Adequate Serum Concentrations Research Articles

The effect of motivation type on intake and nutritional status of vitamin B12, omega-3 fatty acids, iron and nutrition knowledge in individuals following a vegan diet

The fundamental principle of veganism is to avoid all possible animal exploitation and therefore, animal ethics has always been a primary motivator. Nowadays, the environment and health are also common motivators. Omission of all animal products leads to dietary exclusion of vitamin B12, limited intake of omega-3 fatty acids, specifically EPA and DHA, and intake of low bioavailable iron sources1. Obtaining the knowledge to appropriately plan and replace nutrients through food or supplementation is key to avoiding deficiencies and subsequent consequences. This study aimed to determine the effect of motivation for being vegan on intake of key nutrients and nutritional knowledge. This cross-sectional, observational study recruited participants, who had followed a vegan diet for minimum 2 years. Demographics and nutrition knowledge were obtained from questionnaires. Motivation type was determined using the validated vegetarian eating motives inventory (VEMI) – participants scored the importance of animal ethic, environment and health. Intakes of vitamin B12 and iron, were collected using a 4-day food diary and assessed against Estimated Average Requirement (EAR). Blood samples were taken to determine status of vitamin B12, haemoglobin, serum ferritin, and omega-3 index. Omega-3 index score ≤4 indicates increased risk of coronary heart disease. Animal ethics was the greatest motivator to become vegan, with 83.5% of participants scoring it as very important, compared to 71.7% of people stating the environment, and 53.3% stating health. No association was found between all motivation types and intake of vitamin B12 and iron, nor omega-3 index. Mean vitamin B12 intake (supplements excluded) of 2.11ug/day ± 3.43 exceeded the EAR of 2.0ug/day for both men and women, however intakes ranged between 0.00 and 37.63ug/day. Mean intake of iron (18.77mg/day) exceeded the EAR for both men and women. Overall mean omega-3 index was 3.16%. Both men (162.24g/L) and women (151.44g/L) had adequate mean Hb serum concentrations. Mean serum ferritin was within normal range for both men (64.86ug/L ± 43.48) and women (32.55ug/L ± 26.04). Overall mean serum vitamin B12 was within normal range (316.54pmol/L ± 146.18), however a large range was observed from 72.00pmol/L to 1,015pmol/L. Males and females had similar knowledge, with only one question regarding fibre content in cornflakes found to be significantly different (P = 0.012). Knowledge was varied e.g., 100% of participants could identify that pasta was a carbohydrate source, yet could not identify which fats are most important to reduce. Mean vitamin B12 intake exceeding EAR and normal status despite limited vegan sources, indicates high consumption of high bioavailable fortified foods, and supplementation. Iron status shows large consumption of iron rich foods to overcome bioavailability issues, reflected by adequate iron intake, after increasing EAR by 80% to meet recommendations. The mean omega-3 index shows a low cardioprotective omega-3 fatty acid intake.

WHICH TOOL IS THE BEST GUIDE OPTIMIZE THE VORICONAZOLE DOSAGE: THERAPEUTIC DRUG MONITORING OR CYTOCHROME P450 POLYMORPHISM?

Voriconazole (VCZ) is the drug of choice for invasive aspergillosis (IA). However, narraow therapeutic range and variable pharmacokinetics can effect the success of the therapy. VCZ serum concentration is influenced by several factor including CYP450 polymorphisms primarily by CY2C19. Therapeutic drug monitoring (TDM) of VCZ is highly recommended to check adequate serum concentrations. Herein, we investigated the usefulness of detecting CYP450 polymorphism. Patients with hematological malignancies were included in the study.CYP450 polymorphisms which are responsible for metabolism of VCZ were investigated using RT-PCR. TDM of VCZ was peformed usingLC/MS/MS.11 patients were included in the study. Frequencies of CYP2C19 genotypes are 27% for intermediate metabolizer; 36% rapid metabolizer, 18% for ultra rapid metabolizer, 18% for normal metabolizer. Two patients experienced dose related side effects and one of these patient’s voriconazole blood concentration was supratherapeuticAlthough VCZ is the drug of choice for thetreatment of IA, the variabality of the pharmacokinetics can influence the success of therapy significantly. Therefore implementing the pharmacogenetic testing and therapeutic drug monitoring to clinical practice might help clinicians to provide improved care to patients and improve treatment outcomes.

Morphometric variants of remodeling and diastolic function of the left ventricle in late postmenopausal patients with vitamin D deficiency

Aim. To reveal the features of the structural-geometric remodeling of the left chambers of the heart, the diastolic function of the left ventricle and to assess the presence of calcification of the valvular structures of the heart in late postmenopausal women with different levels of vitamin D. Material and methods. The cross-sectional study included 123 postmenopausal women. A standard transthoracic echocardiography was performed with an assessment of morphometric variants of remodeling of the left chambers of the heart and its diastolic function according to the transmitral flow. The significance of differences was assessed using the Mann–Whitney test, χ2 Pearson. Differences and correlations were considered significant at p < 0.05. Results. The median concentration of 25(OH)D in the sample was 20.51 ng/ml (15.8÷26.73). Adequate serum concentration of 25(OH)D was observed in 23 (19%) patients (group 1), in 100 (81%) cases vitamin D deficiency was detected (group 2). In group 1 — 7 (31%) patients had normal geometry (NG) of the left ventricle (LV), LV concentric remodeling (CR) was diagnosed in 1 (4%) case, LV concentric hypertrophy (CH) was diagnosed in 3 (13%) cases, and LV eccentric hypertrophy (EH) was detected in 12 (52%) cases. In Group 2, LV NG was diagnosed in 27 (27%) cases, LV CR was detected in 8 (8%) cases, LV CH was detected in 31 (31%) cases, and LV EH was verified in 34 (34%) cases, the differences are insignificant (p = 0.24). Patients of group 2 showed a statistically significant increase in the volume of the right atrium (RA) and thickness of the posterior wall of the left ventricle (TZSLV). In group 1, in 11 (50%) cases, rigid-type diastolic dysfunction (DD) was detected, and in 11 (50%) cases, a pseudo-normal type of DD was detected. In group 2, pseudonormal myocardial DD was detected in 26 (26%) patients, 74 (74%) patients had rigid-type DD, differences between groups were significant (p < 0.001). Calcifications were found in the annulus fibrosus in 16 (70%) cases in group 1 and in 88 (88%) patients in group 2, the differences were significant (p = 0.04). Conclusion. In the study, data were obtained indicating a significant contribution of vitamin D deficiency to changes in the geometry of the left chambers of the heart, diastolic function of the left ventricle, and calcification of valvular structures.

The Relevance of Integrating CYP2C19 Phenoconversion Effects into Clinical Pharmacogenetics.

CYP2D6 and CYP2C19 functional status as defined by genotype is modulated by phenoconversion (PC) due to pharmacokinetic interactions. As of today, there is no data on the effect size of PC for CYP2C19 functional status. The primary aim of this study was to investigate the impact of PC on CYP2C19 functional status. Two patient cohorts (total n=316; 44.2±15.4 years) were investigated for the functional enzyme status of CYP2C19 applying two different correction methods (PCBousman, PCHahn&Roll) as well as serum concentration and metabolite-to-parent ratio of venlafaxine, amitriptyline, mirtazapine, sertraline, escitalopram, risperidone, and quetiapine. There was a decrease in the number of normal metabolizers of CYP2C19 and an increase in the number of poor metabolizers. When controlled for age, sex, and, in the case of amitriptyline, venlafaxine, and risperidone, CYP2D6 functional enzyme status, an association was observed between the CYP2C19 phenotype/functional enzyme status and serum concentration of amitriptyline, sertraline, and escitalopram. PC of CYP2C19 changes phenotypes but does not improve correlations with serum concentrations. However, only a limited number of patients received perturbators of CYP2C19. Studies with large numbers of patients are still lacking, and thus, it cannot be decided if there are minor differences and which method of correction to use. For the time being, PC is relevant in individual patients treated with CYP2C19-affecting drugs, for example, esomeprazole. To ensure adequate serum concentrations in these patients, this study suggests the use of therapeutic drug monitoring.

Oral Antibiotics for Bacteremia and Infective Endocarditis: Current Evidence and Future Perspectives.

Bacteremia and endocarditis are two clinical syndromes that, for decades, were managed exclusively with parenteral antimicrobials, irrespective of a given patient's clinical condition, causative pathogen, or its antibiotic susceptibility profile. This clinical approach, however, was based on low-quality data and outdated expert opinions. When a patient's condition has improved, gastrointestinal absorption is not compromised, and an oral antibiotic regimen reaching adequate serum concentrations is available, a switch to oral antibacterials can be applied. Although available evidence has reduced the timing of the oral switch in bacteremia to three days/until clinical improvement, there are only scarce data regarding less than 10-day intravenous antibiotic therapy in endocarditis. Many standard or studied oral antimicrobial dosages are smaller than the approved doses for parenteral administration, which is a risk factor for treatment failure; in addition, the gastrointestinal barrier may affect drug bioavailability, especially when the causative pathogen has a minimum inhibitory concentration that is close to the susceptibility breakpoint. A considerable number of patients infected by such near-breakpoint strains may not be potential candidates for oral step-down therapy to non-highly bioavailable antibiotics like beta-lactams; different breakpoints should be determined for this setting. This review will focus on summarizing findings about pathogen-specific tailoring of oral step-down therapy for bacteremia and endocarditis, but will also present laboratory and clinical data about antibiotics such as beta-lactams, linezolid, and fosfomycin that should be studied more in order to elucidate their role and optimal dosage in this context.

The dose-dependent effect of estrogen on bone mineral density in trans girls.

Treatment in transgender girls can consist of puberty suppression (PS) with a gonadotropin-releasing hormone agonist (GnRHa) followed by gender-affirming hormonal treatment (GAHT) with estrogen. Bone mineral density (BMD) Z-scores decrease during PS and remain relatively low during GAHT, possibly due to insufficient estradiol dosage. Some adolescents receive high-dose estradiol or ethinyl estradiol (EE) to limit growth allowing comparison of BMD outcomes with different dosages. Retrospective study. Adolescents treated with GnRHa for ≥1 year prior to GAHT followed by treatment with a regular estradiol dose (gradually increased to 2 mg), 6 mg estradiol or 100-200 µg EE were included to evaluate height-adjusted BMD Z-scores (HAZ scores) on DXA. Eighty-seven adolescents were included. During 2.3 ± 0.7 years PS, lumbar spine HAZ scores decreased by 0.69 [95% confidence interval (CI) -0.82 to -0.56)]. During 2 years HT, lumbar spine HAZ scores hardly increased in the regular group (0.14, 95% CI -0.01 to 0.28, n = 59) vs 0.42 (95% CI 0.13 to 0.72) in the 6 mg group (n = 13), and 0.68 (95% CI 0.20 to 1.15) in the EE group (n = 15). Compared with the regular group, the increase with EE treatment was higher (0.54, 95% CI 0.05 to 1.04). After 2 years HT, HAZ scores approached baseline levels at start of PS in individuals treated with 6 mg or EE (difference in 6 mg group -0.20, 95% CI -0.50 to 0.09; in EE 0.17, 95% CI -0.16 to 0.50) but not in the regular group (-0.64, 95% CI -0.79 to -0.49). Higher estrogen dosage is associated with a greater increase in lumbar spine BMD Z-scores. Increasing dosage up to 2 mg estradiol is insufficient to optimize BMD and approximately 4 mg may be required for adequate serum concentrations.

Itraconazole Serum Trough Concentrations Using Oral Capsules for the Treatment of Chronic Pulmonary Aspergillosis: What is the Target?

In regions where there is only itraconazole capsule as a therapeutic option for treatment of chronic pulmonary aspergillosis (CPA), measuring the serum concentrations becomes even more important for therapeutic success. Evaluate the initial itraconazole serum trough concentrations after the administration of oral capsule of itraconazole for the treatment of CPA. The measurement was performed at least 7-days after initiation of therapy. The standard treatment at our institution was a 200mg capsule every 12h. We defined that an adequate serum trough concentration of itraconazole during treatment was 1-4mg/L. This study recruited 28 patients. The median value was 0.30mg/L (IQR 0.01-0.70). Only 11% (n = 3) had adequate serum concentrations based on guideline recommendation. All patients with clinical deterioration had itraconazole serum levels ≤ 0.8mg/L. The initial serum concentrations of itraconazole after capsule formulation administration were low. Increasing the dose should be considered when the itraconazole concentration is low, especially if it is ≤ 0.8mg/L, and the patient presents with clinical deterioration. Larger studies are needed to evaluate the adequate concentrations recommended for CPA.

Diagnosis and prognosis of serum Fut8 for epilepsy and refractory epilepsy in children.

With adequate serum concentration of antiepileptic drugs, the epilepsy symptoms in many patients still cannot be controlled well. The alteration of glycosyltransferase has obvious influence on the pathogenesis of epilepsy. In this study, we focus on the diagnostic and prognostic value of fucosyltransferase 8 (Fut8) on epilepsy and refractory epilepsy. Serum samples of 199 patients with epilepsy, 59 patients with refractory epilepsy and 22 healthy controls who were diagnosed in Shenzhen Children's hospital from August 2018 to August 2019 were collected. The level of lectins was further analyzed by lectin chip and enzyme linked immunosorbent assay (ELISA). The diagnostic value of serum Fut8 for epilepsy and refractory epilepsy was evaluated by receiver operating characteristic curve. Finally, the difference in the recurrence rate of convulsion in patients with epilepsy or refractory epilepsy within 2 years were observed in different Fut8 expression patients. The concentration of valproic acid (VPA) were significant different between epilepsy and refractory epilepsy group. The expression of α1, 6-fucosylation and Fut8 was significantly increased in the refractory epilepsy group compared with healthy controls. The area under the curve of Fut8 as a biomarker for predicting epilepsy or refractory epilepsy was 0.620 and 0.856, respectively. There was a significant difference in the recurrence rate of convulsion within 2 years in the children with refractory epilepsy (p = 0.0493) not epilepsy (p = 0.1865) between the high and low Fut8 expression groups. Fut8 was one of the effective indicators for the diagnosis and prognosis of refractory epilepsy.

Factors Affecting the Vitamin C Dose-Concentration Relationship: Implications for Global Vitamin C Dietary Recommendations

Vitamin C status is known to be associated with several demographic and lifestyle factors. These include gender, age, ethnicity, pregnancy/lactation, body weight, smoking status and dietary habits. In the present study, our aim was to investigate the National Health and Nutrition Examination Survey (NHANES) 2017-2018 datasets to assess the impact of these factors on vitamin C dose-concentration relationships to establish if there are higher requirements for vitamin C in certain subpopulations, and the possible extent of these additional requirements. The final cohort comprised 2828 non-supplementing adult males and females (aged 18-80+ years) with both vitamin C serum concentrations and dietary intake data available. The data were subsequently stratified by gender, age tertiles (≤36, 37-58, ≥59 years), ethnicity (non-Hispanic white, non-Hispanic black, and total Hispanic), socioeconomic tertiles (poverty income ratios: ≤1.35, 1.36-3.0, >3.0), weight tertiles (<72, 72-91, >91 kg), BMI tertiles (<26, 26-32, >32 kg/m2) and smoking status. Sigmoidal (four parameter logistic) curves with asymmetrical 95% confidence intervals were fitted to the dose-concentration data. We found that males required vitamin C intakes ~1.2-fold higher than females to reach 'adequate' serum vitamin C concentrations of 50 µmol/L. Males had both higher body weight and a higher prevalence of smoking than females. Smokers required vitamin C intakes ~2.0-fold higher than non-smokers to reach adequate vitamin C concentrations. Relative to adults in the lighter weight tertile, adults in the heavier weight tertile required ~2.0-fold higher dietary intakes of vitamin C to reach adequate serum concentrations. We did not observe any impact of ethnicity or socioeconomic status on the vitamin C dose-concentration relationship, and although no significant difference between younger and older adults was observed at vitamin C intakes > 75 mg/day, at intakes < 75 mg/day, older adults had an attenuated serum response to vitamin C intake. In conclusion, certain demographic and lifestyle factors, specifically gender, smoking and body weight, have a significant impact on vitamin C requirements. Overall, the data indicate that the general population should consume ~110 mg/day of vitamin C to attain adequate serum concentrations, smokers require ~165 mg/day relative to non-smokers, and heavier people (100+ kg) require ~155 mg/day to reach comparable vitamin C concentrations. These findings have important implications for global vitamin C dietary recommendations.

Dramatic Response to Lidocaine Infusion for Pain from Brachial Plexus Avulsion Injury

BACKGROUND: Traumatic brachial plexus avulsion injury (tBPI) can cause a severe chronic pain syndrome that is very difficult to treat. Though lidocaine has been shown to be effective for other pain syndromes, effectiveness in tBPI has not previously been reported. CASE REPORT: A 55-year-old man with tBPI had severe pain and minimal relief with numerous analgesic agents. He was able to access intravenous lidocaine as he was being treated at a cancer center, and had a sustained response to 7 mg/kg given over an hour. CONCLUSION: There is potential for a single bolus intravenous lidocaine infusion to provide good pain control sustained over many months in patients with traumatic brachial plexus injury. An adequate serum concentration of lidocaine is required for analgesic effect. If initial doses of lidocaine are tolerated but ineffective, higher doses may still be beneficial. KEY WORDS: Brachial plexus avulsion, lidocaine, lignocaine, pain management, palliative care, therapeutics, trauma

Epidemiologic Data of Vitamin D Deficiency and Its Implication in Cardio-Cerebrovascular Risk in a Southern Italian Population

Background Vitamin D (25(OH)D) deficiency is a prevalent condition worldwide. However, the highest prevalence rates of 25(OH)D deficiency have been attributed to regions with higher latitude. A close association between 25(OH)D and cardio-cerebrovascular (CCV) risk factors and major health problems has been identified. Aim To establish the prevalence of 25(OH)D deficiency and to investigate the relationship between 25(OH)D levels and CCV risk factors (blood cholesterol, triglycerides, glucose concentrations, body mass index, and systolic and diastolic blood pressure) in a cohort representative of Southern Italy. Methods The prevalence of 25(OH)D levels was evaluated in 1200 subjects aged 25–74 years (600 males and 600 females), enrolled in the “VIP” (from Italian for Irno Valley Prevention) Project, whereas multiple linear regression analysis was used to determine the relationship between 25(OH)D levels and CCV risk factors. Results Only 13.3% of females and 11.1% of males showed adequate serum concentrations of 25(OH)D (≥30 ng/ml), while 59.3% of females and 55.1% of males showed 25(OH)D deficient levels (<20 ng/ml). We observed an independent association between 25(OH)D concentrations and metabolic syndrome score, LDL cholesterol, HDL cholesterol, and corrected QT (cQT). Conclusions We report a high prevalence of 25(OH)D deficiency across the largest Italian adult population studied so far and, in particular, the first across Southern Italy; furthermore, we provide data on the association between 25(OH)D deficiency and higher CCV risk factors.

Tissue Exposure does not Explain Non-Response in Ulcerative Colitis Patients with Adequate Serum Vedolizumab Concentrations.

Some patients with ulcerative colitis [UC] do not respond to vedolizumab treatment despite adequate drug exposure in serum. This study aimed to investigate vedolizumab in tissue and questioned whether insufficient tissue exposure could explain non-response in UC patients with adequate serum vedolizumab concentrations. A paired serum sample and colonic mucosal biopsy was collected from 40 UC patients [20 endoscopic responders, 20 non-responders] at week 14 of vedolizumab treatment. Vedolizumab, soluble [s]-mucosal addressin cell adhesion molecule-1 [MAdCAM-1], s-vascular cell adhesion molecule-1 [VCAM-1] and s-intercellular adhesion molecule-1 [ICAM-1] were measured in serum and/or tissue. Endoscopic response was defined as Mayo endoscopic sub-score ≤1. A significant positive correlation was observed between vedolizumab serum and colonic tissue concentrations [ρ = 0.84, p < 0.0001], regardless of the macroscopic inflammatory state of the tissue. Vedolizumab tissue concentrations were lower in non-responders than in responders [0.07 vs 0.11 µg/mg, p = 0.04]. In the subgroup of patients with adequate vedolizumab serum concentrations [>14.6 µg/mL], tissue vedolizumab was not significantly different between responders and non-responders [0.15 vs 0.13 µg/mg; p = 0.92]. Serum sMAdCAM-1 concentrations, but not serum sICAM-1 or sVCAM-1 concentrations, were significantly higher in responders than in non-responders with adequate vedolizumab serum concentrations [1.04 vs 0.83 ng/mL, p = 0.03]. Vedolizumab concentrations in colonic mucosal tissue of UC patients reflect the concentration in serum regardless of the macroscopic inflammatory state of the tissue. Our data show that insufficient tissue exposure does not explain non-response in UC patients with adequate serum vedolizumab concentrations.

Influence of Body Weight Category on Outcomes in Candidemia Patients Treated With Anidulafungin

Background: Case reports and pharmacokinetic data suggest off-label echinocandin dosing may be needed to reach adequate serum concentrations in obese patients. Few outcome studies exist evaluating this population. Objectives: Of this study were to (1) determine the association of body mass index (BMI) with clinical outcomes of candidemia patients on standard doses of anidulafungin and (2) characterize fungal infections by body weight. Methods: A retrospective cohort was conducted to evaluate hospitalized patients treated for candidemia with anidulafungin at Food and Drug Administration–labeled dosing for at least 72 hours from January 1, 2014, through January 31, 2018. Candidemia was diagnosed by blood culture or T2 magnetic resonance (T2MR). Patients were compared according to BMI category. Results: One hundred seventy-three patients were included. Candida albicans and Candida glabrata were identified in 58 (33%) and 57 (33%) patients, respectively. Mortality was comparable according to BMI category: 4 (36.4%) underweight, 8 (25.8%) normal weight, 16 (32.0%) overweight, 20 (33.9%) obese, and 7 (31.8%) morbidly obese, P = .976. Variables associated with mortality included: severe sepsis (adjusted odds ratio [OR] = 5.1, 95% CI: 1.7-14.8) and liver disease (adjusted OR = 3.2, 95% CI: 1.1-9.4). Variables that were protective of mortality included: line removal (adjusted OR = 0.05, 95% CI: 0.02-0.2) and receipt of anidulafungin for at least 5 days (adjusted OR = 0.35, 95% CI: 0.15-0.8). Conclusion: There was no difference detected in mortality among patients with candidemia across BMI category. Larger studies are needed to confirm whether standard doses of anidulafungin are sufficient for candidemia in obese patients.

Impact of Obesity on Ceftriaxone Efficacy.

Background: Ceftriaxone has standard, set dosing regimens that may not achieve adequate serum concentrations in obese patients compared to non-obese patients. The purpose of this study was to evaluate the effect of obesity on ceftriaxone efficacy when used as definitive monotherapy to treat infections. Methods: This retrospective cohort included adult inpatients treated with ceftriaxone monotherapy for ≥72 h between July 01, 2015–July 31, 2017. Patients were excluded if their infection lacked source control within 72 h or if they had polymicrobial infections requiring more than one antibiotic for definitive therapy. The primary outcome was the rate of clinical failure between obese versus non-obese patients, defined as a composite of (1) change in definitive therapy > 72 h due to clinical worsening; (2) residual leukocytosis (white blood cell count (WBC) > 10 × 109/L) > 72 h after treatment initiation; (3) presence of a fever (single temperature > 100.9 °F) > 72 h after treatment initiation; or (4) readmission within 30 days due to re-infection with the same organism. Results: A total of 101 patients were included in the study: 39 obese and 62 non-obese. The most common indications for ceftriaxone were urinary tract (52.5%), respiratory tract (24.8%), and bloodstream (24.8%) infections. The most commonly isolated organisms were Escherichia coli (48.5%) and Klebsiella species (15.8%). Most patients received 1g every 24 h. Clinical failure was observed in 61.5% of obese patients versus 40.3% of non-obese patients (p = 0.038). Conclusion: Obese patients treated with ceftriaxone were more likely to experience clinical failure when compared to non-obese patients. Further analyses are warranted to determine if weight-based dosing is required in obese patients treated with ceftriaxone.

Therapeutic Drug Monitoring of Antifungal Drugs: Another Tool to Improve Patient Outcome?

IntroductionThis study aimed to examine the relationship among adequate dose, serum concentration and clinical outcome in a non-selected group of hospitalized patients receiving antifungals.MethodsProspective cross-sectional study performed between March 2015 and June 2015. Dosage of antifungals was considered adequate according to the IDSA guidelines, whereas trough serum concentrations (determined with HPLC) were considered adequate as follows: fluconazole > 11 µg/ml, echinocandins > 1 µg/ml, voriconazole 1–5.5 µg/ml and posaconazole > 0.7 µg/ml.ResultsDuring the study period, 84 patients (65.4% male, 59.6 years) received antifungals for prophylaxis (40.4%), targeted (31.0%) and empirical therapy (28.6%). The most frequent drug was micafungin (28/84; 33.3%) followed by fluconazole (23/84; 27.4%), voriconazole (15/84; 17.9%), anidulafungin (8/84; 9.5%), posaconazole (7/84; 8.3%) and caspofungin (3/84; 3.6%). Considerable interindividual variability was observed for all antifungals with a large proportion of the patients (64.3%) not attaining adequate trough serum concentrations, despite receiving an adequate antifungal dose. Attaining the on-target serum antifungal level was significantly associated with a favorable clinical outcome (OR = 0.02; 95% CI 0.01–0.64; p = 0.03), whereas the administration of an adequate antifungal dosage was not.ConclusionsWith the standard antifungal dosage, a considerable proportion of patients have low drug concentrations, which are associated with poor clinical outcome.

&lt;p&gt;Serum Concentration of Vancomycin Is a Diagnostic Predictor of Nephrotoxic Acute Kidney Injury in Septic Patients in Clinical and Surgical Wards&lt;/p&gt;

Introduction and AimThere have been few studies to evaluate the monitoring of plasmatic concentrations of vancomycin in septic patients and their association with acute kidney injury (AKI) and death. This study aimed to evaluate the prevalence of adequate, subtherapeutic, and toxic serum concentrations of vancomycin in hospitalized septic patients and to associate the adequacy of therapeutic monitoring with clinical outcomes.MethodologyThis was a cohort-unicentric study that evaluated septic patients aged >18 years using vancomycin admitted to clinical and surgical wards of a Brazilian university center from August 2016 to July 2017 in a daily and uninterrupted way. We excluded patients with AKI prior to the introduction of vancomycin or with AKI development <48 hours after use, patients with AKI of other etiologies, stage V chronic kidney disease, and pregnant women.ResultsWe evaluated 225 patients, and 135 were included. Evaluation of serum concentration of vancomycin was realized in 94.1%, and of those, 59.3% presented toxic concentrations. The prevalence of AKI was 27.4% and happened on average on the ninth day of vancomycin usage. Between the fourth and sixth days, vancomycin serum concentration of >21.5 mg/L was a predictor of AKI, with area under the curve of 0.803 (95% CI 0.62–0.98, p=0.005), preceding the diagnosis of AKI by at least 3 days. Of these patients, 20.7% died, and serum concentrations of vancomycin between the fourth and sixth days were identified as risk factors associated with negative outcomes.ConclusionSerum concentration of vancomycin is an excellent predictor of AKI in patients admitted to wards, preceding the diagnosis of AKI by at least 72 hours. Toxic concentrations of vancomycin are associated with AKI, and AKI was a risk factor for death. Also, serum concentration of vancomycin >21.5 mg/L was the only variable associated with death in the Cox model.

Central Diabetes Insipidus in a Young Feline

Background: Central diabetes insipidus (CDI) is an endocrine disorder caused by the failure to produce, transport, or release ADH. This disease may show a primary etiology (idiopathic or congenital) or a secondary one (trauma or neoplasms). It is characterized by signs such as polyuria and polydipsia. The definitive diagnosis is obtained by the two-step water deprivation test; the absence of adequate urinary concentration in the first stage confirms the diagnosis of diabetes insipidus and, in the second stage, the response to the application of synthetic desmopressin confirms a central origin. Because CDI is rare in felines, the aim of this study was to report the occurrence of a case of CDI, probably of congenital primary origin, in an 8-month-old kitten.Case: An 8-month-old male feline, castrated, 3.2 kg, was brought to consultation with a report of polydipsia, polyuria, smaller size and weight, and lower activity when compared to his brother, for several months. On physical examination, lethargy, body score 2/5, and mild dehydration were noted, as well as deciduous teeth that should have already been replaced. Abdominal ultrasound and laboratory tests were requested, which ruled out chronic kidney disease (CKD), diabetes mellitus (DM), hyperadrenocorticism (HAC), and hyperthyroidism. Due to the fact that urinalysis evidenced hyposthenuria (urinary density [UD] 1.004), CDI was suspected. The patient underwent a water deprivation test and, after 7.5 h, lost 4.7% of his initial weight, while UD was 1.012, confirming the diagnosis of DI. The investigation then proceeded to the evaluation of the response to synthetic desmopressin by the application of 5 U IM. Two h later, UD was 1.019, confirming the diagnosis of CDI. The prescribed treatment was oral desmopressin at a dose of 100 μg BID. Upon return after 30 days, the feline had gained weight, was well hydrated, and the tutor reported higher activity. A new urinalysis showed a UD of 1.004 and inactive sediment. The tutor was asked to start administering the drug three times a day. However, noting that the patient’s quality of life had significantly improved, and wishing to spare the animal from the stress of taking medication once more a day, she chose not to modify the therapy and not to perform additional tests, due to financial limitation.Discussion: First, CKD, DM, HAC, and hyperthyroidism, more common conditions, were ruled out, and the investigation then proceeded to a water deprivation test. The feline lost 3% to 5% of the initial weight and UD was on the borderlinebetween hypo- and isosthenuria, as described in the literature for the diagnosis of DI. In the second stage of the test, slight urinary concentration was observed after the application of synthetic desmopressin, which confirmed the diagnosis of CDI. The dose of desmopressin prescribed for home treatment, 100 μg BID, was effective to relieve the clinical signs, but urine remained in hyposthenuria in the interval between administrations, suggesting that, for this patient, treatment would be more effective by administering the medication three times a day, in order to maintain an adequate serum concentration. Due to the diagnosis of CDI and the feline being young, the condition’s primary origin is believed to be congenital. It is also suspected that the patient may still have congenital hypothyroidism, due to the clinical signs of late tooth exchange and constant lethargy, in addition to laboratory results of thyroid hormones below reference levels. However, because thyroid tests were made by chemiluminescence, a repetition by radioimmunoassay is indicated. If hypothyroidism is confirmed,it would be possible to assume a common etiological factor between CDI and hypothyroidism, such as hypothalamicpituitary malformation.

Cow's milk allergic infants on amino acid-based medical nutrition formula maintain adequate serum concentrations of phosphorus, calcium and magnesium despite the use of acid-suppressive medication

Cow's milk allergic infants on amino acid-based medical nutrition formula maintain adequate serum concentrations of phosphorus, calcium and magnesium despite the use of acid-suppressive medication

Clinical impact of vancomycin heteroresistance in staphylococcal strains involved in neonatal sepsis: Discussion of a case report

Heteroresistance to vancomycin (HRV) represents a decreased susceptibility to vancomycin and is frequently observed in multidrug-resistant coagulase-negative staphylococci. The clinical significance of such heteroresistance is controversial, but several failures of vancomycin therapy have been related to HRV, especially in the neonatal population. Here we report the case of a preterm neonate, born at 26 weeks of gestation, who developed sepsis due to a multidrug-resistant HRV Staphylococcuscapitis isolate. Bacteremia persisted despite adequate vancomycin serum concentration and catheter removal. The patient finally recovered after replacing vancomycin by linezolid. Through this case report, we would like to alert clinicians of the potential clinical impact of HRV and to discuss the lack of therapeutic alternatives in neonates.

The Revised D-A-CH-Reference Values for the Intake of Vitamin B12 : Prevention of Deficiency and Beyond.

ScopeThe nutrition societies of Germany, Austria, and Switzerland are the joint editors of the “D‐A‐CH reference values for nutrient intake”, which are revised regularly.Methods and ResultsBy reviewing vitamin‐B12‐related biomarker studies, the reference values for vitamin B12 were revised in 2018. For adults, the estimated intake is based on the adequate serum concentrations of holotranscobalamin and methylmalonic acid. The estimated values for children and adolescents are extrapolated from the adult reference value by considering differences in body mass, an allometric exponent, and growth factors. For infants below 4 months of age, an estimated value is set based on the vitamin B12 intake via breast milk. The reference values for pregnant and lactating women consider the requirements for the fetus and for loss via breast milk. The estimated values for vitamin B12 intake for infants, children, and adolescents range from 0.5 to 4.0 µg d−1. For adults, the estimated values are set at 4.0 µg d−1, and for pregnant and lactating women, they are set at 4.5 and 5.5 µg d−1, respectively.ConclusionBased on the data of several vitamin B12 status biomarkers studies, the reference value for vitamin B12 intake for adults is raised from 3.0 to 4.0 µg d−1.