Diabetes remission and relapse following an intensive metabolic intervention combining insulin glargine/lixisenatide, metformin and lifestyle approaches: Results of a randomised controlled trial.

AIM: Non-surgical options for inducing type 2 diabetes remission are limited. We examined whether remission can be achieved by combining lifestyle approaches and short-term intensive glucose-lowering therapy. METHODS: In this trial, 160 patients with type 2 diabetes on none to two diabetes medications other than insulin were randomised to (a) an intervention comprising lifestyle approaches, insulin glargine/lixisenatide and metformin, or (b) standard care. Participants with glycated haemoglobin (HbA1c) <7.3% (56 mmol/mol) at 12 weeks were asked to stop diabetes medications and were followed for an additional 52 weeks. The primary outcome was diabetes relapse defined as HbA1c ≥6.5% (48 mmol/mol) at 24 weeks or thereafter, capillary glucose ≥10 mmol/L on ≥50% of readings, or use of diabetes medications, analysed as time-to-event. Main secondary outcomes included complete or partial diabetes remission at 24, 36, 48 and 64 weeks defined as HbA1c <6.5% (48 mmol/mol) off diabetes medications since 12 weeks after randomisation. A hierarchical testing strategy was applied. RESULTS: The intervention significantly reduced the hazard of diabetes relapse by 43% (adjusted hazard ratio 0.57, 95% confidence interval 0.40-0.81; p = .002). Complete or partial diabetes remission was achieved in 30 (38.0%) intervention group participants versus 16 (19.8%) controls at 24 weeks and 25 (31.6%) versus 14 (17.3%) at 36 weeks [relative risk 1.92 (95% confidence interval 1.14-3.24) and 1.83 (1.03-3.26), respectively]. The relative risk of diabetes remission in the intervention versus control group was 1.88 (1.00-3.53) at 48 weeks and 2.05 (0.98-4.29) at 64 weeks. CONCLUSIONS: A 12-week intensive intervention comprising insulin glargine/lixisenatide, metformin and lifestyle approaches can induce remission of diabetes.

Mutant prolactin receptor and familial hyperprolactinemia.

Hyperprolactinemia that is not associated with gestation or the puerperium is usually due to tumors in the anterior pituitary gland and occurs occasionally in hereditary multiple endocrine neoplasia syndromes. Here, we report data from three sisters with hyperprolactinemia, two of whom presented with oligomenorrhea and one with infertility. These symptoms were not associated with pituitary tumors or multiple endocrine neoplasia but were due to a heterozygous mutation in the prolactin receptor gene, PRLR, resulting in an amino acid change from histidine to arginine at codon 188 (His188Arg). This substitution disrupted the high-affinity ligand-binding interface of the prolactin receptor, resulting in a loss of downstream signaling by Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5). Thus, the familial hyperprolactinemia appears to be due to a germline, loss-of-function mutation in PRLR, resulting in prolactin insensitivity.

Comparison of Tracheal Intubation Using the Storz's C-Mac D-blade(TM) Video-Laryngoscope Aided by Truflex(TM) Articulating Stylet and the Portex(TM) Intubating Stylet.

BACKGROUND: Tracheal intubation using Storz's C-Mac D-blade(TM) videolaryngoscope is associated with difficult negotiation of the tracheal tube into the glottis due to steep angulation of its blade. OBJECTIVES: In this study, we hypothesized that Truflex(TM) articulating stylet with its ability to dynamically tailor the ETT shape to patients' oropharyngeal anatomy would be better suited to the D-blade angulation and ease tracheal intubation compared to Portex(TM) intubation stylet. PATIENTS AND METHODS: Following approval by the Ethical Issues Committee and informed consent, 218 ASA I and II patients of either sex were enrolled in this interventional, single-blind, randomized controlled trial. Tracheal intubation was performed following a uniform general anesthetic technique using the Storz's C-Mac D-blade(TM) videolaryngoscope aided by either Truflex(TM) articulating stylet or the Portex(TM) intubation stylet by an experienced anesthesiologist. The outcome measures included success or failure to intubate in the first attempt, total intubation time, hemodynamic disturbances, trauma if any and user satisfaction. RESULTS: The number of patients in whom intubation was successful in the first attempt was significantly higher by using Truflex™ articulating stylet (99.1%) compared to Portex(TM) intubation stylet (90.0%; P-Value = 0.003). User satisfaction grade was significantly better while using Truflex(TM) articulating stylet (8.5 ± 0.88) compared to the Portex(TM) intubation stylet (8.23 ± 0.99; P-Value = 0.035). We did not observe any significant difference in total intubation time, hemodynamic disturbances or trauma. CONCLUSIONS: Storz's C-Mac D-blade(TM) videolaryngoscope provides grade I Cormack and Lehane's glottic view in 99.1% patients. First attempt successful tracheal intubation and user satisfaction significantly improved by Truflex(TM) articulating stylet compared to the Portex(TM) intubation stylet.

Change in tear protein profile in diabetic retinopathy with duration of diabetes.

AIMS: To study change in tear protein profile with duration of diabetes and severity of diabetic retinopathy (DR) in type 2 diabetes patients. MATERIALS AND METHODS: Tear protein profile was ascertained by SDS PAGE method in 30 patients with DR (group A) and 37 patients without DR (group B). RESULTS: Six distinct bands of proteins were identified; these proteins are as follows: 91kDa (P1), 66kDa (P2), 60kDa (P3), 30kDa (P4), 18.4kDa (P5) and 14.4kDa (P6). Prevalence of P3 was significant (p=0.036) in group A, especially in cases with diabetes ≤8 years compared with diabetes >8 years (p=0.0107). In group B, P2 was significantly prevalent (p<0.0013) in cases with diabetes ≤8 years compared to diabetes >8 years. Considering the changes in terms of duration of diabetes in general, patients with diabetes of ≤8 years, P3 was significantly prevalent in group A compared to group B (p=0.004); and when the duration of diabetes is >8 years, P2 was found significantly more in group A compared to group B (p=0.01). No significant difference in P3 (p=0.025), P4 (p=0.2877), P5 (p=0.4801), P6 (p=0.0985) was observed in mild to moderate NPDR group compared to severe NPDR to PDR group. P1 and P2 were present only in severe NPDR and PDR. CONCLUSION: Variable protein expression was observed with duration of diabetes and severity of diabetic retinopathy.

Symmetrical peripheral gangrene due to Plasmodium falciparum malaria.

A 45-year-old man presented with a 4-day history of high-grade fever with rigours and a 2-day history of painful bluish black discolouration of extremities (acrocyanosis). He was haemodynamically stable and all peripheral pulses palpable, but the extremities were cold with gangrene involving bilateral fingers and toes. Mild splenomegaly was present on abdominal examination but rest of the physical examinations were normal. On investigating he was found to have anaemia, thrombocytopaenia with gametocytes of Plasmodium falciparum on peripheral blood smear. His blood was uncoagulable during performance of prothrombin time with a raised D-dimer. Oxygen saturation was normal and the arterial Doppler test showed reduced blood flow to the extremities. A diagnosis of complicated P. falciparum malaria with disseminated intravascular coagulation (DIC) leading to symmetrical peripheral gangrene was performed. Artemisinin combination therapy was started and heparin was given for DIC. A final line of demarcation of gangrene started forming by 12th day.

Neurocysticercosis presenting as focal hydrocephalus.

A 40-year-old man presented with a 2-month history of headache, nausea and vomiting, with generalised seizures for the past 15 days. On examination he had bilateral papilloedema, visual acuity was 6/6 in both eyes but perimetry showed right homonymous inferior quadrantanopia. His MRI showed numerous small cystic lesions with eccentric nodules, diffusely distributed in bilateral cerebral and cerebellar hemispheres. There was also focal hydrocephalus involving occipital and temporal horns of the left lateral ventricle leading to its selective dilation. Stool examination showed ova of Taenia solium. He was treated with albendazole, prednisone and sustained release sodium valproate for 1 month. His headache resolved and he is free of seizures. Repeat perimetry at 1 month also showed resolution of visual field defect.

Bilateral subhyaloid haemorrhage in a conscious patient: a new spectrum of ocular involvement by Plasmodium falciparum.

A 24-year-old woman presented with a history of high-grade fever with rigours since 3 days and bilateral sudden loss of vision since 6 h. She was conscious, oriented and her vitals were stable. She had a temperature of 101°F, anaemia, thrombocytopaenia, normal white cell count and moderate splenomegaly. On testing visual activity, she could only perceive hand movements although her pupils were bilaterally equal, and normal in size and reaction. On indirect ophthalmoscopy, optic discs were normal bilaterally; however, fovea of both eyes was masked by subhyaloid haemorrhage. Peripheral smear showed gametocytes of Plasmodium falciparum. The patient was started on arteminsinin-combined therapy and advised to be in propped-up position to help resolution of the haemorrhage. The patient was afebrile in 4 days and follow-up fundus examination showed gradual resolution of the haemorrhage. After two months, the patient regained normal visual acuity in both eyes; however, it took nearly 3 months for complete resolution of the haemorrhage.

Glomus jugulare: high index of clinical suspicion is important for optimal management.

Glomus tumour is a type of extra-adrenal chemodectoma or paraganglioma, originating within the wall of jugular bulb. We report a case of a 60-year-old woman who presented with hearing loss and pulsatile tinnitus. High index of suspicion and appropriate use of imaging led to early diagnosis. However, the patient did not give consent for surgery and was managed satisfactorily with radiotherapy.

Neonatal sacrococcygeal teratoma with acute renal failure.

Teratomas are germ cell tumours composed of multiple types of cells derived from more than a single germ cell layer. The most common site of an extragonadal teratoma is the sacrococcygeal region. We report a case of a 16-day-old female child with a large swelling in the sacrococcygeal region extending laterally into the buttocks with severely deranged renal functions. Ultrasonography and CT helped in making the diagnosis and, more importantly, to delineate the extent of the tumour and the involvement of adjacent organs and tissues: in our case, lower bilateral ureters. Imaging findings and clinical presentation led to the diagnosis of sacrococcygeal teratoma with renal failure.

Assessment of Truflex articulating stylet versus conventional rigid Portex stylet as an intubation guide with the D-blade of C-Mac videolaryngoscope during elective tracheal intubation: study protocol for a randomized controlled trial.

BACKGROUND: A variety of videolaryngoscopes with angulated blade have been recently introduced into clinical practice. They provide an indirect view of the glottic structures in normal and challenging clinical settings. Despite the very good visualization of the laryngeal structures by these devices, the insertion and advancement of the endotracheal tube may be prolonged and occasionally fail as it does not conform to the enhanced angulation of the blade. To overcome this handicap, it is recommended to use a pre-shaped, styleted tracheal tube during intubation. Unfortunately, these malleable rigid stylets permit only a fixed shape to the advancing endotracheal tube. This may necessitate withdrawal of endotracheal tube-stylet assembly for reshaping, before undertaking a new attempt. This may cause soft tissue injury and hemodynamic disturbance.This single-blinded randomized clinical trial aims to overcome these handicaps using a novel method of dynamically changing the shape of the advancing endotracheal tube by Truflex articulating stylet as per need during D-blade C-Mac videolaryngoscopy. METHODS: One hundred and fifty four patients between 18 and 60 years of age belonging to either sex undergoing tracheal intubation under uniform general anesthetic technique will be randomly divided into Portex malleable stylet group and Truflex articulating stylet group. The primary efficacy variable of success/failure between the two groups will be analyzed using the chi square test. For comparison of intubation times and the Intubation Difficulty Score, ANOVA will be used. Primary efficacy endpoint results will be successful or failed tracheal intubation in the first attempt, total intubation time and the intubation difficulty score. Secondary efficacy endpoints will be overall user satisfaction graded from 1 to 10 (1 = very poor, 10 = excellent), Cormack and Lehane's grading, glotticoscopy time and ETT negotiation time and total number of intubation attempts. Result of safety endpoints will include dental and airway trauma, hemodynamic disturbances, arrhythmias or cardiac arrest. TRIAL REGISTRATION: Current Controlled Trials ISRCTN57679531; Date of registration 12/02/2013.

HPLC method for plasma vitamin K1: effect of plasma triglyceride and acute-phase response on circulating concentrations.

BACKGROUND: The plasma concentration of vitamin K(1) (phylloquinone) is the most reliable index for assessing vitamin K status. Our aim was to analytically validate an HPLC method for quantifying phylloquinone in plasma and to examine the effect of plasma triglyceride concentration on the phylloquinone reference interval. We also examined the effect of acute-phase response on phylloquinone concentration in plasma. METHODS: Phylloquinone was extracted from fasting plasma samples by deproteinization and C18 solid-phase extraction, separated by reversed-phase HPLC, and detected fluorometrically after postcolumn reduction with a platinum catalyst. We synthesized a novel internal calibrator, docosyl naphthoate. RESULTS: The recovery of phylloquinone was >90%. Between-run imprecision was 8.7%-9.0%, and within-run imprecision was 3.8%-7.0%. The linearity was up to 44.8 nmol/L, limit of detection 0.08 nmol/L, and limit of quantification 0.14 nmol/L. The correlation between plasma phylloquinone and triglyceride concentrations was r = 0.7 in the reference population. The 95% reference interval for the phylloquinone:triglyceride ratio was 0.20 to 2.20 nmol/mmol. Plasma concentrations of C-reactive protein were significantly increased, whereas triglyceride and phylloquinone but not the phylloquinone:triglyceride ratio were transiently decreased >50% after surgery. CONCLUSION: Phylloquinone population reference intervals should be expressed as a ratio of the triglyceride concentration. Phylloquinone concentrations in plasma are decreased in acute-phase response and, unless corrected for plasma triglyceride concentration, are unlikely to be a reliable index of vitamin K status.

Biological variation of vitamins in blood of healthy individuals.

BACKGROUND: Components of biological variation can be used to define objective quality specifications (imprecision, bias, and total error), to assess the usefulness of reference values [index of individuality (II)], and to evaluate significance of changes in serial results from an individual [reference change value (RCV)]. However, biological variation data on vitamins in blood are limited. The aims of the present study were to determine the intra- and interindividual biological variation of vitamins A, E, B(1), B(2), B(6), C, and K and carotenoids in plasma, whole blood, or erythrocytes from apparently healthy persons and to define quality specifications for vitamin measurements based on their biology. METHODS: Fasting plasma, whole blood, and erythrocytes were collected from 14 healthy volunteers at regular weekly intervals over 22 weeks. Vitamins were measured by HPLC. From the data generated, the intra- (CV(I)) and interindividual (CV(G)) biological CVs were estimated for each vitamin. Derived quality specifications, II, and RCV were calculated from CV(I) and CV(G). RESULTS: CV(I) was 4.8%-38% and CV(G) was 10%-65% for the vitamins measured. The CV(I)s for vitamins A, E, B(1), and B(2) were lower (4.8%-7.6%) than for the other vitamins in blood. For all vitamins, CV(G) was higher than CV(I), with II <1.0 (range, 0.36-0.95). The RCVs for vitamins were high (15.8%-108%). Apart from vitamins A, B(1), and erythrocyte B(2), the imprecision of our methods for measurement of vitamins in blood was within the desirable goal. CONCLUSIONS: For most vitamin measurements in plasma, whole blood, or erythrocytes, the desirable imprecision goals based on biological variation are obtainable by current methodologies. Population reference intervals for vitamins are of limited value in demonstrating deficiency or excess.