Search

Stan D Atkin,1 Shadaan Abid,1 Michael Foster,1 Moumita Bose,1 Ashley Keller,1 Rita Hollaway,2 Helio S Sader,3 David E Greenberg,1,4 James D Finklea,1 Mariana Castanheira,3 Raksha Jain1,4 1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA; 2Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA; 3JMI Laboratories, North Liberty, IA, USA; 4Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA Purpose: Ceftazidime–avibactam is a novel antimicrobial combining a third-generation cephalosporin with a non-β-lactam β-lactamase inhibitor that was recently approved to treat Gram-negative hospital- and ventilator-acquired pneumonia. The use of ceftazidime–avibactam to treat Pseudomonas aeruginosa respiratory infections in patients with cystic fibrosis (CF) has not been evaluated. In this study, we assessed the ceftazidime–avibactam susceptibility of multidrug-resistant (MDR) P. aeruginosa sputum isolates from adults with CF.Methods: Sputum was collected from individuals with CF, aged ≥18 years, known to be colonized with MDR P. aeruginosa, and tested for susceptibility to 11 different antipseudomonal antimicrobial agents. Isolates were included in the analysis if they were resistant to both ceftazidime and at least one agent in ≥3 different antimicrobial categories routinely used to treat P. aeruginosa. Subject demographics and clinical characteristics were collected. Ceftazidime–avibactam-resistant isolates were screened for the presence of β-lactam-resistant mechanisms.Results: Thirty-two P. aeruginosa isolates were analyzed, of which 23 isolates were sensitive to ceftazidime–avibactam (71.9%). Ten of the isolates were mucoid and 22 isolates were nonmucoid, both demonstrating >70% susceptibility to ceftazidime–avibactam. The most notable difference in the subjects with resistant strains was an older age and lower body mass index (BMI). Ceftazidime–avibactam-resistant strains showed elevated AmpC expression in >60% of the strains and loss of OprD detection in >70% of the strains.Conclusion: Ceftazidime–avibactam demonstrated a significant in vitro activity against highly resistant P. aeruginosa sputum isolates from individuals with CF. Further evaluation of the cause of resistance and clinical impact of ceftazidime–avibactam in CF patients with MDR P. aeruginosa is warranted. Keywords: ceftazidime, avibactam, cystic fibrosis, Pseudomonas aeruginosa, multidrug-resistant

Polycystic ovary syndrome (PCOS) has been associated with increased cardiovascular risk (CVR) markers, but population studies have not clarified whether there is an increase in cardiovascular morbidity and mortality. Four different PCOS phenotypes resulted from the Rotterdam criteria that may differ in their CVR potential, thus introducing further complexity. This has led to studies using surrogate CVR markers including biomarkers in blood and imaging such as flow-mediated vasodilatation. In PCOS, both peripheral and central insulin resistance (IR) have been shown. Weight loss has been shown to improve IR and visceral fat, while insulin sensitizer therapies with metformin or thiazolidinediones improve IR and endothelial dysfunction. IR is also found in non-alcoholic fatty liver disease that in turn is very common in PCOS; studies have suggested that IR may be improved by treatment with metformin and omega-3 fish oils. PCOS patients have a more dyslipidemic phenotype that is worse in 'classical PCOS' associated with a higher CVR. Studies with atorvastatin and simvastatin have reported a decrease in the lipid parameters and an improvement in CVR indices including IR, but it is unclear whether this is due to their lipid-lowering action or a pleiotropic effect of the statin. In this expert opinion review, the relevant literature published during the last 2 years was considered. It focuses on some recent important data that has emerged while also exposing the gaps that remain in our knowledge that need to be addressed. [ABSTRACT FROM AUTHOR]

Pollutants emitted to the atmosphere in urban areas have indirect effects through deposition onto the ground, which, over time, could negatively affect the quality of soil, plants, water and groundwater. In this baseline study, evaluation of topsoil contamination in an urban area of France has been carried out to correlate concentrations observed in the soil with the local air emission sources. The analytical program is an extensive study carried out over a 200 km² area and the results confirm pronounced anthropogenic contributions to the geochemical background for some metals (Cu, Zn, Pb, and Hg) over the entire area under assessment. In addition, PAH concentrations in topsoil have been noted to be significantly higher around heavily trafficked areas, confirming the contribution of road traffic. The contribution of domestic combustion and industrial sources has also been highlighted with elevated concentrations of dioxins and furans; with some sites in exceedance of current international soil guidelines. The results confirm the significant contribution of anthropogenic deposition from former and present-day industrial and road traffic sources to soft composition in an urban area. The high concentrations of trace metals and other hazardous pollutants in many urban soils in inner-city areas give rise to concerns about potential human health effects through ingestion of soil and vegetables grown locally. [ABSTRACT FROM AUTHOR]

BACKGROUND: The dual effects of insulin and androgen on the ovary act to promote early folliculogenesis. In the context of polycystic ovarian syndrome (PCOS), the presence of hyperinsulinaemia, resulting from increased insulin resistance (IR), and hyperandrogenaemia lead to the appearance of multiple antral follicles and frequently a multi-folliclular response to gonadotrophin stimulation for assisted reproductive treatments (ARTs). The effect of IR and androgen status in women without PCOS on the follicular outcome of controlled ovarian hyperstimulation (COH) is not known. [ABSTRACT FROM PUBLISHER]

Background: There is an assumption that the mean and biological variation of insulin resistance (IR) is less in polycystic ovary syndrome (PCOS), and intuitively higher in type 2 diabetes (T2DM). To test this hypothesis we compared the mean and biological variation in IR in PCOS to that of T2DM and to age- and weight-matched controls. Methods: Twelve PCOS, 11 matched healthy women; 12 postmenopausal diet-controlled T2DM and 11 matched healthy postmenopausal women were recruited. Blood samples were collected at 4-d intervals on 10 consecutive occasions. The biological variability of IR was derived on duplicate samples. Results: Mean and biological variability of HOMA-IR for PCOS did not differ from T2DM. Both measures were higher than the matched controls. There was no difference in insulin or IR measures between the body mass index matched pre- and postmenopausal women. Percentage β cell function were 208.8%, 62.3%, 106.5% and 111.9%, respectively, in PCOS, postmenopausal women with T2DM, healthy premenopausal and healthy postmenopausal women. Conclusions: The progression from PCOS to the development of T2DM is unlikely to be due to a further increase in IR (or variability), but rather the progressive failure of pancreatic beta cells with a decrease in insulin production. The clinical trial registration number for this study is ISRCTN65353256. [ABSTRACT FROM AUTHOR]

Objective The introduction of ready-to-use lanreotide Autogel® has presented the possibility of patients receiving their acromegaly treatment at home. The objective of this study was to assess the ability of patients (or their partners) to administer repeat, unsupervised, injections of lanreotide Autogel without compromising efficacy or safety. Design Multicentre (10 UK regional endocrine centres), open-label, nonrandomised, controlled study. Patients elected either to receive/administer unsupervised home injections after injection technique training (Test group) or continued to receive injections from a healthcare professional (Control group). Patients received monthly injections of lanreotide Autogel® at their established dose. Effects were monitored for up to 40 weeks. Patients Thirty patients (15 per treatment group) with acromegaly treated with a stable dose of lanreotide Autogel® (60, 90 or 120 mg) for ≥ 4 months before screening. Measurements The main outcome measure was the proportion of patients/partners who successfully administered injections throughout the study. Results All Test group patients/partners qualified to administer injections. Fourteen of 15 patients fulfilled all criteria for successful administration of unsupervised injections (95% confidence interval, 70%–99%). Fourteen of 15 Test and 14/15 Control patients maintained growth hormone and IGF-1 control. Local injection tolerability was good for both treatment groups, and safety profiles were similar. All Test group patients continued with unsupervised injections after the study. Conclusions Patients with acromegaly or their partners were able to administer lanreotide Autogel® injections with no detrimental effect on efficacy and safety; therefore, unsupervised home injections are a viable alternative to healthcare professional injections for suitably motivated patients. [ABSTRACT FROM AUTHOR]

It is not known whether mean blood glucose (MBG) predicts the risk of macrovascular complications in diabetes any differently from HbA1c. In this study we therefore analysed data from the Diabetes Control and Complications Trial (DCCT) to assess the relationship between MBG, HbA1c and glucose variability with regard to the risk of cardiovascular disease in patients with type 1 diabetes. Pre- and postprandial seven-point glucose profiles were collected quarterly during the DCCT in 1441 individuals. The relationship between time to first cardiovascular event and MBG, HbA1c and daily SD of blood glucose was assessed by Cox regression after adjusting for the known risk factors of macrovascular disease and the treatment groups of the patients. Cox regression showed MBG to be predictive of a cardiovascular event ( p = 0.019), but not HbA1c ( p = 0.858). A rise of 1 mmol/l in MBG was associated with an 11% rise in cardiovascular risk. MBG remained highly predictive ( p = 0.015) even after adjustment for HbA1c values and glucose variability. This study has shown that during the DCCT MBG was a better predictor of the macrovascular complications of type 1 diabetes than HbA1c. It indicates that the cardiovascular risk associated with hyperglycaemia appeared within the time period of the study and that blood glucose rather than HbA1c may be the preferred means of assessing this risk. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the accuracy of fingerstick glucose measurements in severely hypotensive patients.Design: Prospective, nonrandomized comparison study.Setting: Emergency department in a university hospital.Patients: Twenty-five severely hypotensive patients (systolic blood pressure less than or equal to 80 mm Hg) and 39 normotensive patients.Measurements: Simultaneous fingerstick reagent strip glucose, venous reagent strip glucose, and laboratory glucose values were compared. Data were analyzed using error-grid analysis.Results: In hypotensive patients, the mean fingerstick glucose values were significantly lower than the values obtained either by venous reagent strip or laboratory glucose measurements. Fingerstick glucose values in the hypotensive group were 67.5% of laboratory glucose values, and were significantly lower than the values obtained in the normotensive group (91.8%, P less than 0.001). Only 36% of the hypotensive patients had fingerstick glucose values within the acceptable range of 20% of the laboratory glucose value. Thirty-two percent of hypotensive patients were incorrectly diagnosed as hypoglycemic (glucose less than 3.89 mmol/L [70 mg/dL]); 2 of these patients were actually hyperglycemic (glucose greater than 11.10 mmol/L [200 mg/dL]). Venous reagent strip measurements accurately reflected laboratory glucose values in both hypotensive and normotensive patients.Conclusions: Fingerstick glucose testing does not accurately represent venous glucose levels in severely hypotensive patients. If fingerstick glucose testing is relied on for these patients, errors in clinical management may be made. Venous reagent strip glucose testing correlates well with laboratory glucose measurements and should be the preferred method for rapid assessment of glucose level in critically ill patients with severe hypotension. [ABSTRACT FROM AUTHOR]

The pleiotropic effect of statins may be mediated in part through raising 25 hydroxy vitamin D ( 25OHD) concentrations. It has also been shown that an increase in oxidative stress and inflammatory markers are a feature of the patients with type 2 diabetes ( T2DM). A cross-over study of 26 patients with T2DM taking either simvastatin 40 mg or atorvastatin 10 mg was undertaken. After 3 months on one statin, lipids, C-reactive protein ( hsCRP), 25OHD and malondialdehyde ( MDA) were measured repeatedly. The same procedure was then followed taking the other statin. Despite similar lipid-lowering, the mean 25OHD was higher on atorvastatin compared with simvastatin and the mean MDA and hsCRP levels lower, irrespective of which statin the patients were taking before crossover. The changes in 25OHD predicted changes in CRP and MDA levels. Thus, compared with simvastatin, atorvastatin shows apparently beneficial pleiotropic effects with respect to 25OHD concentrations as well as markers of oxidative stress and inflammation in patients with T2DM. [ABSTRACT FROM AUTHOR]

It is unknown whether glycaemic variability adds to the risk of microvascular complications of diabetes over and above the mean glucose value for a patient. We examined the effect of purposefully induced short-term glycaemic variability on oxidative stress markers. Eleven healthy subjects underwent three sequential glycaemic states; sustained hyperglycaemia, sustained euglycaemia and variable glycaemia, using glycaemic clamps for 3 h. Twenty-four hours urinary 8-isoprostane- PGF2α was measured before and after each glycaemic state to assess oxidative stress. The median and interquartile range of the urinary 8-iso- PGF2α in ng/24 h were (1373, 513), (996, 298) and (1227, 472) for the euglycaemic, hyperglycaemic and variable states, respectively. There was no significant difference in urinary isoprostanes between the three different states; mean ranks 20.9, 11.9 and 18.2 for the euglycaemic state, hyperglycaemic state and glycaemic variability state, respectively, p = 0.083. In conclusion, we did not see a significant increase in the urinary isoprostanes when glycaemic variability was induced under controlled conditions in healthy individuals. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 70 year old man complaining of recurrent lightheadedness for two or three weeks when getting up at night to urinate. During physical examination, the patient's blood pressure was 130/80 millimeters mercury (mm Hg) when supine and 105/69 mm Hg when standing, his heart rate was 88 beats per minute when supine. Also discussed is the best use of important diagnostic investigation of the clinical presentations of postural hypertension. INSET: Risk factors for postural hypotension.

Objective: To consolidate the key features of carcinoma showing thymus-like element, including its management. Method: We present our experience of the difficult diagnosis and management of this rare tumour. We also present the results of an extensive literature search, documenting those aspects of the clinical picture, natural history and management of carcinoma showing thymus-like element which are relevant to head and neck surgeons. Result: Intrathyroidal, epithelial carcinoma showing thymus-like element is a rare, malignant tumour of the thyroid gland, with histopathological features similar to squamous cell carcinoma but a more favourable prognosis. It is usually treated surgically using a combination of total thyroidectomy and selective neck dissection, with radiotherapy and chemotherapy in selected cases. Conclusion: Carcinoma showing thymus-like element of the thyroid gland is a rare condition. Head and neck surgeons with a thyroid interest should be aware of this tumour, because of its close histological resemblance to other, commoner malignancies of the thyroid gland. [ABSTRACT FROM AUTHOR]

The article discusses the clinical case of a 25-year-old woman who complained of amenorrhoea for the 10 months since she had discontinued taking oral contraceptives. The patient claimed that her menstrual cycle was regular before taking oral contraceptives. Amenorrhoea can be caused by hypothalamic amenorrhoea, polycystic ovarian syndrome, hyperprolactinaemia or premature ovarian failure. Information on the patient's laboratory findings is offered, along with the treatment administered to her.

Myint M Aye,1 Stephen L Atkin21Hull Royal Infirmary, Michael White Diabetes Centre, Hull, UK; 2Weill Cornell Medical College Qatar, Qatar Foundation, Doha, QatarAbstract: Diabetes is a lifelong condition requiring ongoing medical care and patient self-management. Exogenous insulin therapy is essential in type 1 diabetes and becomes a necessity in patients with longstanding type 2 diabetes who fail to achieve optimal control with lifestyle modification, oral agents, and glucagon-like peptide 1-based therapy. One of the risks that hinders insulin use is hypoglycemia. Optimal insulin therapy should therefore minimize the risk of hypoglycemia while improving glycemic control. Insulin degludec (IDeg) is a novel basal insulin that, following subcutaneous injection, assembles into a depot of soluble multihexamer chains. These subsequently release IDeg monomers that are absorbed at a slow and steady rate into the circulation, with the terminal half-life of IDeg being ~25 hours. Thus, it requires only once-daily dosing unlike other basal insulin preparations that often require twice-daily dosing. Despite its long half-life, once-daily IDeg does not cause accumulation of insulin in the circulation after reaching steady state. IDeg once a day will produce a steady-state profile with a lower peak:trough ratio than other basal insulins. In clinical trials, this profile translates into a lower frequency of nocturnal hypoglycemia compared with insulin glargine, as well as an ability to allow some flexibility in dose timing without compromising efficacy and safety. Indeed, a study that tested the extremes of dosing intervals of 8 and 40 hours showed no detriment in either glycemic control or hypoglycemic frequency versus insulin glargine given at the same time each day. While extreme flexibility in dose timing is not recommended, these findings are reassuring. This may be particularly beneficial to elderly patients, patients with learning difficulties, or others who have to rely on health-care professionals for their daily insulin injections. Further studies are required to confirm whether this might benefit adherence to treatment, reduce long-term hypoglycemia or reduce diabetes-related complications.Keywords: basal insulin, diabetes, hypoglycemia, safety

Keypoints • Radioiodine and thionamide treatment are the most frequently used treatment modalities for thyrotoxicosis in Europe and North America with surgery being reserved for selected cases. • In our clinic patients were offered all three modalities via simultaneous interview with an endocrinologist and a surgeon, with international risk benefit data for radioiodine and thionamide therapy, and local risk benefit data for total thyroidectomy provided. • When given the choice, at least 15% of patients opted for total thyroidectomy over the other modalities. • In our series of 100 consecutive surgical patients there was a 4% malignancy rate. • Total thyroidectomy should be offered equally, with radioiodine and thionamide treatment, as a first line treatment modality in the management of thyrotoxicosis. [ABSTRACT FROM AUTHOR]

A case of a successful induction of lactation in a commissioning mother of a surrogate pregnancy is reported. Induction of lactation was achieved with oral metoclopramide which was well tolerated. Alternative methods to induce lactation are reviewed. The advantages of breast-feeding and the relative ease with which lactation can be induced after a surrogate pregnancy would suggest that this could be offered to all commissioning mothers. [ABSTRACT FROM AUTHOR]

The results of a combined clinical and laboratory study in 55 patients throughout the leprosy spectrum are reported. Thirty one of these patients suffered from an inflammatory peripheral polyarthritis which has not been previously described and which was unassociated with the characteristics of erythema nodosum leprosum reactions or with Charcot's joints. alpha 2 Macroglobulin was raised significantly only in those patients with leprosy and arthritis. [ABSTRACT FROM PUBLISHER]