The association between lung cancer stigma and race: A descriptive correlational study.

BACKGROUND: Stigma is a formidable burden for survivors of lung cancer that can reduce the quality of life (QOL), resulting in physical, social and psychological challenges. This study investigates associations between stigma and depression, QOL and demographic and health-related characteristics, including race. DESIGN: An adapted conceptual model derived from the Cataldo Lung Cancer Stigma Scale guided this descriptive correlation study assessing stigma in African American and Caucasian survivors of lung cancer. Self-reported, written surveys measuring depression, QOL, lung cancer stigma and demographics were administered. Statistical analysis was conducted to assess associations between stigma and depression, stigma and QOL and stigma and race, while adjusting for demographic characteristics. RESULTS: Participants (N = 56) included 30 Caucasian and 26 African American survivors of lung cancer recruited from a cancer registry of an American College of Surgeons-accredited programme, a survivors' support club and an ambulatory oncology practice in the southeastern United States. Statistical analysis yielded (1) a significant moderate positive association between depression and lung cancer stigma; (2) a significant moderate negative association between QOL and lung cancer stigma; and (3) significant relationships between race and lung cancer stigma, specifically higher degree of stigma among African Americans compared to Caucasians. CONCLUSION: Stigma affects many aspects of survivors' lives. Healthcare professionals need to consider how health-related stigma may further complicate the physical burdens, psychological distresses and social challenges that accompany the disease, especially among African American survivors. Additional enquiry and interventions are needed to assist with mitigating the negative effects of stigma on survivors and their family members and friends. PATIENT OR PUBLIC CONTRIBUTION: Fifty-six survivors of lung cancer participated in this descriptivecorrelation study. They completed written surveys measuring depression, QOL, and lung cancer stigma, plus an investigator-developed demographic information form.

Challenges Predicting the Cardiovascular Future for Survivors of Childhood Cancer.

Cardiovascular disease (CVD) risk stratification relies on assessment of nonmodifiable (age, sex, family history) and modifiable (weight, tobacco, physical activity, blood pressure, glucose/lipid levels) risk factors. Cancer therapy, itself a potential risk factor, may alter metabolism in long-term survivors of childhood cancer resulting in premature acquisition of age-related modifiable CVD risk factors. For survivors exposed to cardiotoxic therapies, the risk for CVD is significantly augmented by obesity, diabetes, dyslipidemia, and hypertension. An understanding of these risks may not be well communicated as survivors return to primary care and general population screening practices may be insufficient. Lipshultz and colleagues recruited childhood cancer survivors to return to their treating institution for a comprehensive clinical assessment. Interestingly, compared with a noncancer age-, sex-, and race/ethnicity-matched National Health and Nutrition Examination Survey population, cardiometabolic profiles were largely similar. However, cancer survivors had a higher prevalence of prehypertension/hypertension (38.4% vs. 30.1%, P = 0.04) and a lower prevalence of the metabolic syndrome (11.9% vs. 18.7%, P = 0.05). Applying general population CVD risk calculators and a cancer-specific model from the Childhood Cancer Survivor Study, risk estimates were notably higher when cardiotoxic cancer treatment exposures were included. See related article by Lipshultz et al., p. 536.

Adherence to Guideline-Recommended Cancer Screening in Stroke Survivors: A Nationwide Analysis.

OBJECTIVES: Cancer can present as stroke. Several cancer types have established screening guidelines. We investigated adherence to guideline-recommended cancer screening in stroke survivors versus the general population. MATERIALS AND METHODS: We performed a cross-sectional analysis using 2012-2018 data from the CDC's Behavioral Risk Factor Surveillance System (BRFSS) survey. BRFSS is a nationally-representative telephone survey of non-institutionalized Americans that collects data about health conditions and behaviors, including cancer screening. We defined guideline-recommended colorectal, lung, and breast cancer screening based on the U.S. Preventive Services Task Force recommendations. We used survey-specific methods to estimate up-to-date screening rates for those with and without prior stroke. We used logistic regression to estimate the odds of up-to-date screening in stroke survivors compared to those without history of stroke after adjustment for potential confounders. RESULTS: Among 1,018,440 respondents eligible for colorectal cancer screening, 66% were up-to-date. Among 6,880 respondents eligible for lung cancer screening, 16% were up-to-date. Among 548,434 women eligible for breast cancer screening, 78% were up-to-date. After adjustment for demographics and confounders, stroke survivors were more likely to have up-to-date colorectal cancer screening (OR, 1.10; 95% CI, 1.05-1.16), equally likely to undergo lung cancer screening (OR, 0.99; 95% CI, 0.62-1.59), and less likely to undergo breast cancer screening (OR, 0.87; 95% CI, 0.80-0.94). CONCLUSIONS: In a nationwide analysis, stroke survivors had similar suboptimal adherence to guideline-recommended cancer screening as the general population.

The long term participation trend for the colorectal cancer screening after the 2011 triple disaster in Minamisoma City, Fukushima, Japan.

Colorectal cancer (CRC) screening is a well-established cancer screening method, and its effectiveness depends on maintaining a high participation rate in the target population. In this study, we analyzed the trends in CRC screening participation rates over 10 years in Minamisoma City, where residents were forced to evacuate after the 2011 triple disaster in Fukushima, Japan. The immunochemical fecal occult blood test is provided as municipal CRC screening. We calculated the annual CRC screening participation rate and analyzed the factors associated with participation in screening. Overall, 4069 (12.3%) and 3839 (11.7%) persons participated in CRC screening in 2009 and 2010, respectively; however, the number decreased significantly to 1090 (3.4%) in 2011 when the earthquake occurred. Over the following 3 years, the rate gradually recovered. Multivariable logistic analysis showed that age < 65 years, living alone, and evacuation were significant associated factors for non-participation after 2011 (p < 0.05). In conclusion, the CRC screening participation rate decreased significantly during the Great East Japan Earthquake but recovered over the next 3 years. Further analysis of factors preventing CRC screening participation and research on the long-term effects of its post-disaster decline are important to consider in assessing the need for intervention in post-disaster cancer screening.

An epigenetic aging analysis of randomized metformin and weight loss interventions in overweight postmenopausal breast cancer survivors.

Metformin and weight loss relationships with epigenetic age measures-biological aging biomarkers-remain understudied. We performed a post-hoc analysis of a randomized controlled trial among overweight/obese breast cancer survivors (N = 192) assigned to metformin, placebo, weight loss with metformin, or weight loss with placebo interventions for 6 months. Epigenetic age was correlated with chronological age (r = 0.20-0.86; P < 0.005). However, no significant epigenetic aging associations were observed by intervention arms. Consistent with published reports in non-cancer patients, 6 months of metformin therapy may be inadequate to observe expected epigenetic age deceleration. Longer duration studies are needed to better characterize these relationships.Trial Registration: Registry Name: ClincialTrials.Gov.Registration Number: NCT01302379.Date of Registration: February 2011.URL: https://clinicaltrials.gov/ct2/show/NCT01302379.

AGING OF THE CHORNOBYL CATASTROPHE SURVIVORS AND PROBLEMS OF THEIR MENTAL HEALTH SURVEY. / STARINNIa POSTRAZhDALYKh VNASLIDOK ChORNOBYL'S'KOÏ KATASTROFY TA PROBLEMY DOSLIDZhENNIa ÏKhN'OGO PSYKhIChNOGO ZDOROV'Ia.

BACKGROUND: Depopulation processes in Ukraine have been affected by the Chornobyl catastrophe (ChC), but therate of demographic aging of survivors remains uncertain. Although the mental health disorders of the survivors arerecognized internationally, problems of their research remain unresolved. Thus, these areas of research are relevant.Objective is to determine the rate of demographic aging of survivors of the Chornobyl NPP (ChNPP) accident and toanalyze the state of their mental health survey, outlining solutions. MATERIALS AND METHODS: Information and statistical sources for 1986-2019 of the Ministry of Health of Ukraine andthe State Statistics Service of Ukraine on the age of the ChC survivors are used. The results of previous own researchand other scientists using the data of the Clinical and Epidemiological Register (CER) of the State Institution«National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine¼(NRCRM), the State Register of ChC survivors (SRU), and the Department of Radiation Psychoneurology, Institute ofClinical Radiology, NRCRM are integrated. Theoretical, general scientific, demographic and mathematical-statisticalresearch methods and documentary analysis are used. RESULTS: It is shown that in 2018, compared to 1995, the number of the ChC survivors, who are under the supervi-sion of the Ministry of Health of Ukraine, decreased by almost 987 thousand. The part of people born from personsof the 1st-3rd accounting groups increased in the structure of survivors (from 13.1 % in 1995 to 13.6 %), and thisdecreased in persons living or lived in the territories subject to supervision (75.1 % and 63.1 %, respectively), butin evacuees and Chornobyl clean-up workers (liquidators) this did not change significantly. A high level of aging ofthe ChC survivors (except for the 4th group) is revealed: liquidators - 59.0 %; evacuees - 25.0 %, and residents ofradioactively contaminated territories (RCT) - 30.7 %. It has been proved that the countries of RCT differ signifi-cantly in the number of the ChC survivors and their structure. The increase in the post-accident period indicators ofthe level of aging and the average age of the RCT population indicates negative changes in age parameters and theneed to continue research to identify factors «responsible¼ for such changes. Long-term mental health disordersand neuropsychiatric effects in the ChC survivors have been identified - an excess of cerebrovascular pathology andneurocognitive deficits, especially in liquidators, which may indicate an accelerated aging. Radiation risks havebeen revealed for acute and chronic cerebrovascular pathology and organic mental disorders of non-psychotic andpsychotic levels. Neurophysiological and molecular-biological atypia of aging processes under an exposure to lowdoses of and low dose rate of ionizing radiation have been found. The psyche under the age of 40 years old at thetime of exposure is more vulnerable. Existing statistical and registry data underestimate the level of mental disor-ders in the population of Ukraine, including the ChC survivors by an order of magnitude. CONCLUSIONS: The ChC survivors are aging in the country. The negative tendencies in age parameters of survival indi-cate the need to continue research to identify the factors «responsible¼ for such changes. Mental health disordersand neuropsychiatric effects in the ChC survivors are underestimated. It is necessary to create a national psychiatricregistry of Ukraine and long-term (lifelong) monitoring of survivors with well-planned clinical and epidemiologicalstudies of general and mental health with reliable dosimetric support based on national registries using the latest information technologies.

THYROID DISEASE IN THE LATE OBSERVATION PERIOD UPON CHEMO AND RADIOTHERAPY IN CHILDREN/SURVIVORS OF ACUTE LYMPHOBLASTIC LEUKEMIA. / KhVOROBY ShchYTOPODIBNOÏ ZALOZY PISLIa KhIMIO TA PROMENEVOÏ TERAPIÏ U DITEI, IaKI PERENESLY GOSTRU LIMFOBLASTNU LEIKEMIIu, U VIDDALENOMU PERIODI SPOSTEREZhENNIa.

OBJECTIVE: to assess the thyroid disease in the late observation period in children who had received chemo- andradiotherapy for the acute lymphoblastic leukemia (ALL) taking into account gender, age period and disease sub-type. MATERIALS AND METHODS: The incidence and nature of thyroid disease (hypothyroidism, thyroiditis, and thyroid can-cer) were studied in children-survivors of acute lymphoblastic leukemia (ALL) being in remission from 6 to 25 years.The distribution of patients by leukemia subtypes was as follows: «common¼ - 67.4 %, pre-B - 23.9 %, pro-B andT-cell - 4.3 %. Children had been receiving chemo- and radiotherapy according to the protocol. Regarding the ageof patients at the time of ALL diagnosis the prepubertal, pubertal and postpubertal periods were taken into account.The endocrine diseases in family history, body weight at birth, serum content of free thyroxine, pituitary thyroid-stimulating hormone, cortisol, iron, ferritin and thyroperoxidase antibodies were evaluated and assayed. RESULTS: Thyroid disease in children was emerging in the first 2-3 years after the ALL treatment with an incidenceof 22.8 % (hypothyroidism - 14.1 %, autoimmune thyroiditis - 7.6 %, papillary cancer - 1.1 %). Seven children inthis group had received radiotherapy (12-18 Gy doses) on the central nervous system (CNS). No correlation wasfound between the radiation exposure event itself, radiation dose to the CNS and thyroid disease in the long-termfollow-up period. Thyroid cancer had developed in a child 11 years upon chemo- and radiotherapy. Hypothyroidismwas more often diagnosed in the patients of prepubertal age (rs = 0.49). There were endocrine diseases in thefamily history in about a half of children, being significantly higher than in the general sample (р < 0.05). The bodyweight at birth of a child who had later developed hypothyroidism was less than in children having got thyroiditis(rs = 0.57). CONCLUSIONS: Disorders in endocrine regulation and of thyroid in particular can affect the prognosis of blood can-cer course in the long-term follow-up in children, especially in prepubertal age, which requires systematic supervi-sion by hematologist and endocrinologist.

CLINICAL-METABOLIC AND HORMONAL RELATIONSHIPS BETWEEN PARATHYROID DISEASE AND OTHER NON-CANCEROUS ENDOCRINE DISORDERS IN THE CHORNOBYL NPP ACCIDENT SURVIVORS. / KLINIKO-METABOLIChNI TA GORMONAL'NI VZAIeMOZV'IaZKY MIZh PATOLOGIIeIu PRYShchYTOPODIBNYKh ZALOZ TA INShYMY NEZLOIaKISNYMY ENDOKRYNNYMY ZAKhVORIuVANNIaMY U POSTRAZhDALYKh VNASLIDOK AVARIÏ NA ChAES.

OBJECTIVE: to investigate the clinical, hormonal-metabolic and structural features of parathyroid injuries in sur-vivors exposed to ionizing radiation after the Chornobyl NPP accident in adulthood and childhood, both with theirconnections to other non-cancerous endocrine disorders, and to establish the respective interhormonal and dys-metabolic relationships. MATERIALS AND METHODS: Clinical effects of ionizing radiation on the endocrine system in persons affected by theChornobyl NPP accident (n = 224) and their descendants (n = 146), compared with the general population sample(n = 70) were the study object. All patients underwent the ultrasound thyroid and parathyroid examination. Thegenerally recognized clinical, anthropometric (body weight, height, thigh volume, body mass index), instrumental(ultrasound examination of thyroid and parathyroid glands), laboratory (biochemical, hormonal), and statisticalmethods were applied. Parametric and nonparametric statistical methods were used in data processing. The value ofp < 0.05 was considered a statistically significant. RESULTS: No significant difference was found in the incidence of carbohydrate metabolic disorders in the ChornobylNPP (ChNPP) accident consequences clean-up workers (ACCUW), evacuees from the NPP 30-km exclusion zone, res-idents of radiologically contaminated areas and in the control group in whom the parathyroid hyperplasia wasdetected. There was a significant increase in the incidence of arterial hypertension among ACCUW who had parathy-roid hyperplasia (76.9%) vs. the control group (51.2%). In cases of parathyoid hyperplasia the vitamin D levels weresignificantly lower than without it. Vitamin D insufficiency/deficiency was found in 94% of the surveyed subjects.The average level of parathyroid hormone in blood serum was significantly higher in the ACCUW of «iodine¼ period withdiagnosed parathyroid hyperplasia than in the control group: (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml,p < 0.05. Results of multivariative analysis indicated a strong association of vitamin 25(OH)D insufficiency/defi-ciency with development of thyroid disease, carbohydrate metabolic disorders, cardiovascular disease, osteo-penia/osteoporosis. parathyroid ultrasound scan was at that an effective diagnostic method for primary screeningfor parathyroid hyperplasia and regular monitoring of the treatment efficiency. When examining children bornto parents irradiated after the ChNPPA the parathyroid hyperplasia (58%) and low serum content of vitamin D(11.6 ± 3.5) nmol / l were most often found in children living on radiologically contaminated territories (RCT).A strong correlation was established between the HOMA insulin resistance index and serum content of vitamin D(r = 0.65), parathyroid hormone (r = 0.60), and free thyroxine (r = 0.68) in the group of children born to parents irra-diated after the ChNPPA, having got chronic autoimmune thyroiditis, which indicated a relationship between thy-roid function, impaired carbohydrate and fat metabolism and the state of parathyroids. CONCLUSIONS: No difference in the incidence of carbohydrate metabolic disorders was found in the ChNPP ACCUW,evacuees from the 30-km exclusion zone, and residents of radiologically contaminated territories in whom parathy-roid hyperplasia was detected vs. the control group. Patients with parathyroid hyperplasia were found to be defi-cient in vitamin D in 94% of cases, and level of latter was significantly lower than under the normal parathyroid size.There was a significant increase in the incidence of diagnosed arterial hypertension among ACCUW who had parathy-roid hyperplasia vs. the control group: (76.9 ± 3.5)% vs. (51.2 ± 3.7)%. According to multivariate analysis a strongassociation between the vitamin 25(OH)D insufficiency/deficiency and development of thyroid disease, carbohydratemetabolic disorders, cardiovascular disease, and osteopenia/osteoporosis was established. The average level of pa-rathyroid hormone in the blood serum of the ChNPP ACCUW of the «iodine¼ period with diagnosed parathyroid hyper-plasia was significantly higher (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml; p <0,05) in the control group.

Deep phenotyping of T cell populations under long-term treatment of tacrolimus and rapamycin in patients receiving renal transplantations by mass cytometry.

Tacrolimus (FK506) and rapamycin (RAPA) are widely used to maintain long-term immunosuppression after organ transplantation. However, the impact of accumulative drug administration on the recipients' immune systems remains unclear. We investigated the impact of 3-year FK506 or RAPA treatment after renal transplantation on the human immune systems. A discovery cohort of 30 patients was first recruited, and we discovered two distinctive T lineage suppressive regulatory patterns induced by chronic treatment of FK506 and RAPA. The increased percentage of senescent CD8+ CD57+ T lineages and less responsive T cell receptor (TCR) pathway in the FK506 group indicate better graft acceptance. Meanwhile, percentages of regulatory T cells (Tregs) and expression of CTLA-4 were both up to two-fold higher in the RAPA group, suggesting the inconsistent reactivation potential of the FK506 and RAPA groups when an anti-tumour or anti-infection immune response is concerned. Additionally, up-regulation of phosphorylated signaling proteins in T lineages after in vitro CD3/CD28 stimulation suggested more sensitive TCR-signaling pathways reserved in the RAPA group. An independent validation cohort of 100 renal transplantation patients was further investigated for the hypothesis that long-term RAPA administration mitigates the development of tumours and infections during long-term intake of immunosuppressants. Our results indicate that RAPA administration indeed results in less clinical oncogenesis and infection. The deep phenotyping of T-cell lineages, as educated by the long-term treatment of different immunosuppressants, provides new evidence for personalized precision medicine after renal transplantations.

World Trade Center Health Program - United States, 2012-2020.

PROBLEM/CONDITION: After the September 11, 2001, terrorist attacks on the United States, approximately 400,000 persons were exposed to toxic contaminants and other factors that increased their risk for certain physical and mental health conditions. Shortly thereafter, both federal and nonfederal funds were provided to support various postdisaster activities, including medical monitoring and treatment. In 2011, as authorized by the James Zadroga 9/11 Health and Compensation Act of 2010, the CDC World Trade Center (WTC) Health Program began providing medical screening, monitoring, and treatment of 9/11-related health conditions for WTC responders (i.e., persons who were involved in rescue, response, recovery, cleanup, and related support activities after the September 11, 2001, terrorist attacks) and affected WTC survivors (i.e., persons who were present in the dust or dust cloud on 9/11 or who worked, lived, or attended school, child care centers, or adult day care centers in the New York City disaster area). REPORTING PERIOD COVERED: 2012-2020. DESCRIPTION OF SYSTEM: The U.S. Department of Health and Human Services WTC Health Program is administered by the director of CDC's National Institute for Occupational Safety and Health. The WTC Health Program uses a multilayer administrative claims system to process members' authorized program health benefits. Administrative claims data are primarily generated by clinical providers in New York and New Jersey at the Clinical Centers of Excellence and outside those states by clinical providers in the Nationwide Provider Network. This report describes WTC Health Program trends for selected indicators during 2012-2020. RESULTS: In 2020, a total of 104,223 members were enrolled in the WTC Health Program, of which 73.4% (n = 76,543) were responders and 26.6% (n = 27,680) were survivors. WTC Health Program members are predominantly male (78.5%). The median age of members was 51 years (interquartile range [IQR]: 44-57) in 2012 and 59 years (IQR: 52-66) in 2020. During 2012-2020, enrollment and number of certifications of WTC-related health conditions increased among members, with the greatest changes observed among survivors. Overall, at enrollment, most WTC Health Program members lived in New York (71.7%), New Jersey (9.3%), and Florida (5.7%). In 2020, the total numbers of cancer and noncancer WTC-related certifications among members were 20,612 and 50,611, respectively. Skin cancer, male genital system cancers, and in situ neoplasms (e.g., skin and breast) are the most common WTC-related certified cancer conditions. The most commonly certified noncancer conditions are in the aerodigestive and mental health categories. The average number of WTC-related certified conditions per certified member is 2.7. In 2020, a total of 40,666 WTC Health Program members received annual monitoring and screening examinations (with an annual average per calendar year of 35,245). In 2020, the total number of WTC Health Program members who received treatment was 41,387 (with an annual average per calendar year of 32,458). INTERPRETATION: Since 2011, the WTC Health Program has provided health care for a limited number of 9/11-related health conditions both for responders and survivors of the terrorist attacks. Over the study period, program enrollment and WTC certification increased, particularly among survivors. As the members age, increased use of health services and costs within the WTC Health Program are expected; chronic diseases, comorbidities, and other health-related conditions unrelated to WTC exposures are more common in older populations, which might complicate the clinical management of WTC-related health conditions. PUBLIC HEALTH ACTION: Analysis of administrative claims data in the context of WTC research findings can better clarify the health care use patterns of WTC Health Program members. This information guides programmatic decision-making and might also help guide future disaster preparedness and response health care efforts. Strengthening the WTC Health Program health informatics infrastructure is warranted for timely programmatic and research decision-making.

Comparison of functional dorsal attention network alterations in breast cancer survivors before and after chemotherapy.

ABSTRACT: Breast cancer is the leading type of cancer among women worldwide, and a high number of breast cancer patients are suffering from psychological and cognitive disorders. This cross-sectional study used resting-state functional magnetic resonance imaging (rs-fMRI) and clinical neuropsychological tests to evaluate the possible underlying mechanisms.We enrolled 32 breast cancer patients without chemotherapy (BC), 32 breast cancer patients within 6 to 12 months after the completion of chemotherapy (BC_CTx) and 46 healthy controls. Participants underwent neuropsychological tests and rs-fMRI with mean fractional amplitude of low-frequency fluctuation and mean regional homogeneity analyses. Between groups whole-brain voxel-wise rs-fMRI comparisons were calculated using two-sample t test. rs-fMRI and neuropsychological tests correlation analyses were calculated using multiple regression. Age and years of education were used as covariates. A false discovery rate-corrected P-value of less than .05 was considered statistically significant.We found significantly alteration of mean fractional amplitude of low-frequency fluctuation and mean regional homogeneity in the frontoparietal lobe and occipital lobe in the BC group compared with the other 2 groups, indicating alteration of functional dorsal attention network (DAN). Furthermore, we found the DAN alteration was correlated with neuropsychological impairment.The majority of potential underlying mechanisms of DAN alteration in BC patients may due to insufficient frontoparietal lobe neural activity to drive DAN and may be related to the effects of neuropsychological distress. Further longitudinal studies with comprehensive images and neuropsychological tests correlations are recommended.

Chest wall injuries due to cardiopulmonary resuscitation and the effect on in-hospital outcomes in survivors of out-of-hospital cardiac arrest.

BACKGROUND: This study aimed to assess the prevalence of chest wall injuries due to cardiopulmonary resuscitation for out-of-hospital cardiac arrest (OHCA) and to compare in-hospital outcomes in patients with versus without chest wall injuries. METHODS: A retrospective cohort study of all intensive care unit (ICU)-admitted patients who underwent cardiopulmonary resuscitation for OHCA between January 1, 2007, and December 2019 was performed. The primary outcome was the occurrence of chest wall injuries, as diagnosed on chest computed tomography. Chest wall injury characteristics such as rib fracture location, type, and dislocation were collected. Secondary outcomes were in-hospital outcomes and subgroup analysis of patients with good neurological recovery to identify those who could possibly benefit from the surgical stabilization of rib fractures. RESULTS: Three hundred forty-four patients were included, of which 291 (85%) sustained chest wall injury. Patients with chest wall injury had a median of 8 fractured ribs (P25-P75, 4-10 ribs), which were most often undisplaced (on chest computed tomography) (n = 1,574 [72.1%]), simple (n = 1,948 [89.2%]), and anterior (n = 1,785 [77.6%]) rib fractures of ribs 2 to 7. Eight patients (2.3%) had a flail segment, and 136 patients (39.5%) had an anterior flail segment. Patients with chest wall injury had fewer ventilator-free days (0 days [P25-P75, 0-16 days] vs. 13 days [P25-P75, 2-22 days]; p = 0.006) and a higher mortality rate (n = 102 [54.0%] vs. n = 8 [22.2%]; p < 0.001) than those without chest wall injury. For the subgroup of patients with good neurological recovery, the presence of six or more rib fractures or a single displaced rib fracture was associated with longer hospital and ICU length of stay, respectively. CONCLUSION: Cardiopulmonary resuscitation-related chest wall injuries in survivors of OHCA and especially rib fractures are common. Patients with chest wall injury had fewer ventilator-free days and a higher mortality rate. Patients with good neurological recovery might represent a subgroup of patients who could benefit from surgical stabilization of rib fractures. LEVEL OF EVIDENCE: Therapeutic, level IV; Epidemiological, Level IV.

Performance of a Machine Learning Algorithm Using Electronic Health Record Data to Identify and Estimate Survival in a Longitudinal Cohort of Patients With Lung Cancer.

Importance: Electronic health records (EHRs) provide a low-cost means of accessing detailed longitudinal clinical data for large populations. A lung cancer cohort assembled from EHR data would be a powerful platform for clinical outcome studies. Objective: To investigate whether a clinical cohort assembled from EHRs could be used in a lung cancer prognosis study. Design, Setting, and Participants: In this cohort study, patients with lung cancer were identified among 76 643 patients with at least 1 lung cancer diagnostic code deposited in an EHR in Mass General Brigham health care system from July 1988 to October 2018. Patients were identified via a semisupervised machine learning algorithm, for which clinical information was extracted from structured and unstructured data via natural language processing tools. Data completeness and accuracy were assessed by comparing with the Boston Lung Cancer Study and against criterion standard EHR review results. A prognostic model for non-small cell lung cancer (NSCLC) overall survival was further developed for clinical application. Data were analyzed from March 2019 through July 2020. Exposures: Clinical data deposited in EHRs for cohort construction and variables of interest for the prognostic model were collected. Main Outcomes and Measures: The primary outcomes were the performance of the lung cancer classification model and the quality of the extracted variables; the secondary outcome was the performance of the prognostic model. Results: Among 76 643 patients with at least 1 lung cancer diagnostic code, 42 069 patients were identified as having lung cancer, with a positive predictive value of 94.4%. The study cohort consisted of 35 375 patients (16 613 men [47.0%] and 18 756 women [53.0%]; 30 140 White individuals [85.2%], 1040 Black individuals [2.9%], and 857 Asian individuals [2.4%]) after excluding patients with lung cancer history and less than 14 days of follow-up after initial diagnosis. The median (interquartile range) age at diagnosis was 66.7 (58.4-74.1) years. The area under the receiver operating characteristic curves of the prognostic model for overall survival with NSCLC were 0.828 (95% CI, 0.815-0.842) for 1-year prediction, 0.825 (95% CI, 0.812-0.836) for 2-year prediction, 0.814 (95% CI, 0.800-0.826) for 3-year prediction, 0.814 (95% CI, 0.799-0.828) for 4-year prediction, and 0.812 (95% CI, 0.798-0.825) for 5-year prediction. Conclusions and Relevance: These findings suggest the feasibility of assembling a large-scale EHR-based lung cancer cohort with detailed longitudinal clinical measurements and that EHR data may be applied in cancer progression with a set of generalizable approaches.

Activities of daily living associated with postoperative intensive care unit survival in elderly patients following elective major abdominal surgery: An observational cohort study.

ABSTRACT: Elderly patients who undergo major abdominal surgery are being in increasing numbers. Intensive care unit (ICU) survival is critical for surgical decision-making process. Activities of daily living (ADL) are associated with clinical outcomes in the elderly. We aimed to investigate the relationship between ADL and postoperative ICU survival in elderly patients following elective major abdominal surgery.We conducted a retrospective cohort study involving patients aged ≥65 years admitted to the surgical intensive care unit (SICU) following elective major abdominal surgery. Data from all patients were extracted from the electronic medical records. The Barthel Index (BI) was used to assess the level of dependency in ADL at the time of hospital admission.ICU survivors group had higher Barthel Index (BI) scores than non-survivors group (P < .001). With the increase of BI score, postoperative ICU survival rate gradually increased. The ICU survivals in patients with BI 0-20, BI 21-40, BI 41-60, BI 61-80 and BI 81-100 were 55.7%, 67.6%, 72.4%, 83.3% and 84.2%, respectively. In logistic regression, The Barthel Index (BI) was significantly correlated with the postoperative ICU survival in elderly patients following elective major abdominal surgery (OR = 1.33, 95% CI: 1.20-1.47, P = .02). The area under the receiver operating characteristic (ROC) curve of Barthel Index in predicting postoperative ICU survival was 0.704 (95% CI, 0.638-0.771). Kaplan-Meier survival curve in BI≥30 patients and BI < 30 patients showed significantly different.Activity of daily living upon admission was associated with postoperative intensive care unit survival in elderly patients following elective major abdominal surgery. The Barthel Index(BI) ≥30 was associated with increased postoperative ICU survival. For the elderly with better functional status, they could be given more surgery opportunities. For those elderly patients BI < 30, these results provide useful information for clinicians, patients and their families to make palliative care decisions.

Association of Copy Number Variation Signature and Survival in Patients With Serous Ovarian Cancer.

Importance: Tailoring therapeutic regimens to individual patients with ovarian cancer is informed by severity of disease using a variety of clinicopathologic indicators. Although DNA repair variations are increasingly used for therapy selection in ovarian cancer, molecular features are not widely used for general assessment of patient prognosis and disease severity. Objective: To distill a highly dynamic characteristic, signature of copy number variations (CNV), into a risk score that could be easily validated analytically or repurposed for use given existing US Food and Drug Administration (FDA)-approved multigene assays. Design, Setting, and Participants: This genetic association study used the Cancer Genome Atlas Ovarian Cancer database to assess for genome-wide survival associations agnostic to gene function. Regions enriched for significant associations were compared to associations from scrambled data. CNV associations were condensed into a risk score, which was internally validated using bootstrapping. The participants were patients with serous ovarian cancer (stages I-IV) diagnosed from 1992 to 2013. Statistical analysis was performed from April to July 2020. Main Outcomes and Measures: Overall survival (OS). Results: Among 564 patients with serous ovarian cancer, the mean (SD) age was 59.7 (11.5) years; 34 (6%) identified as Black or African American. A total of 13 genome regions, comprising 14 alterations, were identified as significantly risk associated. Composite risk score was independent of total CNV burden, total mutational burden, BRCA status, and open-source genome-wide DNA repair deficiency signatures. Binned terciles yielded high-, standard-, and low-risk groups with respective median OS estimates of 2.9 (95% CI, 2.3-3.2) years, 4.1 (95% CI, 3.7-4.8) years, and 5.7 (95% CI, 4.7-7.4) years, respectively (P < .001). Associated 5-year survival estimates in each tercile were 15% (95% CI, 10%-22%), 36% (95% CI, 29%-46%), and 53% (95% CI, 45%-62%). The risk score had more discriminatory ability to prognosticate OS than age, clinical stage, grade, and race combined, and was strongly additive to significant clinical features (P < .001). Simulated adaptation of FDA-approved assays showed similar performance. Gene ontology analyses of identified regions showed an enrichment for regulatory miRNAs and protein kinase regulators. Conclusions and Relevance: This study found that a CNV-based risk score is independent to and stronger than current or near-future ovarian cancer genomic biomarkers to prognosticate OS. CNV regions identified were not strongly associated with canonical ovarian cancer biological pathways, identifying candidates for future mechanistic investigations. External validation of the CNV risk score, especially in concert with more extensive clinical features, could be pursued via existing FDA-approved assays.

Interleukin-6 as potential mediator of long-term neuropsychiatric symptoms of COVID-19.

The majority of COVID-19 survivors experience long-term neuropsychiatric symptoms such as fatigue, sleeping difficulties, depression and anxiety. We propose that neuroimmune cross-talk via inflammatory cytokines such as interleukin-6 (IL-6) could underpin these long-term COVID-19 symptoms. This hypothesis is supported by several lines of research, including population-based cohort and genetic Mendelian Randomisation studies suggesting that inflammation is associated with fatigue and sleeping difficulties, and that IL-6 could represent a possible causal driver for these symptoms. Immune activation following COVID-19 can disrupt T helper 17 (TH17) and regulatory T (Treg) cell responses, affect central learning and emotional processes, and lead to a vicious cycle of inflammation and mitochondrial dysfunction that amplifies the inflammatory process and results in immuno-metabolic constraints on neuronal energy metabolism, with fatigue being the ultimate result. Increased cytokine activity drives this process and could be targeted to interrupt it. Therefore, whether persistent IL-6 dysregulation contributes to COVID-19-related long-term fatigue, sleeping difficulties, depression, and anxiety, and whether targeting IL-6 pathways could be helpful for treatment and prevention of long COVID are important questions that require investigation. This line of research could inform new approaches for treatment and prevention of long-term neuropsychiatric symptoms of COVID-19. Effective treatment and prevention of this condition could also help to stem the anticipated rise in depression and other mental illnesses ensuing this pandemic.

Insights from a Prospective Follow-up of Thyroid Function and Autoimmunity among COVID-19 Survivors.

BACKGROUND: The occurrence of Graves' disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. METHODS: We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months. RESULTS: In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer. CONCLUSION: Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.

Long-Term Kidney Outcomes Following Dialysis-Treated Childhood Acute Kidney Injury: A Population-Based Cohort Study.

BACKGROUND: AKI is common during pediatric hospitalizations and associated with adverse short-term outcomes. However, long-term outcomes among survivors of pediatric AKI who received dialysis remain uncertain. METHODS: To determine the long-term risk of kidney failure (defined as receipt of chronic dialysis or kidney transplant) or death over a 22-year period for pediatric survivors of dialysis-treated AKI, we used province-wide health administrative databases to perform a retrospective cohort study of all neonates and children (aged 0-18 years) hospitalized in Ontario, Canada, from April 1, 1996, to March 31, 2017, who survived a dialysis-treated AKI episode. Each AKI survivor was matched to four hospitalized pediatric comparators without dialysis-treated AKI, on the basis of age, sex, and admission year. We reported the incidence of each outcome and performed Cox proportional hazards regression analyses, adjusting for relevant covariates. RESULTS: We identified 1688 pediatric dialysis-treated AKI survivors (median age 5 years) and 6752 matched comparators. Among AKI survivors, 53.7% underwent mechanical ventilation and 33.6% had cardiac surgery. During a median 9.6-year follow-up, AKI survivors were at significantly increased risk of a composite outcome of kidney failure or death versus comparators. Death occurred in 113 (6.7%) AKI survivors, 44 (2.6%) developed kidney failure, 174 (12.1%) developed hypertension, 213 (13.1%) developed CKD, and 237 (14.0%) had subsequent AKI. AKI survivors had significantly higher risks of developing CKD and hypertension versus comparators. Risks were greatest in the first year after discharge and gradually decreased over time. CONCLUSIONS: Survivors of pediatric dialysis-treated AKI are at higher long-term risks of kidney failure, death, CKD, and hypertension, compared with a matched hospitalized cohort.

Everyday Abilities Scale for India in Screening for Poststroke Dementia Among Young Stroke Survivors.

INTRODUCTION: Cognitive dysfunction after stroke is an important concern. We explored the utility of everyday abilities scale for India (EASI) for screening for dementia among young stroke survivors. METHODS: We interviewed 150 young stroke survivors and caregivers. Vascular dementia was diagnosed according to American Heart Association-American Stroke Association (ASA-AHA) criteria. EASI was administered to all caregivers. Receiver operating characteristic curve analysis was used to determine the area under the curve and optimum cut-points for EASI for the identification of dementia. RESULTS: Median EASI scores among subjects with dementia (n=35; 23.3%) was 2 (interquartile range: 0-4) and significantly different from those without (median: 0; interquartile range: 0-1; P<0.001). The area under the curve was 0.768 (95% confidence interval: 0.674-0.863), and at the optimum cut-point of 2 on EASI, a sensitivity of 60% and specificity of 91.3% was achieved for the identification of dementia. CONCLUSION: EASI appears to be a promising tool to screen for dementia among young stroke survivors.