Vitamin D Repletion and AA/EPA Intake in Children with Type 1 Diabetes: Influences on Metabolic Status.

Our study aimed to show a relationship between metabolic control, vitamin D status (25OHD), and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio in children with type 1 diabetes (T1D). The secondary aim was to evaluate dietary intake and the presence of ketoacidosis (DKA) at the onset of T1D. Methods: A cohort of 40 children with T1D was recruited, mean age 9.7 years (7.1; 13), with onset of T1D in the last 5 years: some at onset (n: 20, group A) and others after 18.0 ± 5 months (n: 20; group B). Twenty healthy children were compared as control subjects (CS). Dietary intakes were assessed through a diary food frequency questionnaire. Moreover, dried blood spots were used to test AA/EPA ratio by gas chromatography. Results: T1D children had a lower percentage of sugar intake (p < 0.02) than CS. Furthermore, group B introduced a greater amount of AA with the diet (g/day; p < 0.05) than CS (p < 0.01) and group A (p < 0.01). Children with an AA/EPA ratio ≤ 22.5 (1st quartile) required a lower insulin demand and had higher 25OHD levels than those who were in the higher quartiles (p < 0.05). Subjects with DKA (9/40) had levels of 25OHD (p < 0.05) and C-peptide (p < 0.05) lower than those without DKA. Moreover, analyzing the food questionnaire in group A, subjects with DKA showed a lower intake of proteins, sugars, fiber (g/day; p< 0.05), vitamin D, EPA, and DHA (g/day; p < 0.01) compared to subjects without DKA. Non-linear associations between vitamin D intake (p < 0.0001; r2:0.580) and linear between EPA intake and C-peptide (p < 0.05; r: 0.375) were found in all subjects. Conclusions: The study shows a relationship between vitamin D status, AA/EPA ratio, and metabolic state, probably due to their inflammatory and immune mechanisms. A different bromatological composition of the diet could impact the severity of the onset.

Does Mediterranean Adequacy Index Correlate with Cardiovascular Events in Patients with Advanced Chronic Kidney Disease? An Exploratory Study.

The Mediterranean Diet (MD) is a healthy dietary pattern, demonstrated to reduce the risk of cancer, diabetes, cardiovascular and neurodegenerative diseases, and early death. The Mediterranean Adequacy Index (MAI) is used to measure adherence to the MD in perspective studies in the general population and correlates with cardiovascular events. The aim of this study was to calculate the MAI among patients with advanced chronic kidney disease (CKD) and correlate it with traditional uremic, microbiota-derived, and proatherogenic toxins as well as nutritional status, quality of life, and cardiovascular events. A total of 60 adult patients with advanced CKD were enrolled and their MAI was calculated. According to the median value, patients were divided into lower (l-MAI, <1.80) and higher (h-MAI, ≥1.80) MAI groups. Biochemical parameters, microbiota-derived and proatherogenic toxins (p-Cresyl sulphate, Indoxyl-sulphate, and Lipoprotein-associated phospholipase A2), nutritional status, quality of life, and cardiovascular events that occurred in the previous three years were recorded. The mean value of the MAI was 2.78 ± 2.86. The MAI was significantly higher in foreigners (median (IQR) 6.38 (8.98) vs. 1.74 (1.67), p < 0.001) and diabetic patients. The l-MAI and h-MAI groups had similar routinary blood, p-Cresyl-sulphate, Indoxyl-sulphate, and Lp-PLA2 as well as nutritional status and quality of life parameters. The MAI was not associated with previous cardiovascular events and did not correlate with cardiovascular events in CKD patients. New and nephro-tailored indexes are warranted to evaluate nutritional therapy in CKD patients.

Probiotics-Supplemented Low-Protein Diet for Microbiota Modulation in Patients with Advanced Chronic Kidney Disease (ProLowCKD): Results from a Placebo-Controlled Randomized Trial.

The probiotics-supplemented low-protein diet in chronic kidney disease (ProLowCKD) was a single-centre, double-blind, placebo-controlled, randomised trial that was conducted to investigate whether the association between a low protein diet (LPD) and a new formulation of probiotics (Bifidobacterium longum and Lactobacillus reuteri) was effective at reducing traditional uremic, microbiota-derived, and proatherogenic toxins in sixty patients affected by advanced CKD. After 2 months of a LPD-a reduction in blood urea nitrogen (52 ± 17 vs. 46 ± 15 mg/dL, p = 0.003), total cholesterol (185 ± 41 vs. 171 ± 34 mg/dL, p = 0.001), and triglycerides (194 ± 148 vs. 161 ± 70 mg/dL, p = 0.03) was observed; 57 subjects were then randomized to receive probiotics or a placebo for the subsequent 3 months. A total of 27 patients in the placebo group showed increased serum values of total cholesterol (169 ± 36 vs. 185 ± 40 mg/dL, p = 0.01), LDL cholesterol (169 ± 36 vs. 185 ± 40 mg/dL, p = 0.02), lipoprotein-associated phospholipase A2 (155.4 ± 39.3 vs. 167.5 ± 51.4 nmol/mL/min, p = 0.006), and indoxyl-sulphate (30.1 ± 17.6 vs. 34.5 ± 20.2 µM, p = 0.026), while the 24 subjects in the probiotics group showed a trend in the reduction of microbiota toxins. A reduction of antihypertensive and diuretic medications was possible in the probiotics group. This study shows that associating probiotics to LPD may have an additional beneficial effect on the control and modulation of microbiota-derived and proatherogenic toxins in CKD patients.

Compliance, Adherence and Concordance Differently Predict the Improvement of Uremic and Microbial Toxins in Chronic Kidney Disease on Low Protein Diet.

BACKGROUND: In medicine, "compliance" indicates that the patient complies with the prescriber's recommendations, "adherence" means that "the patient matches the recommendations" and "concordance" means "therapeutic alliance" between patient and clinician. While a low protein diet (LPD) is a cornerstone treatment of chronic kidney disease (CKD), monitoring the actual performance of LPD is a challenge. PATIENTS: Fifty-seven advanced CKD adult patients were enrolled and LPD prescribed. Compliance was evaluated through the normalized protein catabolic rate (nPCR), adherence by the dietitian by means of a 24-h dietary recall and concordance by the nephrologist during consultations. Traditional parameters as well as total p-Cresyl Sulphate (t-PCS), total Indoxyl Sulphate (t-IS) and Lipoprotein-associated phspholipase A2 (Lp-PLA2) were compared between adherent/not adherent and concordant/not concordant subjects at enrolment and after two months. RESULTS: nPCR, blood urea nitrogen, cholesterol and triglycerides significantly decreased in all patients. t-PCS and t-IS decreased among adherent subjects. Lp-PLA2, t-PCS, free-PCS and t-IS decreased among concordant subjects, while these increased in non-concordant ones. CONCLUSION: This study demonstrates that LPD may improve the control of traditional uremic toxins and atherogenic toxins in "adherent" and "concordant" patients. A comprehensive and multidisciplinary approach is needed to evaluate the compliance/adherence/concordance to LPD for optimizing nutritional interventions.

Short-Term Effects of Supplemental L-Arginine, Diosmin, Troxerutin, and Hesperidin in Diabetic Patients: A Pilot Study.

BACKGROUND AND AIMS: Inflammatory, oxidative stress, and endothelial dysfunction play a key role in the pathogenesis of long-term cardiovascular complications in patients with diabetes. The present observational prospective study is aimed at evaluating the effects of micronutrients and phytochemicals contained in the dietary supplement Flebotrofine® (AMNOL Chimica Biologica) on biochemical markers of inflammation, endothelial dysfunction, and glycemic control in patients with diabetes. METHODS: 105 type 1 or type 2 diabetes patients regularly took a daily dose of the dietary supplement Flebotrofine® for three consecutive months, and haematological and biochemical parameters were checked at baseline, after three months of treatment, and one month after its suspension. Statistical comparison of the laboratory parameters was performed using the two-tailed ANOVA test for repeated samples with a statistical significance level set at p < 0.05. RESULTS: The daily use of Flebotrofine® did not change the glycemic metabolic compensation of enrolled patients. After three months of regular Flebotrofine® intake, the plasma levels of the antioxidant ß-carotene and of arginine were significantly higher compared with the baseline values, with a decrease in the ADMA/arginine ratio. In contrast, apolipoprotein B, ApoB/ApoA1 ratio, and platelet and leukocyte counts significantly dropped. CONCLUSION: The daily use of Flebotrofine® might be a valid supplement of arginine, the precursor of NO, and essential in the prevention of endothelial dysfunction. The regular intake of arginine and phytochemicals also improved the antioxidant and antithrombotic profile of enrolled patients. Therefore, Flebotrofine® could be a useful dietary supplement to prevent long-term complications in patients with diabetes.

Psychotherapy with Music Intervention Improves Anxiety, Depression and the Redox Status in Breast Cancer Patients Undergoing Radiotherapy: A Randomized Controlled Clinical Trial.

The aim of this study was to assess the effects of psychotherapy with music intervention (PMI) on anxiety, depression, redox status, and inflammation in breast cancer patients undergoing radiotherapy (RT). This monocentric randomized clinical trial recruited 60 patients who had a breast cancer operation and were undergoing postoperative RT. Eligible patients were randomized (1:1) in two groups: the control group (CG) received treatment as usual (n = 30), i.e., RT alone; the intervention group (PMI) received RT and psychotherapy with music intervention (n = 30), which was delivered in a group setting. Five patients were excluded after randomization. Assessments were performed at baseline (T0), at the end of RT (T1), and three months after the end of RT (T2). The main objectives of the study were the assessment of anxiety/depression, plasma glutathione (GSH), and thiobarbituric acid reactive substances (TBARS) in the two arms of the study. Our findings revealed a positive effect of PMI on anxiety, depression, resilience, and quality of life. Furthermore, a positive effect of PMI on redox status was found for the first time. Thus, in the PMI group, we found a significant increase of GSH (mean change 2.2 95%, CI 0.7 to 3.7) and a significant reduction of TBARS (mean change -1.1 95%, CI -1.8 to -0.3) at T2 vs. T0.

Biomolecules Responsible for the Total Antioxidant Capacity (TAC) of Human Plasma in Healthy and Cardiopathic Individuals: A Chemical Speciation Model.

(1) Background: Much effort has been expended to investigate the antioxidant capacity of human plasma, attempting to clarify the roles of both metabolic and food substances in determining defenses against oxidative stress. The relationship between the total antioxidant capacity (TAC) and the concentrations of redox-active biomolecules in the human plasma of healthy and cardiopathic individuals was investigated in the present study to develop a chemical speciation model. (2) Methods: Plasma was collected from 85 blood donors and from 25 cardiovascular surgery patients. The TAC was measured using the CUPRAC-BCS (CUPric Reducing Antioxidant Capacity - Bathocuproinedisulfonic acid) method. Biomolecule concentrations were determined via visible spectrophotometry or HPLC/RP techniques. The relationship between the TAC and the concentrations was defined by applying a multiple regression analysis. The significance of the variables was first tested, and chemical models were proposed for the two datasets. The model equation is ßTAC=∑ißi·Ai, where ßi and [Ai] are the electronic exchange and the molar concentrations of the ith antioxidant component, respectively. (3) Results: The major contributions to the TAC, ~80%, come from endogenous compounds in both healthy and cardiopathic individuals, whereas the contributions from exogenous compounds were different between the two datasets. In particular, γ-tocopherol showed a different role in the chemical models developed for the two groups.

Dysmetabolisms Can Affect Total Antioxidant Capacity (TAC) of Human Plasma: Determination of Reference Intervals of TAC by Way of CUPRAC-BCS Method.

The total antioxidant capacity (TAC) of human plasma is an index of the redox buffer capacity of this biological fluid and could be a biomarker for those disorders affecting redox status. Distinguishing physiological from pathological conditions needs a reference. Therefore, this work aims to define the reference intervals for TAC of human plasma of apparently healthy adult individuals. TAC was measured using the CUPRAC-BCS (CUPric reducing antioxidant capacity-bathocuproinedisulfonic acid) method previously optimized and tested in a clinical laboratory. A population of 500 blood donors was selected, plus an additional 222 pathological patients carrying specific defective metabolisms, namely, hyperuricemia, hyperbilirubinemia, and type 2 diabetic mellitus. The reference intervals of TAC were calculated according to international guidelines. Due to the response of a partitioning test, the reference intervals for healthy population were separately defined for male (258) and female (151) groups. The reference intervals (µmol L-1) resulted: 727-1248 for the male subgroup and 637-1048 for the female subgroup. The absence of an age effect on TAC values was verified. The reference intervals evaluated allow a discussion on some pathological conditions overloading the plasma with redox-active waste substances.

Vitamin D and ω-3 Supplementations in Mediterranean Diet During the 1st Year of Overt Type 1 Diabetes: A Cohort Study.

Vitamin D and omega 3 fatty acid (ω-3) co-supplementation potentially improves type 1 diabetes (T1D) by attenuating autoimmunity and counteracting inflammation. This cohort study, preliminary to a randomized control trial (RCT), is aimed at evaluating, in a series of T1D children assuming Mediterranean diet and an intake of cholecalciferol of 1000U/day from T1D onset, if ω-3 co-supplementation preserves the residual endogen insulin secretion (REIS). Therefore, the cohort of 22 "new onsets" of 2017 received ω-3 (eicosapentenoic acid (EPA) plus docosahexaenoic acid (DHA), 60 mg/kg/day), and were compared retrospectively vs. the 37 "previous onsets" without ω-3 supplementation. Glicosilated hemoglobin (HbA1c%), the daily insulin demand (IU/Kg/day) and IDAA1c, a composite index (calculated as IU/Kg/day × 4 + HbA1c%), as surrogates of REIS, were evaluated at recruitment (T0) and 12 months later (T12). In the ω-3 supplemented group, dietary intakes were evaluated at T0 and T12. As an outcome, a decreased insulin demand (p < 0.01), particularly as pre-meal boluses (p < 0.01), and IDAA1c (p < 0.05), were found in the ω-3 supplemented group, while HbA1c% was not significantly different. Diet analysis in the ω-3 supplemented group, at T12 vs. T0, highlighted that the intake of arachidonic acid (AA) decreased (p < 0.01). At T0, the AA intake was inversely correlated with HbA1c% (p < 0.05; r;. 0.411). In conclusion, the results suggest that vitamin D plus ω-3 co-supplementation as well as AA reduction in the Mediterranean diet display benefits for T1D children at onset and deserve further investigation.

Vitamin D Deficiency and Glycemic Status in Children and Adolescents with Type 1 Diabetes Mellitus.

BACKGROUND: Vitamin D (25OHD) effects on glycemic control are unclear in children and adolescents with type 1 diabetes. Aims of this study were to investigate 25OHD status among children with T1DM and its relationship with insulin sensitivity and glycemic status. SUBJECTS AND METHODS: A cross sectional study was carried out between 2008-2014. A total of 141 patients had a T1DM >12 months diagnosis and were enrolled in the present study. Of these 35 (24.8%) were migrants and 106 (75.2%) Italians (T2). We retrospectively analyzed data at the onset of the disease (T0)(64 subjects) and 12-24 months before the last visit (T1,124 subjects). Fasting glucose, glycated hemoglobin (HbA1c), 25OHD levels and daily insulin requirement were evaluated and Cholecalciferol 1000 IU/day supplementation for the management of vitamin D insufficiency (<75 nmol/L) was systematically added. RESULTS: A generalized 25OHD insufficiency was found at each study time, particularly in migrants. At T0, the 25OHD levels were inversely related to diabetic keto-acidosis (DKA) severity (p<0.05). At T1 and T2, subjects with 25OHD ≤25nmol/L (10 ng/mL) showed higher daily insulin requirement (p<0.05) and HbA1c values (p<0.01) than others vitamin D status. The 25OHD levels were negatively related with HbA1c (p<0.001) and daily insulin dose (p<0.05) during follow up. There was a significant difference in 25OHD (p<0.01) between subjects with different metabolic control (HbA1c <7.5%,7.5-8%,>8%), both at T1 and T2. In supplemented subjects, we found a significant increase in 25OHD levels (p<0.0001) and decrease of HbA1c (p<0.001) between T1 and T2, but this was not significant in the migrants subgroup. Multivariate regression analysis showed a link between HbA1c and 25OHD levels (p<0.001). CONCLUSIONS: Children with T1DM show a generalized 25OHD deficiency that impact on metabolic status and glycemic homeostasis. Vitamin D supplementation improves glycemic control and should be considered as an additional therapy.

High Prevalence of Vitamin D Deficiency in Native versus Migrant Mothers and Newborns in the North of Italy: A Call to Act with a Stronger Prevention Program.

BACKGROUND: Vitamin D status during pregnancy is related to neonatal vitamin D status. Vitamin D deficiency has been associated with an increased risk of rickets in children and osteomalacia in adults. Aim of this study was to investigate 25OHD levels in maternal serum and in neonatal blood spots in native and migrant populations living in Novara (North Italy, 45°N latitude). METHODS AND FINDINGS: We carried out a cross sectional study from April 1st 2012 to March 30th 2013, in a tertiary Care Center. Maternal blood samples after delivery and newborns' blood spots were analyzed for 25OHD levels in 533 pairs. Maternal country of origin, skin phototype, vitamin D dietary intake and supplementation during pregnancy were recorded. Multivariate regression analysis, showed a link between neonatal and maternal 25OHD levels (R-square:0.664). Severely deficient 25OHD values (<25 nmol/L) were found in 38% of Italian and in 76.2% of migrant's newborns (p <0.0001), and in 18% of Italian and 48,4% of migrant mothers (p <0.0001) while 25OHD deficiency (≥25 and <50 nmol/L) was shown in 40.1% of Italian and 21.7% of migrant's newborns (p <0.0001), and in 43.6% of Italian and 41.3% of migrant mothers (p <0.0001). Italian newborns and mothers had higher 25OHD levels (34.4±19.2 and 44.9±21.2 nmol/L) than migrants (17.7±13.7 and 29.7±16.5 nmol/L; p<0.0001). A linear decrease of 25OHD levels was found with increasing skin pigmentation (phototype I 42.1 ±18.2 vs phototype VI 17.9±10.1 nmol/l; p<0.0001). Vitamin D supplementation resulted in higher 25OHD values both in mothers and in their newborns (p<0.0001). CONCLUSIONS: Vitamin D insufficiency in pregnancy and in newborns is frequent especially among migrants. A prevention program in Piedmont should urgently be considered and people identified as being at risk should be closely monitored. Vitamin D supplementation should be taken into account when considering a preventative health care policy.

Vitamin D levels at birth and risk of type 1 diabetes in childhood: a case-control study.

AIMS: To assess whether vitamin D levels at birth were associated with risk of having type 1 diabetes up to 10 years of age and the potential modifier effect of ethnic group. METHODS: The Piedmont Diabetes Registry and the Newborn Screening Regional data were linked to identify cases (n = 67 incident children aged ≤10 years at diabetes onset, 2002-2012) and up to five controls (n = 236) matched for birthday and ethnic group. Cards with neonatal blood spot were used and 25-hydroxyvitamin D(3) assessed with tandem mass spectroscopy. RESULTS: In conditional logistic regression, OR for unit increment of log vitamin D was 0.78 (95 % CI 0.56-1.10). Vitamin D was significantly lower in migrant than in Italian control newborn babies (p < 0.0001), and interaction between vitamin D and migrant status was statistically significant (p = 0.04). Compared to migrant newborns babies with vitamin D ≥ 2.14 ng/ml, migrants with lower levels had an OR of 14.02 (1.76-111.70), whereas no association was evident in Italians. CONCLUSIONS: Our case-control study within the Piedmont Diabetes Registry showed no association between vitamin D levels at birth and risk of having type 1 diabetes up to 10 years of age, apart from the subgroup of migrant babies, which might have clinical implications if confirmed.

False negativity to carbohydrate-deficient transferrin and drugs: a clinical case.

INTRODUCTION: In this work we report on the possible effect of the medical therapy on CDT concentration in a chronic alcohol abuser, with known medical history (July 2007 - April 2012) and alcohol abuse confirmed by relatives. CASE HISTORY: At the end of 2007, patient displayed the following laboratory results: AST 137 U/L, ALT 120 U/L, GGT 434 U/L, MCV 101 fL and CDT 3.3%. On December 2007, after double coronary artery bypass surgery, he began a pharmacological treatment with amlodipine, perindopril, atorvastatin, isosorbide mononitrate, carvedilol, ticlopidine and pantoprazole. In the next months, until may 2011, the patient resumed alcohol abuse, as confirmed by relatives; however, CDT values were repeatedly found negative (0.8% and 1.1%) despite elevated transaminases and GGT, concurrent elevated ethyl glucuronide concentration (> 50 mg/L) and blood alcohol concentration (> 1 g/L). Alcohol consumption still continued despite increasing disulfiram doses ordered by an Alcohol Rehab Center. On May 2011, the patient was transferred to a private medical center where he currently lives. CONCLUSIONS: This study suggests the possibility that a medical therapy including different drugs may hamper the identification of chronic alcohol abusers by CDT.

Measurement of total antioxidant capacity of human plasma: setting and validation of the CUPRAC-BCS method on routine apparatus ADVIA 2400.

BACKGROUND: Quantification of Total Antioxidant Capacity (TAC) of human plasma is an important clinical target, since many diseases are suspected to be related with oxidative stress. The CUPRAC-BCS (BCS=Bathocuproinedisulfonic acid) method was chosen since it works using the photometric principle, with stable and inexpensive reagents and at physiological pH. METHODS: The method is based on the complex equilibria between Cu(II)-BCS (reagent) and Cu(I)-BCS. Cu(I)-BCS complex is formed by reducing ability of the plasma redox active substances. The photometric signal is achieved at 478 nm and calibration is performed using urate as a reference substance. RESULTS: Linearity, linear working range, sensitivity, precision, LoD, LoQ, selectivity and robustness have been considered to validate the method. Absorbance at 478 nm was found linear from 0.0025 up to 2.0 mmol L(-1) of urate reference solution. Precision was evaluated as within-day repeatability, Sr=4 µmol L(-1), and intermediate-precision, SI(T)=15 µmol L(-1). LoD and LoQ, resulted equal to 7.0 µmol L(-1) and 21 µmol L(-1) respectively while robustness was tested having care for pH variation during PBS buffer preparation. Tests on plasma (80 samples) and on human cerebrospinal fluid (30 samples) were conducted and discussed. CONCLUSIONS: By the analytical point of view, the photometric method was found to be simple, rapid, widely linear and reliable for the routine analysis of a clinical laboratory. By the clinical point of view, the method response is suitable for the study of chemical plasma quantities related to redox reactivity.

Recognizing purple bag syndrome at first look.

Purple urine bag syndrome is a clinical entity first described in 1978. Its typical discoloration is worrying for clinicians. In the past, these patients sometimes reached the emergency unit only because of this exceptional worrying urinary sign and underwent invasive diagnostic examinations including cystoscopy, without any abnormal finding. It is now clear that this astonishing phenomenon of double discoloration of the urine, appearing purple in the bag and dark blue in the test tube, results from the formation of 2 different pigments (indirubin and indigo) in very alkaline urines due to enzymes produced by gram-negative bacteria, such as indoxyl phosphatase/sulfatase, which can convert urinary metabolites of dietary tryptophan. Practicing physicians should identify purple urine bag syndrome as a usually benign medical condition diagnosed in asymptomatic patients, which only requires treatment of bacteriuria with antibiotics, prevention of constipation, substitution of catheter and acidification of the urine. After these measures, urine typically returns to its normal color.

Accidental digitoxin intoxication: an interplay between laboratory and clinical medicine.

INTRODUCTION: Two Italian adults arrived at the Emergency Department referring diarrhea, nausea and vomiting for 4 days; weakness, fatigue and visual hallucinations were also complained of. Patients reported the ingestion of some leaves of a plant, which they supposed to be "donkey ears", a week before. Physical examination showed hypotension and bradycardia and ECG examination disclosed sinus rhythm and repolarization abnormalities (scooping of the ST-T complex) in both patients and a 2:1 AV block in the man. MATERIALS AND METHODS: Digoxin concentration was evaluated twice for each patient (at the admission and after 4 hours) by the automated immunoassay system ADVIA Centaur. Digitoxin concentration was evaluated by liquid chromatography-mass spectrometry (LC-MS/MS). RESULTS: Despite clinical picture was suggestive of digitalis intoxication, digoxin levels were undetectable. Due to the more severe clinical picture, the male patient was treated with anti-digoxin antibodies (Digifab) achieving a good clinical improvement and remission of the AV block within two hours. Initial diagnosis was confirmed by LC-MS/MS showing high digitoxin concentrations, but digoxin was undetectable. Patients remained stable and 48 hours later were discharged from the hospital. CONCLUSION: Whereas digoxin determination frequently relies on monoclonal antibodies which do not cross-react to digitoxin, polyclonal antibodies constituting Digifab recognize a large spectrum of cardiac glycosides, including digitoxin. This report emphasizes the primary role of the clinical approach to patients in the emergency setting and how an active communication and a continuous sharing of professional experiences between Laboratory and Clinicians ensure an early and correct diagnosis.

Evaluation of amoxicillin plasma and tissue levels in pediatric patients undergoing tonsillectomy.

OBJECTIVE: Tonsillectomy is the most common surgery performed in the pediatric and young adult populations. Although recent guidelines based on meta-analysis suggest that perioperative chemoprophylaxis plays a role in reducing bacteraemia-related post-tonsillectomy complications, there is no evidence or agreement upon which specific antibiotic, dosage or administration route should be preferred. Since few previous studies have assessed the effectiveness of prophylaxis by direct measurement of antibiotic levels both in plasma and tissue, we designed an experimental study to quantitatively evaluate amoxicillin concentrations in children ready for tonsillectomy and compare these plasma and tissue levels with the Minimal Inhibitory Concentrations (MIC) of the bacteria more commonly involved in the upper airway infections. METHODS: Thirty-three pediatric patients under 14 years of age (median 5.0, IQR 4-7, range 3-11; M:F 18:15) with recurrent tonsillitis were treated with 3 doses (established on patient's weight) of amoxicillin-clavulanic acid given orally the day before plus a further dose 2h before tonsillectomy. Amoxicillin concentrations on both homogenated tonsillar cores and plasma were measured by HPLC-UV. Bacterial epidemiology and susceptibility were derived respectively from survey data collected by Microbiology Unit and MIC according to the National Committee for Clinical Laboratory Standards (NCCLS). RESULTS: Median plasma and tissue amoxicillin concentrations were respectively 4.7 microg/ml (IQR 2.1-8.0; min-max 0.4-14.3) and 1.1 microg/g (IQR 0.4-2.1; min-max 0.4-12.9), considerably below the selected target MIC of pathogens involved in the upper respiratory tract infections (S. aureus, H. influenzae, M. catarrhalis). 20 Children showed undetectable amoxicillin levels in one or both tonsils. Interestingly, 7 out of these patients (35%) had plasma concentrations higher than the target MIC (8 microg/ml). No patient displayed plasma concentrations under the limit of sensitivity of the method. Poor core-plasma and left-right core correlation was observed among patients, suggesting that fibrosis developed after recurrent tonsillitis may hamper antibiotic penetration. CONCLUSIONS: Based upon direct measurement of antibiotic levels in plasma and tissue, this study suggests that a revision of the oral prophylaxis in children is required in order to reduce microbial charge in the operative field and accordingly improve the recovery after tonsillectomy.

[Amoxicillin in tonsillectomy: preliminary data on the evaluation of serum and tissue concentrations]. / L'amoxicillina nella tonsillectomia: dati preliminari sulla valutazione delle concentrazioni sieriche e tessutali.

Amoxicillin was administered to 50 patients with chronic recurrent tonsillitis waiting for tonsillectomy. Group A (N=16) received 2.2 g of amoxicillin plus clavulanic acid with intravenous injection 10 minutes before tonsillectomy Group B (N=34) was treated with 3 doses of amoxicillin-clavulanic acid administered orally the day before surgery, plus one oral administration 2 hours before tonsillectomy. Antibiotic doses were established on patient's weight using maximum suggested. The measures were, estimated in serum and in tonsils using High Performance Liquid Chromatography, (HPLC). The data show better efficacy of intravenous administration than oral administration.