sample of 499 participants with self-diagnosed ME/CFS, we investigated perceived stigma as a pathway through which perceived others’ causal attributions relate to lower satisfaction with social roles and activities and functional status. Higher perceived attributions by others to controllable and unstable causes predicted lower health-related and social outcomes via higher perceived stigma.

Objectives To develop a scale for the severity of mononucleosis. Study design One to 5 percent of college students develop infectious mononucleosis annually, and about 10% meet criteria for chronic fatigue syndrome (CFS) 6 months following infectious mononucleosis. We developed a severity of mononucleosis scale based on a review of the literature. College students were enrolled, generally when they were healthy. When the students developed infectious mononucleosis, an assessment was made as to the severity of their infectious mononucleosis independently by 2 physicians using the severity of mononucleosis scale. This scale was correlated with corticosteroid use and hospitalization. Six months following infectious mononucleosis, an assessment is made for recovery from infectious mononucleosis or meeting 1 or more case definitions of CFS. Results In total, 126 severity of mononucleosis scales were analyzed. The concordance between the 2 physician reviewers was 95%. All 3 hospitalized subjects had severity of mononucleosis scores ≥2. Subjects with severity of mononucleosis scores of ≥1 were 1.83 times as likely to be given corticosteroids. Students with severity of mononucleosis scores of 0 or 1 were less likely to meet more than 1 case definition of CFS 6 months following infectious mononucleosis. Conclusions The severity of mononucleosis scale has interobserver, concurrent and predictive validity for hospitalization, corticosteroid use, and meeting criteria for CFS 6 months following infectious mononucleosis.

Background : Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness affecting over a million people in the US. About 9-12% of individuals develop this syndrome six months following Infectious Mononucleosis (IM); those who meet > 1 set of criteria for ME/CFS are termed severe ME/CFS. We sought to determine why some individuals develop ME/CFS following IM while most recover. Methods: Our study was a prospective cohort study conducted at Northwestern University. We recruited a cohort of college students before, during, and after being infected with IM. Those who developed IM were followed-up with at six months to determine whether they recovered or met criteria for ME/CFS. We explored baseline levels and severity at follow-up of IM variables for those who recovered from IM and those who developed severe ME/CFS 6 months following IM. Findings: Pre-illness variables that differentiated these groups included baseline gastrointestinal symptoms and certain cytokines. At onset of IM, gastrointestinal symptoms differentiated the two groups. Interpretation: The differences that emerged predicted the onset of severe ME/CFS following IM. Our research has thus uncovered risk factors predisposing to non-recovery following IM so that preventative and treatment strategies for ME/CFS may now be devised and studied. Funding: This work was supported by the National Institute of Allergy and Infectious Diseases [grant number AI 105781]. Declaration of Interest: The authors declare no competing interests. Ethical Approval: Institutional Review Board approval was obtained.

This chapter provides insights about why certain procedures were used in order to guide other investigators who are conceptualizing and implementing their research in similar or overlapping areas. It begins with a discussion of the challenges faced by patients, particularly given the stigma associated with myalgic encephalomyelitis (ME) and Chronic fatigue syndrome (CFS). The chapter describes existing case definitions for ME and CFS, highlighting their limitations and the resulting methodological complications for researchers and clinicians. Researchers have incorporated methods pioneered by immunologists to examine potential biomarkers using multiplex assays identifying cytokines too small and localized to evaluate effectively. Despite inconclusive evidence, individuals with ME and CFS continue to be referred for psychological treatments, such as cognitive behavioral therapy and graded exercise therapy that presume a psychogenic illness etiology. The chapter concludes with a summary of the strengths and limitations of current research and suggests areas for future research.

The COVID-19 pandemic, resulting from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has severely impacted the population worldwide with a great mortality rate. The current article r...

This study adapted a chronic illness stigma scale and explored its psychometric properties. The main purposes were to confirm the factor structure of the instrument with this population and address the previous factor intercorrelation discrepancies. Five hundred and fifty-four individuals with myalgic encephalomyelitis or chronic fatigue syndrome completed the adapted stigma scale. Results document the stigma experienced by an international sample of individuals with myalgic encephalomyelitis and chronic fatigue syndrome. Factors demonstrated good internal consistency, and a model fit was found in a confirmatory factor analysis. Participants endorsed high levels of stigma, estrangement, and disclosure. Implications of these findings and future directions are discussed.

Considerable controversy has existed with efforts to assess post-exertional malaise (PEM), which is one of the defining features of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). While a number of self-report questionnaires have been developed to assess this symptom, none have been comprehensive, and a recent federal government report has recommended the development of a new PEM measure. The current study involved a community-based participatory research process in an effort to develop a comprehensive PEM instrument, with critical patient input shaping the item selection and overall design of the tool. A survey was ultimately developed and was subsequently completed by 1534 members of the patient community. The findings of this survey suggest that there are key domains of this symptom, including triggers, symptom onset, and duration, which have often not been comprehensively assessed in a previous PEM instrument. This study indicates that there are unique benefits that can be derived from patients collaborating with researchers in the measurement of key symptoms defining ME and CFS.

Post-exertional malaise, or a variation of this term, is a key symptom of myalgic encephalomyelitis and chronic fatigue syndrome, as this symptom is mentioned in almost all myalgic encephalomyelitis and chronic fatigue syndrome case definitions. Until now there has not been a comprehensive questionnaire to assess post-exertional malaise. To rectify this situation, in this article we describe the development of a new questionnaire, called the DePaul Post-Exertional Malaise Questionnaire, which was based on input from hundreds of patients. Preliminary validation was provided by the findings of significant and predictable relationships between different domains of this post-exertional malaise questionnaire and physical functioning.