Erythropoietin as candidate for supportive treatment of severe COVID-19

In light of the present therapeutic situation in COVID-19, any measure to improve course and outcome of seriously affected individuals is of utmost importance. We recap here evidence that supports the use of human recombinant erythropoietin (EPO) for ameliorating course and outcome of seriously ill COVID-19 patients. This brief expert review grounds on available subject-relevant literature searched until May 14, 2020, including Medline, Google Scholar, and preprint servers. We delineate in brief sections, each introduced by a summary of respective COVID-19 references, how EPO may target a number of the gravest sequelae of these patients. EPO is expected to: (1) improve respiration at several levels including lung, brainstem, spinal cord and respiratory muscles; (2) counteract overshooting inflammation caused by cytokine storm/ inflammasome; (3) act neuroprotective and neuroregenerative in brain and peripheral nervous system. Based on this accumulating experimental and clinical evidence, we finally provide the research design for a double-blind placebo-controlled randomized clinical trial including severely affected patients, which is planned to start shortly

Computer Aided Model for a Low Voltage Varistor with Increased Thermal Stability

Metal Oxide Varistors are a very common power electronic device, applied for efficient overvoltage protection at any voltage level. This piece of equipment has a high non-linear current response function of the applied voltage, and, it provides a relatively high heat absorption capacity in case of accidental overvoltage pulse (shock)s. The crossing response current is clearly activated by temperature of that device, and, by consequent, overheating could be disastrous. Actual researches must be carried out both for a new more performant material as well as for new technical solutions for the design of all equipment integrating them, by studying heat extraction and heat transfer inside a new complex varistor device. Our article proposes a totally new device, used basically for low voltage applications, having a supplementary metal mass added to the body of that varistor, shaped as small disk. It actions like a heat pump immediately after the voltage pulse (shock) and as additional radiators at the end of the heating process caused by a transitory overvoltage. A CAD solution combined with a finite element model, followed by some experimental results are also presented, for confirming the performance of that newly design. By placing additional metal alloy masses inside a new varistor structure it will have a higher heat pumping and dissipation capability, in order to reduce temperature stress and all aging effects

Treatment algorithm in patients with ovarian cancer

Most ovarian cancer patients are diagnosed only at advanced stages when survival outcomes are worse, and when therapeutic decisions might prove challenging. The fundamental treatment for women with ovarian cancer includes debulking surgery whenever possible and appropriate systemic therapy (chemotherapy, targeted and antiangiogenic agents). In the last few years, knowledge about histological and molecular characteristics of ovarian cancer subtypes and stages has increased considerably. This has enabled the development and improvement of several options for the diagnosis and treatment of ovarian cancer in a patient-tailored approach. Accordingly, therapeutic decisions are guided by the characteristics of the patient and the tumour, especially the molecular features of the cancer subtype and disease stage. Particularly relevant are the advances in early genetic testing of germline and somatic mutations involved in DNA repair, and the clinical development of targeted agents. In order to implement the best individual medical strategies, in this article, we present an algorithm of treatment options, including recently developed targeted agents, for primary and recurrent ovarian cancer patients in Belgium

Deescalating Follow-up after Hemithyroidectomy for Patients with Low-risk Papillary Thyroid Microcarcinoma

Importance: Structural recurrent disease (RD) after surgical treatment of papillary thyroid microcarcinoma (mPTC) is rare. We hypothesized that the RD rate after hemithyroidectomy in low-risk patients with mPTC is low.Objective: To assess the occurrence of RD in Dutch patients with mPTC who received surgical treatment according to the Dutch guidelines.Design, Setting, and Participants: This nationwide retrospective cohort study included all patients who had undergone surgery with a diagnosis of cN0/cNx mPTC in the Netherlands between January 2000 and December 2020 were identified from the Netherlands Cancer Registry database. Patients with preoperative lymph node metastases were excluded. Two groups were defined: group 1 (incidental), mPTC in pathology report after thyroid surgery for another indication; and group 2 (nonincidental), patients with a preoperative highly suspect thyroid nodule (Bethesda 5) or proven mPTC (Bethesda 6). Dutch guidelines state that a hemithyroidectomy is sufficient in patients with unifocal, intrathyroidal mPTC. Main Outcomes and Measures: The occurrence of RD in patients with low-risk mPTC after hemithyroidectomy.Results: In total, 1636 patients with mPTC were included. Patients had a median (IQR) follow-up time of 71 (32-118) months. Median (IQR) age at time of diagnosis was 51 (41-61) years and 1292 (79.0%) were women. Overall, RD after initial treatment was seen in 25 patients (1.5%). The median (IQR) time to RD was 8.2 (3.6-16.5) months and 22 of the 25 (88%) patients developed RD within 2 years. Recurrent disease was not significantly different between both groups (group 1, n = 15 [1.3%]; group 2, n = 10 [2.1%]; difference, 0.8%; 95% CI, -0.5% to 2.5%). Of the 484 patients with nonincidental mPTC (group 2), 246 (50.8%) patients were treated with a hemithyroidectomy and follow-up in accordance with Dutch guidelines. Lymph node metastases were found in 1 of 246 (0.4%) patients after hemithyreoidectomy, and new mPTC in the contralateral thyroid was detected in 3 of 246 (1.2%) patients. Median (IQR) follow-up of this patient group was 37 (18-71) months. The 10-year probability of RD was 1.3% for patients without vascular invasion and 24.4% for patients with vascular invasion. Conclusions and Relevance: This nationwide cohort study found that overall, RD after hemithyroidectomy for patients with low-risk mPTC was rare (&lt;2%). Based on these results, it seems reasonable to deescalate follow-up of patients with low-risk mPTC without vascular invasion after hemithyroidectomy. From a health care perspective, deescalation of follow-up may contribute to increased sustainability and accessibility to health care, both large challenges for the future..</p

Addressing the 'hypoxia paradox' in severe COVID-19: literature review and report of four cases treated with erythropoietin analogues

Since fall 2019, SARS-CoV-2 spread world-wide, causing a major pandemic with estimated ~ 220 million subjects affected as of September 2021. Severe COVID-19 is associated with multiple organ failure, particularly of lung and kidney, but also grave neuropsychiatric manifestations. Overall mortality reaches > 2%. Vaccine development has thrived in thus far unreached dimensions and will be one prerequisite to terminate the pandemic. Despite intensive research, however, few treatment options for modifying COVID-19 course/outcome have emerged since the pandemic outbreak. Additionally, the substantial threat of serious downstream sequelae, called 'long COVID' and 'neuroCOVID', becomes increasingly evident. Main body of the abstract Among candidates that were suggested but did not yet receive appropriate funding for clinical trials is recombinant human erythropoietin. Based on accumulating experimental and clinical evidence, erythropoietin is expected to (1) improve respiration/organ function, (2) counteract overshooting inflammation, (3) act sustainably neuroprotective/neuroregenerative. Recent counterintuitive findings of decreased serum erythropoietin levels in severe COVID-19 not only support a relative deficiency of erythropoietin in this condition, which can be therapeutically addressed, but also made us coin the term 'hypoxia paradox'. As we review here, this paradox is likely due to uncoupling of physiological hypoxia signaling circuits, mediated by detrimental gene products of SARS-CoV-2 or unfavorable host responses, including microRNAs or dysfunctional mitochondria. Substitution of erythropoietin might overcome this 'hypoxia paradox' caused by deranged signaling and improve survival/functional status of COVID-19 patients and their long-term outcome. As supporting hints, embedded in this review, we present 4 male patients with severe COVID-19 and unfavorable prognosis, including predicted high lethality, who all profoundly improved upon treatment which included erythropoietin analogues. Short conclusion Substitution of EPO may among other beneficial EPO effects in severe COVID-19 circumvent downstream consequences of the 'hypoxia paradox'. A double-blind, placebo-controlled, randomized clinical trial for proof-of-concept is warranted

Diminished impact of ethnicity as a risk factor for chronic kidney disease in the current HIV treatment era

BACKGROUND: Chronic kidney disease (CKD) is an important comorbidity during human immunodeficiency virus (HIV) infection. Historically, HIV-associated nephropathy has been the predominant cause of CKD and has primarily been observed in people of African ancestry. This study aims to investigate the role of ethnicity in relation to CKD risk in recent years.METHODS: Analyses were performed including 16 836 patients from the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort. Baseline was defined as the first available creatinine level measurement after 1 January 2007; CKD was defined as a glomerular filtration rate of &lt;60 mL/min/1.73 m(2). The associations between ethnicity and both prevalent CKD at baseline and incident CKD during follow-up were analyzed.RESULTS:The prevalence of baseline CKD was 2.7% (460 of 16 836 patients). Birth in a sub-Saharan African country (hereafter, "SSA origin") was significantly associated with baseline CKD (adjusted odds ratio 1.49; 95% confidence interval [CI], 1.04-2.13). During follow-up (median duration, 4.7 years; interquartile range, 2.4-5.2), the rate of incident CKD was 6.0 events per 1000 person-years. The risk of newly developing CKD was similar between patients of SSA origin and those born in Western Europe, Australia, or New Zealand (adjusted hazard ratio, 1.00; 95% CI, .63-1.59).CONCLUSIONS: Among HIV-infected patients in the Netherlands, being of SSA origin was associated with a higher baseline CKD prevalence but had no impact on newly developing CKD over time. This suggests a shift in the etiology of CKD from HIV-associated nephropathy toward other etiologies.</p

Analysis of the National Adult Nutrition Survey (Ireland) and the Food4Me Nutrition Survey Databases to Explore the Development of Food Labelling Portion Sizes for the European Union

The present study set out to explore the option of developing food portion size for nutritional labelling purposes using two European Union (EU) dietary surveys. The surveys were selected as they differed in (a) methodologies (food diary versus food frequency questionnaire), (b) populations (Irish National Adult Nutrition Survey (NANS) versus a seven-country survey based on the pan EU study Food4Me), (c) food quantification (multiple options versus solely photographic album) and (d) duration (4 consecutive days versus recent month). Using data from these studies, portion size was determined for 15 test foods, where portion size was defined as the median intake of a target food when consumed. The median values of the portion sizes derived from both the NANS and Food4Me surveys were correlated (r = 0.823; p < 0.00) and the mean of the two survey data sets were compared to US values from the Recognized as Customarily Consumed (RACC) database. There was very strong agreement across all food categories between the averaged EU and the US portion size (r = 0.947; p < 0.00). It is concluded that notwithstanding the variety of approaches used for dietary survey data in the EU, the present data supports using a standardized approach to food portion size quantification for food labelling in the EU

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

INTRODUCTION: There is paucity of data related to potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) among HIV-positive individuals. We investigated whether such differences exist in the observational D:A:D cohort study.METHODS:Participants were followed from study enrolment until the earliest of death, six months after last visit or February 1, 2015. Initiation of CVD interventions [lipid-lowering drugs (LLDs), angiotensin-converting enzyme inhibitors (ACEIs), anti-hypertensives, invasive cardiovascular procedures (ICPs) were investigated and Poisson regression models calculated whether rates were lower among women than men, adjusting for potential confounders.RESULTS:Women (n = 12,955) were generally at lower CVD risk than men (n = 36,094). Overall, initiation rates of CVD interventions were lower in women than men; LLDs: incidence rate 1.28 [1.21, 1.35] vs. 2.40 [2.34, 2.46]; ACEIs: 0.88 [0.82, 0.93] vs. 1.43 [1.39, 1.48]; anti-hypertensives: 1.40 [1.33, 1.47] vs. 1.72 [1.68, 1.77] and ICPs: 0.08 [0.06, 0.10] vs. 0.30 [0.28, 0.32], and this was also true for most CVD interventions when exclusively considering periods of follow-up for which individuals were at high CVD risk. In fully adjusted models, women were less likely to receive CVD interventions than men (LLDs: relative rate 0.83 [0.78, 0.88]; ACEIs: 0.93 [0.86, 1.01]; ICPs: 0.54 [0.43, 0.68]), except for the receipt of anti-hypertensives (1.17 [1.10, 1.25]).CONCLUSION:The use of most CVD interventions was lower among women than men. Interventions are needed to ensure that all HIV-positive persons, particularly women, are appropriately monitored for CVD and, if required, receive appropriate CVD interventions.</p