Intraoperative hemodynamics and risk of cardiac surgery-associated acute kidney injury: An observation study and a feasibility clinical trial.

Targeting greater pump flow and mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) could potentially alleviate renal hypoxia and reduce the risk of postoperative acute kidney injury (AKI). Therefore, in an observational study of 93 patients undergoing on-pump cardiac surgery, we tested whether intraoperative hemodynamic management differed between patients who did and did not develop AKI. Then, in 20 patients, we assessed the feasibility of a larger-scale trial in which patients would be randomized to greater than normal target pump flow and MAP, or usual care, during CPB. In the observational cohort, MAP during hypothermic CPB averaged 68.8 ± 8.0 mmHg (mean ± SD) in the 36 patients who developed AKI and 68.9 ± 6.3 mmHg in the 57 patients who did not (p = 0.98). Pump flow averaged 2.4 ± 0.2 L/min/m2 in both groups. In the feasibility clinical trial, compared with usual care, those randomized to increased target pump flow and MAP had greater mean pump flow (2.70 ± 0.23 vs. 2.42 ± 0.09 L/min/m2 during the period before rewarming) and systemic oxygen delivery (363 ± 60 vs. 281 ± 45 mL/min/m2 ). Target MAP ≥80 mmHg was achieved in 66.6% of patients in the intervention group but in only 27.3% of patients in the usual care group. Nevertheless, MAP during CPB did not differ significantly between the two groups. We conclude that little insight was gained from our observational study regarding the impact of variations in pump flow and MAP on the risk of AKI. However, a clinical trial to assess the effects of greater target pump flow and MAP on the risk of AKI appears feasible.

Association Between Changes in Norepinephrine Infusion Rate and Urinary Oxygen Tension After Cardiac Surgery.

OBJECTIVES: To determine if the administration of norepinephrine to patients recovering from on-pump cardiac surgery is associated with changes in urinary oxygen tension (PO2), an indirect index of renal medullary oxygenation. DESIGN: Single center, prospective observational study. SETTING: Surgical intensive care unit (ICU). PARTICIPANTS: A nonconsecutive sample of 93 patients recovering from on-pump cardiac surgery. MEASUREMENTS AND MAIN RESULTS: In the ICU, norepinephrine was the most commonly used vasopressor agent (90% of patients, 84/93), with fewer patients receiving epinephrine (48%, 45/93) or vasopressin (4%, 4/93). During the 30-to-60-minute period after increasing the infused dose of norepinephrine (n = 89 instances), urinary PO2 decreased by (least squares mean ± SEM) 1.8 ± 0.5 mmHg from its baseline level of 25.1 ± 1.1 mmHg. Conversely, during the 30-to-60-minute period after the dose of norepinephrine was decreased (n = 134 instances), urinary PO2 increased by 2.6 ± 0.5 mmHg from its baseline level of 22.7 ± 1.2 mmHg. No significant change in urinary PO2 was detected when the dose of epinephrine was decreased (n = 21). There were insufficient observations to assess the effects of increasing the dose of epinephrine (n = 11) or of changing the dose of vasopressin (n <4). CONCLUSIONS: In patients recovering from on-pump cardiac surgery, changes in norepinephrine dose are associated with reciprocal changes in urinary PO2, potentially reflecting an effect of norepinephrine on renal medullary oxygenation.

Intra-operative and early post-operative prediction of cardiac surgery-associated acute kidney injury: Urinary oxygen tension compared with plasma and urinary biomarkers.

Acute kidney injury (AKI) is a common and serious post-operative complication of cardiac surgery. The value of a predictive biomarker is determined not only by its predictive efficacy, but also by how early this prediction can be made. For a biomarker of cardiac surgery-associated AKI, this is ideally during the intra-operative period. Therefore, in 82 adult patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB), we prospectively compared the predictive efficacy of various blood and urinary biomarkers with that of continuous measurement of urinary oxygen tension (UPO2 ) at pre-determined intra- and post-operative time-points. None of the blood or urine biomarkers we studied showed predictive efficacy for post-operative AKI when measured intra-operatively. When treated as a binary variable (≤ or > median for the whole cohort), the earliest excess risk of AKI was predicted by an increase in urinary neutrophil gelatinase-associated lipocalin (NGAL) at 3 h after entry into the intensive care unit (odds ratio [95% confidence limits], 2.86 [1.14-7.21], p = 0.03). Corresponding time-points were 6 h for serum creatinine (3.59 [1.40-9.20], p = 0.008), and 24 h for plasma NGAL (4.54 [1.73-11.90], p = 0.002) and serum cystatin C (6.38 [2.35-17.27], p = 0.001). In contrast, indices of intra-operative urinary hypoxia predicted AKI after weaning from CPB, and in the case of a fall in UPO2 to ≤10 mmHg, during the rewarming phase of CPB (3.00 [1.19-7.56], p = 0.02). We conclude that continuous measurement of UPO2 predicts AKI earlier than plasma or urinary NGAL, serum cystatin C, or early post-operative changes in serum creatinine.

Dynamic responses of renal oxygenation at the onset of cardiopulmonary bypass in sheep and man.

INTRODUCTION: The renal medulla is susceptible to hypoxia during cardiopulmonary bypass (CPB), which may contribute to the development of acute kidney injury. But the speed of onset of renal medullary hypoxia remains unknown. METHODS: We continuously measured renal medullary oxygen tension (MPO2) in 24 sheep, and urinary PO2 (UPO2) as an index of MPO2 in 92 patients, before and after induction of CPB. RESULTS: In laterally recumbent sheep with a right thoracotomy (n = 20), even before CPB commenced MPO2 fell from (mean ± SEM) 52 ± 4 to 41 ±5 mmHg simultaneously with reduced arterial pressure (from 108 ± 5 to 88 ± 5 mmHg). In dorsally recumbent sheep with a medial sternotomy (n = 4), MPO2 was even more severely reduced (to 12 ± 12 mmHg) before CPB. In laterally recumbent sheep in which a crystalloid prime was used (n = 7), after commencing CPB, MPO2 fell abruptly to 24 ±6 mmHg within 20-30 minutes. MPO2 during CPB was not improved by adding donor blood to the prime (n = 13). In patients undergoing cardiac surgery, UPO2 fell by 4 ± 1 mmHg and mean arterial pressure fell by 7 ± 1 mmHg during the 30 minutes before CPB. UPO2 then fell by a further 12 ± 2 mmHg during the first 30 minutes of CPB but remained relatively stable for the remaining 24 minutes of observation. CONCLUSIONS: Renal medullary hypoxia is an early event during CPB. It starts to develop even before CPB, presumably due to a pressure-dependent decrease in renal blood flow. Medullary hypoxia during CPB appears to be promoted by hypotension and is not ameliorated by increasing blood hemoglobin concentration.

Intraoperative renal hypoxia and risk of cardiac surgery-associated acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is common after cardiac surgery requiring cardiopulmonary bypass. Renal hypoxia may precede clinically detectable AKI. We compared the efficacy of two indices of renal hypoxia, (i) intraoperative urinary oxygen tension (UPO2 ) and (ii) the change in plasma erythropoietin (pEPO) during surgery, in predicting AKI. We also investigated whether the performance of these prognostic markers varies with preoperative patient characteristics. METHODS: In 82 patients undergoing on-pump cardiac surgery, blood samples were taken upon induction of anesthesia and upon entry into the intensive care unit. UPO2 was continuously measured throughout surgery. RESULTS: Thirty-two (39%) patients developed postoperative AKI. pEPO increased during surgery, but this increase did not predict AKI, regardless of risk of postoperative mortality assessed by EuroSCORE-II. For patients categorized at higher risk by EuroSCORE-II >1.98 (median score for the cohort), UPO2 ≤10 mmHg at any time during surgery predicted a 4.04-fold excess risk of AKI (p = .04). However, UPO2 did not significantly predict AKI in lower-risk patients. UPO2 significantly predicted AKI in patients who were older, had previous myocardial infarction, diabetes, lower preoperative serum creatinine, or shorter bypass times. pEPO and UPO2 were only weakly correlated. CONCLUSIONS: Intraoperative change in pEPO does not predict AKI. However, UPO2 shows promise, particularly in patients with higher risk of operative mortality. The disparity between these two markers of renal hypoxia may indicate that UPO2 reflects medullary oxygenation whereas pEPO reflects cortical oxygenation.

Ductal arterial spasm: a nightmare.

Ductal arterial spasm is a very potentially dangerous incidence during percutaneous device closure of patent ductus arteriosus (PDA), which, otherwise, is a very safe catheter intervention. It is essential to notice its occurrence before device sizing and deploying. Without awareness, it can mislead device selection and can result in serious complication. In this report, we shared our nightmare of ductal spasm during transcatheter closure of PDA in two children which had led to death in one patient.

High-sensitivity C-reactive protein and interleukin-6-dominant inflammation and ischemic stroke risk: the northern Manhattan study.

BACKGROUND AND PURPOSE: Interleukin-6 (IL-6) is a proinflammatory cytokine with known autoregulatory feedback mechanisms. We hypothesized that elevated high-sensitivity C-reactive protein (hsCRP) relative to IL-6 confers an increased risk of ischemic stroke (IS), and low hsCRP relative to IL-6 a decreased risk, for individuals in the prospective, multiethnic, population-based Northern Manhattan Study (NOMAS). METHODS: Serum hsCRP and IL-6 were measured in NOMAS participants at baseline. We created a trichotomized predictor based on the dominant biomarker in terms of quartiles: hsCRP-dominant, IL-6-dominant, and codominant groups. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for the association between inflammatory biomarker group status and risk of incident IS. RESULTS: Of 3298 participants, both hsCRP and IL-6 were available in 1656 participants (mean follow-up, 7.8 years; 113 incident IS). The hsCRP-dominant group had increased risk of IS (adjusted hazard ratio, 2.62; 95% confidence interval, 1.56-4.41) and the IL-6-dominant group had decreased risk (adjusted hazard ratio, 0.38; 95% confidence interval, 0.18-0.82) when compared with the referent group, after adjusting for potential confounders. Model fit was improved using the inflammation-dominant construct, over either biomarker alone. CONCLUSIONS: In this multiethnic cohort, when hsCRP-quartile was higher than IL-6 quartile, IS risk was increased, and conversely when IL-6 quartiles were elevated relative to hsCRP, IS risk was decreased. Construct validity requires confirmation in other cohorts.

Challenges in universal coverage and utilization of insecticide-treated bed nets in migrant plantation workers in Myanmar.

BACKGROUND: High coverage of the bed nets can reduce mortality and morbidity of mosquito-borne diseases including malaria. Although the migrant workers are at high risk of malaria, there are many hidden challenges in universal coverage and utilization of the insecticide-treated nets (ITNs) in this populations. METHODS: Cross sectional study was conducted in 170 migrant workers in palm oil plantation sites in Tanintharyi Region and 175 in rubber plantation sites in Mon State. A multistage stratified cluster sampling was applied to select the participants. During household visit, face-to-face interviews using structured pre-coded, pre tested questionnaires and direct observation on installation of the bed nets was conducted. Two focus group discussions in each site were done by sample stratified purposive sampling method mainly focused on effective utilization of bed nets. RESULTS: Among them, 332 (96.2%) had a bed net and 284 (82.3%) had an ITN, while 204 (59.1%) had unused extranets. Among the ITNs users, 28.9% reported problems including insecticide smell (56.9%), dizziness (20.2%), headache (12.8%) and itchiness (9.2%). More than 75% received ITNs from health authorities and NGOs free-of-charge. More than 70% wanted to buy a net but they were unaffordable for 64% of them. On observation, only five families could show no bed net, but 80% showed 1-3 ITNs. Consistent utilization in all seasons was noted in 189 (53.1%), that was higher in palm oil plantation than rubber plantation workers (p = 0.0001) due to the nature of the work at night. Perceived malaria risk was also significantly higher ITNs consistent users than non-users (p = 0.0004) and better willingness to buy an ITN by themselves (p = 0.0005). They said that effectiveness of the ITNs was reduced after 6 months and 2-3 times washing. They wished to receive more durable smooth nets with small holes in lace. Misuses of the ITNs such as use the nets for animals and fishing, were also noted. CONCLUSION: There should be efforts to improve effective utilization of ITNs by continuous mass free distribution, durability monitoring, surveillance of insecticide resistance of the vector and behaviour change interventions in migrant plantation workers.

Field evaluation of HRP2 and pan pLDH-based immunochromatographic assay in therapeutic monitoring of uncomplicated falciparum malaria in Myanmar.

BACKGROUND: Malaria rapid diagnostic tests (RDT) are used for diagnostic purpose in malaria-endemic areas where reliable microscopy is not available. Persistence of the antigenaemia causes over-diagnosis and may limit the usefulness of the RDT in monitoring treatment. In this study, the usefulness of histidine-rich protein-2 (HRP2) and pan-specific or species-specific Plasmodium lactate dehydrogenase (pLDH) in treatment monitoring of uncomplicated falciparum malaria was carried out in an endemic setting in Myanmar. METHODS: A prospective longitudinal, single-arm, cohort study was done by microscopy to confirm Plasmodium falciparum mono-infected cases. After direct treatment with an artemether-lumefantrine combination, patients were followed up on day 3, 7, 14, 21, 28 and any other day of recurrent fever. Blood film examination and RDT were carried out on day 0 and all follow-up days. RESULTS: Out of 77 recruited falciparum cases, 63 became adequate clinical and parasitological response (ACPR) cases, and 60.3% of them were still positive for HRP2 up to day 28. Eleven out of 12 treatment failure cases (91.6%) were detected by pan pLDH. The mean duration required to become negative of HRP2 was 20 days (SD ± 6.03) and that of pan pLDH was six days with or without gametocytes and 3.7 days without gametocytes. CONCLUSION: Although treatment monitoring cannot be performed by HRP2, it can be assessed by pan pLDH-based assay after day 3 if a gametocidal drug has been administered and after day 7 if the presence of gametocytes was not excluded. The pan pLDH-based assay was a suitable test to monitor the treatment response of uncomplicated falciparum malaria patients.

Infectious burden and carotid plaque thickness: the northern Manhattan study.

BACKGROUND AND PURPOSE: The overall burden of prior infections may contribute to atherosclerosis and stroke risk. We hypothesized that serological evidence of common infections would be associated with carotid plaque thickness in a multiethnic cohort. METHODS: Antibody titers to 5 common infectious microorganisms (ie, Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpesvirus 1 and 2) were measured among stroke-free community participants and a weighted index of infectious burden was calculated based on Cox models previously derived for the association of each infection with stroke risk. High-resolution carotid duplex Doppler studies were used to assess maximum carotid plaque thickness. Weighted least squares regression was used to measure the association between infectious burden and maximum carotid plaque thickness after adjusting for other risk factors. RESULTS: Serological results for all 5 infectious organisms were available in 861 participants with maximum carotid plaque thickness measurements available (mean age, 67.2+/-9.6 years). Each individual infection was associated with stroke risk after adjusting for other risk factors. The infectious burden index (n=861) had a mean of 1.00+/-0.35 SD and a median of 1.08. Plaque was present in 52% of participants (mean, 0.90+/-1.04 mm). Infectious burden was associated with maximum carotid plaque thickness (adjusted increase in maximum carotid plaque thickness 0.09 mm; 95% CI, 0.03 to 0.15 mm per SD increase of infectious burden). CONCLUSIONS: A quantitative weighted index of infectious burden, derived from the magnitude of association of individual infections with stroke, was associated with carotid plaque thickness in this multiethnic cohort. These results lend support to the notion that past or chronic exposure to common infections, perhaps by exacerbating inflammation, contributes to atherosclerosis. Future studies are needed to confirm this hypothesis and to define optimal measures of infectious burden as a vascular risk factor.

Chemical composition and biological effects of kratom (Mitragyna speciosa): In vitro studies with implications for efficacy and drug interactions.

The safety and efficacy of kratom (Mitragyna speciosa) for treatment of pain is highly controversial. Kratom produces more than 40 structurally related alkaloids, but most studies have focused on just two of these, mitragynine and 7-hydroxymitragynine. Here, we profiled 53 commercial kratom products using untargeted LC-MS metabolomics, revealing two distinct chemotypes that contain different levels of the alkaloid speciofoline. Both chemotypes were confirmed with DNA barcoding to be M. speciosa. To evaluate the biological relevance of variable speciofoline levels in kratom, we compared the opioid receptor binding activity of speciofoline, mitragynine, and 7-hydroxymitragynine. Mitragynine and 7-hydroxymitragynine function as partial agonists of the human µ-opioid receptor, while speciofoline does not exhibit measurable binding affinity at the µ-, δ- or ƙ-opioid receptors. Importantly, mitragynine and 7-hydroxymitragynine demonstrate functional selectivity for G-protein signaling, with no measurable recruitment of ß-arrestin. Overall, the study demonstrates the unique binding and functional profiles of the kratom alkaloids, suggesting potential utility for managing pain, but further studies are needed to follow up on these in vitro findings. All three kratom alkaloids tested inhibited select cytochrome P450 enzymes, suggesting a potential risk for adverse interactions when kratom is co-consumed with drugs metabolized by these enzymes.

Strategy and Efficacy of Generic and Pan-genotypic Sofosbuvir/Velpatasvir in Chronic Hepatitis C Virus: A Myanmar Experience.

BACKGROUND: In resource-constrained areas, generic direct-acting antivirals (DAAs) have considerably reduced the cost of hepatitis C virus (HCV) therapy while there remain significant costs related to the baseline and follow-up virologic assays. AIM: The aim was to assess the efficacy and safety of HCV therapy in Myanmar with pan-genotypic generic DAA sofosbuvir/velpatasvir (SOF/VEL) and with and without the baseline genotype testing, while the duration of treatment and use of ribavirin (RBV) was dictated by cirrhosis and prior treatment failure. METHODS: Between September 2016 and June 2017, data from the 359 participants who completed treatment with SOF/VEL (± RBV) for 12-24 weeks were analyzed. Two hundred one patients did not have the baseline HCV genotype tested. RESULTS: Regimens included SOF/VEL for 12 weeks (n = 43), SOF/VEL/RBV for 12 weeks (n = 275), or SOF/VEL/RBV for 24 weeks (n = 41). The mean age was 52 years, 44% were men (n = 159), 41 (11.4%) had a history of previous DAA therapy, 7 (1.9%) had a history of hepatocellular carcinoma, and 55 (15.3%) had cirrhosis. Overall, the sustained viral response (SVR)12 rate was 98.6% (354/359) and with a good adverse event profile. SVR rates were similar to those with and without baseline genotype testing and also across all genotypes in those who had genotype tested. CONCLUSIONS: In Myanmar, generic and pan-genotypic SOF/VEL ± RBV is a highly effective and safe treatment for HCV, regardless of the HCV genotype, and therefore, the requirement for the baseline genotype can be eliminated. Future strategies should include elimination of treatment and end of treatment HCV RNA testing to enhance treatment uptake and further reduce cost.

Advances in space radiation physics and transport at NASA.

The space radiation environment is a complex mixture of particle types and energies originating from sources inside and outside of the galaxy. These environments may be modified by the heliospheric and geomagnetic conditions as well as planetary bodies and vehicle or habitat mass shielding. In low Earth orbit (LEO), the geomagnetic field deflects a portion of the galactic cosmic rays (GCR) and all but the most intense solar particle events (SPE). There are also dynamic belts of trapped electrons and protons with low to medium energy and intense particle count rates. In deep space, the GCR exposure is more severe than in LEO and varies inversely with solar activity. Unpredictable solar storms also present an acute risk to astronauts if adequate shielding is not provided. Near planetary surfaces such as the Earth, moon or Mars, secondary particles are produced when the ambient deep space radiation environment interacts with these surfaces and/or atmospheres. These secondary particles further complicate the local radiation environment and modify the associated health risks. Characterizing the radiation fields in this vast array of scenarios and environments is a challenging task and is currently accomplished with a combination of computational models and dosimetry. The computational tools include models for the ambient space radiation environment, mass shielding geometry, and atomic and nuclear interaction parameters. These models are then coupled to a radiation transport code to describe the radiation field at the location of interest within a vehicle or habitat. Many new advances in these models have been made in the last decade, and the present review article focuses on the progress and contributions made by workers and collaborators at NASA Langley Research Center in the same time frame. Although great progress has been made, and models continue to improve, significant gaps remain and are discussed in the context of planned future missions. Of particular interest is the juxtaposition of various review committee findings regarding the accuracy and gaps of combined space radiation environment, physics, and transport models with the progress achieved over the past decade. While current models are now fully capable of characterizing radiation environments in the broad range of forecasted mission scenarios, it should be remembered that uncertainties still remain and need to be addressed.

Hyperglycemia and cystic fibrosis alter respiratory fluid glucose concentrations estimated by breath condensate analysis.

In animals, glucose concentrations are 3-20 times lower in lung lining fluid than in plasma. In humans, glucose concentrations are normally low (<1 mmol/l) in nasal and bronchial fluid, but they are elevated by inflammation or hyperglycemia. Furthermore, elevated bronchial glucose is associated with increased respiratory infection in intensive care patients. Our aims were to estimate normal glucose concentrations in fluid from distal human lung sampled noninvasively and to determine effects of hyperglycemia and lung disease on lung glucose concentrations. Respiratory fluid was sampled as exhaled breath condensate, and glucose was measured by chromatography with pulsed amperometric detection. Dilution corrections, based on conductivity, were applied to estimate respiratory fluid glucose concentrations (breath glucose). We found that breath glucose in healthy volunteers was 0.40 mmol/l (SD 0.24), reproducible, and unaffected by changes in salivary glucose. Breath-to-blood glucose ratio (BBGR) was 0.08 (SD 0.05). Breath glucose increased during experimental hyperglycemia (P < 0.05) and was elevated in diabetic patients without lung disease [1.20 mmol/l (SD 0.69)] in proportion to hyperglycemia [BBGR 0.09 (SD 0.06)]. Breath glucose was elevated more than expected for blood glucose in cystic fibrosis patients [breath 2.04 mmol/l (SD 1.14), BBGR 0.29 (SD 0.17)] and in cystic fibrosis-related diabetes [breath 4.00 mmol/l (SD 2.07), BBGR 0.54 (0.28); P < 0.0001]. These data indicate that 1) this method makes a biologically plausible estimate of respiratory fluid glucose concentration, 2) respiratory fluid glucose concentrations are elevated by hyperglycemia and lung disease, and 3) effects of hyperglycemia and lung disease can be distinguished using the BBGR. This method will support future in vivo investigation of the cause and effect of elevated respiratory fluid glucose in human lung disease.

Airway glucose concentrations and effect on growth of respiratory pathogens in cystic fibrosis.

BACKGROUND: Pulmonary decline accelerates in cystic fibrosis-related diabetes (CFRD) proportional to severity of glucose intolerance, but mechanisms are unclear. In people without CF, airway glucose (AG) concentrations are elevated when blood glucose (BG)> or =8 mmol L(-1) (airway threshold), and are associated with acquisition of respiratory infection. METHODS: To determine the relationship between BG and AG, 40 CF patients underwent paired BG and AG (nasal) measurements. Daily time with BG>airway threshold was compared in 10 CFRD, 10 CF patients with normal glucose tolerance (CF-NGT) and 10 healthy volunteers by continuous BG monitoring. The effect of glucose at airway concentrations on bacterial growth was determined in vitro by optical densitometry. RESULTS: AG was present more frequently (85%-vs.-19%, p<0.0001) and at higher concentrations (0.5-3 mmol L(-1)-vs.-0.5-1 mmol L(-1), p<0.0001) when BG was > or =8 mmol L(-1)-vs.-<8 mmol L(-1). Daily time with BG> or =8 mmol L(-1) was CFRD (49+/-25%), CF-NGT (6+/-5%), healthy volunteers (1+/-3%), p<0.0001. Staphylococcus aureus growth increased at > or =0.5 mmol L(-1) (p=0.006) and Pseudomonas aeruginosa growth above 1-4 mmol L(-1) glucose (p=0.039). CONCLUSIONS: BG> or =8 mmol L(-1) predicted elevated AG concentrations in CF, at least in nasal secretions. CFRD patients spent approximately 50% day with BG>airway threshold, implying persistently elevated AG concentrations. Further studies are required to determine whether elevated airway glucose concentrations contribute to accelerated pulmonary decline in CFRD.

Pregnancy in cystic fibrosis lung transplant recipients: case series and review.

A single centre experience of four pregnancies in four cystic fibrosis (CF) lung transplant recipients is reported. Six more cases were identified from the literature review and combined data analysis on 10 pregnancies in 10 CF lung transplant recipients was performed to determine maternal, foetal and graft outcome. There were nine live births and one therapeutic abortion. Three required caesarean sections. Five babies were premature but all nine children were well at follow-up. Five recipients who had a long, stable interval (i.e. at least three years) between transplant and pregnancy had a favourable outcome. Three recipients developed rejection during the pregnancy and one already had obliterative bronchiolitis before pregnancy. All showed progressive decline in lung function and subsequently died of chronic rejection within 38 months of delivery. Pregnancy in CF lung transplant recipients is feasible but should still be regarded as a risky undertaking.

Temocillin in the treatment of Burkholderia cepacia infection in cystic fibrosis.

BACKGROUND: Infections due to Burkholderia cepacia complex (Bcc) strains increase morbidity and mortality in cystic fibrosis (CF). Some transplant centres reject Bcc infected patients. We reviewed the results in patients treated with i.v temocillin. METHODS: Twenty-three patients who received 38 courses of temocillin (1988-1998) were identified from the CF database at Royal Brompton Hospital. In three patients' data were inadequate; therefore analysis was done in 20. Outcome was measured as improvement, deterioration or no change (compared to admission) in the following categories: clinical (temperature, dyspnoea, sputum volume, chest pain), physiological (FEV1, FVC, oxygen saturation) and inflammatory markers (WBC, ESR, CRP). Patients who improved in two categories were classified as having improved. Antibiotic sensitivities and outcome were recorded. RESULTS: In 18 of 32 courses (56.25%) improvement occurred. The organism (Bcc) in eight patients' sputum became resistant (three died). The antibiotics was changed in five patients with Bcc strains sensitive to temocillin because of no improvement and one patient due to allergy (rash). The average time to the next i.v antibiotic was 41 days. Eight patients died (in three the Bcc strain was resistant to temocillin). Fourteen patients with Bcc were transplanted and eight patients survived. Another patient who developed Bcc infection post-operatively, failing to respond to temocillin. CONCLUSIONS: These results suggest the potential benefit of i.v temocillin in CF patients with Bcc for exacerbations and at the time of transplantation.

Relationship between glycosylated haemoglobin and mean plasma glucose concentration in cystic fibrosis.

BACKGROUND: HbA(1c) is recommended for monitoring glycaemic control in people with cystic fibrosis-related diabetes (CFRD). However the relationship between HbA(1c) and mean plasma glucose concentration (MPG) has not been established in CFRD, as in other forms of diabetes mellitus. METHODS: 20 people (13 male, 29.7+/-8.8 years, 10 CFRD) with cystic fibrosis (CF) underwent HbA(1c) measurement and 48 h continuous glucose monitoring for estimation of MPG. The relationship between HbA(1c) and MPG was established and compared to the reported relationship for type 1 diabetes. RESULTS: HbA(1c) was strongly correlated with MPG (R(2)=0.888, p<0.0001) in CF. The relationship of MPG to HbA(1c) was described by the equation MPG=(1.47xHbA(1c))-1.15, giving a 1.47 mmol L(-1) change in MPG per 1% change in HbA(1c). This equation predicts that MPG in people with CF and HbA(1c) <7.0% will be similar to MPG in people with type 1 diabetes who achieve the same HbA(1c) target. CONCLUSIONS: These results imply that HbA(1c)<7.0% will predict good blood glucose control in CF as in type 1 diabetes. However, although HbA(1c) predicts complications in type 1 diabetes, further studies are required to establish the relationship between HbA(1c) and diabetic complications in people with CFRD.

HbA1c as a screening tool for cystic fibrosis related diabetes.

AIMS: Early diagnosis of cystic fibrosis (CF) related diabetes (CFRD) is important to improve outcomes. International guidelines recommend an oral glucose tolerance test (OGTT) for all CF patients aged ≥10 years - this approach is controversial. The aim of this study was to develop an effective screening tool and reduce the need for a universal OGTT. METHODS: Adult CF patients (without CFRD) attending an annual review assessment were recruited prospectively (March 2009-July 2012) into two sequential studies - a primary investigative study followed by validation study. All patients underwent an OGTT and were simultaneously screened by predetermined biochemical/clinical criteria to identify their risk of CFRD. A sensitivity/specificity analysis was performed using the World Health Organisation diabetes criteria as gold standard; modifications were made to improve the screening tool's accuracy and determine the optimal screening thresholds. This was tested in the validation study. RESULTS: 429 patients (primary, n=94; validation, n=335: mean age=31.7 ± 10.4(SD), 43% female, 77% on pancreatic supplements). Primary study: in predicting a positive OGTT, the test sensitivity was 66.7% and specificity 60%. HbA1c was carried over to the validation study as it was the most discriminative (optimal threshold ≥5.8% (40 mmol/mol); receiver operating curve, ROC, score 0.60). Validation study: the number of patients with a normal, impaired and diabetic OGTT was 268(80%), 51(15.2%) and 16(4.8%), respectively. HbA1c provided a test sensitivity, specificity and ROC score of 93.8%, 53.0% and 0.73, respectively. CONCLUSIONS: The use of HbA1c ≥ 5.8%(40 mmol/mol) is an effective tool for CFRD screening and reduced the need for an OGTT by 50.7%.