Interleukin-18 Antagonism Improved Histopathological Conditions of Malaria Infection in Mice

Background: Interleukin 18 (IL-18) exerts pleiotropic roles in many inflammatory-related diseases including parasitic infection. Previous studies have demonstrated the promising therapeutic potential of modulating IL-18 bioactivity in various pathological conditions. However, its involvement during malaria infection has yet to be established. In this study, we demonstrated the effect of modulating IL-18 on the histopathological conditions of malaria infected mice. Methods: Plasmodium berghei ANKA infection in male ICR mice was used as a model for malaria infection. Modulation of IL-18 release was carried out by treatment of malarial mice with recombinant mouse IL-18 (rmIL-18) and recombinant mouse IL-18 Fc chimera (rmIL-18Fc) intravenously. Histopathological study and analysis were performed on major organs including brain, liver, spleen, lungs and kidney. Results: Treatment with rmIL-18Fc resulted in significant improvements on the histopathological conditions of the organs in malaria-infected mice. Conclusion: IL-18 is an important mediator of malaria pathogenesis and targeting IL-18 could prove beneficial in malaria-infected host.Key Words: Malaria, Interleukin-18, Plasmodium berghei, Histopathology     

EUS-guided FNA of the left adrenal gland in patients with thoracic or GI malignancies

BACKGROUND: The diagnostic yield and safety of trans-gastric EUS-guided FNA of the left adrenal gland are not well defined. METHODS: All patients with an enlarged left adrenal gland on abdominal imaging and known or suspected malignancy referred to two EUS centers over a 3-year period were included in this study. EUS-guided FNA was performed on an outpatient basis by one of 4 experienced endosonographers. RESULTS: Thirty-one consecutive patients (21 men, 10 women; mean age 64.8 years) were evaluated. Tissue adequate for interpretation was obtained in all patients; no attempt to obtain tissue was unsuccessful. The median number of needle passes was 4.5 (range 1-8). No immediate complications were encountered. EUS-guided FNA confirmed malignant left adrenal involvement in 42% (13/31) of the patients. Patients with malignant left adrenal masses were more likely to have known cancer at another site (OR 12.0: 95% CI[1.6, 87.9]). Patients with benign masses were more likely to have preservation of the normal sonographic appearance of the adrenal gland ("seagull" configuration) compared with those with malignant masses (OR 9.8: 95% CI[1.9, 51.0]). The accuracy of EUS imaging based on size (> or =3 cm) alone was 81%: 95% CI[63, 93]). Of the patients with malignant adrenal masses, 85% (11/13) died or their clinical condition deteriorated during follow-up, while 15% (2/13) were being treated and were stable clinically. CONCLUSIONS: EUS-guided FNA of the left adrenal gland is a minimally invasive, safe, and highly accurate method that confirms or excludes malignant adrenal involvement in patients with thoracic or GI malignancies.     

Effect of continuous positive airway pressure on the rapid shallow breathing index in patients following cardiac surgery

OBJECTIVES: To compare the rapid shallow breathing index (RSBI) under different ventilatory support settings prior to extubation trials. DESIGN: Prospective study. SETTING: Cardiac surgery unit at a university hospital. PATIENTS: A total of 33 coronary artery bypass grafting patients ready for extubation. INTERVENTIONS: Enrolled patients received a continuous positive airway pressure (CPAP) trial of 5 cm H(2)O and fraction of inspired oxygen (FIO(2)) of 40% (condition 1), a CPAP trial of 5 cmH(2)O and FIO(2) of 21% (condition 2), and a 1-min spontaneously breathing room air trial without ventilatory support (condition 3). These trials were applied in random order. Measurements and main results: Average values of respiratory frequency and tidal volume were measured under the three experimental conditions in all patients immediately prior to extubation. The RSBIs were determined for each patient under each condition; the average RSBIs under conditions 1, 2, and 3 were compared for significance. The average RSBIs (+/- SD) were significantly smaller under condition 1 (34 +/- 13) and condition 2 (36 +/- 14) compared to condition 3 (71 +/- 24). There was no significant difference in RSBI between conditions 1 and 2. CONCLUSIONS: The administration of 5 cm H(2)O of CPAP can influence the determination of the RSBI. In contrast, changes in FIO(2) have no effect on RSBI determination. We speculate that using the RSBI during CPAP may mislead the clinician into premature discontinuation of mechanical ventilation. Consequently, different threshold values for the RSBI should be derived for different ventilatory support levels.     

Anemia in remote interior communities in Sarawak,Malaysia

A cross-sectional survey of 365 individuals, (51.9% males, 48.1% females; ages 5-85 years), from five remote interior communities in upper Rejang River basin Sarawak, Malaysia, found 24.4% were anemic. The range and mean of Hb concentration in male and female were: 7.2-17.0 mg/ml and 13.7 mg/ml and 7.9-15.7 mg/ml and 12.9 mg/ml respectively. Amongst the five tribes surveyed, the prevalence of anemia (range: 10.6-46.7%), was higher among the Penans (46.7%), Kenyahs (31.1%), Kajangs (27.8%) and Kayans (19.3%), than amongst the Ukits (10.6%). Anemia is more common among males >40 years and among adolescents and young reproductive females, as well as elderly females > 61 years old. Of the 83 anemic individuals, 6.0% and 3.6% had Trichuris trichiura or hookworm respectively; however there is no clear association with intestinal worm infection.     

Interventricular mechanical dyssynchrony: a novel marker of cardiac events in Brugada syndrome.

BACKGROUND: Risk stratification in Brugada syndrome is controversial, especially in asymptomatic individuals. OBJECTIVE: The purpose of this study was to evaluate tissue Doppler echocardiography in risk stratification of Brugada syndrome. METHODS: Patients with Brugada ECG pattern were enrolled in the study. Left ventricular (LV) preejection period was defined as the time interval between onset of the QRS complex and onset of LV lateral wall systolic wave. Right ventricular (RV) preejection period was defined as the time interval between onset of the QRS complex and onset of RV lateral wall systolic wave. Delay in onset of contraction between RV and LV was defined as RV preejection time - LV preejection time [PET((RV-LV))]. RESULTS: Type 1, 2, and 3 Brugada ECG pattern was found in 30, 56, and 31 patients, respectively. PET((RV-LV)) was significantly greater in type 1 Brugada patients (39.2 +/- 3.2 ms) compared with type 2 (5 +/- 0.3 ms) and 3 (5 +/- 0.4 ms) Brugada patients as well as controls (4.6 +/- 0.3 ms, P <.01 for all comparisons). Among type 1 Brugada patients, PET((RV-LV)) was significantly greater in patients who had previous cardiac events compared with asymptomatic subjects (48.2 +/- 4.3 ms vs 29.5 +/- 3.6 ms, P <.05). In the presence of type 1 Brugada ECG pattern, PET((RV-LV)) > or =40 ms identifies patients likely to have cardiac events, with 85.7% sensitivity and 93.7% specificity. CONCLUSION: PET((RV-LV)) is an important risk indicator for Brugada syndrome.     

Thyroid function and structure are affected in childhood obesity

OBJECTIVE: Alterations in thyroid function are reported in obesity, although no relevant data exist on the thyroid structure of these patients and the frequency of autoimmunity. The aim of our study was to evaluate the involvement of the thyroid gland in a large group of obese children. DESIGN: This was a cross-sectional study. METHODS: The study was conducted between March 2004 and December 2007 in 186 overweight and obese children. In all subjects, serum free T(3), free T(4), TSH, antithyroid antibodies, and a thyroid ultrasound were assessed. A total ot 40 healthy children matched for age and of normal weight for height served as controls. RESULTS: A total of 23 children (12.4%) showed antithyroid antibodies and an ultrasound pattern suggestive of Hashimoto's thyroiditis (group A). Of them, 20 (10.8%) showed antithyroid antibodies and normal ultrasound (group B). A total of 70 subjects (37.6%) showed absent antithyroid antibodies and an ultrasound pattern suggestive of Hashimoto's thyroiditis (group C), and 73 children (39.2%) showed no thyroid antibodies with normal ultrasound (group D). TSH was higher in groups A and C compared with groups B and C, and controls (P < 0.05). Mean free T(4) was lower in group B (P < 0.05) than in controls, whereas free T(3) was higher in group C than in controls (P < 0.05). TSH and body mass index sd scores were significantly correlated in group C (P < 0.001), and TSH was also significantly associated with the degree of thyroid structure alterations (P < 0.05). CONCLUSION: Obese children frequently show alterations of thyroid structure and function that are not completely explained by the presence of an autoimmune involvement.     

Coronary artery disease is associated with the ratio of apolipoprotein A-I/B and serum concentration of apolipoprotein B, but not with paraoxonase enzyme activity in Iranian subjects

To determine the association of serum apolipoprotein (apo) A-I and B concentrations, and paraoxonase (PON) high-density lipoprotein (HDL) associated enzyme activity with angiographically determined coronary artery disease (CAD) in Iranian diabetic and non-diabetic CAD patients and non-diabetic control subjects, 251 subjects aged 30-70 years, who underwent their first coronary angiography were matched and randomly assigned into three groups: CAD(+)DM(+), CAD(+)DM(-), and CAD(-)DM(-) (control). Stenosis of > or =50% in one or more coronary arteries was classified as CAD(+). CAD(-) was defined as a maximum stenosis of 10% in any coronary artery. Fasting serum concentrations of cholesterol (TC), triglycerides (TGs), LDL-C, HDL-C, apo A-I/B and PON activity were determined. Apolipoprotein concentrations were measured in a fasting serum sample by immunoturbidometric assay and paraoxonase/arylesterase activities by spectrophotometric assay of p-nitrophenol/phenol production following addition of paraoxon/phenylacetate. Information concerning non-lipid risk factors were collected by questionnaires. No significant difference was observed in HDL-C, LDL-C, apo A-I, and PON/arylesterase activity between the study groups. The values of TC (213+/-38 vs 196+/-45, P<0.05), TGs (209+/-187 vs 151+/-113, P<0.01), apo B (99+/-22 vs 96+/-24, P<0.0001), TC/HDL-C (4.8+/-1.5 vs 4.0+/-1.3, P<0.001) and LDL-C/HDL-C (2.9+/-1.1 vs 2.4+/-1.1, P<0.05) were higher and apo A-I/B (1.7+/-0.4 vs 2.0+/-0.6, P<0.01) was lower in CAD(+)DM(+) patients than in control subjects. In CAD(+)DM(-) group, only the level of apo B (96+/-24 vs 85+/-18, P<0.01), and the ratio of apo A-I/B (1.8+/-0.4 vs 2.0+/-0.6, P<0.01), were significantly higher than those of control group. On multiple logistic regression analysis, the best markers for discrimination between CAD(+) groups and CAD(-) control subjects were the ratio of apo A-I/B in diabetic and apo B in non-diabetic patients. The results suggest that in Iranian diabetic and non-diabetic patients with CAD the concentration of apolipoproteins are better markers than traditional lipid parameters in discriminating between CAD(+) and CAD(-) subjects. Lack of significant difference in PON activity between CAD patients and CAD(-) controls supports the concept of interethnic variability in PON polymorphism and unimodal distribution of its activity in non-Europid populations observed in other studies.     

Short-term Effects of Alfacalcidol on Hospital Length of Stay in Patients Undergoing Valve Replacement Surgery: A Randomized Clinical Trial

PurposeVitamin D deficiency is highly prevalent in critically ill patients, and has been associated with more prolonged length of hospital stay and poor prognosis. Patients undergoing open-heart surgery are at higher risk due to the associated life-threatening postoperative complications. This study investigated the effect of alfacalcidol treatment on the length of hospital stay in patients undergoing valve-replacement surgery.MethodsThis single-center, randomized, open-label, controlled trial was conducted at El-Demerdash Cardiac Academy Hospital (Cairo, Egypt), from April 2017 to January 2018. This study included adult patients undergoing valve-replacement surgery who were randomized to the intervention group (n = 47; alfacalcidol 2 μg/d started 48 h before surgery and continued throughout the hospital stay) or to the control group (n = 42). The primary end points were lengths of stay (LOS) in the intensive care unit (ICU) and in the hospital. Secondary end points were the prevalence of postoperative hospital-acquired infections, cardiac complications, and in-hospital mortality.FindingsA total of 86 patients were included in the final analysis, with 51 (59.3%) being vitamin D deficient on hospital admission. Treatment with alfacalcidol was associated with a statistically significant decrease in ICU LOS (hazard ratio = 1.61; 95% CI, 1.77–2.81; P = 0.041) and hospital LOS (hazard ratio = 1.63; 95% CI, 1.04–2.55; P = 0.034). Treated patients had a significantly lower postoperative infection rate than did the control group (35.5% vs 56.1%; P = 0.017). The median epinephrine dose was lower in the intervention group compared to that in the control group (5.9 vs 8.2 mg; P = 0.019). The rate of in-hospital mortality was not significantly different between the 2 groups.ImplicationsEarly treatment with 2 μg of alfacalcidol in patients undergoing valve-replacement surgery is promising and well tolerated. This effect may be attributed to its immunomodulatory and cardioprotective mechanisms. ClinicalTrials.gov identifier: NCT04085770.