Assessing the clinical significance of echocardiograms in determining treatment of patent ductus arteriosus in neonates.

BACKGROUND: To evaluate the utility of echocardiogram (ECHO) in detection and treatment of patent ductus arteriosus (PDA) and hemodynamically significant PDA (hsPDA) in preterm neonates. METHODS: This was a retrospective case-control study of all preterm infants born or admitted to the level III Neonatal Intensive Care Unit in McMaster Children's Hospital from January 2009 to January 2013. These cases were further classified into the following sub-groups: group A) hsPDA confirmed on ECHO; and the control, group B) PDA (but not hemodynamically significant) confirmed on ECHO. Patients without an ECHO were excluded from all analyses. The primary outcome was incidence of treatment for PDA. RESULTS: PDA treatment was administered in 83.3% and 11.2% of patients in groups A and B respectively (P < 0.05). Among patients with a hsPDA within group A, 17% did not receive treatment, while 11% of patients with non-hemodynamically significant PDA received treatment for the PDA. Within the cohort of patients who received treatment for a hsPDA, gestational age below 35 weeks as well as murmurs heard on auscultation were both found to be predictors of treatment. CONCLUSION: While the ECHO remains the gold standard for detecting pathological PDA, there is evidence that other traditional clinical measures continue to guide clinical practice and treatment decisions. Further research is required to gain an understanding of how clinical measures and ECHO may be used in conjunction to optimize resource utilization.

Open abdomen in liver transplantation.

INTRODUCTION: Damage control laparotomy with vacuum assisted closure (VAC) is used for selective cases in trauma. In liver transplantation, VAC has also been applied for management of intra-operative hemorrhage. The primary objective was to evaluate peri-operative blood loss and blood product utilization in VAC compared to primary abdominal closure (PAC) at the index transplant operation. METHODS: Retrospective review of all adults undergoing deceased donor liver transplantation (2007-2011) at a single center tertiary care institution. RESULTS: 201 deceased donor liver transplantations were performed, with 167 PAC and 34 VAC cases. Intra-operative blood loss (4.4L vs 10.7L), cell saver return (1399 ml vs 3998 ml), FFP (7.6U vs 15.9U) and PLT requirements (8.5U vs 18.3U), were all significantly elevated in VAC compared to PAC. VAC patients had significantly increased RBC, FFP, PLT, and total volume requirements during initial ICU admission. 30 PAC cases required on demand laparotomy and most commonly for post-operative bleeding. CONCLUSION: In liver transplantation, application of VAC secondary to massive intra-operative exsanguination was safely utilized. Further evaluation is required to identify long-term morbidity and mortality.

Rising incidence of head and neck mucosal melanoma in Australia.

OBJECTIVE: To establish Australian population-based incidence trends for mucosal melanoma of the head and neck. METHODS: Cases between 1985 and 2009 were identified in the Australian Cancer Database. Age-standardised incidence trends were established, including subgroup stratification by sex and site. RESULTS: A continuously progressive increase in incidence was evident in the 353 cases identified over the 25-year study period. This was particularly evident in sinonasal mucosal melanoma in men, despite the overall incidence remaining higher in women. CONCLUSION: There is such paucity in published global incidence trends of head and neck mucosal melanoma. Comparisons of incidence patterns between countries can provide insight into aetiological factors of this rare disease.

Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis.

AIM: To assess the comparative efficacy and safety of sodium-glucose co-transporter-2 (SGLT2) inhibitors in adults with type 2 diabetes. METHODS: We electronically searched randomized controlled trials (≥24 weeks) including canagliflozin, dapagliflozin or empagliflozin that were published up to 3 November 2015. Data were collected on cardiometabolic and safety outcomes and synthesized using network meta-analyses. RESULTS: A total of 38 trials (23 997 participants) were included. Compared with placebo, all SGLT2 inhibitors reduced glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and blood pressure, and slightly increased HDL cholesterol. Canagliflozin 300 mg reduced HbA1c, FPG and systolic blood pressure and increased LDL cholesterol to a greater extent compared with other inhibitors at any dose. At their highest doses, canagliflozin 300 mg reduced: HbA1c by 0.2% [95% confidence interval (CI) 0.1-0.3] versus both dapagliflozin 10 mg and empagliflozin 25 mg; FPG by 0.6 mmol/l (95% CI 0.3-0.9) and 0.5 mmol/l (95% CI 0.1-0.8) versus dapagliflozin and empagliflozin, respectively; and systolic blood pressure by 2 mmHg (95% CI 1.0-3.0) versus dapagliflozin; and increased LDL cholesterol by 0.13 mmol/l (95% CI 0.03-0.23) and 0.15 mmol/l (95% CI 0.06-0.23) versus dapagliflozin and empagliflozin, respectively. The highest doses of inhibitors had similar effects on body weight reduction. Canagliflozin 300 and 100 mg increased the risk of hypoglycaemia versus placebo, dapagliflozin 10 mg and empagliflozin 10 mg [odds ratios (ORs) 1.4-1.6]. Dapagliflozin 10 mg increased the risk of urinary tract infection versus placebo and empagliflozin 25 mg (ORs 1.4). All inhibitors similarly increased the risk of genital infection (ORs 4-6 versus placebo). CONCLUSIONS: Although they increase the risk of genital infection, SGLT2 inhibitors are effective in improving cardiometabolic markers in type 2 diabetes, with canagliflozin 300 mg performing better in this respect than other inhibitors. Further studies will clarify whether these differences are likely to translate into differing long-term outcomes.

A Multicenter Experience from Lebanon in Childhood and Adolescent Acute Myeloid Leukemia: High rate of Early Death in Childhood Acute Promyelocytic Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a disease with marked heterogeneity. Despite major improvement in outcome, it remains a life-threatening malignancy. Demographic and clinical data on pediatric AML is lacking among the Lebanese population. PURPOSE: We aimed to identify clinical, molecular and outcome data in children with AML in Lebanon. METHODS: A retrospective chart review of children with AML diagnosed in three Lebanese hospitals during the past 8 years was conducted. RESULTS: From May 2002 through March 2010, we identified 24 children with AML in Saint George Hospital University Medical Center, University Medical Center Rizk Hospital, and Abou-Jaoude Hospital. Males and females were equally represented; median age at diagnosis was 9 years (range 1-24) and median WBC at diagnosis was 31 × 10(9)/L (range: 2.1-376 × 10(9)/L). Twenty five percent of patients (6 out of 24) had acute promyelocytic leukemia (APL). Karyotype was normal in 33% of patients; t(8;21), inv (16), t(8;9), t(7;11), t(9;11), complex chromosomal abnormality, monosomy 7 and trisomy 8 were the most common cytogenetic abnormalities encountered. Patients were treated on different European and North American protocols. Twelve patients (50%) achieved morphologic CR after cycle 1, 6 of them (50%) had bone marrow relapse within 11 months from diagnosis. Nine patients underwent allogeneic stem cell transplant, and 3 of them are alive at 5 years post-transplant. Early death rate was 16.6% of patients, mainly those with APL and a presenting WBC > 10 × 10(9)/L. Fifty per cent of APL patients had an early death due to DIC despite starting ATRA therapy. Overall, median survival for AML patients who died from disease progression was 25.8 months (range: 1-60 months). Overall disease-free survival was 30.4%. Patients < 10 years of age had a 50% survival rate compared to 0% in patients > 10 years. CONCLUSIONS: Our report highlights the needs in Lebanon for better supportive care of children with APL, including faster ATRA administration and, aggressive transfusions, easy access to stem cell transplant for high-risk AML patients and the need for a national homogenous treatment strategy for children with AML.

Proceraside A, a new cardiac glycoside from the root barks of Calotropis procera with in vitro anticancer effects.

We have studied the ethyl acetate fraction of the methanolic extract of the root barks of Calotropis procera (Asclepiadaceae) from Egypt. Bioassay-directed fractionation and final purification of the extract resulted in the identification of a new cardenolide glycoside named proceraside A (1) together with two known compounds, frugoside (2) and calotropin (3). Their structures were elucidated by extensive NMR studies and mass spectrometric data. The in vitro cytotoxicity of the isolated compounds was evaluated against A549 non-small cell lung cancer, U373 glioblastoma and PC-3 prostate cancer cell lines. They showed potent activity against the tested cancer cell lines with IC50 ranging from 0.005 to 0.3 µg/mL. Cisplatin was used as positive control.

Effective strategy for decreasing blood culture contamination rates: the experience of a Veterans Affairs Medical Centre.

Contaminated blood cultures constitute diagnostic challenges and place a burden on healthcare services. An observational retrospective study was undertaken to evaluate the effect of routine labelling of blood culture bottles with the initials of the healthcare worker who drew them, followed by individualized feedback, on blood culture contamination rates. The contamination rate of the entire facility was 2.6% before the procedural change, and this decreased significantly to 1.5% after the procedural change (P < 0.001) over the first 12 months of the intervention. Routine labelling of blood culture bottles with the initials of the healthcare worker who drew them, followed by individualized feedback, was effective in reducing blood culture contamination rates.

Healthcare costs of methicillin resistant Staphylococcus aureus and Pseudomonas aeruginosa infections in veterans: role of vitamin D deficiency.

Methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa) infections are frequently associated with hospitalization and increased healthcare costs. Vitamin D deficiency may contribute to increased costs for patients with these infections and there is evidence that vitamin D may have an antimicrobial role. To evaluate the role of vitamin D deficiency in the costs incurred with these infections, we studied the relationship of serum 25(OH)D levels to healthcare costs in veterans in the southeastern United States. Patients with both infections were vitamin D deficient to a similar extent and so were combined for further analysis. Vitamin D deficient patients had higher costs and service utilization than those who were not vitamin D deficient. Those with vitamin D deficiency had higher inpatient costs compared to the non-deficient group, and this difference was across most categories except for the number of inpatient hospitalizations or total number of days as an inpatient. Vitamin D deficiency was not significantly related to outpatient cost or service utilization parameters. We conclude that vitamin D deficiency is intimately linked to adverse healthcare costs in veterans with MRSA and P. aeruginosa infections. Vitamin D status should be assayed in patients with these infections.

Prediction of steroid response in nephrotic syndrome by humoral immunity assessment.

The purpose of this study was to estimate the serum levels of IgG, IgM, and IgA in nephrotic syndrome (NS) cases, in activity or in remission, and to detect their levels in relation to steroid response by evelautingthe relationship between IgG/IgM ratio and response to steroids. We investigated 27 cases with NS in activity and in remission and 20 healthy children as controls. Group A included 16 NS patients (12.3±1.4 years) who were steroid-resistant, frequent relapsers, or steroid dependent. Group B included 11 steroid-sensitive NS patients with a mean age of 11.6±2.1 years. Group C included 20 healthy children with a mean age of 12.1±2.3 years who were the control group. We found lower serum IgG level in NS cases compared with the control group; and it was lower in activity than in remission. The levels were lower in Group A compared with those of Group B. Serum IgG levels in Group A were as follows: in activity, 2.29±1.13 g/L and in remission, 4.3±2 g/L. In Group B, they were 6.2±1.2 g/L and 6.5±1.15 g/L in activity and in remission, respectively, and 11.8±2.5 g/L in the healthy control group (P<0.05). There was a direct correlation between serum albumin and serum IgG. We found no significant difference in serum IgM and IgA levels among studied groups whether in activity or in remission. Serum IgG/IgM ratio was lower in activity and in remission in the patient groups than in the control group as it was 9.3±4.7 in healthy subjects. It was 1.8±1.5 in Group A in activity and 3.2±2 in remission, and in Group B 4.8±2.39 in activity and 4.8±2.4 in remission. We conclude that IgM and IgA show no significant difference in NS patients. Serum IgG is lower in NS than in the control group and is much lower in activity than in remission. It is lower in patients with poor steroid response. We propose a predictive value of IgG/IgM ratio in activity, that is, the higher the IgG/IgM ratio in activity, the better the prognosis.

Healthcare costs of Staphylococcus aureus and Clostridium difficile infections in veterans: role of vitamin D deficiency.

Clostridium difficile and staphylococcal infections are associated with increased morbidity, mortality and healthcare costs. Vitamin D deficiency may also contribute to increased healthcare costs. There is increasing evidence that vitamin D may have an antimicrobial role. We examined the relationship of serum 25(OH)D levels to staphylococcal and C. difficile infections to determine if vitamin D deficiency was associated with adverse outcomes. In the outpatient setting, vitamin D deficiency in patients with C. difficile and staphylococcal infections were associated with significantly increased total outpatients costs and fee-based consultation. Laboratory expenses had a trend towards higher costs in the vitamin D-deficient group but did not reach statistical significance. The differences were most clearly seen in the in-patient group with enhanced laboratory, pharmacy and radiology costs. These differences resulted in vitamin D-deficient patients with C. difficile or staphylococcal infections having costs more than five times higher than the non-deficient patients. The total length of hospital stay was four times greater in the vitamin D-deficient group. In addition, the total number of hospitalizations was also significantly greater in the vitamin D-deficient group. Surgery costs demonstrated a tendency to be higher in the vitamin D-deficient group but failed to reach statistical significance. Vitamin D deficiency is intimately linked to adverse health outcomes and costs in Veterans with staphylococcal and C. difficile infections in North East Tennessee. We recommend that vitamin D status be checked in patients with these infections and appropriate therapy be instituted to restore vitamin D level to normal in an expeditious manner.

Reconstruction of partial maxillary defects with the double-barrel fibula free flap.

Maxillary reconstruction still remains challenging for surgeons despite the fact that maxilla is a static structure. The correct shape and volume of the reconstruction can guarantee the best result in terms of soft tissue support and functional outcome for the patients restoring three-dimensional support of the mid third. The fibula free flap seems to be the best free flap to apply in this type of reconstruction, partial maxillectomy, in particular, can benefit from reconstruction with the double barrelled fibula free flap. In fact, this shape can provide the best support to cheek tissue and minimize the tendency of upper retraction of the alar base of the nose and lips. Moreover, the free flap, containing bone, can restore a skeletal structure that will provide adequate bony support for osteointegrated implant prosthesis rehabilitation. All these conditions can be achieved with the double barrel fibula flap that we consider a good approach for maxillary reconstruction.

[Complete androgen insensitivity syndrome: a novel mutation in a Tunisian family]. / Syndrome de résistance complète aux androgènes: nouvelle mutation chez une famille tunisienne.

INTRODUCTION: Complete androgen insensitivity is a rare syndrome. It is caused by a mutation in the androgen receptor gene. We describe a novel mutation in exon 1. MATERIALS AND METHODS: We report the case of a 29 year-old girl with complete androgen insensitivity syndrome discovered during the exploration of a primary amenorrhoea. The family investigation revealed two other cases. RESULTS: The diagnosis was oriented by the clinical and the biological features and confirmed by the molecular study. A new mutation of the androgen receptor gene, as a deletion in exon 1 not described previously, was identified. CONCLUSION: Through these cases, clinical, hormonal and histological particularities were analysed.

[Hydatid disease of bone: a report of 2 cases]. / Kyste hydatique primitif intraosseux: à propos de deux cas.

INTRODUCTION: The hydatid cyst of Echinococcus granulosus tends to develop in liver. The primary bone hydatidosis is rare. EXEGISIS: The authors report 2 cases of primary hydatidosis of bone in a 57 year old men and 60 year old diabetic women. The symptoms and signs were not specific. The ultrasound investigation: standard radiography and computed tomographic scan, was suggestive of the lesion. The chest radiograph and the abdominal ultrasound were normal. Serological tests for hydatid disease were positive. The two patients have surgical excision and medical treatment: Albendazole administrated for 6 months. Histologic evidence confirmed the diagnosis. The outcome was good for both patients without recurrence after 2 years. CONCLUSION: Through these 2 cases and a review of the literature, the authors analyse the epidemiological and clinical aspects of bone hydatidosis and discuss the therapeutic procedures.

Cytotoxic cyclic norterpene peroxides from a Red Sea sponge Diacarnus erythraenus.

Investigation of the lipophilic extract of the Red Sea sponge Diacarnus erythraenus revealed one new norsesterterpene cyclic peroxide, aikupikoxide A (1), three new norditerpene cyclic peroxides, aikupikoxide B-D (2-4), and the known norterpene peroxides muqubilin and nuapapuin A methyl ester. In addition, a new sesquiterpene, O-methyl guaianediol, was isolated. Their structures were determined by means of spectroscopic methods. The cytotoxic activities for the isolated compounds have been reported.

Cytotoxic quaternary alkaloids from the flowers of Narcissus tazetta.

Intensive chromatographic separation of the polar fraction of an ethanolic extract of the fresh flowers of Narcissus tazetta L. (Amaryllidaceae) yielded two new quaternary alkaloids with a phenanthrene skeleton, N-methyl-8,9-methylenedioxy-phenantridinium methylsulfate (1) and N-methyl-8,9-methylenedioxy-phenantridinium malate (2). The structure determination of the alkaloids was based on one- and two-dimensional NMR studies including HMQC, and HMBC studies, and mass spectroscopic analysis. The existence, in 1, of the methylsulfate group was confirmed by X-ray diffraction analysis. Cytotoxic activities for 1 and 2 against a panel of cancer cell lines are also reported.

Alkaloids of the flowers of Hippeastrum vittatum.

Investigation of an ethanolic extract of the fresh flowers of Hippeastrum vittatum yielded the new alkaloids vittacarboline (1) and O-methylismine (3), together with the known compound ismine (2). The structures of 1--3 were established by spectroscopic methods including one- and two-dimensional NMR and mass spectrometry.

Polyacetylenes from a red sea sponge Callyspongia species.

From the methanolic extract of the Red Sea sponge Callyspongia sp. six new polyacetylenic compounds, aikupikanynes A-F, together with octahydrosiphonochalyne, were isolated and identified. Their structures, which comprise four hydrocarbons, two alcohols, and one unprecedented alpha-hydroxy carboxylic acid, were determined by extensive 1D and 2D NMR studies and mass spectral determinations.

Alkaloids of the flowers of Pancratium maritimum.

The defatted ethanolic extract of the fresh flowers of Pancratium maritimum L. yielded the four known alkaloids lycorine, maritidine, lycoramine, and galanthamine. The structures of the isolated alkaloids were determined mainly through spectroscopic studies including one- and two-dimensional NMR (COSY, NOESY, DEPT, HETCOR, and HMBC) and CD techniques. Some spectral data are newly reported or revised.

Constituents of the Egyptian Centaurea scoparia. III. Phenolic constituents of the aerial parts.

The ethanolic extract of the aerial parts of Centaurea scoparia Sieb. (Asteraceae) afforded five polyoxygenated flavones apigenin, luteolin, salvigenin, cirsimaritin, and hispidulin, the two lignans (-)-matairesinol and (-)-arctigenin together with omega-hydroxypropioguaiacone and vanillin. The structure elucidations of the isolated compounds are based on spectroscopic methods including 1D- and 2D-NMR spectra. Some proton and carbon signals are revised or newly reported.