Micronutrients in Sepsis and COVID-19: A Narrative Review on What We Have Learned and What We Want to Know in Future Trials.

Sepsis remains the leading cause of mortality in hospitalized patients, contributing to 1 in every 2-3 deaths. From a pathophysiological view, in the recent definition, sepsis has been defined as the result of a complex interaction between host response and the infecting organism, resulting in life-threatening organ dysfunction, depending on microcirculatory derangement, cellular hypoxia/dysoxia driven by hypotension and, potentially, death. The high energy expenditure driven by a high metabolic state induced by the host response may rapidly lead to micronutrient depletion. This deficiency can result in alterations in normal energy homeostasis, free radical damage, and immune system derangement. In critically ill patients, micronutrients are still relegated to an ancillary role in the whole treatment, and always put in a second-line place or, frequently, neglected. Only some micronutrients have attracted the attention of a wider audience, and some trials, even large ones, have tested their use, with controversial results. The present review will address this topic, including the recent advancement in the study of vitamin D and protocols based on vitamin C and other micronutrients, to explore an update in the setting of sepsis, gain some new insights applicable to COVID-19 patients, and to contribute to a pathophysiological definition of the potential role of micronutrients that will be helpful in future dedicated trials.

[Vitamin C and D supplementation in critically ill patients]. / Supplementierung von Vitamin C und D bei kritisch Kranken.

Micronutrient supplementation as part of the medical nutrition therapy for critically ill patients has received much attention in the past few years. Nevertheless, in clinical practice uncertainty remains about the optimal supplementation strategy, including which substance at which dosage should be administered at what time to specific groups of patients. Thus, the aim of this narrative review is to summarize the current evidence and recommendations for the micronutrients vitamin C and vitamin D. The physiological and pathophysiological roles of both vitamins are presented, recently published clinical trials are discussed, and the recommendations of the current guidelines are summarized. In addition, pragmatic tips for use in everyday clinical practice in the intensive care unit are given.

A Comparison of the Representation of Women in Editor Positions at Major Medical Journals in 2021 vs 2011.

PURPOSE: There continues to be a disparity in the representation of women across medicine, including in editor positions at major medical journals. The authors repeated a study they had conducted in 2011 to compare the representation of women in editor-in-chief and editorial board member positions in 2011 and 2021. METHOD: The authors included in their analysis the 60 journals from their original 2011 study and the top 5 ranked journals by Journal Impact Factor in each of 12 disciplines in 2021. This led to the inclusion of 86 journals. The authors collected the names and genders of the editors-in-chief and editorial board members at these journals, using information provided by the journals and a Google search for the photos and/or pronouns of the remaining editors. They compared results across years (2021 vs 2011), editor positions, disciplines, Journal Impact Factors, and ranks. RESULTS: Twenty-two of the 90 editors-in-chief (24.4%) were women in 2021 compared with 10 of 63 (15.9%) in 2011, an increase of 8.5%. Of the 6,285 editorial board members, 1,756 were women (27.9%) in 2021 compared with 719 of 4,112 (17.5%) in 2011, an increase of 10.4%. Journals with women editors-in-chief gained 3.5 ranks and 9.1 points in Journal Impact Factor on average over this 10-year period, compared with no gain in rank and an increase of 4.7 points in Journal Impact Factor for journals with men editors-in-chief; both are statistically significant differences (P = .045 and P = .016, respectively). CONCLUSIONS: In almost all evaluated disciplines and editor positions, there was an increase in the percentage of women at top-ranked medical journals over a 10-year period. Despite this increase, improvements are still needed to accelerate the currently slow rate of change in these positions to enhance diversity, equity, and inclusion for women in medicine.

Hospitalizations, emergency room visits and causes of death in 198 patients with permanent hypoparathyroidism: a retrospective Austrian study (2005-2022).

Objective: Chronic hypoparathyroidism (HP) is associated with acute and chronic complications, especially those related to hypocalcemia. We aimed to analyze details on hospital admissions and the reported deaths in affected patients. Design and methods: In a retrospective analysis, we reviewed the medical history of 198 patients diagnosed with chronic HP over a continuous period of up to 17 years at the Medical University Graz. Results: The mean age in our mostly female cohort (70.2%) was 62.6 ± 18.7 years. The etiology was predominantly postsurgical (84.8%). About 87.4% of patients received standard medication (oral calcium/vitamin D), 15 patients (7.6%) used rhPTH1-84/Natpar® and 10 patients (4.5%) had no/unknown medication. Two hundred and nineteen emergency room (ER) visits and 627 hospitalizations were documented among 149 patients, and 49 patients (24.7%) did not record any hospital admissions. According to symptoms and decreased serum calcium levels, 12% of ER (n = 26) visits and 7% of hospitalizations (n = 44) were likely attributable to HP. A subgroup of 13 patients (6.5%) received kidney transplants prior to the HP diagnosis. In eight of these patients, parathyroidectomy for tertiary renal hyperparathyroidism was the cause of permanent HP. The mortality was 7.8% (n = 12), and the causes of death appeared to be unrelated to HP. Although the awareness for HP was low, calcium levels were documented in 71% (n = 447) of hospitalizations. Conclusions: Acute symptoms directly related to HP did not represent the primary cause of ER visits. However, comorbidities (e.g. renal/cardiovascular diseases) associated with HP played a key role in hospitalizations and deaths. Significance statement: Hypoparathyroidism (HP) is the most common complication after anterior neck surgery. Yet, it remains underdiagnosed as well as undertreated, and the burden of disease and long-term complications are usually underestimated. There are few detailed data on emergency room (ER) visits hospitalizations and death in patients with chronic HP, although acute symptoms due to hypo-/hypercalcemia are easily detectable. We show that HP is not the primary cause for presentation but that hypocalcemia is a typical laboratory finding (when ordered) and thus may contribute to subjective symptoms. Patients often present with renal/cardiovascular/oncologic illness for which HP is known to be a contributing factor. A small but very special group (n = 13, 6.5%) are patients after kidney transplantations who showed a high ER hospitalization rate. Surprisingly, HP was never the cause for their frequent hospitalizations but rather the result of chronic kidney disease. The most frequent cause for HP in these patients was parathyroidectomy due to tertiary hyperparathyroidism. The causes of death in 12 patients appeared to be unrelated to HP, but we found a high prevalence of chronic organ damages/comorbidities related to it in this group. Less than 25% documented HP correctly in the discharge letters, which indicates a high potential for improvement.

An update of the effects of vitamins D and C in critical illness.

Many critically ill patients are vitamin D and vitamin C deficient and the current international guidelines state that hypovitaminoses should be compensated. However, uncertainty about optimal dosage, timing and indication exists in clinical routine, mainly due to the conflicting evidence. This narrative review discusses both micronutrients with regards to pathophysiology, clinical evidence of benefits, potential risks, and guideline recommendations. Evidence generated from the most recent clinical trials are summarized and discussed. In addition, pragmatic tips for the application of these vitamins in the clinical routine are given. The supplementations of vitamin D and C represent cost-effective and simple interventions with excellent safety profiles. Regarding vitamin D, critically ill individuals require a loading dose to improve 25(OH)D levels within a few days, followed by a daily or weekly maintenance dose, usually higher doses than healthy individuals are needed. For vitamin C, dosages of 100-200 mg/d are recommended for patients receiving parenteral nutrition, but needs may be as high as 2-3 g/d in acutely ill patients.

Celiac Disease and the Thyroid: Highlighting the Roles of Vitamin D and Iron.

Celiac disease (CD) and autoimmune thyroid diseases (AITD) like Hashimoto's thyroiditis (HT) and Graves' disease (GD) frequently coexist, entailing numerous potential impacts on diagnostic and therapeutic approaches. Possible correlations might exist through gut microbiota, regulating the immune system and inflammatory responses, promoting autoimmune diseases, as well as shared cytokines in pathogenesis pathways, cross-reacting antibodies or malabsorption of micronutrients that are essential for the thyroid like iron or vitamin D. Vitamin D deficiency is a common finding in patients with AITD, but might protect from autoimmunity by wielding immunoregulatory and tolerogenic impacts. Additionally, vitamin D is assumed to be involved in the onset and progression of CD, presumably plays a substantial protective role for intestinal mucosa and affects the thyroid via its immunomodulatory effects. Iron is an essential micronutrient for the thyroid gland needed for effective iodine utilization by the iron-dependent enzyme thyroid iodine peroxidase (TPO). Despite being crucial for thyroid hormone synthesis, iron deficiency (ID) is a common finding in patients with hypothyroidism like HT and is frequently found in patients with CD. A literature research was conducted to examine the interplay between CD, AITD, vitamin D and iron deficiency. This narrative review highlights the relevant correlation of the two disease entities CD and AITD, their reciprocal impact and possible therapeutic options that should be further explored by future studies.

Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function?

A healthy gut microbiota not only has beneficial effects on the activity of the immune system, but also on thyroid function. Thyroid and intestinal diseases prevalently coexist-Hashimoto's thyroiditis (HT) and Graves' disease (GD) are the most common autoimmune thyroid diseases (AITD) and often co-occur with Celiac Disease (CD) and Non-celiac wheat sensitivity (NCWS). This can be explained by the damaged intestinal barrier and the following increase of intestinal permeability, allowing antigens to pass more easily and activate the immune system or cross-react with extraintestinal tissues, respectively. Dysbiosis has not only been found in AITDs, but has also been reported in thyroid carcinoma, in which an increased number of carcinogenic and inflammatory bacterial strains were observed. Additionally, the composition of the gut microbiota has an influence on the availability of essential micronutrients for the thyroid gland. Iodine, iron, and copper are crucial for thyroid hormone synthesis, selenium and zinc are needed for converting T4 to T3, and vitamin D assists in regulating the immune response. Those micronutrients are often found to be deficient in AITDs, resulting in malfunctioning of the thyroid. Bariatric surgery can lead to an inadequate absorption of these nutrients and further implicates changes in thyroid stimulating hormone (TSH) and T3 levels. Supplementation of probiotics showed beneficial effects on thyroid hormones and thyroid function in general. A literature research was performed to examine the interplay between gut microbiota and thyroid disorders that should be considered when treating patients suffering from thyroid diseases. Multifactorial therapeutic and preventive management strategies could be established and more specifically adjusted to patients, depending on their gut bacteria composition. Future well-powered human studies are warranted to evaluate the impact of alterations in gut microbiota on thyroid function and diseases.

Risks in Management of Enteral Nutrition in Intensive Care Units: A Literature Review and Narrative Synthesis.

Critically ill patients in the intensive care unit (ICU) have a high risk of developing malnutrition, and this is associated with poorer clinical outcomes. In clinical practice, nutrition, including enteral nutrition (EN), is often not prioritized. Resulting from this, risks and safety issues for patients and healthcare professionals can emerge. The aim of this literature review, inspired by the Rapid Review Guidebook by Dobbins, 2017, was to identify risks and safety issues for patient safety in the management of EN in critically ill patients in the ICU. Three databases were used to identify studies between 2009 and 2020. We assessed 3495 studies for eligibility and included 62 in our narrative synthesis. Several risks and problems were identified: No use of clinical assessment or screening nutrition assessment, inadequate tube management, missing energy target, missing a nutritionist, bad hygiene and handling, wrong time management and speed, nutritional interruptions, wrong body position, gastrointestinal complication and infections, missing or not using guidelines, understaffing, and lack of education. Raising awareness of these risks is a central aspect in patient safety in ICU. Clinical experts can use a checklist with 12 identified top risks and the recommendations drawn up to carry out their own risk analysis in clinical practice.