Extra-skeletal impact of vitamin D supplementation protocol in an adult population with cystic fibrosis.

BACKGROUND: Due to lack of vitamin D absorption in patients with cystic fibrosis (CF), vitamin D supplementation becomes necessary. Our aim was to study the association between serum vitamin D levels and key clinical factors, such as nutritional status, pulmonary function and pulmonary exacerbations (PEx) frequency, in an adult CF population. METHODS: Prospective analysis of a published vitamin D (VitD3) supplementation protocol (N = 200 adult patients) over a follow-up period of 5 years. Data were collected from the medical files before (baseline) and after (follow-up) the implementation of the VitD3 supplementation protocol, between 2009 and 2014. Serum samples to measure vitamin D were also collected at baseline and follow-up. RESULTS: A positive relationship between serum vitamin D and lung function was observed at baseline (R = 0.158, P = 0.027), but it disappeared at follow-up (P = 0.454). There was no association between serum vitamin D levels and body mass index. At follow-up, patients with significantly higher serum vitamin D levels were women, older in age, had CF-related diabetes or had a history of recurring PEx. CONCLUSION: No direct link was observed between heightened serum vitamin D and lung function or BMI in an adult CF population. We suggest that better compliance to treatments and closer follow-up from health professionals could partially explain why such patients reached higher vitamin D serum levels.

Myocardial Perfusion Scans and Mortality in Asymptomatic Patients Awaiting Renal Transplantation.

Cardiac risk assessment for asymptomatic patients awaiting renal transplantation is controversial. Patients awaiting renal transplantation in Southern Saskatchewan from 2005 to 2015 were retrospectively reviewed. Patients underwent cardiac risk stratification with stress myocardial perfusion scan. Baseline clinical characteristics, nuclear scan results, all-cause mortality, and cardiovascular events were analyzed. Abnormal scans were defined as studies with reversible defects, wall motion abnormalities, lung uptake, or transient ischemic dilation. Descriptive statistics and survival analysis were calculated. Charts from 285 consecutive patients with 608 nuclear scans were analyzed. Mean age was 55.2 ± 11.7 years and 34.7% were female. Forty-three (15.1%) patients were transplanted and 99 (40.9%) patients died while awaiting renal transplantation. One hundred fifty-three patients (63.2%) had at least one abnormal scan. The mean follow-up period was 5.47 ± 3.11 years. An abnormal scan was not associated with decreased survival and/or coronary events (hazard ratio: 0.94, P = .77; 95% confidence intervals: 0.62 to 1.43). Patients awaiting renal transplantation in Saskatchewan with abnormal myocardial perfusion scans were not at greater risk of death or coronary events.

Association between glucose intolerance and bacterial colonisation in an adult population with cystic fibrosis, emergence of Stenotrophomonas maltophilia.

BACKGROUND: Diabetes is common in cystic fibrosis (CF). Glucose can be detected in the airway when the blood glucose is elevated, which favours bacterial growth. We investigated the relationship between dysglycemia and lung pathogens in CF. METHODS: Cross-sectional and prospective analysis of CF patients (N=260) who underwent a 2h-oral glucose tolerance test. Clinical data was collected. RESULTS: Stenotrophomonas maltophilia (S. maltophilia) was the sole bacteria increased in dysglycemic (AGT: 20.2%, CFRD: 21.6%) patients compared to normotolerants (NGT: 8.7%). S. maltophilia positive patients with dysglycemia had more pulmonary exacerbation events compared to NGTs (1.22 vs 0.63, P=0.003). The interaction between S. maltophilia colonisation and glucose tolerance status significantly increases the risk of lower lung function (P=0.003). Its growth was not affected by the evolution of the glucose tolerance after three years follow-up. CONCLUSION: Prevalence of S. maltophilia was higher in dysglycemic patients, supporting the idea that S. maltophilia is a marker of disease severity in CF.

Ralstonia mannitolilytica in cystic fibrosis: A new predictor of worse outcomes.

BACKGROUND: Patients with Cystic Fibrosis are subject to repeated respiratory tract infections, with recent increasing isolation of unusual pathogens. Ralstonia species have lately been isolated at our institution, an organism historically frequently misidentified as Burkholderia or Pseudomonas. The prevalence of Ralstonia spp. in cystic fibrosis populations has yet to be determined, along with its clinical implications. CASE PRESENTATIONS: Seven patients out of the 301 followed at our cystic fibrosis clinic have had Ralstonia strains identified in their respiratory tract. Most strains identified were multi-drug resistant. After aquisition of Ralstonia spp., the patients' clinical course was characterized by more frequent and more severe respiratory infections along with prolonged hospitalizations, greater decline of lung function, and greater mortality. The mortality rate in this group of patients was 86%. No other factor that could explain such a dramatic evolution was identified upon review of patient data. Some of the strains involved were recognized as clones on Pulse Field Electrophoresis Gel, raising the question of person-to-person transmission. CONCLUSION: New pathogens are identified with the evolution of the microbiota in cystic fibrosis respiratory tracts. In our cohort of patients, acquisition of Ralstonia spp. was associated with dramatic outcomes in terms of disease acceleration and raised mortality rates. It is of critical importance to continue to better define the prevalence and clinical impact of Ralstonia in cystic fibrosis populations.

[Monitoring of vancomycin in pediatrics]. / Suivi des concentrations sériques de la vancomycine en pédiatrie.

OBJECTIVES: The authors wanted to determine if the current local practice (initial prescription and monitoring) in pediatrics allowed reaching vancomycin therapeutic concentrations. PATIENTS AND METHODS: Thirty patients that had received vancomycin for at least five days with at least one evaluation of serum concentration, at the Sainte-Justine university hospital center, were retrospectively studied. Vancomycin trough and peak levels were analyzed. RESULTS: The values of vancomycin serum concentration were within therapeutic ranges (local standards of 5 to 10mg/L for trough level and 20 to 40 mg/L for peak level) in 60% and 33% of cases at the fifth day of treatment for trough and peak levels, respectively. CONCLUSION: The current practice does not allow reaching vancomycin serum concentrations in the target range. Using a wider range for the trough values could be considered.

[Regenerative medicine: stem cells, cellular and matricial interactions in the reconstruction of skin and cornea by tissue engineering]. / La médecine régénératrice : les cellules souches, les interactions cellulaires et matricielles dans la reconstruction cutanée et cornéenne par génie tissulaire.

Considering that there is a shortage of organ donor, the aim of tissue engineering is to develop substitutes for the replacement of wounded or diseased tissues. Autologous tissue is evidently a preferable transplant material for long-term graft persistence because of the unavoidable rejection reaction occuring against allogeneic transplant. For the production of such substitutes, it is essential to control the culture conditions for post-natal human stem cells. Furthermore, histological organization and functionality of reconstructed tissues must approach those of native organs. For self-renewing tissues such as skin and cornea, tissue engineering strategies must include the preservation of stem cells during the in vitro process as well as after grafting to ensure the long-term regeneration of the transplants. We described a tissue engineering method named the self-assembly approach allowing the production of autologous living organs from human cells without any exogenous biomaterial. This approach is based on the capacity of mesenchymal cells to create in vitro their own extracellular matrix and then reform a tissue. Thereafter, various techniques allow the reorganization of such tissues in more complex organ such as valve leaflets, blood vessels, skin or cornea. These tissues offer the hope of new alternatives for organ transplantation in the future. In this review, the importance of preserving stem cells during in vitro expansion and controlling cell differentiation as well as tissue organization to ensure quality and functionality of tissue-engineered organs will be discussed, while focusing on skin and cornea.

Dichotomy between postprandial glucose and lipid profiles in adults with cystic fibrosis: a pilot study.

BACKGROUND: Cystic fibrosis (CF) patients present a high incidence of glucose tolerance abnormalities. Altered insulin secretion combined with recommended high-fat intake could be associated with dysregulation of glucose and lipid metabolism. We examined postprandial glucose and lipid profiles during an oral glucose tolerance test (OGTT) and following a standardized high-fat test meal (TM). METHODS: Sixteen CF patients with normal glucose tolerance (NGT) or CF-related diabetes (CFRD) and 16 controls underwent a 4 h OGTT and a TM. We then measured plasma glucose, insulin, free fatty acid (FFA) and triglyceride (TG) concentrations. RESULTS: CF patients presented higher glucose excursion compared to controls after the OGTT and TM. However, in CF patients, this excursion was significantly reduced in both amplitude and length after the TM. The TM provoked a comparable increase in TG levels in both groups whereas they remained stable during the OGTT. FFAs were suppressed similarly in both groups after both challenges. CONCLUSION: CF is associated with abnormal glucose excursion in the presence of relatively normal lipid excursion. The rapid normalization of glucose values after a mixed meal should be further explored and, if confirmed, might have significant implications for CFRD diagnostic.

[Pilot study about pharmaceutical care implantation in a general paediatric unit in a French hospital. France-Québec collaboration and comparison]. / Etude pilote sur la mise en place des soins pharmaceutiques dans le service de pédiatrie générale d'un hôpital français. Collaboration et comparaison franco-québécoise.

UNLABELLED: STATE OF THE PROBLEM AND OBJECTIVES: French pharmacists are quasi absent from hospital wards. Our objective was to describe the implantation of pharmaceutical care in a patient unit of a French paediatric hospital. MATERIAL AND METHODS: Following an internship in pharmaceutical care at the Sainte-Justine hospital (SJ) in Montreal, a French pharmacist returned to France to implement the pharmaceutical model in a paediatric unit at Robert Debré hospital (RD) in Paris. We first collected pharmaceutical interventions carried out during a 5-month period. In a second phase, we compared pharmaceutical interventions provided by the team composed of the same French pharmacist and a pharmacist from Québec in both settings during 14 days respectively. RESULTS: In the first phase, 556 interventions were done (8.2+/-2,0 per day) with a significant increase observed during the first 2 months. In the second phase, 216 interventions were done at RD and 174 at SJ. The interventions were mainly related to drug information, modification of treatment and seamless care with the pharmacy of the hospital or a community pharmacy. The interventions targeted junior (30.5 to 55.4%), senior physicians (16.2 to 38.5%) and pharmacy (11.5 to 16.2%) in the different phases and sites. A high level of physician acceptance was observed, with respectively 86.0 and 93.1% at RD and SJ. DISCUSSION: French pharmacists can apply the pharmaceutical care model following a specific training. Further studies are required to evaluate the feasibility and the impact of pharmaceutical care in France.

[The use of head CT scan in adult trauma victims: an algorithm]. / Le scanner cérébral chez les adultes victimes de traumatismes crâniens mineurs: un arbre décisionnel.

INTRODUCTION: The purpose of this study was to identify, through recursive partitioning, clinically relevant criteria which predict the need for acute neurosurgical intervention in a group of patients with mild head injury. MATERIALS AND METHODS: A retrospective cohort of all adult patients, from April 2000 to March 2001, who sustained a blunt trauma and underwent head CT scan, was reviewed. The following inclusion criteria for mild head injury were used: initial Glasgow Coma Scale (GCS) ranging from 13 to 15; no loss of consciousness lasting more than one hour; no obvious skull fracture; a cranial CT scan performed. We collected demographic and trauma related data, interventions and outcome. Univariate and multivariate analyses were undertaken. In parallel, recursive partitioning was carried out using all variables to elaborate a decision algorithm. RESULTS: There were 405 patients in the sample. CT identified lesions in 12% of patients. Twelve patients (3%) required acute neurosurgical intervention. The recursive partitioning analysis identified three significant sequential nodes: deterioration of the GCS; an initial GCS of 13 vs 14 or 15; and the presence of associated injuries or comorbid conditions. CONCLUSIONS: A simple three step rule predicts the need for acute neurosurgical intervention based on clinical findings: a deteriorating GCS; an initial GCS of 13; and the presence of associated injuries or comorbid conditions.

Diabetes: a major co-morbidity of cystic fibrosis.

Cystic fibrosis-related diabetes (CFRD) is a frequent complication of cystic fibrosis, its prevalence increases with age of patient and is close to 30% at the age of 30 years. As life expectancy greatly increases, the number of cystic fibrosis patients developing diabetes will increase too. CFRD shares some features with type 1 and type 2 diabetes, initial phase is characterised by postprandial hyperglycaemia followed by a progression toward insulin deficiency. Insulin deficiency is an essential factor in the development of diabetes with an additional contribution of insulin resistance. Systematic screening with an oral glucose tolerance test is recommended from the age of 14 years because clinical signs of CFRD are often confused with signs of pulmonary infection and CFRD occurrence is associated with weight and pulmonary function deterioration. In observational studies CFRD diagnosis is associated with a significant increase in mortality, while treatment allow correction of weight and lung deterioration suggesting that CFRD has a significant impact on CF evolution. Microvascular complications are recognised, although paucity of data does not permit a clear description of their natural history. Annual screening for microvascular complication is recommended. There is no evidence by now that CF patients develop macrovascular complications. The only recommended pharmacological treatment is insulin therapy.

Analysis of SWAP-70 as a candidate gene for non-X-linked hyper IgM syndrome and common variable immunodeficiency.

SWAP-70 is a recently identified protein that functions as the only B cell-specific component of an isotype switch recombination complex called SWAP. The SWAP complex has specificity for the switch regions upstream of the constant region immunoglobulin genes and it facilitates the transfer of DNA between switch regions. These features suggested that mutations in the gene encoding SWAP-70 might result in humoral immunodeficiency. To test this hypothesis we determined the genomic structure of this gene and used single-stranded conformational polymorphism (SSCP) analysis to screen DNA from 38 patients with either non-X-linked hyper IgM syndrome or common variable immunodeficiency. The results demonstrated that SWAP-70 consists of 12 exons spread over 89 kb at chromosome 11p15.2. SSCP analysis of the patient population revealed five polymorphic variants in the gene, one of which (Q505E) is an amino acid substitution in the putative nuclear export signal of SWAP-70. However, none of the alterations appeared to be associated with disease in the patients screened.

Enantioselective routes to both enantiomers of aryl alcohols with a single catalyst antipode: Ru and Os transfer hydrogenation catalysts.

[reaction--see text] The kinetic resolution of secondary aryl alcohols has been investigated. When (CyRuCl(2))(2), (1R,2S)-(+)-cis-1-amino-2-indanol, and KOH or (t)BuOK (catalyst 1) were combined in the presence of (+/-)-alcohols, ee's > 90% were generally observed. When applied to the kinetic resolution of (+/-)-indanol and (+/-)-tetralol, ee's = 99% (R) were observed. In addition, the asymmetric transfer hydrogenation of ketones was investigated with a catalyst, 2, generated in situ from (CyOsCl(2))(2), (1R,2S)-(+)-cis-1-amino-2-indanol, and (t)BuOK, yielding ee's of up to 98% (S).

Mutations in activation-induced cytidine deaminase in patients with hyper IgM syndrome.

Recent studies have shown that mutations in a newly described RNA editing enzyme, activation-induced cytidine deaminase (AID), can cause an autosomal recessive form of hyper IgM syndrome. To determine the relative frequency of mutations in AID, we evaluated a group of 27 patients with hyper IgM syndrome who did not have defects in CD40 ligand and 23 patients with common variable immunodeficiency. Three different mutations in AID were identified in 18 patients with hyper IgM syndrome, including 14 French Canadians, 2 Lumbee Indians, and a brother and sister from Okinawa. No mutations were found in the remaining 32 patients. In the group of patients with hyper IgM syndrome, the patients with mutations in AID were older at the age of diagnosis, were more likely to have positive isohemagglutinins, and were less likely to have anemia, neutropenia, or thrombocytopenia. Lymphoid hyperplasia was seen in patients with hyper IgM syndrome and normal AID as well as the patients with hyper IgM syndrome and defects in AID.

The incidence and pathogenesis of cardiopulmonary deterioration after abrupt withdrawal of inhaled nitric oxide.

We studied the effect of abrupt discontinuation of inhaled nitric oxide (iNO) in patients receiving this drug for treatment of acute hypoxemic respiratory failure (AHRF), in order to determine the need for continued therapy, the incidence and nature of adverse events, and the risk factors predicting these adverse events. Thirty-one patients who showed an initial increase in Pa(O(2)) of > 20 mm Hg in response to iNO underwent a discontinuation trial at 10 to 30 h after beginning iNO. Indwelling arterial and pulmonary artery catheters facilitated monitoring of hemodynamic and gas-exchange parameters. For the group, discontinuation of iNO caused a significant decrease in Pa(O2 ), arterial and mixed venous oxygen saturation, and ratio of Pa(O(2)) to fraction of inspired oxygen (FI(O(2))). Three patterns of response were observed. Eight of 31 (25.8%) patients had minimal changes in oxygenation or hemodynamics, suggesting no need for ongoing therapy. Fifteen of 31 (48%) patients had worsened gas exchange as a predominant response. Eight of 31 patients exhibited hemodynamic collapse, defined as > 20% fall in cardiac output and/or mean arterial blood pressure. In this last subgroup, the pattern of cardiovascular changes suggested that this response arose from an acute increase in right ventricular afterload, and was not a consequence of gas-exchange abnormalities. In all cases, reinstitution of iNO promptly reversed worsened hemodynamics and gas exchange. Independent factors associated with an increased risk of cardiovascular collapse included multisystem organ failure, older age, and initial blood pressure increase in response to iNO; a smaller change in the ratio of Pa(O(2)) to FI(O(2)) with initiation of iNO therapy also tended to correlate with this phenomenon. We conclude that careful and monitored discontinuation of iNO in patients with AHRF will identify substantial fractions of patients who are either receiving no benefit from this therapy or who require iNO to maintain an adequate circulation and are therefore at risk for adverse outcome with transport or inadvertent discontinuation of iNO. Future trials of iNO should recognize this complication of such therapy and include assessments for it.

Cardiopulmonary resuscitation: errors made by pre-hospital emergency medical personnel.

The purpose of the current study was to evaluate the CPR techniques of emergency healthcare professionals (emergency medical technicians, firemen, emergency first responders, CPR instructors). Skills were evaluated using a Laerdal Skillmeter Manikin, which provided a computerized printout of the quantifiable data during the CPR sequence. All of the 66 subjects in the study had completed a recertification course within the last 2 years (mean = 0.86 +/- 0.18, 95% CI). The sequence was videotaped for later viewing and for correlating the errors with the data. In addition, the participants were required to fill in a questionnaire. The most frequently occurring errors were observed in landmarking, overcompression, palpating a carotid pulse and insufficient ventilation. Although 98.5% of participants made an attempt to landmark their position for compression on the sternum, 35.9% of the total compressions performed by all subjects were incorrectly positioned on the patient's chest. Overcompression of the patient's chest accounted for 55.3% of incorrect compressions. Although 94% of participants attempted to verify a carotid pulse, only 45% were able to feel it and therefore stop performing cardiac massage. Of the total ventilations, 49% were below the American Heart Association (AHA) recommended minimum (800 ml). The results of this study showed a high rate of errors occurring in the CPR provided by emergency healthcare professionals.

Trauma care regionalization: a process-outcome evaluation.

BACKGROUND: Regionalization of trauma care services in our region was initiated in 1993 with the designation of four tertiary trauma centers. The process continued in 1995 with the implementation of patient triage and transfer protocols. Since 1995, the network of trauma care has been expanded with the designation of 33 secondary, 30 primary, and 32 stabilization trauma centers. In addition, during this period emergency medical personnel have been trained to assess and triage trauma victims within minimal prehospital time. The objective of the present study was to evaluate the impact of trauma care regionalization on the mortality of major trauma patients. METHODS: This was a prospective study in which patients were entered at the time of injury and were followed to discharge from the acute-care hospital. The patients were identified from the Quebec Trauma Registry, a review of the records of acute-care hospitals that treat trauma, and records of the emergency medical services in the region. The study sample consisted of all patients fulfilling the criteria of a major trauma, defined as death, or Injury Severity Score (ISS) > 12, or Pre-Hospital Index > 3, or two or more injuries with Abbreviated Injury Scale scores > 2, or hospital stay of more than 3 days. Data collection took place between April 1, 1993, and March 31, 1998. During this period, four distinct phases of trauma care regionalization were defined: pre-regionalization (phase 0), initiation (phase I), intermediate (phase II), and advanced (phase III). RESULTS: A total of 12,208 patients were entered into the study cohort, and they were approximately evenly distributed over the 6 years of the study. During the study period, there was a decline in the mean age of patients from 54 to 46 years, whereas the male/female ratio remained constant at 2:1. There was also an increase in the mean ISS, from 25.5 to 27.5. The proportion of patients injured in motor vehicle collisions increased from less than 45% to more than 50% (p < 0.001). The mortality rate during the phases of regionalization were: phase 0, 52%; phase I, 32%; phase II, 19%; and phase III, 18%. These differences were clinically important and statistically significant (p < 0.0001). Stratified analysis showed a significant decline in mortality among patients with ISS between 12 and 49. The change in mortality for patients with fatal injuries (ISS > or = 50) was not significant. During the study period, the mean prehospital time decreased significantly, from 62 to 44 minutes. The mean time to admission after arrival at the hospital decreased from 151 to 128 minutes (p < 0.001). The latter decrease was primarily attributable to changes at the tertiary centers. The proportion of patients with ISS between 12 and 24 and between 25 and 49 who were treated at tertiary centers increased from 56 to 82% and from 36 to 84%, respectively (p < 0.001). Compared with the secondary and primary centers, throughout the course of the study the mortality rate in the secondary and tertiary centers showed a consistent decline (p < 0.001). In addition, the mortality rate in the tertiary centers remained consistently lower (p < 0.001). The results of multivariate analyses showed that after adjusting for injury severity and patient age, the primary factors contributing to the reduced mortality were treatment at a tertiary center, reduced prehospital time, and direct transport from the scene to tertiary centers. CONCLUSION: This study produced empirical evidence that the integration of trauma care services into a regionalized system reduces mortality. The results showed that tertiary trauma centers and reduced prehospital times are the essential components of an efficient trauma care system.

Response to inhaled nitric oxide in patients with acute right heart syndrome.

Inhaled nitric oxide (iNO), a selective pulmonary vasodilator, has been shown to decrease pulmonary artery pressures but not increase cardiac output in hemodynamically stable patients with a variety of causes of pulmonary hypertension. The response to iNO in hemodynamically unstable patients with acute right heart syndrome has not been previously described. We determined the response to iNO in 26 critically ill adult patients with acute right heart failure defined by echocardiographic criteria. Patients received iNO through the inspiratory limb of the ventilator in increments of 10 ppm with hemodynamic and gas-exchange measurements made before and after each level. When maximal effect was seen, iNO was discontinued to compare parameters with baseline. iNO significantly increased cardiac output (5.5 +/- 3 to 6.4 +/- 4 L/min), stroke volume (54 +/- 27 to 65 +/- 38 ml), and mixed-venous oxygen saturation (69 +/- 8 to 73 +/- 10%), all p < 0.01. With discontinuation of iNO, all parameters returned immediately to baseline. These parameters of improved perfusion were related to a decrease in pulmonary vascular pressures and resistance. In a subset of approximately 50% of patients, these changes were substantial (> 20%) and in approximately 25% of all patients, the improvement in hemodynamic measures permitted a decrease in other vasoactive drug administration. The mean concentration of iNO required to achieve these effects was 35 ppm, and 85% of patients exhibiting a substantial improvement in hemodynamics did so at a concentration of iNO of less than or equal to 40 ppm. Underlying causes of right heart failure and baseline hemodynamics did not predict response to iNO, but the use of alpha-agonist catecholamines did. We conclude iNO improves hemodynamics in patients with respiratory failure, shock, and right ventricular dysfunction. Although mortality was not a key end point in this pilot study, it was high for both responders and nonresponders to this therapy. Further evaluation of the role of iNO in this patient population is supported by these data.

Activation and deactivation rates of recombinant GABA(A) receptor channels are dependent on alpha-subunit isoform.

The role of subunit composition in determining intrinsic maximum activation and deactivation kinetics of GABA(A) receptor channels is unknown. We used rapid ligand application (100-micros solution exchange) to examine the effects of alpha-subunit composition on GABA-evoked activation and deactivation rates. HEK 293 cells were transfected with human cDNAs encoding alpha1beta1gamma2- or alpha2beta1gamma2-subunits. Channel kinetics were similar across different transfections of the same subunits and reproducible across several GABA applications in the same patch. Current rise to peak was at least twice as fast for alpha2beta1gamma2 receptors than for alpha1beta1gamma2 receptors (reflected in 10-90% rise times of 0.5 versus 1.0 ms, respectively), and deactivation was six to seven times slower (long time constants of 208 ms versus 31 ms) after saturating GABA applications. Thus alpha-subunit composition determined activation and deactivation kinetics of GABA(A) receptor channels and is therefore likely to influence the kinetics and efficacy of inhibitory postsynaptic currents.