Flash Fabrication of Orally Targeted Nanocomplexes for Improved Transport of Salmon Calcitonin across the Intestine.

Salmon calcitonin (sCT) is a potent calcium-regulating peptide hormone and widely applied for the treatment of some bone diseases clinically. However, the therapeutic usefulness of sCT is hindered by the frequent injection required, owing to its short plasma half-life and therapeutic need for a high dose. Oral delivery is a popular modality of administration for patients because of its convenience to self-administration and high patient compliance, while orally administered sCT remains a great challenge currently due to the existence of multiple barriers in the gastrointestinal (GI) tract. Here, we introduced an orally targeted delivery system to increase the transport of sCT across the intestine through both the paracellular permeation route and the bile acid pathway. In this system, sCT-based glycol chitosan-taurocholic acid conjugate (GC-T)/dextran sulfate (DS) ternary nanocomplexes (NC-T) were produced by a flash nanocomplexation (FNC) process in a kinetically controlled mode. The optimized NC-T exhibited well-controlled properties with a uniform and sub-60 nm hydrodynamic diameter, high batch-to-batch reproducibility, good physical or chemical stability, as well as sustained drug release behaviors. The studies revealed that NC-T could effectively improve the intestinal uptake and permeability, owing to its surface functionalization with the taurocholic acid ligand. In the rat model, orally administered NC-T showed an obvious hypocalcemia effect and a relative oral bioavailability of 10.9%. An in vivo assay also demonstrated that NC-T induced no observable side effect after long-term oral administration. As a result, the orally targeted nanocomplex might be a promising candidate for improving the oral transport of therapeutic peptides.

[Effects of application of vancomycin in the early stage of patients with extremely severe burn].

Objective: To evaluate the effects of application of vancomycin in the early stage of patients with extremely severe burn, in order to provide reference to drug for anti-infection treatment in the early stage of patients with extremely severe burn. Methods: Data of 15 patients of Kunshan explosion on August 2nd, 2014, admitted to the Department of Intensive Care in our hospital were retrospectively analyzed. The clinical efficacy of continuously intravenous dripping of vancomycin (combined with imipenem) in the early stage of burns (before and on post burn day 14) was analyzed. (1) The steady state plasma concentration of vancomycin was monitored respectively 30 min before the third, sixth, and tenth medication with direct chemiluminescent imaging method. (2) The distribution of Gram-positive bacteria of patients during hospitalization and their drug resistance to 14 antibiotics commonly used in clinic were analyzed. (3) Serum level of procalcitonin (PCT), white blood cell count, percentage of neutrophils before and after treatment, and efficacy grade of anti-infection treatment in the early stage of burns were analyzed. (4) Serum levels of aspartate transaminase (AST), alanine aminotransferase (ALT), creatinine before and after treatment, and the adverse effects during medication were analyzed. The WHONET 5.5 statistical software was used to analyze the distribution of Gram-positive bacteria in all the pathogens, and the status of drug resistance of Gram-positive bacteria to 14 antibiotics. Data were processed with Wilcoxon rank sum test. Results: (1) Twenty-nine times of steady state plasma concentration monitoring were performed in the patients in total, with the steady state plasma concentration of vancomycin from 4.3 to 42.1 µg/mL. In the monitoring before third, sixth, and tenth medication, the percentages of result reaching the standard were respectively 1, 3/14, and 2/7. (2) A total of 79 Gram-positive bacteria were isolated, including 49 (62.03%) strains of Staphylococcus aureus, 9 (11.39%) strains of Staphylococcus haemolyticus, 7 (8.86%) strains of Staphylococcus epidermidis, 12 (15.19%) strains of Enterococcus faecium, and 2 (2.53%) strains of Enterococcus faecalis. The above-mentioned Staphylococcus strains were with high drug resistance to antibiotics including penicillins, erythromycin, ciprofloxacin, and low drug resistance to linezolid, teicoplanin, and nitrofurantoin. The above-mentioned Enterococcus strains were with high drug resistance to antibiotics including erythromycin, ciprofloxacin, gentamicin, and low drug resistance to linezolid and teicoplanin. The above-mentioned Staphylococcus strains were all sensitive to vancomycin. Two strains of vancomycin-resistant Enterococcus were detected in the above-mentioned Enterococcus strains. (3) Serum level of PCT, white blood cell count, percentage of neutrophils of patients were (8.1±7.5) ng/mL, (24±10)×10(9)/L, and 0.898±0.029 before treatment, which were significantly higher than (3.0±2.8) ng/mL, (12±5)×10(9)/L, and 0.867±0.016 after treatment (with Z values respectively -2.103, -3.237, and -3.068, P<0.05 or P<0.01). After the early treatment, excellence, progess, and invalid results were achieved in 7, 5, and 3 patients, with the effective percentage of 4/5 in clinic. (4) There were no statistically significant differences in serum levels of AST, ALT, and creatinine of patients between before and after treatment (with Z values respectively-0.057, -1.508, and -1.363, P values above 0.05). Only one patient had liver and renal dysfunction during treatment. Conclusions: The positive and reasonable use of vancomycin can remove most of the Gram-positive bacteria, and control the development of sepsis combined with imipenem in the early stage of patients with extremely severe burn. However, the dose of vancomycin should be individualized and the steady state plasma concentration should be monitored to maintain the blood concentration within the safe and effective range, so as to improve the rational use of vancomycin.

Association of plasma calcium concentrations with alcohol craving: New data on potential pathways.

Recently, calcium was suggested to be the active moiety of acamprosate. We examined plasma calcium concentrations in association with severity of alcohol dependence and its interaction with regulating pathways and alcohol craving in alcohol-dependent patients. 47 inpatient alcohol-dependent patients undergoing detoxification treatment underwent laboratory testing, including calcium, sodium, liver enzymes as well as serum concentrations of calcitonin, parathyroid hormone and vitamin D. The psychometric dimension of craving was analyzed with the Obsessive Compulsive Drinking Scale (OCDS). The severity of withdrawal was measured with the Alcohol Dependence Scale (ADS) and with the Alcohol Dependence Scale for high-risk sample (ADS-HR). The main findings of our investigation are: a) a negative correlation of plasma calcium concentrations with alcohol craving in different dimensions of the OCDS; b) a negative correlation of plasma calcium concentrations with breath alcohol concentration; c) lowered calcitonin concentration in the high-risk sample of alcoholics; d) lowered plasma vitamin D concentrations in all alcoholic subjects. Our study adds further support for lowered plasma calcium concentrations in patients with high alcohol intake and especially in patients with increased craving as a risk factor for relapse. Lowered calcitonin concentrations in the high-risk sample and lowered vitamin D concentrations may mediate these effects. Calcium supplementation could be a useful intervention for decreasing craving and relapse in alcohol-dependent subjects.

Adjunctive hyperbaric oxygen therapy in severe burns: Experience in Taiwan Formosa Water Park dust explosion disaster.

BACKGROUND: Despite major advances in therapeutic strategies for the management of patients with severe burns, significant morbidity and mortality is observed. Hyperbaric oxygen therapy (HBOT) increases the supply of oxygen to burn areas. The aim of this study was to determine whether HBOT is effective in the treatment of major thermal burns. METHODS: On June 27, 2015 in New Taipei, Taiwan, a mass casualty disaster occurred as fire erupted over a large crowd, injuring 499 people. Fifty-three victims (20 women and 33 men) were admitted to Tri-Service General Hospital. Thirty-eight patients underwent adjunctive HBOT (HBOT group), and 15 patients received routine burn therapy (control group). Serum procalcitonin (PCT) level, a sepsis biomarker, was measured until it reached normal levels (<0.5µg/L). The records of all patients from June 2015 to March 2016 were analyzed retrospectively. Outcome measures that were compared between the groups included the use of tracheostomy and hemodialysis, total body surface area (TBSA) and the number of skin graft operations, length of hospital stay, infection status, and mortality. RESULTS: The mean age of the patients was 22.4 years, and the mean TBSA was 43%. All the patients survived and were discharged without requiring limb amputation or being permanently disabled. Patient characteristics did not differ significantly between the groups. PCT levels returned to normal significantly faster (p=0.007) in the HBOT group. CONCLUSION: Multidisciplinary burn care combined with adjunctive HBOT improves sepsis control compared with standard treatment without HBOT. Prospective studies are required to define the role of HBOT in extensive burns.

Efficacy of lenvatinib in treating thyroid cancer.

INTRODUCTION: Radioiodine [RAI]-resistant advanced and progressive differentiated thyroid cancer [DTC], although rare, constitutes a real challenge as its prognosis is poor and available therapeutic options, until now, have been limited. Discovery of a crucial role of distinct tyrosine kinases in DTC pathogenesis opened up new options in systemic treatment. Lenvatinib is an oral potent multi kinase inhibitor [MKI] of different growth factor receptors including VEGFR1/Flt-1, VEGFR2/KDR, VEGFR3, FGFR1,2,3,4, PDGFR-ß as well as RET and KIT signaling networks. Its activity against RAI-refractory DTC was demonstrated in clinical studies fulfilling evidence-based medicine [EBM] criteria. The drug showed acceptable tolerance and manageable toxicity. AREAS COVERED: published results of phase II and III studies and other reports evaluated the efficacy and safety of lenvatinib in DTC and in medullary thyroid carcinoma. EXPERT OPINION: Currently there are two different MKIs, lenvatinib and sorafenib, which have demonstrated effectiveness against RAI-refractory DTC. However, to date, the question of which drug should be chosen for first line treatment remains open. The other question: when to start the treatment seems to be no less important. Whether disease progression, even by RECIST, is enough to initiate a therapy or tumor burden also plays an important role? EBM study, to resolve these issues, is our task for the nearest future.

Intraoperative high-dose calcium stimulation test in patients with sporadic medullary thyroid carcinoma is highly accurate in predicting lateral neck metastases.

BACKGROUND: Intraoperative measurement of calcitonin is not highly accurate in predicting the completeness of the operative resection after total thyroidectomy combined with central neck dissection (TT-CND) in patients with medullary thyroid carcinoma (MTC). We evaluated whether an intraoperative, high-dose calcium stimulation test (IO-CST) after TT-CND can predict lateral neck involvement. METHODS: Eleven patients who underwent primary operation for sporadic MTC were included. High-dose (25 mg/kg) calcium gluconate was administered after TT-CND with calcitonin measured at 2, 5, and 10 minutes after the calcium gluconate infusion. RESULTS: There were 2 males and 9 females (mean age, 51 years; range, 18-88). Three patients showed lateral neck metastases. At a mean follow-up of 7.0 months (range, 2-10), 1 patient showed distant metastases and 1 a slightly increased calcitonin level. After IO-CST, serum calcitonin increased in all the 3 patients with lateral neck metastases, and it remained unchanged or decreased in the other patients without lateral neck metastases. Percent variation of serum calcitonin after IO-CST was 92% in patients with lateral neck metastases and -3.1 ± 4.9% in patients without lateral neck metastases. CONCLUSION: Calcitonin measurement after IO-CST in patients with sporadic MTC can be highly accurate in predicting lateral neck nodes involvement. These results could represent a stimulus toward the development of a quick calcitonin assay.

Protective effect of Xuebijing injection on myocardial injury in patients with sepsis: a randomized clinical trial.

OBJECTIVE: To investigate the protective effect and possible mechanism of Xuebijing Injection on myocardial injury in patients with sepsis, and to evaluate its prognostic implications. METHODS: Patients with septic myocardial injury were recruited, and were randomly divided into two groups: treatment group and control group. All patients in two groups received conventional cluster treatment, the patients in treatment group additional received Xuebijing injection dissolved in 0.9% sodium chloride injection, and the patients in control group received the same amount of 0.9% sodium chloride injection. At the beginning of treatment and 3, 7 and 10-day after treatment, laboratory indicators of cardiac troponin Ⅰ (cTnI), N-terminal proB-type natriuretic peptide (NT-proBNP) and procalcitonin (PCT) were respectively tested in venous blood. The patient's length of stay in Intensive Care Unit (ICU) and the mortality in 28 days were recorded. RESULTS: At 3, 7 and 10-day after treatment, the improvements of cTnI, NT-proBNP and PCT in treatment group were better than those in control group, and the differences were statistically significant (P < 0.05). The mortality of treatment group in 28 days was not significantly different from that of control group (P > 0.05). The ICU length of stay of treatment group was shorter than that of control group (P > 0.05). CONCLUSION: Xuebijing injection could improve the levels of cTnI, NT-proBNP and PCT in patients with septic myocardial injury .and it had a protective effect on myocardial injury.

Efficacy of thymosin α1 and interferon α for the treatment of severe acute pancreatitis in a rat model.

The present study aimed to investigate the effects of treatment with thymosin α1 (TA1) or interferon α (IFNα) following the establishment of severe acute pancreatitis (SAP) in rats. A total of 144 Sprague­Dawley rats were randomly divided into four groups. The rats in all four groups were celiotomized, and the rats in the control group were administered with an intravenous injection of saline. The three other groups were administered with 5% 1 ml/kg sodium taurocholate via the cholangiopancreatic duct. SAP group rats were administered with an intravenous injection of saline; TA1 group rats received 26.7 µg/kg TA1; and interferon α (INFα) group rats received 4.0x105 U/kg IFNα. The rats were anesthetized and blood samples were collected from the animals 3, 12 and 24 h after surgery. The levels of T cell subsets, serum enzyme indicators, cytokines and procalcitonin (PCT) were measured. The general conditions of the rats were observed until sacrifice, and pancreatic and lung tissue samples were sampled for hematoxylin and eosin staining and histological scoring. The expression levels of aspartate transaminase, lactate dehydrogenase, α­amylase (AMY), P­type­amylase, lipase, PCT, tumor­necrosis factor α, interleukin (IL)­4, IL­5, and IL­18 in the TA1 and IFNα­treated rats were significantly lower, compared with those of the SAP rats within the first 24 h of model establishment (P<0.05). The TA1 and IFNα­treated rats exhibited significantly increased levels of CD3+, CD4+ and CD8+ T cells, and an increased ratio of CD4+/CD8+ cells, compared with SAP rats. Histological analysis revealed that the TA1 and IFNα­treated rats exhibited significantly ameliorated pancreas and lung damage, and mortality rates were reduced from 50.0% (6/12) to 25.0% (3/12) and 33.3% (4/12), respectively. The immunomodulatory agents TA1 and IFNα reduced acute inflammation, decreasing cell damage and enhancing immune function and survival rates in the SAP rats.

Shortening the course of antibiotic treatment in the intensive care unit.

Effective antimicrobial stewardship is an increasingly important concern for healthcare providers globally. Antibiotics are frequently prescribed for patients who develop sepsis in the intensive care unit and traditionally courses are prolonged, with uncertain benefit and probable harm. There is little evidence to support many guidelines recommending between 10 and 14 days, and a number of studies suggest substantially shorter courses of less than 7 days may suffice. Safely reducing course length is likely to depend on a number of preconditions, including thorough eradication of any septic foci; optimization of serum antibiotic concentrations, particularly when there is physiological derangement; and use of novel biomarkers such as procalcitonin. The critical care environment is well suited to this aim as patients are closely monitored. With these measures in place, it is reasonable to believe short antibiotic courses can safely be used for the majority of intensive care infections.

Correlation of hypocalcemia with serum parathyroid hormone and calcitonin levels in pediatric intensive care unit.

OBJECTIVES: To investigate factors involved in causing hypocalcemia in critically ill patients. METHODS: The patients aged 1 mo to 18 y, admitted to PICU at Nemazee Hospital, from May through November 2012, were reviewed. Those with impaired calcium hemostasis or on vitamin-D supplement were excluded. Calcitonin and parathyroid hormone levels were checked if ionized calcium level was less than 3.2 mg/d. Patient's demographic data, length of stay, Pediatric Risk of Mortality-III (PRISM-III) score, the need for mechanical ventilation, inotropic drug administration and outcome were recorded. RESULTS: Among the 294 patients enrolled in the study, the incidence of ionized hypocalcemia was 20.4 %. The mortality rate was 45 % in hypocalcemic groups and 24.8 % in normocalcemic patients. Highly significant negative correlations were found between serum ionized calcium, PRISM-III score (r = -0.371, P = 0.004), and calcitonin level (r = -0.256, P = 0.049), but no significant correlation between hypocalcemia and parathyroid hormone level (P = 0.206) was found. A significant difference was observed between survivor and non-survivor groups regarding PRISM-III score (P = 0.00), ionized calcium (P = 0.00), and calcitonin (P = 0.022) but not parathyroid hormone level (P = 0.206). CONCLUSIONS: Hypocalcemia was associated with increased mortality rate in PICU patients. A negative correlation was found between ionized calcium level and calcitonin. There was also a link between PTH level and severity of illness. It can therefore be concluded that evaluating serum ionized calcium, calcitonin, and PTH levels can be used as prognostic factors in critically ill patients.

Omega-3 fatty acids inhibit the up-regulation of endothelial chemokines in maintenance hemodialysis patients.

BACKGROUND: Chronic systemic inflammation is common in patients with chronic kidney disease on dialysis (CKD5D) and has been considered a key mediator of the increased cardiovascular risk in this patient population. In this study, we tested the hypothesis that supplementation of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) will attenuate the systemic inflammatory process in CKD5D patients. METHODS: The design was a randomized, double-blinded, placebo controlled pilot trial (NCT00655525). Thirty-eight patients were randomly assigned in a 1 : 1 fashion to receive 2.9 g of eicosapentaenoic acid (C20:5, n-3) plus docosahexaenoic acid (C22:6, n-3) versus placebo for 12 weeks. The primary outcome was change in pro-inflammatory chemokines measured by lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). Secondary outcomes were changes in systemic inflammatory markers. Analysis of covariance was used to compare percent change from baseline to 12 weeks. RESULTS: Thirty-one patients completed 12 weeks and three patients completed 6 weeks of the study. Median age was 52 (interquartile range 45, 60) years, 74% were African-American and 79% were male. Supplementation of ω-3 PUFAs effectively decreased the LPS-induced PBMC expression of RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted) and MCP-1 (Monocyte Chemotactic Protein-1; unadjusted P = 0.04 and 0.06; adjusted for demographics P = 0.02 and 0.05, respectively). There was no significant effect of the intervention on serum inflammatory markers (C-reactive protein, interleukin-6 and procalcitonin). CONCLUSIONS: The results of this pilot study suggest that supplementation of ω-3 PUFAs is beneficial in decreasing the levels of endothelial chemokines, RANTES and MCP-1. Studies of larger sample size and longer duration are required to further evaluate effects of ω-3 PUFAs on systemic markers of inflammation, other metabolic parameters and clinical outcomes, particularly cardiovascular outcomes in CKD5D patients.

Pretreatment with an intravenous lipid emulsion increases plasma eicosapentanoic acid and downregulates leukotriene b4, procalcitonin, and lymphocyte concentrations after open heart surgery in infants.

BACKGROUND: The effect of providing a lipid emulsion containing medium-chain triglyceride (MCT), soybean oil, and fish oil in critically ill infants is not widely studied. This study investigated lipid emulsion effects on plasma phospholipids and immune biomarkers. MATERIALS AND METHODS: Thirty-two infants undergoing cardiopulmonary bypass (CPB) and dependent on parenteral nutrition (PN) were randomized to receive either soybean oil (control, n = 16) or a 50:40:10 mixture of MCT, soybean oil, and fish oil (treatment, n = 16). PN was administered for 3 days preoperatively and 10 days postoperatively. Fatty acids, procalcitonin (PCT), leukotriene B4 (LTB4), and lymphocytes were quantified at baseline, before surgery, and days 1, 7 and 10 after surgery. RESULTS: PCT was significantly lower in the treatment vs control group 1 day postoperatively (P = .01). The treatment group exhibited a lower ω-6 to ω-3 ratio (P = .0001) and a higher ω-3 concentration at all postoperative study periods (P = .001). Treatment resulted in higher (P < .05) plasma phospholipid eicosapentaenoic acid (EPA) on days 7 and 10, while α-linolenic acid, arachidonic acid, and docosahexaenoic acid remained constant. An increase in plasma phospholipid EPA concentration was associated with a decrease in plasma phospholipid LTB4 concentration (P < .05). On postoperative day 10, treatment infants with high Pediatric Risk of Mortality III scores exhibited a 45% lower lymphocyte concentration (P < .05). CONCLUSION: These findings suggest that treating infants undergoing CPB with a lipid emulsion containing ω-3 improves fatty acid status and results in a lower inflammatory response after surgery. Overall, this alternative ω-3-enriched lipid emulsion may benefit clinical outcomes of critically ill infants after cardiac surgery.

[Value of the calcium-regulating system in the development of microcirculatory and hemostatic disorders in recurrent peptic ulcer disease].

AIM: To elucidate the state and importance of the calcium-regulating system, calcium and phosphorus balances, their impact on ulcer activity, regional microcirculation, and hemostasis during recurrent peptic ulcer disease (PUD). SUBJECTS AND METHODS: Sixty patients with recurrent PUD were examined. They underwent determinations of blood parathyrin and calcitonin and blood and urinary calcium and phosphorus levels and studies of regional microcirculation in the gastroduodenal mucosa and systemic hemostatic parameters in addition to clinical and endoscopic examinations. RESULTS: Recurrent PUD is accompanied by a significant blood parathyrin rise and some calcitonin increase and by calcium-phosphorus imbalance. Impaired calcium-regulating system functions attend significant microcirculatory disorders in the gastroduodenal mucosa and hemostatic changes characteristic of consumptive coagulopathy. CONCLUSION: A clear relationship between calcium-regulating hormone impairments, calcium and phosphorus metabolism with ulcer activity and microcirculatory and hemostatic changes may suggest the found shifts in ulcerogenesis and the pathogenetic substantiation of correction of these disorders may be of importance for the treatment of a disease recurrence.

Refining calcium test for the diagnosis of medullary thyroid cancer: cutoffs, procedures, and safety.

CONTEXT: Calcitonin (CT) measurement is crucial to the early diagnosis and the follow-up of medullary thyroid cancer (MTC). If the evaluation of stimulated CT levels is required, a provocative test can be performed, being the high-dose Ca test recently reintroduced in clinical practice. OBJECTIVE: Our objective was to identify gender-specific thresholds for MTC diagnosis in a large series of patients who underwent the Ca test. PATIENTS AND METHODS: A total of 91 patients (49 females and 42 males) underwent the Ca test (calcium gluconate, 25 mg/kg) before thyroidectomy and both basal CT (bCT) and stimulated CT (sCT) were compared with histological results by receiver operating characteristic plot analyses. To evaluate possible side effects of Ca administration, cardiac function has been extensively studied. RESULTS: bCT levels were found to harbor the same accuracy as sCT in the preoperative diagnosis of MTC. The best Ca thresholds for the identification of MTC were >26 and >68 for bCT and >79 and >544 pg/mL for sCT in females and males, respectively. The high tolerability and safety of the Ca test was demonstrated and advice offered to be followed before and during the test. CONCLUSIONS: Gender-specific bCT and sCT cutoffs for the identification of C-cell hyperplasia and/or MTC have been defined. The bCT and sCT were found to have a similar accuracy, indicating that serum CT assays with improved functional sensitivity may likely decrease the relevance of the stimulation test in several conditions. Finally, systematic cardiac monitoring confirms the safety of the Ca test.

The evaluation and comparison of consecutive high speed centrifugation and LipoClear® reagent for lipemia removal.

BACKGROUND: The aim of this study was to evaluate and compare the efficiency of high speed centrifugation and LipoClear® reagent for lipemia removal in plasma samples spiked with Intralipid®, for 26 biochemistry analytes. MATERIALS AND METHODS: A plasma pool was collected. Aliquots of the pool were spiked with Intralipid® (final concentrations of 300mg/dL and 500mg/dL Intralipid®). The lipemia was removed from the aliquots by high speed centrifugation or LipoClear® reagent. 26 analytes were determined in native, lipemic plasma and in samples after lipemia removal. The bias from the concentration in the native sample was calculated for each parameter for Intralipid® concentrations, 300 and 500mg/dL of Intralipid®, respectively. Also, the recovery for each parameter after processing the samples using high speed centrifugation and LipoClear® was calculated. The biases and test recoveries were compared with the desirable specification for imprecision (DSI) according to Ricos available at the Wesgard's website. The bias and recovery for procalcitonin were compared with DSI according to Barassi and colleagues. RESULTS: The bias of the spiked samples exceeded the DSI at 300mg/L Intralipid® for creatinine, glucose, total protein, iron and albumin; and for all previously mentioned parameters including CK-MB, sodium, potassium, chlorides, magnesium and ALP at concentration of 500mg/L Intralipid®. For the test recovery the DSI criteria were not met for calcium, total protein, sodium and chlorides after high speed centrifugation and for glucose, calcium, phosphates, magnesium, sodium, potassium, chlorides, ALP, GGT, CK-MB, total protein, albumin and troponin T after using LipoClear®. CONCLUSIONS: LipoClear® is not suitable for lipemia removal from samples designated for glucose, sodium, potassium, chlorides, phosphates, magnesium, CK-MB, ALP, GGT, total protein, albumin, CRP and troponin T measurements. High speed centrifugation should be used for lipemia removal instead for glucose, potassium, phosphates, magnesium, CK-MB, ALP, GGT, albumin, CRP and TnT measurements.

The impact of microbial immune enteral nutrition on the patients with acute radiation enteritis in bowel function and immune status.

The aim of the study was to investigate the effect of microbial immune enteral nutrition by microecopharmaceutics and deep sea fish oil and glutamine and Peptisorb on the patients with acute radiation enteritis in bowel function and immune status. From June 2010 to January 2013, 46 acute radiation enteritis patients in Liaocheng People's Hospital were randomized into the microbial immune enteral nutrition group and the control group: 24 patients in treatment group and 22 patients in control group. The immune microbial nutrition was given to the study group, but not to the control group. The concentration of serum albumin and prealbumin and the number of CD3 (+) T cell, CD4 (+) T cell, CD8 (+) T cell, CD4 (+)/CD8 (+) and natural killer cell of the two groups were detected on the 1, 7 and 14 days after treatment. The arm muscle circumference and triceps skinfold thickness (TSF) were recorded, and the tolerance of the two groups for enteral nutrition and intestinal symptoms was collected and then comparing the two indicators and get results. The tolerance of microbial immune enteral nutrition group about abdominal pain, bloating and diarrhea was better than the control group (P values were 0.018, 0.04 and 0.008 after 7 days; P values were 0.018, 0.015 and 0.002 after 14 days); and the cellular immune parameters were better than the control group((△) P = 0.008,([Symbol: see text]) P = 0.039, (☆) P = 0.032); No difference was found in nutrition indicators. To the patients with acute radiation enteritis, microbial immune enteral nutrition could improve the patient's immune status, and the tolerance of enteral nutrition could be better for the bowel function and the patients' rehabilitation.

Tumor marker and measurement fluctuations may not reflect treatment efficacy in patients with medullary thyroid carcinoma on long-term RET inhibitor therapy.

BACKGROUND: RET kinase inhibitors have significant activity in patients with medullary thyroid carcinoma (MTC). PATIENTS AND METHODS: We retrospectively reviewed the electronic medical record for patterns of calcitonin, carcinoembryonic antigen (CEA) and tumor measurement responses in consecutive patients with MTC who received treatment with a RET inhibitor for at least 6 months. RESULTS: Twenty-six patients who received RET kinase inhibitors for at least 6 months were included. All patients experienced an initial decline in calcitonin; 20 (77%) demonstrated later fluctuations in calcitonin, which spiked above baseline levels in 9 individuals (35%). Twenty of the 22 patients (91%) with elevated CEA experienced a decline with treatment, with 11 individuals (50%) later demonstrating transient fluctuations in CEA, including spikes above baseline in 7 patients (32%). Ten of the 26 patients (38%) also demonstrated short-lived fluctuations in RECIST measurements, including changes of over 20% from nadir values. Vacillations in calcitonin, CEA and measurements often occurred repeatedly in individual patients and did not regularly correlate with each other. CONCLUSIONS: Repeated transient fluctuations in tumor markers and measurements are a characteristic of patients with MTC receiving treatment with RET inhibitors, and such short-term vacillations may not reflect responsiveness over the long term. CLINICAL TRIALS INCLUDED: NCT00215605; NCT00244972; NCT00121680; NCT00495872.

Fish oil-supplemented parenteral nutrition in patients following esophageal cancer surgery: effect on inflammation and immune function.

Our aim was to investigate whether adding ω-3 polyunsaturated fatty acids (PUFAs) to parenteral nutrition (PN) could reduce inflammation and improve immune function in patients following esophageal cancer surgery. In this pilot study, 60 patients with esophageal cancer were divided into 2 groups (30 patients in each group). All patients had total scores of more than or equal to 3 on the nutritional risk screening (NRS2002) test recommended by the European Society of Parenteral Enteral Nutrition, which showed that all patients had nutritional risk and should receive nutritional support. Both groups received isocaloric and isonitrogenous PN. One group received a ω-3 PUFAs supplement. Key indicators of inflammation [serum procalcitonin (PCT) level and the ratio of CD4(+) to CD8(+) (CD4(+)/CD8(+) ratio)] were determined intraoperatively and 24, 72, and 144 h postoperatively. PCT level was notably lower and CD4(+)/CD8(+) ratio was markedly higher in the ω-3 PUFAs group (P = 0.007 for PCT level and P = 0.012 for CD4(+)/CD8(+) ratio) on postoperative day 6 but not on postoperative days 1 and 3. ω-3 PUFAs supplemented PN can reduce inflammation and improve immune function in patients following esophageal cancer surgery. A larger trial is required to see whether ω-3 PUFAs supplementation of PN improves the clinical outcomes of patients following esophageal cancer surgery.

Measurement of calcitonin and calcitonin gene-related peptide mRNA refines the management of patients with medullary thyroid cancer and may replace calcitonin-stimulation tests.

BACKGROUND: Serum calcitonin (sCT) is the main tumor marker for medullary thyroid cancer (MTC), but it has certain limitations. Various sCT assays may have important intra-assay or interassay variation and may yield different and sometimes conflicting results. A pentagastrin- or calcium-stimulation calcitonin (CT) test may be desirable in some situations. Alternatively, or in the absence of the stimulation test, mRNA detection offers the advantages of being more comfortable and less invasive; it only requires blood collection and has no side effects. The objective of this study was to investigate the applicability of measuring calcitonin-related polypeptide alpha (CALCA) gene transcripts (CT-CALCA and calcitonin gene-related peptide [CGRP]-CALCA) in patients with MTC and in relatives diagnosed with a RET mutation and to test mRNA as an alternative diagnostic tool for the calcitonin-stimulation test. METHODS: Twenty-three healthy controls and 26 individuals evaluated for MTC were selected, including patients with sporadic or hereditary MTC and RET mutation-carrying relatives. For molecular analysis, RNA was extracted from peripheral blood, followed by cDNA synthesis using 3.5 µg of total RNA. Quantitative real-time polymerase chain reaction (RT-qPCR) was performed with SYBR Green and 200 nM of each primer for the two specific mRNA targets (CT-CALCA or CGRP-CALCA) and normalized with the ribosomal protein S8 as the reference gene. RESULTS: We detected CALCA transcripts in the blood samples and observed a positive correlation between them (r=0.946, p<0.0001). Both mRNAs also correlated with sCT (CT-CALCA, r=0.713, p<0.0001; CGRP-CALCA, r=0.714, p<0.0001). The relative expression of CT-CALCA and CGRP-CALCA presented higher clinical sensitivity (86.67 and 100, respectively), specificity (97.06 and 97.06), positive predictive value (92.86 and 93.75), and negative predictive value (94.29 and 100), than did sCT (73.33, 82.35, 64.71, and 87.50, respectively). In addition, the CALCA transcript measurement mirrored the response to the pentagastrin test. CONCLUSION: We demonstrate that the measurement of CALCA gene transcripts in the bloodstream is feasible and may refine the management of patients with MTC and RET mutation-carrying relatives. We propose considering the application of this diagnostic tool as an alternative to the calcitonin-stimulation test.