Small fibre neuropathy (SFN), a condition dominated by neuropathic pain, is frequently encountered in clinical practise either as prevalent manifestation of more diffuse neuropathy or distinct ...nosologic entity. Aetiology of SFN includes pre-diabetes status and immune-mediated diseases, though it remains frequently unknown. Due to their physiologic characteristics, small nerve fibres cannot be investigated by routine electrophysiological tests, making the diagnosis particularly difficult. Quantitative sensory testing (QST) to assess the psychophysical thresholds for cold and warm sensations and skin biopsy with quantification of somatic intraepidermal nerve fibres (IENF) have been used to determine the damage to small nerve fibres. Nevertheless, the diagnostic criteria for SFN have not been defined yet and a ‘gold standard’ for clinical practise and research is not available. We screened 486 patients referred to our institutions and collected 124 patients with sensory neuropathy. Among them, we identified 67 patients with pure SFN using a new diagnostic ‘gold standard’, based on the presence of at least two abnormal results at clinical, QST and skin biopsy examination. The diagnosis of SFN was achieved by abnormal clinical and skin biopsy findings in 43.3% of patients, abnormal skin biopsy and QST findings in 37.3% of patients, abnormal clinical and QST findings in 11.9% of patients, whereas 7.5% patients had abnormal results at all the examinations. Skin biopsy showed a diagnostic efficiency of 88.4%, clinical examination of 54.6% and QST of 46.9%. Receiver operating characteristic curve analysis confirmed the significantly higher performance of skin biopsy comparing with QST. However, we found a significant inverse correlation between IENF density and both cold and warm thresholds at the leg. Clinical examination revealed pinprick and thermal hypoesthesia in about 50% patients, and signs of peripheral vascular autonomic dysfunction in about 70% of patients. Spontaneous pain dominated the clinical picture in most SFN patients. Neuropathic pain intensity was more severe in patients with SFN than in patients with large or mixed fibre neuropathy, but there was no significant correlation with IENF density. The aetiology of SFN was initially unknown in 41.8% of patients and at 2-year follow-up a potential cause could be determined in 25% of them. Over the same period, 13% of SFN patients showed the involvement of large nerve fibres, whereas in 45.6% of them the clinical picture did not change. Spontaneous remission of neuropathic pain occurred in 10.9% of SFN patients, while it worsened in 30.4% of them.
The antagonistic interaction between adenosine and dopamine receptors could have important pathophysiological and therapeutic implications in Parkinson's disease (PD). The primary aim of this study ...was to investigate the expression, affinity, and density of A1, A2A, A2B, and A3 adenosine receptors (ARs) and D2 dopamine receptors (D2Rs) in PD. An increase in A2AAR density in putamen was found. The presence and functionality of ARs in human lymphocyte and neutrophil membranes from patients with PD revealed a specific A2AAR alteration compared with healthy subjects. A statistically significant linear correlation among the A2AAR density, functionality, or tumor necrosis factor‐α (TNF‐α) levels and Unified Parkinson's Disease Rating Scale (UPDRS) motor score was reported. Adenosine concentration and TNF‐α levels were increased in plasma of patients with PD. In rat adrenal pheochromocytoma (PC12) cells, a widely useful model, adenosine antagonists decreased dopamine uptake, and an opposite effect was mediated by A2A agonists. This is the first report showing the presence of an A2AAR alteration in putamen in PD that mirrors a similar up‐regulation in human peripheral blood cells. Moreover, the correlation found between A2AAR density or A2A agonist potency and UPDRS motor score highlights the central role of A2AARs in the pharmacological treatment of PD.—Varani, K., Vincenzi, F., Tosi, A., Gessi, S., Casetta, I., Granieri, G., Fazio, P., Leung, E., MacLennan, S., Granieri, E., Borea, P. A. A2A adenosine receptor overexpression and functionality, as well as TNF‐α levels, correlate with motor symptoms in Parkinson's disease. FASEB J. 24, 587–598 (2010). www.fasebj.org
► We analyzed the thermal behavior of electrical insulation of Nb-Ti superconducting cables cooled by superfluid helium. ► We addressed the insulation scheme of the LHC main magnets and of the ...magnets foreseen for the High Luminosity LHC upgrade (HL-LHC). ► We developed a heat transfer model based on coupled He II and solid conduction heat transport mechanisms. ► We identified the main mechanisms for heat extraction, as well as the dimensions of the main He II micro-channels. ► The dimensions identified were confirmed by microscope images.
The operation of Nb–Ti superconducting magnets in He II relies on superfluidity to overcome the severe thermal barrier represented by the cable electrical insulation. In wrapped cable insulations, like those used for the main magnets of the Large Hadron Collider (LHC) particle accelerator, the micro-channels network created by the insulation wrappings allows to efficiently transfer the heat deposited or generated in the cable to the He bath.
In this paper, available experimental data of heat transfer through polyimide electrical insulation schemes are analyzed. A steady-state thermal model is developed to describe the insulation of the LHC main dipole magnets and the Enhanced Insulation proposed for the High Luminosity LHC upgrade (HL-LHC), according to the relevant geometric parameters. The model is based on the coupled mechanisms of heat transfer through the bulk of the dielectric insulation and through micro-channels between the insulation tapes.
A good agreement is found between calculations and tests performed at different applied pressures and heating configurations. The model allows identifying the heat fluxes in the cable cross-section as well as the dimensions of the micro-channels. These dimensions are confirmed by microscope images of the two insulations schemes.
Purpose
To analyze outcomes of posterior urethroplasty following pelvic fracture urethral injuries (PFUI) and to determine risk factors for surgical complexity and success.
Methods
Patients who ...underwent posterior urethroplasty following PFUI were identified in the Trauma and Urologic Reconstructive Network of Surgeons (TURNS) database. Demographics, injury patterns, management strategies, and prior interventions were evaluated. Risk factors for surgical failure and the impact of ancillary urethral lengthening maneuvers (corporal splitting, pubectomy and supracrural rerouting) were evaluated.
Results
Of the 436 posterior urethroplasties identified, 122 were following PFUI. 83 (68%) patients were acutely managed with suprapubic tubes, while 39 (32%) underwent early endoscopic realignment. 16 (13%) patients underwent pelvic artery embolization in the acute setting. 116 cases (95%) were completed via a perineal approach, while 6 (5%) were performed via an abdominoperineal approach. The need for one or more ancillary maneuvers to gain urethral length occurred in 4 (36%) patients. Of these, 44 (36%) received corporal splitting, 16 (13%) partial or complete pubectomy, and 2 (2%) supracrural rerouting. Younger patients, those with longer distraction defects, and those with a history of angioembolization were more likely to require ancillary maneuvers. 111 patients (91%) did not require repeat intervention during follow-up. Angioembolization (
p
= 0.03) and longer distraction defects (
p
= 0.01) were associated with failure.
Conclusions
Posterior urethroplasty provides excellent success rates for patients following PFUI. Pelvic angioembolization and increased defect length are associated with increased surgical complexity and risk of failure. Surgeons should be prepared to implement ancillary maneuvers when indicated to achieve a tension-free anastomosis.
To review a robotic approach to recalcitrant bladder neck obstruction and to assess success and incontinence rates.
Patients with a recalcitrant bladder neck contracture or vesicourethral anastomotic ...stenosis who underwent robotic bladder neck reconstruction (RBNR) were identified. We reviewed patient demographics, medical history, etiology, previous endoscopic management, cystoscopic and symptomatic outcomes, urinary continence, and complications. Stricture success was anatomic and functional based upon atraumatic passage of a 17 Fr flexible cystoscope or uroflowmetry rate >15 ml/s. Incontinence was defined as the use of >1 pad per day or procedures for incontinence.
Between 2015 and 2017, 12 patients were identified who met study criteria and underwent RBNR. Etiology of obstruction was endoscopic prostate procedure in 7 and radical prostatectomy in 5. The mean operative time was 216 minutes (range 120-390 minutes), with a mean estimated blood loss of 85 cc (range 5-200 cc). Median length of stay was 1 day (range 1-5 days). Three of 12 patients had recurrence of obstruction for a 75% success rate. Additionally, 82% of patients without preoperative incontinence were continent with a median follow-up of 13.5 months (range 5-30 months). There was 1 Clavien IIIb complication of osteitis pubis and pubovesical fistula that required vesicopubic fistula repair with pubic bone debridement.
RBNR is a viable surgical option with high patency rates and favorable continence outcomes. This is in contrast to perineal reconstruction, which has high incontinence rates. If future incontinence procedures are needed, outcomes may be improved given lack of previous perineal dissection.
In the years 2009–2013 the Large Hadron Collider (LHC) has been operated with the top beam energies of 3.5 and 4 TeV per proton (from 2012) instead of the nominal 7 TeV. The currents in the ...superconducting magnets were reduced accordingly. To date only seventeen beam-induced quenches have occurred; eight of them during specially designed quench tests, the others during injection. There has not been a single beam-induced quench during normal collider operation with stored beam. The conditions, however, are expected to become much more challenging after the long LHC shutdown. The magnets will be operating at near nominal currents, and in the presence of high energy and high intensity beams with a stored energy of up to 362 MJ per beam. In this paper we summarize our efforts to understand the quench levels of LHC superconducting magnets. We describe beam-loss events and dedicated experiments with beam, as well as the simulation methods used to reproduce the observable signals. The simulated energy deposition in the coils is compared to the quench levels predicted by electrothermal models, thus allowing one to validate and improve the models which are used to set beam-dump thresholds on beam-loss monitors for run 2.
To evaluate the presenting complications of patients to reconstructive urologists after masculinizing gender affirming genital reconstructive surgery (GRS) performed elsewhere.
We identified patients ...who underwent revision surgery by one of the co-authors for sequelae of masculinizing GRS. We reviewed patient demographics, medical history, details of prior GRS, and complications from GRS. Specific attention was paid to the presence of the following: suprapubic tube dependence, vaginal remnant, urethrocutaneous fistula (UCF) within the fixed urethra (pars fixa), UCF in the phallic urethra, phallic urethral stricture, meatal stenosis, and anastomotic urethral stricture. Statistical analysis was performed using the Fisher's exact test to determine differences in presenting symptoms by GRS.
Fifty-five patients who had reconstructive surgery for complications from masculinizing GRS from September 2004 to September 2017 were identified. The median age at surgical correction was 33 years. Fifteen (27%) patients had prior metoidioplasty and 40 (73%) had prior phalloplasty. The median time from date of GRS to presentation to a reconstructive urologist was 4 months. Urethral strictures (n = 47, 86%) were the most common indication for subsequent surgery, followed by urethrocutaneous fistulae (n = 31, 56%) and vaginal remnant (n = 26, 47%). The majority of patients presented with 2 or more simultaneous complications (n = 40, 73%).
There are several common presenting urologic complications after masculinizing GRS. Patients may present to reconstructive urologists early after GRS performed elsewhere. The long-term outcomes of GRS deserve further study.
The full energy exploitation of the Large Hadron Collider (LHC), a planned increase of the beam energy beyond the present 6.5 TeV, will result in more demanding working conditions for the ...superconducting dipoles and quadrupoles operating in the machine. It is hence crucial to analyze, understand, and predict the quench levels of these magnets for the required values of current and generated magnetic fields. A one-dimensional multi-strand electro-thermal model has been developed to analyze the effect of beam-losses heat deposition. Critical elements of the model are the ability to capture heat and current distribution among strands, and heat transfer to the superfluid helium bath. The computational model has been benchmarked against experimental values of LHC quench limits measured at 6.5 TeV for the Main Bending dipole magnets.
Purpose Anterior urethroplasty has been shown to negatively impact erectile function. Recovery of function is common but the likelihood and extent of recovery have not been fully elucidated. ...Materials and Methods Between October 2006 and May 2008 men undergoing anterior urethroplasty were enrolled in a prospective study to evaluate the effects of urethroplasty on erectile function. The International Index of Erectile Function was completed preoperatively and on all subsequent postoperative visits. Preoperative and postoperative erectile function was compared. Results A total of 52 patients who underwent anterior urethroplasty were included in the study. Repair locations were bulbar (35) and penile (17). Of the patients undergoing bulbar urethroplasty 20 had excision and primary anastomosis, and 15 had augmented anastomotic repair. All penile repairs were ventral onlay repair (11) or inlay repair in 2 stages (6). Postoperative erectile dysfunction was noted in 20 (38%) men, of whom 18 recovered fully at a mean postoperative period of 190 days (range 92 to 398). In patients with normal preoperative erectile function bulbar urethroplasty was more likely than penile urethroplasty to cause erectile dysfunction (76% vs 38%, p = 0.05). Within the bulbar urethra excision and primary anastomosis repairs led to slightly higher erectile dysfunction rates than augmented anastomotic repairs (50% vs 26%, p = 0.16). Conclusions Anterior urethroplasty caused erectile dysfunction in approximately 40% of patients, although recovery was seen in most by 6 months. Bulbar urethroplasty appears to affect erectile function to a greater extent than penile urethroplasty, which may be explained by the proximity of the bulbar urethra to the nerves responsible for erection.
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