Prospective Evaluation of the Effect of Thigh Dissection for Removal of Transobturator Mid Urethral Slings on Refractory Thigh Pain.

PURPOSE: Transobturator slings have higher rates of de novo neurologic symptoms than retropubic slings, most commonly related to the thigh. Cases refractory to conservative management may require removal of the thigh portion of the sling. In this series we prospectively examine the effect of thigh dissection with mesh removal on refractory thigh pain. MATERIALS AND METHODS: All thigh dissections for refractory neurologic symptoms after transobturator sling placement were followed prospectively from October 2012 to October 2015. Patients were assessed preoperatively, with a pain score using a visual analog scale, and postoperatively with a global response assessment. RESULTS: A total of 12 thigh dissections were performed from October 2012 to October 2015 in 8 patients. Mean (±SD) time from original mesh placement to presentation was 2.7 (±1.5) years. Average preoperative pain score was 7.9 (±1.7) out of 10, with pain in the thigh in all patients. Seven cases involved unilateral thigh dissection and 1 had concomitant bilateral thigh dissection. Five patients underwent concurrent transvaginal excision. On postoperative evaluation the average global response rating was 1.6, with 1 defined as very much better and 2 defined as much better. Of the 8 patients 3 went on to have the contralateral side done with an average global response rating of 1.3 (±0.6). One patient underwent further treatment for stress urinary incontinence with placement of a retropubic mid urethral sling. CONCLUSIONS: Our prospective series supports the use of thigh dissection in patients with refractory neurologic symptoms after transobturator sling placement. The procedure can be performed safely with positive outcomes for the patient.

Insulin degludec improves long-term glycaemic control similarly to insulin glargine but with fewer hypoglycaemic episodes in patients with advanced type 2 diabetes on basal-bolus insulin therapy.

The aim of the present study was to compare the long-term safety and efficacy of insulin degludec with those of insulin glargine in patients with advanced type 2 diabetes (T2D) over 78 weeks (the 52-week main trial and a 26-week extension). Patients were randomized to once-daily insulin degludec or insulin glargine, with mealtime insulin aspart ± metformin ± pioglitazone, and titrated to pre-breakfast plasma glucose values of 3.9-4.9 mmol/l (70-88 mg/dl). After 78 weeks, the overall rate of hypoglycaemia was 24% lower (p = 0.011) and the rate of nocturnal hypoglycaemia was 31% lower (p = 0.016) with insulin degludec in the extension trial set, while both groups of patients achieved similar glycaemic control. Rates of adverse events and total insulin doses were similar for both groups in the safety analysis set. During 18 months of treatment, insulin degludec + mealtime insulin aspart ± oral antidiabetic drugs in patients with T2D improves glycaemic control similarly, but confers lower risks of overall and nocturnal hypoglycaemia than with insulin glargine treatment.

Randomized controlled pilot trial of the rigid and flexing laryngoscope versus the fiberoptic bronchoscope for intubation of potentially difficult airway.

BACKGROUND: The flexible fiberoptic bronchoscope (FOB) is viewed as the gold standard device for awake intubation in the difficult airway. The newer rigid flexible laryngoscope (RIFL) was developed for similar indications. In this study we compare these two devices for management of potentially difficult airways after induction of general anesthesia. METHODS: Adult surgical patients requiring endotracheal intubation and having a predicted difficult airway based on airway examination, BMI≥35, and/or history of prior difficult intubation were randomized to undergo endotracheal intubation with either the RIFL or FOB. Induction was performed in usual manner, and intubation was performed by providers proficient with both airway devices after induction of general anesthesia. The primary outcomes measured were intubation success, time to intubation, number of attempts, and the need for airway assist maneuvers. The lowest observed oxygen saturation and airway trauma were also recorded. RESULTS: A total of 41 patients were enrolled, with 20 randomized to each group and 1 withdrawal. Intubation was successful in all patients with both devices. The median time for successful intubation was significantly shorter in the RIFL group compared to the FOB group (49 vs. 64 seconds; P=0.048). Airway assist maneuvers were required in 2 (10%) intubations with the RIFL compared to 16 (80%) intubations with the FOB (P<0.001). There were no significant differences in lowest oxygen saturation or airway trauma. CONCLUSION: The RIFL required significantly less time and fewer airway assist maneuvers for successful endotracheal intubation compared to FOB when used by experienced providers in patients with anticipated difficult airways.

Ureteroscopy with laser lithotripsy for urolithiasis in the spinal cord injury population.

STUDY DESIGN: Retrospective study. OBJECTIVES: The purpose of this investigation was to review the outcomes and safety of retrograde ureteroscopic laser lithotripsy (URS) for the treatment of urolithiasis in the spinal cord injury (SCI) population. SETTING: Virginia, USA. METHODS: All patients with SCI who underwent URS with holmium:YAG laser lithotripsy for urolithiasis over a 15-year period were identified. Stone size, location and number at presentation were recorded. Information regarding patient characteristics, intra-operative complications, surgical efficacy, stone clearance, peri-operative complications, and follow-up stone events was collected and analyzed. RESULTS: A total of 67 URS procedures were performed on 29 SCI patients during the study period with an average follow-up of 3.4 years. Patients had an average of 2.3 ipsilateral ureteroscopies. The majority (85.1%) used indwelling catheters for long-term bladder management, and complete stone clearance after the first procedure was 34.3%. Of the 44 cases with residual stones >4 mm, 20 (45.5%) were secondary to technical or procedural limitations. The intra-operative complication rate was comparable to non-SCI studies at 1.5%, but peri-operative complications were significantly higher at 29.9% with the majority due to urosepsis. Factors associated with peri-operative complications include chronic obstructive pulmonary disease, motor incomplete injuries and lack of a pre-operative ureteral stent. CONCLUSION: URS in the SCI population is an effective treatment for ureteral or renal stones but may be associated with greater risks and reduced efficacy.

A review of modern insulin analogue pharmacokinetic and pharmacodynamic profiles in type 2 diabetes: improvements and limitations.

Insulin analogues have been engineered to enhance desired molecular properties without altering immunogenicity. The majority of insulin pharmacology studies are conducted in healthy volunteers and patients with type 1 diabetes. At present, there are more patients with type 2 than type 1 diabetes receiving insulin treatment. As the responsibility for initiating insulin therapy in these patients continues to shift to primary care, it will be important for general practitioners to understand the different pharmacological properties of insulin preparations in patients with type 2 diabetes, so that treatment can be adapted to meet patients' physiological and lifestyle requirements. The purpose of this review is to summarize pharmacological studies of insulin analogues in patients with type 2 diabetes. Faster onset of action of rapid acting insulin analogues has improved postprandial glycaemic control. Biphasic insulin analogues are associated with a lower incidence of nocturnal hypoglycaemia compared with human biphasic preparations and allow for intensification from once to twice or thrice daily dosing. More predictable glycaemic-lowering profiles of the insulin analogues have also led to reductions in nocturnal hypoglycaemia, particularly comparing long-acting insulin analogues with protaminated human insulin. Enhancing insulin self-association and reversible binding with albumin has led to further reductions in variability. However, improvements can still be made. Effective once daily clinical dosing of long-acting insulin analogues is not possible in all patients. In addition, the protaminated component of biphasic insulin analogues do not provide the duration of action or profile for physiological basal insulin replacement and neither insulin glargine nor insulin detemir are suitable for mixing with other insulin analogues as this would substantially alter their pharmacokinetic properties. Enhancing the pharmacological predictability and extending the duration of action could simplify insulin titration and further reduce the incidence of hypoglycaemia.

Once-daily insulin detemir is comparable to once-daily insulin glargine in providing glycaemic control over 24 h in patients with type 2 diabetes: a double-blind, randomized, crossover study.

Once-daily dosing with insulin detemir and insulin glargine were compared in a double-blind, randomised, crossover study in type 2 diabetes subjects previously treated with other antihyperglycaemic medications. Blood glucose was measured through continuous glucose monitoring (CGM). Insulin dose was adjusted daily during the titration phase to achieve target blood glucose values of (70-120 mg/dL) during the basal period, defined as 2400-0600 hours. The last meal of the day started at 1800 h and basal insulin was injected at 2000 h. The CGM data for a 24-h period on the second consecutive day after achieving target blood glucose levels were compared between treatments. Twenty-nine subjects completed the study. Over a 24-h measurement period, once-daily dosing with insulin detemir provided glycaemic control very similar to that of once-daily insulin glargine in patients with type 2 diabetes after both had been titrated to the same glucose target. Insulin detemir- and insulin glargine-treated subjects had similar mean 24-h glucose values (133 +/- 21 mg/dL compared with 126+/-20 mg/dL respectively, p = 0.385) and similar glucose values during the basal period (105 +/- 23 mg/dL compared with 98 +/- 19 mg/dL, respectively p = 0.204).Target basal glycaemic control was achieved in all subjects in a mean of 3.8 days for detemir and 3.5 days for glargine (p = 0.360). The mean dose of detemir was similar to that of glargine (26.3 and 26.6 units/day, respectively, p = 0.837). In this study, once-daily dosing of insulin detemir provided 24-h glycaemic control similar to that of insulin glargine in patients with type 2 diabetes.

Human forebrain activation by visceral stimuli.

Visceral function is essential for survival. Discreet regions of the human brain controlling visceral function have been postulated from animal studies (Cechetto and Saper [1987] J. Comp. Neurol. 262:27-45) and suspected from lethal cardiac arrythmias (Cechetto [1994] Integr. Physiol. Behv. Sci. 29:362-373). However, these visceral sites remain uncharted in the normal human brain. We used 4-Tesla functional magnetic resonance imaging (fMRI) to identify changes in activity in discrete regions of the human brain previously identified in animal studies to be involved in visceral control. Five male subjects underwent heart rate (HR) and/or blood pressure (BP) altering tests: maximal inspiration (MX), Valsalva's maneuver (VM), and isometric handgrip (HG). Increased neuronal activity was observed during MX, VM, and HG, localized in the insular cortex, in the posterior regions of the thalamus, and in the medial prefrontal cortex. To differentiate special visceral (taste) regions from general visceral (HR, BP) regions in these areas, response to gustatory stimulation was also examined; subjects were administered saline (SAL) and sucrose (SUC) solutions as gustatory stimuli. Gustatory stimulation increased activity in the ventral insular cortex at a more inferior level than the cardiopulmonary stimuli. The observed neural activation is the first demonstration of human brain activity in response to visceral stimulation as measured by fMRI.

Antibacterial activity of lonchocarpol A.

Lonchocarpol A, a flavanone, demonstrates in vitro inhibitory activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. This activity is antagonized by mouse plasma, which may account for its lack of in vivo activity. This compound demonstrates no differentiation with respect to the inhibition of RNA, DNA, cell wall, and protein synthesis.