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Burn injury risk, severity, and outcomes have been associated with socioeconomic status. Limited data exist to evaluate health access-related influences at a structural population level. This study evaluated factors at the Census-tract level, specifically evaluating food access and social vulnerability in pediatric scald burns.A single-institution retrospective review using the trauma registry and electronic medical record was conducted of pediatric burns between 2016 and 2020. Home address was coded to the Census-tract level and bulk analyzed. Socioeconomic metrics of the home environment were evaluated from publicly available databases, the United States Food and Drug Administration Food Access Research Atlas, and the Centers for Disease Control's Social Vulnerability Index.There were 840 patients that met inclusion criteria (49.8% scald, N = 418). The mean total body surface area for scalds was 6.6% with an age of 10.2 years; 76% (n = 317) of scalds had Medicaid, and 15% (n = 63) were due to hot noodles. Scalds occurred more in females (45.7%, N = 191 vs 28.0%, N = 118; Plt; .0001), non-White race (62.7%, N = 262 vs 29.1%, N = 123; Plt; .0001), and low-income and low-food access populations (39.8%, N = 147 vs 30.4%, N = 116; P = .007). Low-food access Black populations showed increased scald injury (18% [interquartile range 6-35] vs 10% [interquartile range 4-25]), whereas all other populations showed no association. The patients with scalds had a higher overall social vulnerability index (0.67 vs 0.62, P = .008).Often related to poverty, health access, and health equity, population-level social determinants of health like social vulnerability and food access have significant impact on health care and should influence health outreach and systems improvement.

Little is known about metabolic and nutrition characteristics of patients with coronavirus disease 2019 (COVID-19) and persistent critical illness. We aimed to compare those characteristics in patients with PCI and COVID-19 and patients without COVID-19 infection (non-CO)-primarily, their energy balance. This is a prospective observational study including two consecutive cohorts, defined as needing intubation for >10 days. We collected demographic data, severity scores, nutrition variables, length of stay, and mortality. Altogether, 104 patients (52 per group) were included (59 ± 14 years old [mean ± SD], 75% men) between July 2019 and May 2020. SAPSII, Nutrition Risk Screening (NRS) score, proportion of obese patients, duration of intubation (18.2 ± 11.7 days), and mortality rates were similar. Patients with COVID-19 (vs non-CO) had lower SOFA scores (P = 0.013) and more frequently needed prone position (P < 0.0001) and neuromuscular blockade (P < 0.0001): lengths of ICU (P = 0.03) and hospital stays were shorter (P < 0.0001). Prescribed energy targets were below those of the ICU protocol. The energy balance of patients with COVID-19 was significantly more negative after day 10. Enteral nutrition (EN) started earlier (P < 0.0001). During the first 10 days, COVID-19 patients received more lipid (propofol sedation) and less protein. Higher admission C-reactive protein (P = 0.002) decreased faster (P < 0.001). Whereas intestinal function was characterized by constipation in both groups during the first 10 days, diarrhea was less common in patients with COVID-19 thereafter. Compared with non-CO patients, COVID-19 patients were not more obese, had lower SOFA scores, and were fed more rapidly with EN, because of a more normal gastrointestinal function possibly due to fewer non-respiratory organ failures: their energy balances were more negative after the first 10 days. Propofol sedation reduced protein delivery.

Background The enormous health impact of the COVID-19 pandemic has refocused attention on measures to optimize immune function and vaccine response. Dietary deficiencies of micronutrients can weaken adaptive immunity. The aim of this review was to examine links between micronutrients, immune function and COVID-19 infection, with a focus on nutritional risks in subgroups of the Swiss population. Methods Scoping review on the associations between selected micronutrients (vitamins D and C, iron, selenium, zinc, and n-3 PUFAs) and immunity, with particular reference to the Swiss population. These nutrients were chosen because previous EFSA reviews have concluded they play a key role in immunity. Results The review discusses the available knowledge on links between sufficient nutrient status, optimal immune function, and prevention of respiratory tract infections. Because of the rapid spread of the COVID-19 pandemic, controlled intervention studies of micronutrients in the context of COVID-19 infection are now underway, but evidence is not yet available to draw conclusions. The anti-inflammatory properties of n-3 PUFAs are well established. In Switzerland, several subgroups of the population are at clear risk of nutrient deficiencies; e.g., older adults, multiple comorbidities, obesity, pregnancy, and institutionalized. Low intakes of n-3 PUFA are present in a large proportion of the population. Conclusion There are clear and strong relationships between micronutrient and n-3 PUFA status and immune function, and subgroups of the Swiss population are at risk for deficient intakes. Therefore, during the COVID-19 pandemic, as a complement to a healthy and balanced diet, it may be prudent to consider supplementation with a combination of moderate doses of Vitamins C and D, as well as of Se, Zn and n-3 PUFA, in risk groups., Clinical Nutrition ESPEN, 43, ISSN:2405-4577

BACKGROUND The US Preventive Services Task Force (USPSTF) includes multitarget stool DNA (mt-sDNA) testing as a colorectal cancer (CRC) screening option in average-risk individuals, but data on colonoscopy outcomes after positive mt-sDNA tests in community settings are needed. AIM The aim of this study was to investigate colonoscopy outcomes and quality following positive mt-sDNA in the population-based New Hampshire Colonoscopy Registry. METHODS We compared colonoscopy outcomes and quality between age-matched, sex-matched, and risk-matched patients from 30 endoscopy practices with and without a preceding positive mt-sDNA test. Main outcomes were colonoscopy findings of CRC, advanced noncancerous neoplasia, nonadvanced neoplasia, or normal examination. Quality measures included withdrawal time, bowel preparation quality, examination completion, and percentage of average-risk individuals with normal colonoscopies receiving a USPSTF-recommended 10 year rescreening interval. RESULTS Individuals with positive mt-sDNA tests (N=306, average age 67.0 y; 61.8% female) were significantly more likely than colonoscopy-only patients (N=918, 66.2 y; 61.8% female) to have CRC (1.3% vs. 0.4%) or advanced noncancerous neoplasia (27.1% vs. 8.2%) (P

Amino acid (AA) metabolism is severely disturbed in critically ill ICU patients. To be able to make a more scientifically based decision on the type of protein or AA nutrition to deliver in ICU patients, comprehensive AA phenotyping with measurements of plasma concentrations and whole body production (WBP) is needed. Therefore, we studied ICU patients and matched control subjects using a novel pulse isotope method to obtain in-depth metabolic analysis. In 51 critically ill ICU patients (SOFA~6.6) and 49 healthy controls, we measured REE and body composition/phase-angle using BIA. In the postabsorptive state, we collected arterial (ized) blood for CRP and AA. Then, we administered an 8 mL solution containing 18 stable AA tracers as a pulse and calculated WBP. Enrichments: LC-MS/MS and statistics: t-test, ANCOVA. Compared to healthy, critically ill ICU patients had lower phase-angle (p 0.00001), and higher CRP (p 0.0001). Most AA concentrations were lower in ICU patients (p 0.0001), except tau-methylhistidine and phenylalanine. WBP of most AA were significantly (p 0.0001) higher with increases in glutamate (160%), glutamine (46%), and essential AA. Remarkably, net protein breakdown was lower. There were only weak relationships between AA concentrations and WBP. Critically ill ICU patients (SOFA 8-16) had lower values for phase angle (p = 0.0005) and small reductions of most plasma AA concentrations, but higher tau-methylhistidine (p = 0.0223) and hydroxyproline (p = 0.0028). Remarkably, the WBP of glutamate and glutamine were lower (p 0.05), as was their clearance, but WBP of tau-methylhistidine (p = 0.0215) and hydroxyproline (p = 0.0028) were higher. Our study in critically ill ICU patients shows that comprehensive metabolic phenotyping was able to reveal severe disturbances in specific AA pathways, in a disease severity dependent way. This information may guide improving nutritional compositions to improve the health of the critically ill patient. CLINICAL TRIAL REGISTRY: Data are from the baseline measurements of study NCT02770092 (URL: https://clinicaltrials.gov/ct2/show/NCT02770092) and NCT03628365 (URL: https://clinicaltrials.gov/ct2/show/NCT03628365).

Through their ability to regulate gene expression in most organs, glucocorticoid (GC) hormones influence numerous physiological processes and are therefore key regulators of organismal homeostasis. In bone, GC hormones inhibit expression of the hormone Osteocalcin for poorly understood reasons. Here, we show that in a classical endocrine feedback loop, osteocalcin in return enhanced the biosynthesis of GC as well as mineralocorticoid hormones (adrenal steroidogenesis) in rodents and primates. Conversely, inactivation of osteocalcin signaling in adrenal glands significantly impaired adrenal growth and steroidogenesis in mice. Embryo-made osteocalcin was necessary for normal Sf1 expression in fetal adrenal cells and adrenal cell steroidogenic differentiation and therefore determined the number of steroidogenic cells present in the adrenal glands of adult animals. Embryonic, not postnatal, osteocalcin also governed adrenal growth, adrenal steroidogenesis, blood pressure, electrolyte equilibrium, and the rise in circulating corticosterone levels during the acute stress response in adult offspring. This osteocalcin-dependent regulation of adrenal development and steroidogenesis occurred even in the absence of a functional hypothalamus/pituitary/adrenal axis and explains why osteocalcin administration during pregnancy promoted adrenal growth and steroidogenesis and improved the survival of adrenocorticotropic hormone signaling-deficient animals. This study reveals that a bone-derived embryonic hormone influences lifelong adrenal functions and organismal homeostasis in the mouse.

BACKGROUND: Cardiac troponins (cTn) have been reported to be predictors for adverse outcomes in atrial fibrillation (AF), patients, but their actual use is still unclear.AIM: To assess the factors associated with cTn testing in routine practice and evaluate the association with outcomes.METHODS: Patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry were stratified into 3 groups according to cTn levels as (i) cTn not tested, (ii) cTn in range (≤99th percentile), (iii) cTn elevated (>99th percentile). The composite outcome of any thromboembolism /any acute coronary syndrome/cardiovascular (CV) death, defined as Major Adverse Cardiovascular Events (MACE) and all-cause death were the main endpoints.RESULTS: Among 10 445 AF patients (median age 71 years, 40.3% females) cTn were tested in 2834 (27.1%). cTn was elevated in 904/2834 (31.9%) and in-range in 1930/2834 (68.1%) patients. Female sex, in-hospital enrollment, first-detected AF, CV risk factors, history of coronary artery disease, and atypical AF symptoms were independently associated with cTn testing. Elevated cTn were independently associated with a higher risk for MACE (Model 1, hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.40-2.16, Model 2, HR 1.62, 95% CI 1.28-2.05; Model 3 HR 1.76, 95% CI 1.37-2.26) and all-cause death (Model 1, HR 1.45, 95% CI 1.21-1.74; Model 2, HR 1.36, 95% CI 1.12-1.66; Model 3, HR 1.38, 95% CI 1.12-1.71).CONCLUSIONS: Elevated cTn levels were associated with an increased risk of all-cause mortality and adverse CV events. Clinical factors that might enhance the need to rule out CAD were associated with cTn testing.

Background or objectives Breast cancer is the most frequent cancer in women. Chronic pain following mastectomy remains a significant problem. This study aimed to evaluate risk factors associated with postoperative chronic pain. Methods Medical records were analyzed retrospectively for 147 consecutive patients with breast cancer who underwent mastectomy between July 2016 and February 2018 with one-year follow-up. All patients received a paravertebral block pre-operatively and then general anesthesia for the surgery. Results The median postoperative pain score was 1.3 on the verbal analgesic score. The average total dose of opioids administered postoperatively was 10.4 mg, expressed in morphine milligram equivalents. The incidence of chronic pain after mastectomy was 16.7% at 6 months and 13.3% at 1 year. The satisfaction rate for anesthesia and surgery was 95.7%. Conclusions The data suggested that preoperative paravertebral nerve blocks, appropriate adjuvants, and a balanced general anesthetic may contribute to better postoperative pain control and decreased the incidence of chronic pain. A history of preoperative use of opioids and/or a history of alcohol consumption were both associated with significant increased levels of postoperative pain, and this subgroup warrants attention to diminish the risk of developing chronic pain.

Sleep-wake disturbances have been associated with episodic memory loss, but past studies were limited by use of single measures of objective or perceived disturbances. Notably, cognitive reserve and depressive symptoms have been associated with sleep-wake disturbances and poorer episodic memory in older adults. The aims of this study were to determine the relationship between episodic memory and sleep-wake disturbances using objective and perceived measures in older adults and to examine cognitive reserve and depressive symptoms as moderators of this relationship. In this descriptive study, 62 healthy older adults (mean age: 69.9 years; 75.8% women) were recruited from the University of Michigan Clinical Research Program. Objective sleep-wake disturbances were measured by 7-day actigraphy and perceived sleep-wake disturbances by the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Episodic memory was measured by the Hopkins Verbal Learning Test-Revised. Analyses involved Pearson’s correlation coefficients and hierarchical multiple regression. Results showed that more objectively measured sleep disruption was associated with poorer episodic memory and more perceived daytime sleepiness was associated with better episodic memory. Cognitive reserve and depressive symptoms were not moderators of this relationship. In this study, the relationship between sleep-wake disturbances and episodic memory differed by type of measure, objective or perceived. Future studies are needed using multiple measures of episodic memory to further understand the sleep-wake disturbances and episodic memory relationship in a larger diverse sample of healthy older adults.

Purpose Ascent to high altitude increases right ventricular (RV) afterload and decreases myocardial energy supply. This study evaluates physiologic variables and comprehensive echocardiographic indices of RV and right atrial (RA) function following rapid ascent to high altitude. Methods Fifty healthy volunteers actively ascended from 1130 to 4559 m in Results sPAP increased from baseline (24 ± 4 mmHg) to the first altitude examination (39 ± 8 mmHg, p p = 0.07) secondary to a significant increase of RA contraction strain (19.2 ± 6.4 vs. 25.4 ± 9.6%, p Conclusion Active and rapid ascent of healthy individuals to 4559 m is associated with an increased contractile performance of the RA that compensates for the increased workload of the RV.

OBJECTIVES: Multitarget stool DNA (MT-sDNA) testing has grown as a noninvasive screening modality for colorectal cancer (CRC), but real-world clinical data are limited in the post-FDA approval setting. The effect of previous colonoscopy on MT-sDNA performance is not known. We aimed to evaluate findings of colorectal neoplasia (CRN) at diagnostic colonoscopy in patients with positive MT-sDNA testing, stratified by patient exposure to previous colonoscopy. METHODS: We identified consecutive patients completing MT-sDNA testing over a 39-month period and reviewed the records of those with positive tests for neoplastic findings at diagnostic colonoscopy. MT-sDNA test positivity rate, adherence to diagnostic colonoscopy, and the positive predictive value (PPV) of MT-sDNA for any CRN and neoplastic subtypes were calculated. RESULTS: Of 16,469 MT-sDNA tests completed, testing returned positive in 2,326 (14.1%) patients. After exclusion of patients at increased risk for CRC, 1,801 patients remained, 1,558 (87%) of whom underwent diagnostic colonoscopy; 918 of 1,558 (59%) of these patients had undergone previous colonoscopy, whereas 640 (41%) had not. Any CRN was found in 1,046 of 1,558 patients (PPV = 67%). More neoplastic lesions were found in patients without previous colonoscopy (73%); however, the rates remained high among those who had undergone previous colonoscopy (63%, P < 0.0001). The large majority (79%) of patients had right-sided neoplasia. DISCUSSION: MT-sDNA has a high PPV for any CRN regardless of exposure to previous colonoscopy. Right-sided CRN was found at colonoscopy in most patients with positive MT-sDNA testing, representing a potential advantage over other currently available screening modalities for CRC.

Objective To determine cross-sectional adherence with the multi-target stool DNA test used for colorectal cancer screening in a large, fully insured Medicare population. Methods All patients aged 65–85 with a valid multi-target stool DNA test order from 1 September 2016 to 31 August 2017 identified from the Exact Sciences Laboratories (Madison, WI; sole-source national multi-target stool DNA test provider) database were evaluated for test adherence. Cross-sectional adherence, defined as multi-target stool DNA test completion within 365 days from order date, was analyzed overall and by time to adherence, as well as by available patient (age, sex, test order date, Medicare coverage type) and provider (specialty, year of first multi-target stool DNA test order, multi-target stool DNA test order frequency, and practice location) factors. Results Among 368,494 Medicare beneficiaries (64% female), overall cross-sectional adherence was 71%. Cumulative adherence rates increased more rapidly at 30 (44%) and 60 (65%) days, followed by more gradual increases at 90 (67%), 180 (70%), and 365 (71%) days. By provider specialty, primary care clinicians represented a higher percentage of multi-target stool DNA orders than gastroenterologists (88% vs. 6%), but had a lower associated patient adherence rate (71% vs. 78%). Conclusions In this large, national sample of Medicare insured older adults, nearly three-quarters of patients adhered with a multi-target stool DNA order for colorectal cancer screening. These real-world data should inform further clinical and population health applications, reimbursement model simulations, and guideline-endorsed colorectal cancer screening strategies adherence.

Background Beginning in 2014-2015, schools nationwide have had the option of offering free meals to all students in qualifying schools through the Community Eligibility Provision (CEP). The CEP has been linked to greater likelihood of eating school meals, but little is known about its impact on broader outcomes. Objective The purpose of this study was to estimate the association between the CEP and school attendance among elementary school students (grades 1 to 5). Design This was a quasi-experimental study in which students’ attendance records were observed over 1 baseline and 2 follow-up years in a sample of CEP and eligible non-CEP schools. Participants/setting The participants were elementary school students in Wisconsin during three consecutive school years beginning 2013-2014. The main sample included 92,126 observation-years for students in 37 CEP and 108 eligible non-CEP elementary schools. Intervention CEP-participating schools offered breakfast and lunch free to all students through the School Breakfast Program and the National School Lunch Program beginning in 2014-2015. Main outcome measures The outcome measures were the attendance rate (defined as the percentage of school days attended) and low attendance (defined as attending fewer than 95% of available days) during the first and second implementation years. Statistical analyses performed Difference-in-difference regression models with student fixed effects were estimated, with separate impacts for the first and second CEP years. Models adjusted for time-varying school and student characteristics. Results Implementing the CEP had no association with attendance in the initial year. The second year of CEP was associated with a 3.5 percentage point reduction in the percentage of students with low attendance (P=0.045). An association between CEP and attendance was only found for economically disadvantaged students. Conclusions Offering meals free to all students through the CEP may modestly reduce the risk of low attendance among economically disadvantaged students in participating schools.

Fatigue is the most reported and most distressing symptom among patients with cancer. However, no questionnaire that measures fatigue and fatigue interference with life has been translated into Arabic.This study aimed to translate and validate the Arabic version of the Brief Fatigue Inventory (BFI-A).The BFI was translated into Arabic using the forward-backward translation technique. This cross-sectional study collected data from cancer patients through a self-administered questionnaire that included the BFI-A, Insomnia Severity Index (ISI), Zung Depression Scale (ZDS), MD Anderson Symptom Inventory total score (MDASI), and Medical Outcome Study Short Form 36 (SF-36) Vitality Subscale. Descriptive and inferential statistics were used including mean, standard deviation, internal consistency, and correlation coefficient using Pearson's correlation.A total of 79 patients were recruited in Amman, Jordan, in 2015. Mean of the total BFI-A was 4.01 (2.4), showing that 83.5% had nonsevere fatigue. Cronbach's α coefficient of the BFI-A was 0.93. The correlations between total BFI-A scores and BFI-A items were significant (P0.05) and ranged from 0.75 to 0.86. BFI-A showed a significant correlation (P0.05) with the following tools: ISI = 0.70, ZDS = 0.69, MDASI = 0.75, and SF-36 Vitality Subscale = -0.57.This study suggests that the BFI-A is a reliable and valid tool to assess fatigue among Arab cancer patients.دراسة للتحقق من النسخة العربية لمقياس التعب الوجيز (BFI–A).خالد سليمان، محمود الكلالدة، لؤي أبو شحرور، برنيس ييتس، آن بيرجر، تيتو مندوزا، ملكة ملك، أيمن بني سلامة، شارلز كليلاند، أحمد المنشاوي.يُعدّ التعب أكثر الأعراض التي يشكو منها مرضى السرطان وأكثرها تكديراً لهم. ومع ذلك، لم يُترجَم إلى اللغة العربية أي استبيان يقيس التعب ومدى إعاقته لحياة المريض.كانت هذه الدراسة تهدف إلى ترجمة "مقياس التعب الوجيز" (BFI-A) والتحقق من نسخته العربية.تُرجم المقياس إلى اللغة العربية بطريقة الترجمة المباشرة والعكسية. وجمعت هذه الدراسة المقطعية بيانات من مرضى السرطان من خلال استبيان ملأه المرضى بأنفسهم وتضمَّن "مقياس التعب الوجيز" (BFI-A)، و"مؤشر شدة الأرق" (ISI)، و"مقياس زونج للاكتئاب" (ZDS)، ومجموع درجات "قائمة أعراض" (MDASI)، و"المقياس الفرعي للحيوية في دراسة النتائج الطبية المختصرة المكونة من 36 بنداً" (SF-36). واستُخدمت إحصاءات وصفية واستنتاجية، منها المتوسط، والانحراف المعياري، والاتساق الداخلي، ومعامل الارتباط باستخدام ارتباط بيرسون.استعين اجمالا بتسعة وسبعين مريضا في مدينة عمان الاردنية عام 2015. وكان متوسط مجموع درجات « مقياس التعب الوجيز (BFI-A) هو 4.1)، مما يدل على ان 83.5٪ كانوا يعانون تعبا غير شديد. وكان معامل كرونباخ الفا لمقياس التعب الوجيز هو 0.93. وكانت علاقات الترابط بين مجموع درجات « مقياس التعب الوجيز » وبنود هذا المقياس علاقات وثيقة (0.05P)، وتراوحت من 0.75 الى 0.86. وتبين وجود ترابط وثيق (0.05P) بين « مقياس التعب الوجيز BFI-A)» والمقاييس التالية: مؤشر شدة الارق (0.70) (ISI)، ومقياس زونج للاكتئاب (0.69) (ZDS)، وقائمة الاعراض (0.75) (MDASI)، والمقياس الفرعي للحيوية في دراسة النتائج الطبية المختصره المكونه من 36 بندا (0.57-) (SF-36).تشير هذه الدراسة إلى أن (BFI-A) أداة موثوقة وصالحة لتقييم التعب لدى مرضى السرطان الناطقين بالعربية.Étude de validation de la version arabe du Brief Fatigue Inventory (BFI-A).La fatigue est le symptôme le plus fréquent et le plus éprouvant chez les patients atteints de cancer. Cependant, aucun questionnaire mesurant la fatigue et son interférence avec la vie quotidienne n’a été traduit en arabe.La présente étude visait à traduire et à valider la version arabe du Brief Fatigue Inventory (BFI-A).Le BFI a été traduit en arabe à l’aide de la technique de traduction/rétro-traduction. La présente étude transversale a permis de collecter des données de patients atteints de cancer en recourant à un auto-questionnaire comprenant le BFI-A, l’index de Sévérité de l’Insomnie (ISI), l’échelle d’auto-évaluation de la dépression de Zung (ZDS), l’inventaire des symptômes M.D. Anderson (MDASI) et la sous-échelle vitalité de la forme abrégée du questionnaire généraliste SF-36 (qualité de vie) du Medical Outcome Study. Des statistiques descriptives et inférentielles ont été utilisées, y compris la moyenne, l’écart type, la cohérence interne et le coefficient de corrélation de Pearson.79 patients au total ont été recrutés à Amman (Jordanie) en 2015. La moyenne totale du BFI-A était de 4,01 (2,4), indiquant que 83,5 % des patients présentaient un état de fatigue non sévère. Le coefficient alpha de Cronbach du BFI-A était de 0,93. Les corrélations entre les scores totaux et les rubriques du BFI-A étaient significatives (p0,05) et étaient comprises entre 0,75 et 0,86. Le BFI-A affichait une corrélation importante (p0,05) avec les instruments suivants : ISI = 0,70 ; ZDS = 0,69 ; MDASI = 0,75 et la sous-échelle vitalité du SF-36 (qualité de vie) = −0,57.La présente étude suggère que le BFI-A est un outil valable et fiable pour évaluer la fatigue chez les patients arabes atteints de cancer.

Purpose Hematopoietic stem cell transplant (HSCT) is an intensive treatment associated with distressing treatment and disease-related symptoms that affect patient outcomes such as functional status and quality of life. Self-efficacy for symptom management (SESM) is a person's belief in their ability to perform behaviors to prevent and relieve symptoms. Presence of SESM can impact symptom distress and functional status. This study describes the changes over time and relationships among SESM, symptom distress, and physical functional status in adults during the acute phase of HSCT. Methods Patients (n = 40) completed measures of symptom distress, SESM, and physical function at time points prior to and at days 7, 15 and 30 post-transplant. Clinical outcomes were length of stay and number of readmissions. Results Symptom distress, physical function, and SESM changed significantly over time. There was a significant negative relationship between symptom distress and physical function and between symptom distress and SESM at all points. The lowest levels of SESM and physical function were at day 7 when symptom distress was highest. Symptom distress was a moderator for the relationship between physical function and SESM at day 15. Conclusion This was the first study to examine SESM in the acute phase of HSCT. Higher SESM was associated with fewer symptoms and increased physical function. Less symptom distress was associated with higher physical function and confidence to manage symptoms. These findings provide the basis for development of patient-centered interventions to enhance SESM when symptoms are at their highest immediately after HSCT.

PURPOSE/BACKGROUND Lithium augmentation of antidepressants represents a common strategy to overcome treatment resistance in patients with major depressive disorder. The use of lithium has been associated with cardiovascular adverse effects such as QTc prolongation and tachyarrhythmia. Although the previous studies investigated monotherapy with lithium, the aim of this study was to investigate electrocardiographic changes in LA. METHODS/PROCEDURES A 12-lead surface electrocardiogram (ECG) was obtained from 38 patients with major depressive disorder before and during LA. Changes in heart rate, PQ, QRS and QTc interval, QT dispersion, ST segment, and T- and U-wave alterations were analyzed using a linear mixed model. FINDINGS/RESULTS The ECG readings of 33 patients were evaluated. Lithium augmentation was not significantly associated with changes in heart rate, QTc, PQ, or QRS interval. We found a significant decrease in QT dispersion. These results were independent of sex, age, stable comedication, and comorbidities. During LA, we observed 9 cases of T-wave alterations and 2 cases of new U waves. CONCLUSIONS Our data provide no evidence for serious ECG abnormalities at therapeutic serum lithium levels in patients treated with LA. In particular, we did not find evidence for QTc time lengthening or tachyarrhythmia, such as torsades des pointes. The recommended intervals for ECG checks should be considered to detect long-term effects of LA.

Serine/threonine-protein kinases 3 and 4 (STK3 and STK4, respectively) are key components of the Hippo signaling pathway, which regulates cell proliferation and death and provides a potential therapeutic target for acute myeloid leukemia (AML). Herein, we report the structure-based design of a series of pyrrolopyrimidine derivatives as STK3 and STK4 inhibitors. In an initial screen, the compounds exhibited low nanomolar potency against both STK3 and STK4. Crystallization of compound 6 with STK4 revealed two-point hinge binding in the ATP-binding pocket. Further characterization and analysis demonstrated that compound 20 (SBP-3264) specifically inhibited the Hippo signaling pathway in cultured mammalian cells and possessed favorable pharmacokinetic and pharmacodynamic properties in mice. We show that genetic knockdown and pharmacological inhibition of STK3 and STK4 suppress the proliferation of AML cells in vitro. Thus, SBP-3264 is a valuable chemical probe for understanding the roles of STK3 and STK4 in AML and is a promising candidate for further advancement as a potential therapy.

Importance: To our knowledge, little is known about antibody development after SARS-CoV-2 vaccination in immunocompromised individuals, such as patients with cancer. Objective: To determine whether hematooncological patients develop anti-SARS-CoV-2 antibodies after vaccination. Design, Setting, and Participants: This retrospective cohort study included 2 independent cohorts of patients who were treated for hematological and solid malignant tumors between October 2020 and May 2021, comprising 901 samples from 595 patients and 58 health care workers (HCWs). Serum samples were collected from patients who were treated at an academic center and a community hospital in a rural area and a control group of HCWs, all of whom received SARS-CoV-2 vaccination. Main Outcomes and Measures: Total anti-SARS-CoV-2 nucleocapsid (anti-NC) and antispike protein (anti-S) antibodies were measured retrospectively. Results: In total, 595 patients (320 women [53.8%] and 275 men [46.2%]; median [range] age, 67 [19-96] years) and 58 HCWs (40 women [69.0%] and 18 men [31.0%]; median [range] age, 42 [24-60] years) were included. Previous SARS-CoV-2 infection was documented in 43 of 595 (7.2%), while anti-NC antibodies that suggested previous infections were observed in 49 of 573 evaluable patients (8.6%). In both cohorts, anti-S antibody levels were higher in fully vaccinated patients compared with patients who received 1 dose. After the first vaccination, patients with hematological cancer who received B cell-targeting agents had lower anti-S levels (median, 1.6 AU/mL; range: 0-17 244 AU/mL) than patients who received other therapies (median, 191.6 AU/mL; range, 0-40 000; P < .001) or patients with solid tumors (median, 246.4 AU/mL; range, 0-40 000 AU/mL; P < .001). Anti-S levels after the first vaccination differed according to ongoing antineoplastic treatment modalities, with the lowest median levels in patients who received chemotherapy alone (157.7 AU/mL; range, 0-40 000 AU/mL) or in combination with immunotherapy (118.7 AU/mL; range, 14.1-38 727 AU/mL) and the highest levels in patients with no ongoing antineoplastic treatment (median, 634.3 AU/mL; range, 0-40 000 AU/mL; P = .01). Antibody levels after full immunization were higher in HCWs (median, 2500 U/mL; range, 485-2500 U/mL) than in patients with cancer (median, 117.0 U/mL; range, 0-2500 U/mL; P < .001). Conclusions and Relevance: In this cohort study of patients with hematooncological diseases and a control group of HCWs, anti-SARS-CoV-2 antibodies after vaccination could be detected in patients with cancer. Lower antibody levels compared with HCWs and differences in seroconversion in specific subgroups underscore the need for further studies on SARS-CoV-2 vaccination in patients with hematooncological disease.

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. Supplementary Information The online version contains supplementary material available at 10.1007/s00439-021-02397-7.

Muscle wasting deteriorates life quality after critical illness and increases mortality. Wasting starts upon admission to intensive care unit (ICU). We aimed to determine whether β-hydroxy-β-methylbutyrate (HMB), a metabolite of leucine, can attenuate this process.Prospective randomized, placebo-controlled double blind trial.ICU patients depending on mechanical ventilation on day 3 having a functional gastrointestinal tract. They were randomized to HMB (3 g/day) or placebo (maltodextrin) from day 4 on for 30 days.magnitude of loss of skeletal muscle area (SMA) of the quadriceps femoris measured by ultrasound at days 4 and 15.body composition, change in protein metabolism assessed by amino acids tracer pulse, and global health at 60 days. Data are mean [95% CI]. Statistics by ANCOVA with correction for confounders sex, age and/or BMI.Thirty patients completed the trial, aged 65 [59, 71] years, SAPS2 score 48 [43, 52] and SOFA 8.5 [7.4, 9.7]. The loss of total SMA was 11% between days 4 and 15 (p 0.001), but not different between the groups (p = 0.86). In the HMB group, net protein breakdown (Δ Estimate HMB-Placebo: -153 [-242, -63]; p = 0.0021) and production of several amino acid was significantly reduced, while phase angle increased more (0.66 [0.09, 1.24]; p = 0.0247), and SF-12 global health improved more (Δ Estimate HMB-Placebo: 27.39 [1.594, 53.19], p = 0.04).HMB treatment did not significantly reduce muscle wasting over 10 days of observation (primary endpoint), but resulted in significantly improved amino acid metabolism, reduced net protein breakdown, a higher phase angle and better global health. CLINICALTRIALS.NCT03628365.

Supplemental Digital Content is available in the text., Background. The ability of transplant (Tx) patients to generate a protective antiviral response under immunosuppression is pivotal in COVID-19 infection. However, analysis of immunity against SARS-CoV-2 is currently lacking. Methods. Here, we analyzed T cell immunity directed against SARS-CoV-2 spike-, membrane-, and nucleocapsid-protein by flow cytometry and spike-specific neutralizing antibodies in 10 Tx in comparison to 26 nonimmunosuppressed (non-Tx) COVID-19 patients. Results. Tx patients (7 renal, 1 lung, and 2 combined pancreas-kidney Txs) were recruited in this study during the acute phase of COVID-19 with a median time after SARS-CoV-2-positivity of 3 and 4 d for non-Tx and Tx patients, respectively. Despite immunosuppression, we detected antiviral CD4+ T cell-response in 90% of Tx patients. SARS-CoV-2–reactive CD4+ T cells produced multiple proinflammatory cytokines, indicating their potential protective capacity. Neutralizing antibody titers did not differ between groups. SARS-CoV-2–reactive CD8+ T cells targeting membrane- and spike-protein were lower in Tx patients, albeit without statistical significance. However, frequencies of anti-nucleocapsid–protein-reactive, and anti-SARS-CoV-2 polyfunctional CD8+ T cells, were similar between patient cohorts. Tx patients showed features of a prematurely aged adaptive immune system, but equal frequencies of SARS-CoV-2–reactive memory T cells. Conclusions. In conclusion, a polyfunctional T cell immunity directed against SARS-CoV-2 proteins as well as neutralizing antibodies can be generated in Tx patients despite immunosuppression. In comparison to nonimmunosuppressed patients, no differences in humoral and cellular antiviral-immunity were found. Our data presenting the ability to generate SARS-CoV-2–specific immunity in immunosuppressed patients have implications for the handling of SARS-CoV-2–infected Tx patients and raise hopes for effective vaccination in this cohort.

Background The treatment and management of massive burns, defined as burns affecting≥ 50% of total body surface area (TBSA) has considerably changed since the 90s. This study aimed at analyzing if the length of intensive care unit (ICU) stay, the success of skin grafting operations and the mortality changed in the last 18 years. Methods Between 2000 and 2018, 77 patients were admitted for massive burns to the ICU of a university hospital. Transfers and early care withdrawal precluded inclusion for 38 patients, leaving 39 for analysis. Study variables were year of admission, demographics, burn characteristics, critical care treatment (fluid resuscitation, ventilation and nutrition) and surgical therapy. Association between outcomes and year of admission were assessed through correlation and logistic regression analysis. Potential confounders were assessed through stepwise linear regression. Results Patients' characteristics were stable over time with a median age of 36[25.0, 48.0] years, burns 65% [55.0, 83.0] TBSA and deep burns 55% [50.0, 68.0] TBSA . Length of ICU stay remained stable at 0.97 [0.6, 1.5] days/%TBSA. Mortality was stable as well. Energy and carbohydrate delivery decreased in parallel with the number of infectious episodes per patient. Number of operations was stable but the take rate of skin grafts increased significantly. The multivariate analysis retained year of admission, weight, total number of infections, daily lipid intakes and fluid resuscitation as independent predicting variables. Conclusion Length of ICU stay and mortality did not change over time but skin grafts take rates improved significantly.

Pianp (also known as Leda-1) is a type I transmembrane protein with preferential expression in the mammalian CNS. Its processing is characterized by proteolytic cleavage by a range of proteases including Adam10, Adam17, MMPs, and the γ-secretase complex. Pianp can interact with Pilrα and the GB1a subunit of the GABAB receptor (GBR) complex. A recent case description of a boy with global developmental delay and homozygous nonsense variant in PIANP supports the hypothesis that PIANP is involved in the control of behavioral traits in mammals. To investigate the physiological functions of Pianp, constitutive, global knockout mice were generated and comprehensively analyzed. Broad assessment did not indicate malformation or malfunction of internal organs. In the brain, however, decreased sizes and altered cellular compositions of the dentate gyrus as well as the cerebellum, including a lower number of cerebellar Purkinje cells, were identified. Functionally, loss of Pianp led to impaired presynaptic GBR-mediated inhibition of glutamate release and altered gene expression in the cortex, hippocampus, amygdala, and hypothalamus including downregulation of Erdr1, a gene linked to autism-like behavior. Behavioral phenotyping revealed that Pianp deficiency leads to context-dependent enhanced anxiety and spatial learning deficits, an altered stress response, severely impaired social interaction, and enhanced repetitive behavior, which all represent characteristic features of an autism spectrum disorder-like phenotype. Altogether, Pianp represents a novel candidate gene involved in autism-like behavior, cerebellar and hippocampal pathology, and GBR signaling.

Objective Neuroimaging studies of hematologic cancer patients report altered activity in dorsal attention and central executive networks. To determine the consequences of these altered brain networks, we evaluated neurophysiological correlates of attention and working memory in hematologic cancer patients prior to initiating treatment. Methods Hematologic cancer patients (19–80 years) were excluded for premorbid cognitive impairment, prior non-hematologic cancer diagnosis, and prior chemotherapy. Attention was manipulated by presenting an irrelevant spatial cue prior to visual search displays. Working memory was manipulated by presenting irrelevant distractors within memory displays. Electroencephalogram was recorded during task performance. Results Patients (n = 28) and controls (n = 15) were balanced on age, gender, and education. Spatial cues evoked larger N2pc amplitudes, a correlate of spatial attention, in patients than controls (p 0.7). Memory distractors evoked larger contralateral delay activity amplitudes, a correlate of working memory load, in patients (p = .028; Cohen’s d = 1.1) but not controls (p = .64). Conclusions Prior to initiating treatment, hematologic cancer patients demonstrated poor control over spatial attention and working memory, consistent with altered dorsal attention and central executive network activity. Significance Hematologic cancer patients may be at a higher risk for selecting, processing, and storing distracting information that would compete with more immediate goal-related behaviors.

Background and objectivesThe significance of intravenous over oral acetaminophen (APAP) as part of multimodal analgesic protocols is contested, particularly when considering its relatively high price and use in a surgical cohort such as total hip or knee arthroplasty (THA/TKA), which generally tolerates oral medications. This study aims to elucidate APAP’s effectiveness in a large, population-based patient sample.Methods1 039 647 THA/TKA procedures were sampled from the Premier Healthcare claims database 2011–2016. APAP use was categorized by intravenous/oral and use on the day of surgery, postoperative day 1 and thereafter. Outcomes were opioid utilization (in oral morphine equivalents), length and cost of hospitalization, and opioid-related adverse effects (respiratory, gastrointestinal, and naloxone use as a proxy). Mixed-effects models measured the associations between intravenous/oral APAP use and outcomes. Percent (%) change and 95% CIs are reported.ResultsOverall, 23.6% (n=245 454) of patients received intravenous APAP; of these, 56.3% (n=138 180) received just one dose on the day of surgery. After adjustment for relevant covariates, particularly use of >1 dose of intravenous APAP (compared with no use) on postoperative day 1 was associated with −6.0% (CI −7.2% to −4.7%) reduced opioid utilization; this was −10.7% (CI −11.4% to -9.9%) for use of > 1 dose oral APAP on postoperative day 1. Further comparisons regarding other outcomes also favored oral (over intravenous) APAP.ConclusionsThese results do not support the routine use of intravenous APAP in patients undergoing lower joint arthroplasty, especially since oral APAP shows more beneficial outcome patterns.

BACKGROUND The School Breakfast Program (SBP) has grown and evolved substantially since its inception, yet relatively little is known about its impact on school engagement and academic outcomes. OBJECTIVES The purpose of this study is to estimate the impact of the SBP on school attendance and standardized test scores, as well as how impacts differ among student subpopulations and between traditional and nontraditional program models. METHODS The study uses administrative data from ∼1000 Wisconsin elementary schools during 2009-2014, including almost all public elementary schools in the state except those in Milwaukee Public School District. Over the 5-y period, 168 schools in our sample introduced a new SBP and/or changed the location of breakfast (classroom or cafeteria) or the payment structure. The impact of breakfast availability and type was evaluated using multivariable regression models with school fixed effects and extensive demographic controls, leveraging within-school changes in SBP availability and type. RESULTS Implementing the SBP was associated with a 3.5-percentage-point reduction in the percentage of students with low attendance and an increase of 0.08 SD in normalized reading scores among likely-participant boys (P = 0.015), with no impact among girls. When breakfast was offered free to all students, the probability of low attendance was 3.5 percentage points lower than with traditional SBP for a broad cross-section of students (P

Summary Background & aims Major burn patients are characterized by large exudative losses of Cu, Se and Zn. Trace element (TE) repletion has been shown to improve clinical outcome. Having increased the TE doses over time, the study aimed at analysing if our repletion protocol corrected TE plasma concentrations and if the necessity for continuous renal replacement therapy (CRRT) might increase the TE needs. Methods Retrospective analysis of prospectively collected data in burn patients requiring intensive care (ICU) between 1999 and 2015. Inclusion criteria: Admission on day 1, full treatment, burned surface area (TBSA) ≥20% and ≥1 TE plasma determination during the stay. Four groups were constituted according to protocol changes. Period 1 (P1): 1999–2000, P2: 2001–2005, P3: 2006–2010, P4: 2011–2015. Changes consisted in increasing TE repletion doses and duration. Demographic data, daily TE intakes and weekly plasma concentrations were retrieved for the first 21 ICU-days. Data as median (IQR). Results 139 patients completed the criteria, aged 37 (28) years, burned on 35 (25) % TBSA. As a result of prescription, Cu, Se and Zn intakes increased significantly between P1 and P4, resulting in normalization of plasma Cu (16 μmol/l) since P3 and Zn (13.5 μmol/l) since P2. Median plasma Se were above reference range (1400 nmol/l) during P3 and P4. CRRT patients required higher doses of Cu for maintenance within normal ranges. Conclusion This dose finding study shows that the latest repletion protocol is safe and normalizes Cu and Zn concentrations. Se doses result in supra-normal Se concentrations, suggesting prescription reduction. CRRT patients are at high risk of Cu depletion and require specific monitoring.

Problem identification Self-efficacy for symptom management plays a key role in outcomes, such as quality of life (QOL), functional status, and symptom distress, for adults with cancer. This integrative review identified and assessed evidence regarding self-efficacy for management of symptoms and symptom distress in adults with cancer. Literature search The authors performed a search of literature published from 2006-2018, and articles that examined the relationship among self-reported self-efficacy, symptom management, symptom distress or frequency, and severity in adults with cancer were selected for inclusion. Data evaluation 22 articles met the inclusion criteria. All articles were critically appraised and met standards for methodologic quality. Synthesis Evidence from this review showed that high self-efficacy was associated with low symptom occurrence and symptom distress and higher general health and QOL. High self-efficacy predicted physical and emotional well-being. Low self-efficacy was associated with higher symptom severity, poorer outcomes, and better overall functioning. Implications for research Self-efficacy can be assessed using developed instruments. Presence of a theoretical model and validated instruments to measure self-efficacy for symptom management have set the groundwork for ongoing research.

Early childbearing is associated with a host of educational and economic disruptions for teenage girls and increased risk of adverse outcomes for their children. Low-income, maltreated, and foster youth have a higher risk of teen motherhood than the general population of youth. In this study, we assessed differences in the risk of early motherhood among these groups and investigated whether differences likely reflect selection factors versus effects of involvement with Child Protective Services (CPS) or foster care. Using a statewide linked administrative data system for Wisconsin, we employed survival analysis to estimate the hazard of early birth (child conceived prior to age 18) among females. We found that both the youth involved in CPS and youth in foster care were at significantly higher risk of early motherhood than low-income youth, and these differences were not explained by a range of sociodemographic and family composition characteristics. Moreover, our findings indicate that CPS and foster care are unlikely to be causal agents in the risk of early motherhood: among foster youth, risk was lower during foster care compared with before; among CPS-involved girls, risk was the same or lower after CPS investigation compared with before. Subsequent analysis showed that after girls exited foster care, those who were reunified with their birth families were at higher risk than those placed in adoption or guardianship. Overall, our findings suggest that whereas CPS and foster youth are high-risk populations for early motherhood, CPS involvement and foster care placement do not exacerbate, and may instead reduce, risk.

Assessment of patient satisfaction following an aesthetic surgery has shown an increasing trend over the past years. To date, there is no prospective and comprehensive study evaluating this aspect after surgical facial and neck rejuvenation. The aim of the current work was to address patient satisfaction after face and neck lift surgery using a validated questionnaire.We present a prospective and multicenter study (five regional centers) involving all patients undergoing face and neck lift surgery between April 2015 and April 2017 in several French centers for aesthetic surgery. All subjects assessed the FACE-Q scales before the procedure, and furtherly at 3-month, 6-month and 12-month follow-ups.Thirty-six patients were included with a median age of 58.5 years old [IQR 54.0-66.0]. The FACE-Q outcomes were significantly higher at 3-month follow-up (p 0.001). Seventy-five percent of the patients underwent an additional surgical procedure associated with face and neck lift. Particularly, a combined blepharoplasty led to a significant increase in the score of global facial appearance. The patients considered themselves a mean of 6 years younger in the third month after surgery. These results remained constant at six and twelve postoperative months.A statistically significant improvement of the FACE-Q scores could be highlighted on every scale, with permanent results at 6 and 12 months postsurgery. We hereby present the first study with evidence that appearance and quality of life outcomes can be reliably assessed after rhytidectomy.This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Objectives Age, sedentary activity, central adiposity, and inflammation have all been independently associated with bone mineral density (BMD). We assessed how the effects of sedentary activity and central adiposity on BMD of the lumbar spine and femoral neck change across early to late adulthood and whether these relationships are mediated by inflammation. Methods We analyzed data from 7135 women and men 20 years of age and older from NHANES 2007 to 2010. Anthropometrics, sedentary activity (min/day), serum CRP (mg/dl), and BMD (gm/cm2 measured by DXA scans) at the femoral neck and lumbar spine. Data were compared by age and sex groups and through causal mediation analysis. Results The effect of waist circumference on BMD was significantly mediated by serum CRP at both skeletal sites in men and at the femoral neck in women. Sedentary activity did not have a direct relationship to BMD but was mediated by waist circumference in men. Least square means differed significantly by sex and age groups with a general age-related decline in BMD at both skeletal sites. Conclusions We found that central adiposity, independent of overall body size and composition as measured through BMI, has an inverse relationship with BMD that is mediated by serum CRP. In addition, the negative impact of increased sedentism acted through changes in central adiposity (waist circumference) but only in men. Although low bone density and osteoporosis are often considered degenerative diseases that primarily impact postmenopausal women, our findings show that sedentary activity and central adiposity impact bone density beginning in early adulthood in both women and men.

Introduction: Regulation of endogenous glucose production (EGP) is essential for glucose homeostasis. It includes gluconeogenesis (GNG) from non-carbohydrate substrates and hepatic glycogenolysis. Both these pathways are dysregulated in acute stress, but the magnitude of this deregulation cannot be assessed in clinical practice. The study aims at identifying clinically available variables predictive of EGP and GNG magnitude by modeling routinely available data. Methods: This exploratory study is based on the data from the Supplemental Parenteral Nutrition study 2 (SPN2), which measured EGP and GNG at days 4 and 10 in 23 critically ill patients. The correlation between EGP and GNG and 83 potential clinical indicators were explored, using single-stage and multivariate analysis. Results: On single-stage analysis, the strongest correlations were noradrenaline dose at day 4 with GNG (R = 0.71; P = 0.0004) and Nutrition risk screening score (NRS) with EGP (R = 0.42; P = 0.05). At day 10, VO2 (R = 0.59, P = 0.04) was correlated with GNG and VCO2 with EGP (R = 0.85, P = 0.00003). Cumulated insulin dose between days 5 and 9 was correlated to EGP at day 10 (R = 0.55, P = 0.03). Our multivariate model could predict EGP at day 4 (VCO2, glucose and energy intake) with an error coefficient (e.c.) between 7.8% and 23.4% (minimal and maximal error), and GNG at day 10 (age, mean and basal blood glucose), with an e.c. of 18.5% and 29.9%. GNG at day 4 and EGP at day 10 could not be predicted with an e.c. < 40%. Conclusion: This preliminary exploratory study shows that GNG and EGP have different predictors on days 4 and 10; EGP is more correlated with the metabolic level, while GNG is dependent on external factors. Nevertheless, a bundle of variables could be identified to empirically assess the magnitude of both values. Our results suggest that a robust model might be built, but requires a prospective study including a larger number of patients. (C) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Cellular and humoral immunity to SARS-CoV-2 is critical to control primary infection and correlates with severity of disease. The role of SARS-CoV-2-specific T cell immunity, its relationship to antibodies, and pre-existing immunity against endemic coronaviruses (huCoV), which has been hypothesized to be protective, were investigated in 82 healthy donors (HDs), 204 recovered (RCs), and 92 active COVID-19 patients (ACs). ACs had high amounts of anti-SARS-CoV-2 nucleocapsid and spike IgG but lymphopenia and overall reduced antiviral T cell responses due to the inflammatory milieu, expression of inhibitory molecules (PD-1, Tim-3) as well as effector caspase-3, -7, and -8 activity in T cells. SARS-CoV-2-specific T cell immunity conferred by polyfunctional, mainly interferon-γ-secreting CD4+ T cells remained stable throughout convalescence, whereas humoral responses declined. Immune responses toward huCoV in RCs with mild disease and strong cellular SARS-CoV-2 T cell reactivity imply a protective role of pre-existing immunity against huCoV., Graphical Abstract, COVID-19 varies from asymptomatic infection to multiorgan failure, but data on cellular immunity against SARS-CoV-2 during disease and beyond are lacking. Bonifacius et al. show a beneficial effect of preexisting immunity to endemic coronaviruses during disease and stable cellular immunity with concomitant decrease of humoral responses early during convalescence.

Objectives In this article, we test theoretical pathways leading to and resulting from periodontal disease to better understand how periodontal disease, which is measurable in both past and present populations, integrates biocultural context and affects whole-body physiology. Methods We use data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 and logistic and linear regressions to test pathways linking psychosocial stress to periodontal disease, and periodontal disease to serum vitamin C levels. We then use causal mediation analysis to test the role of mediating variables in these pathways (n = 1853 individuals). Results Food insecurity was positively associated with periodontal disease and negatively associated with serum counts of C-reactive protein (CRP) and neutrophils. Neither CRP nor neutrophils significantly mediated the relationship between food insecurity and periodontal disease. Periodontal disease was negatively associated with serum vitamin C levels and positively associated with neutrophil counts. Neutrophils may mediate the relationship between periodontal disease and vitamin C. Conclusions We identify two main findings: (a) periodontal disease contributes to and may result from immune dysregulation, particularly of neutrophils, and (b) an immune response to chronic infection such as periodontal disease is metabolically expensive for the body to maintain and likely depletes serum micronutrient levels. Both micronutrient status and serum neutrophil counts affect multiple skeletal and physiological phenotypes and thus position periodontal disease in whole-body context.

Background During the COVID-19 outbreak, healthcare professionals (HCP) are at the frontline of clinical management and at increased risk for infection. The SARS-CoV-2 seroprevalence of oncological HCP and their patients has significant implications for oncological care. Methods HCP and patients with cancer at the Division of Oncology, Medical University of Vienna were included between 21 March and 4 June and tested for total antibodies against SARS-CoV-2 employing the Roche Elecsys Anti-SARS-CoV-2 immunoassay. Reactive samples were confirmed or disproved by the Abbott SARS-CoV-2 IgG test. Additionally, a structured questionnaire regarding basic demographic parameters, travel history and COVID-19-associated symptoms had to be completed by HCP. Results 146 subjects (62 HCP and 84 patients with cancer) were enrolled. In the oncological HCP cohort, 20 (32.3%) subjects were medical oncologists, 28 (45.2%) nurses at our ward and 14 (22.6%) fulfil other functions such as study coordinators. In the patient cohort, most individuals are on active anticancer treatment (96.4%). 26% of the HCP and 6% of the patients had symptoms potentially associated with COVID-19 since the end of February 2020. However, only in 2 (3.2%) HCP and in 3 (3.6%) patients, anti-SARS-Cov-2 total antibodies were detected. The second assay for anti-SARS-Cov-2 IgG antibodies confirmed the positive result in all HCP and in 2 (2.4%) patients, suggesting an initial assay’s unspecific reaction in one case. In individuals with a confirmed test result, an active COVID-19 infection was documented by a positive SARS-CoV-2 RNA PCR test. Conclusion Specific anti-SARS-CoV-2 antibodies were found solely in persons after a documented SARS-CoV-2 viral infection, thus supporting the test methods’ high sensitivity and specificity. The low prevalence of anti-SARS-CoV-2 antibodies in our cohorts indicates a lack of immunity against SARS-CoV-2. It highlights the need for continued strict safety measures to prevent uncontrolled viral spread among oncological HCPs and patients with cancer.

Background & aims: The ICALIC project was initiated for developing an accurate, reliable and user friendly indirect calorimeter (IC) and aimed at evaluating its ease of use and the feasibility of the EE measurements in intensive care unit (ICU).Methods: This was a prospective unblinded, observational, multi-center study. Simultaneous IC measurements in mechanically ventilated ICU patients were performed using the new IC (Q-NRG®) and currently used devices. Time required to obtain EE was recorded to evaluate the ease of use of Q-NRG® versus currently used ICs and EE measurements were compared. Conventional descriptive statistics were used: data as mean ± SD.Results: Six centers out of nine completed the required number of patients for the primary analysis. Mean differences in the time needed by Q-NRG® against currently used ICs were -32.3 ± 2.5 min in Geneva (vs. Deltatrac®; p < 0.01), -32.3 ± 3.1 in Lausanne (vs. Quark RMR®; p < 0.05), -33.7 ± 1.4 in Brussels (vs. V-Max Encore®; p < 0.05), -26.4 ± 7.8 in Tel Aviv (vs. Deltatrac®; p < 0.05), -28.5 ± 3.5 in Vienna (vs. Deltatrac®; p < 0.05), and 0.3 ± 1.2 in Chiba (vs. E-COVX®; p = 0.17). EE (kcal/day) measurements by the Q-NRG® were similar to the Deltatrac® in Geneva and Vienna (mean differences±SD: -63.1 ± 157.8 (p = 0.462) and -22.9 ± 328.2 (=0.650)), but significantly different in Tel Aviv (307.4 ± 324.5, p < 0.001). Significant differences were observed in Lausanne (Quark RMR®: -224.4 ± 514.9, p = 0.038) and in Brussels (V-max®: -449.6 ± 667.4, p < 0.001), but none was found in Chiba (E-COVX®; 55.0 ± 204.1, p = 0.165).Conclusion: The Q-NRG® required a much shorter time than most other ICs to determine EE in mechanically ventilated ICU patients. The Q-NRG® is the only commercially available IC tested against mass spectrometry to ensure gas accuracy, while being very easy-to use.

Cytotoxic T cells are responsible for the elimination of infected cells and are key players in the control of viruses. CD8+ T cells with an effector phenotype express cytotoxic molecules and are able to perform target cell killing. COVID-19 patients with a mild disease course were analyzed for the differentiation status and cytotoxic profile of CD8+ T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8+ T cell response. However, this cytotoxic profile of T cells was not detected in COVID-19 patients over the age of 80 years. Thus, the absence of a cytotoxic response in elderly patients might be a possible reason for the more frequent severity of COVID-19 in this age group than in younger patients., Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces a T cell response that most likely contributes to virus control in COVID-19 patients but may also induce immunopathology. Until now, the cytotoxic T cell response has not been very well characterized in COVID-19 patients. Here, we analyzed the differentiation and cytotoxic profile of T cells in 30 cases of mild COVID-19 during acute infection. SARS-CoV-2 infection induced a cytotoxic response of CD8+ T cells, but not CD4+ T cells, characterized by the simultaneous production of granzyme A and B as well as perforin within different effector CD8+ T cell subsets. PD-1-expressing CD8+ T cells also produced cytotoxic molecules during acute infection, indicating that they were not functionally exhausted. However, in COVID-19 patients over the age of 80 years, the cytotoxic T cell potential was diminished, especially in effector memory and terminally differentiated effector CD8+ cells, showing that elderly patients have impaired cellular immunity against SARS-CoV-2. Our data provide valuable information about T cell responses in COVID-19 patients that may also have important implications for vaccine development.

T cell immunity toward SARS-CoV-2 spike (S-), membrane (M-), and nucleocapsid (N-) proteins may define COVID-19 severity. Therefore, we compare the SARS-CoV-2-reactive T cell responses in moderate, severe, and critical COVID-19 patients and unexposed donors. Overlapping peptide pools of all three proteins induce SARS-CoV-2-reactive T cell response with dominance of CD4+ over CD8+ T cells and demonstrate interindividual immunity against the three proteins. M-protein induces the highest frequencies of CD4+ T cells, suggesting its relevance for diagnosis and vaccination. The T cell response of critical COVID-19 patients is robust and comparable or even superior to non-critical patients. Virus clearance and COVID-19 survival are not associated with either SARS-CoV-2 T cell kinetics or magnitude of T cell responses, respectively. Thus, our data do not support the hypothesis of insufficient SARS-CoV-2-reactive immunity in critical COVID-19. Conversely, it indicates that activation of differentiated memory effector T cells could cause hyperreactivity and immunopathogenesis in critical patients., Graphical Abstract, Highlights M-, N-, and S-proteins induce T cell reactivity with differing immune dominance M-protein triggers a strong CD4+ T cell response ICU and non-ICU COVID-19 patients have comparable SARS-CoV-2 T cell responses Viral clearance and COVID-19 survival are not associated with SARS-CoV-2 immunity, Thieme et al. demonstrate the T cell response against M-, N-, and S-proteins of SARS-CoV-2, with M-protein triggering a stronger CD4+ T cell response. ICU COVID-19 patients are capable of generating functional SARS-CoV-2 immunity non-inferior to non-ICU COVID-19 patients. SARS-CoV-2 clearance and COVID-19 survival are not associated with the magnitude of T cell response.

PURPOSE To analyze the prevalence of SARS-CoV-2 infection in patients with cancer in hospital care after implementation of institutional and governmental safety measurements. METHODS Patients with cancer routinely tested for SARS-CoV-2 RNA by nasal swab and real-time polymerase chain reaction between March 21 and May 4, 2020, were included. The results of this cancer cohort were statistically compared with the SARS-CoV-2 prevalence in the Austrian population as determined by a representative nationwide random sample study (control cohort 1) and a cohort of patients without cancer presenting to our hospital (control cohort 2). RESULTS A total of 1,688 SARS-CoV-2 tests in 1,016 consecutive patients with cancer were performed. A total of 270 of 1,016 (26.6%) of the patients were undergoing active anticancer treatment in a neoadjuvant/adjuvant and 560 of 1,016 (55.1%) in a palliative setting. A total of 53 of 1,016 (5.2%) patients self-reported symptoms potentially associated with COVID-19. In 4 of 1,016 (0.4%) patients, SARS-CoV-2 was detected. At the time of testing at our department, all four SARS-CoV-2–positive patients were asymptomatic, and two of them had recovered from symptomatic COVID-19. Viral clearance was achieved in three of the four patients 14-56 days after testing positive. The estimated odds ratio of SARS-CoV-2 prevalence between the cancer cohort and control cohort 1 was 1.013 (95% CI, 0.209 to 4.272; P = 1), and between control cohort 2 and the cancer cohort it was 18.333 (95% CI, 6.056 to 74.157). CONCLUSION Our data indicate that continuation of active anticancer therapy and follow-up visits in a large tertiary care hospital are feasible and safe after implementation of strict population-wide and institutional safety measures during the current COVID-19 pandemic. Routine SARS-CoV-2 testing of patients with cancer seems advisable to detect asymptomatic virus carriers and avoid uncontrolled viral spread.

High-specificity colorectal cancer screening is desirable to triage patients Prevention Relevance: This study shows that mt-sDNA has high specificity among average-risk 45–49 year olds, supporting its use as a non-invasive option for colorectal cancer screening.

Background & aims: Despite the presumed importance of preventing and treating micronutrient and mineral deficiencies, it is still not clear how to optimize measurement and administration in critically ill patients. In order to design future comparative trials aimed at optimizing micronutrient and mineral management, an important first step is to gain insight in the current practice of micronutrient, phosphate and magnesium monitoring and administration. Methods: Within the metabolism-endocrinology-nutrition (MEN) section of the European Society of Intensive Care Medicine (ESICM), the micronutrient working group designed a survey addressing current practice in parenteral micronutrient and mineral administration and monitoring. Invitations were sent by the ESICM research department to all ESICM members and past members. Results: Three hundred thirty-four respondents completed the survey, predominantly consisting of physicians (321 [96.1%]) and participants working in Europe (262 [78.4%]). Eighty-one (24.3%) respondents reported to monitor micronutrient deficiencies through clinical signs and/or laboratory abnormalities, and 148 (44.3%) reportedly measure blood micronutrient concentrations on a routine basis. Two hundred ninety-two (87.4%) participants provided specific data on parenteral micronutrient supplementation, of whom 150 (51.4%) reported early administration of combined multivitamin and trace element preparations at least in selected patients. Among specific parenteral micronutrient preparations, thiamine (146 [50.0%]) was reported to be the most frequently administered micronutrient, followed by vitamin B complex (104 [35.6%]) and folic acid (86 [29.5%]). One hundred twenty (35.9%) and 113 (33.8%) participants reported to perform daily measurements of phosphate and magnesium, respectively, whereas 173 (59.2%) and 185 (63.4%) reported to routinely supplement these minerals parenterally. Conclusion: The survey revealed a wide variation in current practices of micronutrient, phosphate and magnesium measurement and parenteral administration, suggesting a risk of insufficient prevention, diagnosis and treatment of deficiencies. These results provide the context for future comparative studies, and identify areas for knowledge translation and recommendations., SCOPUS: ar.j, info:eu-repo/semantics/published

AIMS OF THE STUDY Based on an incidental observation made in the context of the Swiss National Science Foundation (SNSF) Project 67 “End-of-life decision-making in extremely low birth weight infants in Switzerland”, this retrospective multicentre observational study aimed to analyse circumstances of delivery room deaths after late termination of pregnancy (LTOP) in Switzerland over a 3-year period. METHODS All delivery room deaths (including live and stillbirths) following LTOP among infants with a gestational age between 22 0/7 and 27 6/7 weeks at the nine Swiss level III perinatal centres between 1 July 2012 and 30 June 2015 were analysed. Indications for LTOP were classified as either (a) maternal emergencies or (b) fetal anomalies severe enough to cause significant maternal psychological distress. Whenever possible, specific diagnoses were recorded. Spontaneous intrapartum death and fetal death caused by injection of a cardioplegic drug were distinguished for stillborn infants. RESULTS A total of 465 delivery room deaths among extremely low gestational age newborns (ELGANs) were identified over the 3-year study period of the SNSF project. Of these, 195 (42%) occurred in the context of LTOP. Central nervous system malformations, chromosomal anomalies, severe congenital heart disease, multiple malformations and maternal emergencies accounted for 70% of all LTOPs. LTOPs resulted in live births in 76 (39%) cases. No correlation between gestational age and rate of live births was observed. Fetal death caused by injection of a cardioplegic drug was documented in only three cases. All infants born alive after LTOP died in the delivery room without resuscitation attempts. The use of drugs for palliative care in these patients was either rare or, alternatively, incompletely documented. CONCLUSION LTOPs contribute significantly to mortality rates among ELGANs and should therefore be included in perinatal registries. Uniform reporting of LTOPs should be established. Infants born alive after LTOP are entitled to comprehensive palliative care like any other infant born under different circumstances. Development of national guidelines for LTOPs (including the role of fetal death caused by injection of a cardioplegic drug and palliative birth as an alternative to induced abortion) would be highly desirable to guarantee acceptable standards of care.

To examine if selected demographic (age, gender), clinical (diabetes, coronary artery disease, hyperlipidemia, myocardial infarction, stroke, lung disease, smoking history, alcohol intake), and biomarker [blood pressure (BP), heart rate, body mass index (BMI), neck circumference, Mallampati score] variables are predictors of apnea-hypopnea index (AHI) from polysomnography (PSG).This cross-sectional study recruited a sample of adults (N = 170) who were being evaluated for OSA. Participants completed self-reported demographic and clinical questionnaires, and then completed PSG (n = 142). Multi-collinearity was assessed. Confounding factors, correlations, and potential interactions were explored.The final regression model was performed on 130 participants; 61 (46.9%) had an AHI ≥ 15. Systolic and diastolic BPs were highly correlated. Interactions were tested between gender and other variables (high cholesterol, BMI, neck circumference, systolic BP) and between systolic BP and other variables (high cholesterol, BMI, neck circumference, and lung disease). No interactions occurred between gender or systolic BP and other variables, meaning that the effects of the variables on AHI levels from PSG did not vary depending on gender or systolic BP. BMI, systolic BP, and absence of lung disease were predictors for AHI levels ≥ 15 from PSG.BMI and systolic BP were significant predictors of OSA in this study. The absence of lung disease as a significant predictor was unique and may be due to the small number of participants who self-reported lung disease. To our knowledge, this is the first study to report this combination of variables to predict AHI levels ≥ 15 from PSG.

Maternal overweight in pregnancy alters the metabolic environment and generates chronic low-grade inflammation. This affects fetal development and programs the offspring’s health for developing cardiovascular and metabolic disease later in life. MME (membrane-metalloendopeptidase, neprilysin) cleaves various peptides regulating vascular tone. Endothelial cells express membrane-bound and soluble MME. In adults, the metabolic environment of overweight and obesity upregulates endothelial and circulating MME. We here hypothesized that maternal overweight increases MME in the feto-placental endothelium. We used primary feto-placental endothelial cells (fpEC) isolated from placentas after normal vs. overweight pregnancies and determined MME mRNA, protein, and release. Additionally, soluble cord blood MME was analyzed. The effect of oxygen and tumor necrosis factor α (TNFα) on MME protein in fpEC was investigated in vitro. Maternal overweight reduced MME mRNA (−39.9%, p < 0.05), protein (−42.5%, p = 0.02), and MME release from fpEC (−64.7%, p = 0.02). Both cellular and released MME protein negatively correlated with maternal pre-pregnancy BMI. Similarly, cord blood MME was negatively associated with pre-pregnancy BMI (r = −0.42, p = 0.02). However, hypoxia and TNFα, potential negative regulators of MME expression, did not affect MME protein. Reduction of MME protein in fpEC and in cord blood may alter the balance of vasoactive peptides. Our study highlights the fetal susceptibility to maternal metabolism and inflammatory state.

Preventing the progression to acute respiratory distress syndrome (ARDS) in COVID-19 is an unsolved challenge. The involvement of T cell immunity in this exacerbation remains unclear. To identify predictive markers of COVID-19 progress and outcome, we analyzed peripheral blood of 10 COVID-19-associated ARDS patients and 35 mild/moderate COVID-19 patients, not requiring intensive care. Using multi-parametric flow cytometry, we compared quantitative, phenotypic and functional characteristics of circulating bulk immune cells, and SARS-CoV-2 S-protein reactive T cell between the two groups. ARDS patients demonstrated significantly higher S-protein reactive CD4+ and CD8+ T cells compared to non-ARDS patients. Of interest, comparison of circulating bulk T cells in ARDS patients to non-ARDS patients demonstrated decreased frequencies of CD4+ and CD8+ T cell subsets with activated memory/effector T cells expressing tissue migration molecule CD11a++. Importantly, survival from ARDS (4/10) was accompanied by a recovery of the CD11a++ T cell subsets in peripheral blood. Conclusively, data on S-protein reactive polyfunctional T cells indicate the ability of ARDS patients to generate antiviral protection. Furthermore, decreased frequencies of activated memory/effector T cells expressing tissue migratory molecule CD11a++ observed in circulation of ARDS patients might suggest their involvement in ARDS development and propose CD11a-based immune signature as a possible prognostic marker., Graphical Abstract, This study shows a strong SARS-CoV-2 S-protein T-cell response and decreased frequencies of activated memory/effector T-cells expressing migratory molecule CD11a++ in ARDS patients. The data suggest the involvement of the analyzed T-cell subsets in ARDS development and propose CD11a-based immune signature as a possible prognostic marker for COVID-19 progression.

OBJECTIVE: To estimate Prenatal Care Coordination’s (PNCC) effect on birth outcomes for Wisconsin Medicaid‐covered deliveries. DATA SOURCE: A longitudinal cohort of linked Wisconsin birth records (2008‐2012), Medicaid claims, and state‐administered social services. STUDY DESIGN: We defined PNCC treatment dichotomously (none vs. any) and by service level (none vs. assessment/care plan only vs. service uptake). Outcomes were birthweight (grams), low birthweight (

PURPOSE: Assess systemic vascular endothelial growth factor-A (VEGF) levels after treatment with intravitreous aflibercept, bevacizumab or ranibizumab. DESIGN: Comparative-effectiveness trial with participants randomly assigned to 2-mg aflibercept, 1.25-mg bevacizumab, or 0.3-mg ranibizumab following a retreatment algorithm. PARTICIPANTS: Participants with available plasma samples (N=436) METHODS: Plasma samples were collected before injections at baseline, 4-week, 52-week and 104-week visits. In a pre-planned secondary analysis, systemic free-VEGF levels from an ELISA immunoassay were compared across anti-VEGF agents and correlated with systemic side effects. MAIN OUTCOME MEASURES: Changes in the natural log (ln) of plasma VEGF levels. RESULTS: Baseline free-VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were −0.30±0.61, −0.31±0.54, −0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted CI; P-value) were −0.01 (−0.12, +0.10; P=0.89), −0.31 (−0.44, −0.18; P

Due to inflammatory and hypermetabolic responses and to extensive exudative trace element (TEs) losses, major burn patients have substantially increased nutritional requirements. To date, information is only available for Cu, Se, and Zn. We aimed at analyzing losses of 12 TEs and Mg through burn wound exudation and corresponding plasma concentrations during the first week after burn injury, and to evaluate the impact of current TE repletion protocols.Burn wound exudate was collected under negative pressure in 15 adult patients burned 29 ± 20% of body surface (TBSA) for 8 days after injury. Two samples were collected daily. The TE concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Losses and serum concentrations were compared to intakes.For the majority of 12 TEs, the highest losses were observed on day 1, and declined thereafter. Despite Cu supplementation (4.23 mg/day) serum levels remained below reference values. Se supplements (745 μg/day) normalized and even increased serum levels to upper normal value. Despite large supplements (Zn 67.5 mg/day), serum Zn values remained below reference range. Large exudative losses of B, Br and Mg were found, as well as of Fe and I, with the latter being probably due to contamination.Current nutritional Cu, Se, Zn repletion protocols in major burn patients which were based on measured exudative losses should be revised to include higher Cu and lower Se doses, as well as planned Mg administration. In burns20% TBSA and for the other TEs the recommended parenteral nutrition TE doses appear sufficient.

Two competing views about alpha oscillations suggest that cortical alpha reflect either cortical inactivity or cortical processing efficiency. We investigated the role of alpha oscillations in attentional control, as measured with a Stroop task. We used neurofeedback to train 22 participants to increase their level of alpha amplitude. Based on the conflict/control loop theory, we selected to train prefrontal alpha and focus on the Gratton effect as an index of deployment of attentional control. We expected an increase or a decrease in the Gratton effect with increase in neural learning depending on whether frontal alpha oscillations reflect cortical idling or enhanced processing efficiency, respectively. In order to induce variability in neural learning beyond natural occurring individual differences, we provided half of the participants with feedback on alpha amplitude in a 3-dimensional (3D) virtual reality environment and the other half received feedback in a 2D environment. Our results showed variable neural learning rates, with larger rates in the 3D compared to the 2D group, corroborating prior evidence of individual differences in EEG-based learning and the influence of a virtual environment. Regression analyses revealed a significant association between the learning rate and changes on deployment of attentional control, with larger learning rates being associated with larger decreases in the Gratton effect. This association was not modulated by feedback medium. The study supports the view of frontal alpha oscillations being associated with efficient neurocognitive processing and demonstrates the utility of neurofeedback training in addressing theoretical questions in the non-neurofeedback literature.