A gestation- and postnatal age-based reference chart for assessing renal function in extremely premature infants

OBJECTIVE: A single value of plasma creatinine cannot be used to define renal dysfunction in premature babies, as levels are influenced by gestation and postnatal age. The aim of this study was to create reference ranges for plasma creatinine in cohort of extremely premature infants. STUDY DESIGN: Retrospective analysis of plasma creatinine levels in the first 8 weeks of life from 161 consecutively admitted premature infants 28 weeks gestation. RESULT: Babies were divided into three groups according to gestation. Peak (10th, 90th percentiles) creatinine levels were 132 (106,162) in 22 to 24 weeks gestational infants, 127 (89,151) in those from 25 to 26 weeks and 110 (87,134) in those from 27 to 28 weeks (P<0.001). Creatinine at birth was similar across the groups with levels increasing during the first few days. It decreases thereafter before reaching stable levels by 5 weeks of age. CONCLUSION: Gestation- and age-based reference charts should be used for interpretation of creatinine values in extremely premature babies.     

Prevalence and risk factors for diabetic neuropathy and painful diabetic neuropathy in primary and secondary healthcare in Qatar

Aims/IntroductionThis study determined the prevalence and risk factors for diabetic peripheral neuropathy (DPN) and painful DPN (pDPN) in patients with type 2 diabetes in primary healthcare (PHC) and secondary healthcare (SHC) in Qatar.Materials and MethodsThis was a cross‐sectional multicenter study. Adults with type 2 diabetes were randomly enrolled from four PHC centers and two diabetes centers in SHC in Qatar. Participants underwent assessment of clinical and metabolic parameters, DPN and pDPN.ResultsA total of 1,386 individuals with type 2 diabetes (297 from PHC and 1,089 from SHC) were recruited. The prevalence of DPN (14.8% vs 23.9%, P = 0.001) and pDPN (18.1% vs 37.5%, P < 0.0001) was significantly lower in PHC compared with SHC, whereas those with DPN at high risk for diabetic foot ulceration (31.8% vs 40.0%, P = 0.3) was comparable. The prevalence of undiagnosed DPN (79.5% vs 82.3%, P = 0.66) was comparably high, but undiagnosed pDPN (24.1% vs 71.5%, P < 0.0001) was lower in PHC compared with SHC. The odds of DPN and pDPN increased with age and diabetes duration, and DPN increased with poor glycemic control, hyperlipidemia and hypertension, whereas pDPN increased with obesity and reduced physical activity.ConclusionsThe prevalence of DPN and pDPN in type 2 diabetes is lower in PHC compared with SHC, and is attributed to overall better control of risk factors and referral bias due to patients with poorly managed complications being referred to SHC. However, approximately 80% of patients had not been previously diagnosed with DPN in PHC and SHC. Furthermore, we identified a number of modifiable risk factors for PDN and pDPN.     

Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): An American Society for Radiation Oncology evidence-based guideline

PurposeTo systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases.Methods and MaterialsKey clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management.ResultsThe choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation).Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3).Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3).Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3).It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis-specific graded prognostic assessment may be helpful.ConclusionsRadiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone).     

Comparison of vildagliptin and acarbose monotherapy in patients with Type 2 diabetes: a 24-week,double-blind,randomized trial

Aims To compare the efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor, vildagliptin, with the alpha glucosidase inhibitor, acarbose, in drug-naive patients with Type 2 diabetes. Methods This multi-centre, randomized, double-blind, parallel-arm study compared the efficacy and tolerability of vildagliptin (100 mg daily, given as 50 mg twice daily, n = 441) and acarbose (up to 300 mg daily, given as three equally divided doses, n = 220) during 24-week treatment in drug-naive patients with Type 2 diabetes. Results Monotherapy with vildagliptin or acarbose decreased glycated haemoglobin (HbA_1c) (baseline ≈ 8.6%) to a similar extent during 24-week treatment. The adjusted mean change from baseline to end-point (AMΔ) in HbA_1c was −1.4 ± 0.1% and −1.3 ± 0.1% in patients receiving vildagliptin and acarbose, respectively, meeting the statistical criterion for non-inferiority (upper limit of 95% confidence interval for between-treatment difference ≤ 0.4%). The decrease in fasting plasma glucose was similar with acarbose (−1.5 ± 0.2 mmol/l) and vildagliptin (−1.2 ± 0.1 mmol/l). Body weight did not change in vildagliptin-treated patients (−0.4 ± 0.1 kg) but decreased in acarbose-treated patients (−1.7 ± 0.2 kg, P < 0.001 vs. vildagliptin). The proportion of patients experiencing any adverse event (AE) was 35% vs. 51% in patients receiving vildagliptin or acarbose, respectively; gastrointestinal AEs were significantly more frequent with acarbose (25.5%) than vildagliptin (12.3%, P < 0.001). No hypoglycaemia was reported for either group. Conclusions Vildagliptin is effective and well tolerated in patients with Type 2 diabetes, demonstrating similar glycaemic reductions to acarbose, but with better tolerability.     

The untold story of Dabigatran etexilate: alveolar hemorrhage in an elderly patient with interstitial pulmonary fibrosis

We report an 85-year-old male, with history of interstitial pulmonary fibrosis (IPF), who was presented with progressive dyspnea, hypoxia, and anemia of 2 months duration. Six months before presentation, the patient was placed on Dabigatran etexilate (Dabigatran) (110 mg BID) for atrial fibrillation. His prior anemia workup included a negative upper endoscopy and colonoscopy. Bronchoscopy revealed copious amounts of bloody secretions. The bronchial tree was washed and Dabigatran was discontinued. The patient’s medical condition improved and was subsequently discharged home. Our case illustrates the failure of current literature to predict the isolated bronchoalveolar bleed secondary to Dabigatran therapy.     

5-fluorouracil and folinic acid-induced mucositis: no effect of oral glutamine supplementation.

In some clinical situations the endogenous production of glutamine may be insufficient to maintain optimal tissue structure and function such that glutamine becomes a conditionally essential amino acid. Studies in laboratory animals have demonstrated that glutamine supplementation can reduce the incidence and severity of cytotoxic-induced mucositis. This study examined the role of oral glutamine supplementation in the management of mucositis caused by 5-fluorouracil (5-FU) and folinic acid. Twenty-eight patients with gastrointestinal cancers were randomised to receive 16 g of glutamine per day for 8 days, or placebo, in a randomised double-blind trial before crossing over to the alternative supplement during the second treatment cycle. The supplement was well tolerated with no apparent adverse effects, but failed to have any significant effect on oral mucositis assessed by the patients or investigator. The possible reasons for this apparent lack of benefit are discussed.     

Botulinum toxin type B micromechanosensor

Botulinum neurotoxin (BoNT) types A, B, E, and F are toxic to humans; early and rapid detection is essential for adequate medical treatment. Presently available tests for detection of BoNTs, although sensitive, require hours to days. We report a BoNT-B sensor whose properties allow detection of BoNT-B within minutes. The technique relies on the detection of an agarose bead detachment from the tip of a micromachined cantilever resulting from BoNT-B action on its substratum, the synaptic protein synaptobrevin 2, attached to the beads. The mechanical resonance frequency of the cantilever is monitored for the detection. To suspend the bead off the cantilever we use synaptobrevin's molecular interaction with another synaptic protein, syntaxin 1A, that was deposited onto the cantilever tip. Additionally, this bead detachment technique is general and can be used in any displacement reaction, such as in receptor-ligand pairs, where the introduction of one chemical leads to the displacement of another. The technique is of broad interest and will find uses outside toxicology.