Patients with medical risk factors for chronic kidney disease are at increased risk of renal impairment despite the use of nephron-sparing surgery.

OBJECTIVE: To determine whether patients with normal preoperative renal function, but who possess medical risk factors for chronic kidney disease (CKD), experience poorer renal function after partial nephrectomy (PN) for renal cell carcinoma (RCC) compared with those without risk factors. PATIENTS AND METHODS: The effects of age, hypertension (HTN) and diabetes mellitus (DM) on estimated glomerular filtration rate (eGFR) were investigated in 488 consecutive operations for RCC performed during 2005-2012 at six Australian tertiary referral centres; 156 patients underwent PN and 332 patients underwent radical nephrectomy (RN). We used chi-squared test and binary logistic regression to analyse new-onset CKD, and multiple linear regression to investigate determinants of postoperative eGFR. RESULTS: The development of new-onset eGFR of <60 mL/min was related to undergoing RN rather than PN (risk ratio [RR] 2.7, P < 0.001), older age (RR 1.6, P < 0.001) and the presence of HTN (RR 1.6, P = 0.001) and DM (RR 1.5, P = 0.003). Patients undergoing PN were still at risk of new-onset CKD if medical risk factors were present. Whereas 7% of patients undergoing PN without CKD risk factors developed new-onset eGFR <60 mL/min, this figure increased to 24%, 30% and 42% for older age, HTN and DM, respectively. Patients with eGFR of 45-59 mL/min were more likely to progress to more severe forms of CKD and end-stage renal failure than those with eGFR of ≥60 mL/min. On multivariate analysis, RN, rather than PN, age and the presence of DM (but not HTN), predicted both the development of new-onset eGFR of <60 mL/min (R(2) = 0.37) and new-onset eGFR <45 mL/min (R(2) = 0.42). CONCLUSION: Patients with medical risk factors for CKD are at increased risk of progressive renal impairment despite the use of PN. Where feasible, nephron-sparing surgery should be considered for these patients.

A Fully-Implantable Cochlear Implant SoC with Piezoelectric Middle-Ear Sensor and Arbitrary Waveform Neural Stimulation.

A system-on-chip for an invisible, fully-implantable cochlear implant is presented. Implantable acoustic sensing is achieved by interfacing the SoC to a piezoelectric sensor that detects the sound-induced motion of the middle ear. Measurements from human cadaveric ears demonstrate that the sensor can detect sounds between 40 and 90 dB SPL over the speech bandwidth. A highly-reconfigurable digital sound processor enables system power scalability by reconfiguring the number of channels, and provides programmable features to enable a patient-specific fit. A mixed-signal arbitrary waveform neural stimulator enables energy-optimal stimulation pulses to be delivered to the auditory nerve. The energy-optimal waveform is validated with in-vivo measurements from four human subjects which show a 15% to 35% energy saving over the conventional rectangular waveform. Prototyped in a 0.18 µm high-voltage CMOS technology, the SoC in 8-channel mode consumes 572 µW of power including stimulation. The SoC integrates implantable acoustic sensing, sound processing, and neural stimulation on one chip to minimize the implant size, and proof-of-concept is demonstrated with measurements from a human cadaver ear.

Anaesthetist prediction of postoperative opioid use: a multicentre prospective cohort study.

Background: The Apfel simplified risk score includes four risk factors: female sex, non-smoking status, postoperative nausea and vomiting or motion sickness history, and postoperative opioid use. The score is calculated preoperatively, so postoperative opioid use must be predicted. We aimed to determine whether anaesthetists can predict patients' postoperative opioid use and dose. Methods: Specialist anaesthetists from eight hospitals preoperatively predicted opioid use and dose in the post-anaesthesia care unit (PACU) and for the first 24 h postoperatively, which was compared with actual opioid use and dose. Opioid doses were converted to oral morphine equivalents (MEQ). Correlations between predicted and actual opioid use and dose were analysed with Spearman's rho and linear regression. Results: A total of 487 anaesthetist-patient pairs were included. Anaesthetists overpredicted opioid use (398 [82%] predicted vs 251 [52%] actual patients requiring opioids in the PACU; 396 [81%] predicted vs 291 [60%] actual in the first 24 h) (Spearman's rho [95% confidence interval] 0.24 [0.16-0.33], P<0.001 in the PACU; 0.36 [0.28-0.44], P<0.001 in the first 24 h). Anaesthetists also overpredicted opioid dose (median [inter-quartile range] 12 [8-20] mg predicted MEQ vs 4 [0-18] mg actual MEQ in the PACU; 32 [18-60] mg vs 24 [0-65] mg MEQ in the first 24 h) (Spearman's rho 0.21 [0.13-0.29], P<0.001 in the PACU; 0.53 [0.40-0.60], P<0.001 in the first 24 h). Conclusions: Specialist anaesthetists cannot accurately predict opioid use or dose in the PACU or the first 24 postoperative hours. The Apfel risk criterion for postoperative opioid use may be inaccurate in clinical practice.

Exploratory study examining barriers to participation in colorectal cancer screening.

OBJECTIVE: To examine the Stage of Change distribution for bowel cancer screening in a regional Australian community and the factors associated with varying positions on the continuum of change. DESIGN: Survey of a convenience sample. SETTING: Community sample. PARTICIPANTS: A total of 59 (31 male, mean age = 59) service club members from a South Australian regional community. MAIN OUTCOME MEASURE: Self-reported Stage of Change for bowel cancer screening behaviour. RESULTS: Attributing greater embarrassment and discomfort to bowel cancer screening was associated with earlier positions on the Stages of Change. Perceiving that bowel cancer screening might have positive value for personal health was associated with more advanced positions on the continuum of change. Those who perceived breast and prostate screening procedures to be embarrassing or to cause discomfort were significantly less likely to be participating in bowel cancer screening. No significant relationships were found between bowel cancer screening Stage of Change and worry about vulnerability; personal, family or wider social network case reports of bowel cancer; and the population-level value attributed to the cancer screening procedures. CONCLUSION: Bowel cancer screening participation rates are currently lower than those associated with breast and prostate screening. Reducing perceptions of embarrassment and discomfort, increasing awareness of potential health benefits and maximising participation in other screening procedures might increase participation in bowel cancer screening.

Deciphering the genetic basis for polyketide variation among mycobacteria producing mycolactones.

BACKGROUND: Mycolactones are immunosuppressive and cytotoxic polyketides, comprising five naturally occurring structural variants (named A/B, C, D, E and F), produced by different species of very closely related mycobacteria including the human pathogen, Mycobacterium ulcerans. In M. ulcerans strain Agy99, mycolactone A/B is produced by three highly homologous type I polyketide megasynthases (PKS), whose genes (mlsA1: 51 kb, mlsA2: 7.2 kb and mlsB: 42 kb) are found on a 174 kb plasmid, known as pMUM001. RESULTS: We report here comparative genomic analysis of pMUM001, the complete DNA sequence of a 190 kb megaplasmid (pMUM002) from Mycobacterium liflandii 128FXT and partial sequence of two additional pMUM replicons, combined with liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis. These data reveal how PKS module and domain differences affecting MlsB correlate with the production of mycolactones E and F. For mycolactone E these differences from MlsB in M. ulcerans Agy99 include replacement of the AT domain of the loading module (acetate to propionate) and the absence of an entire extension module. For mycolactone F there is also a reduction of one extension module but also a swap of ketoreductase domains that explains the characteristic stereochemistry of the two terminal side-chain hydroxyls, an arrangement unique to mycolactone F CONCLUSION: The mycolactone PKS locus on pMUM002 revealed the same large, three-gene structure and extraordinary pattern of near-identical PKS domain sequence repetition as observed in pMUM001 with greater than 98.5% nucleotide identity among domains of the same function. Intra- and inter-strain comparisons suggest that the extreme sequence homogeneity seen among the mls PKS genes is caused by frequent recombination-mediated domain replacement. This work has shed light on the evolution of mycolactone biosynthesis among an unusual group of mycobacteria and highlights the potential of the mls locus to become a toolbox for combinatorial PKS biochemistry.

Energy-efficient waveform for electrical stimulation of the cochlear nerve.

The cochlear implant (CI) is the most successful neural prosthesis, restoring the sensation of sound in people with severe-to-profound hearing loss by electrically stimulating the cochlear nerve. Existing CIs have an external, visible unit, and an internal, surgically-placed unit. There are significant challenges associated with the external unit, as it has limited utility and CI users often report a social stigma associated with prosthesis visibility. A fully-implantable CI (FICI) would address these issues. However, the volume constraint imposed on the FICI requires less power consumption compared to today's CI. Because neural stimulation by CI electrodes accounts for up to 90% of power consumption, reduction in stimulation power will result directly in CI power savings. To determine an energy-efficient waveform for cochlear nerve stimulation, we used a genetic algorithm approach, incorporating a computational model of a single mammalian myelinated cochlear nerve fiber coupled to a stimulator-electrode-tissue interface. The algorithm's prediction was tested in vivo in human CI subjects. We find that implementation of a non-rectangular biphasic neural stimulation waveform may result in up to 25% charge savings and energy savings within the comfortable range of hearing for CI users. The alternative waveform may enable future development of a FICI.

Shedding of Hepatitis C Virus in Semen of Human Immunodeficiency Virus-Infected Men.

Background. The epidemic of sexually transmitted hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) has been documented for over a decade. Despite this, there is no consensus as to the risk factors for sexual acquisition of HCV in these men. Methods. We obtained paired semen and blood samples at 2-week intervals from HIV-infected MSM with recent and chronic HCV infection and quantified HCV in semen. Results. Hepatitis C virus was quantified in 59 semen specimens from 33 men. Hepatitis C virus was shed in 16 (27%) of semen specimens from 11 (33%) of the men. Median HCV viral load (VL) in semen was 1.49 log10 IU/mL. Hepatitis C virus VL in blood was significantly higher at the time of HCV shedding in semen than when HCV shedding in semen was not detected (P = .002). Furthermore, there was a significant correlation between the HCV VL in blood and semen overall (rs = 0.41; P = .001), and in the subgroup with recent HCV infection (rs = 0.37; P = .02), but not in the subgroup with chronic HCV infection (rs = 0.34; P = .1). Conclusions. One third of HIV-infected MSM coinfected with HCV shed HCV into their semen. Based on the HCV VL in semen in this study, an average ejaculate would deliver up to 6630 IU of virus into the rectum of the receptive partner. Therefore, our data strongly support that condoms should be used during anal intercourse among MSM to prevent transmission of HCV.

Case report of deep vein thrombosis caused by artificial urinary sphincter reservoir compressing right external iliac vein.

Artificial urinary sphincters (AUSs) are commonly used after radical prostatectomy for those who are incontinent of urine. However, they are associated with complications, the most common being reservoir uprising or migration. We present a unique case of occlusive external iliac and femoral vein obstruction by the AUS reservoir causing thrombosis. Deflation of the reservoir and anticoagulation has, thus far, not been successful at decreasing thrombus burden. We present this case as a rare, but significant surgical complication; explore the risk factors that may have contributed, and other potential endovascular therapies to address this previously unreported AUS complication.

How should we treat prepubertal labial adhesions? Retrospective comparison of topical treatments: estrogen only, betamethasone only, and combination estrogen and betamethasone.

Labial adhesion is a common finding in prepubertal girls. Traditionally, topical estrogen cream application has been the choice of conservative treatment, however, topical betamethasone treatment has also recently been employed with some success. In this retrospective study, we analysed 131 children with labial adhesions. Eleven of 71 (15.4%) patients were treated successfully with topical estrogen cream only, and 5 of 32 (15.6%) patients were treated successfully with betamethasone cream only. We successfully treated 5 of 28 (28.5%) patients with a combination of estrogen and betamethasone creams. The mean time of treatment for each regimen of therapy was 4 weeks. There was no significance between the single-therapy estrogen and single-therapy betamethasone groups (P = 1.00), between single-therapy estrogen and the combination therapy (P = .16), and the single therapy betamethasone to combination therapy (P = .35) groups. There was also no significant difference between combination estrogen and betamethasone therapy and the combined data of the single therapies (relative risk 1.85; 95% confidence interval 0.89-3.89; P =.11). For the treatment of prepubertal labial adhesions, topical estrogen and betamethasone creams were found to have similar success rates, with limited satisfactory results. The combination therapy was mildly more efficacious than each of the single therapies but was not found to be statistically significant. Surgical separation is recommended if conservative treatment fails.

A flexible pressure monitoring system for pressure ulcer prevention.

Pressure ulcers are painful sores that arise from prolonged exposure to high pressure points, which restricts blood flow and leads to tissue necrosis. This is a common occurrence among patients with impaired mobility, diabetics and the elderly. In this work, a flexible pressure monitoring system for pressure ulcer prevention has been developed. The prototype consists of 99 capacitive pressure sensors on a 17-cm x 22-cm sheet which is flexible in two dimensions. Due to its low cost, the sensor sheet can be disconnected from the reusable electronics and be disposed of after use, suitable for a clinical setting. Each sensor has a resolution of better than 2-mmHg and a range of 50-mmHg and offset is calibrated in software. Realtime pressure data is displayed on a computer. A maximum sampling rate of 12-Hz allows for continuous monitoring of pressure points.

Evolution of Mycobacterium ulcerans and other mycolactone-producing mycobacteria from a common Mycobacterium marinum progenitor.

It had been assumed that production of the cytotoxic polyketide mycolactone was strictly associated with Mycobacterium ulcerans, the causative agent of Buruli ulcer. However, a recent study has uncovered a broader distribution of mycolactone-producing mycobacteria (MPM) that includes mycobacteria cultured from diseased fish and frogs in the United States and from diseased fish in the Red and Mediterranean Seas. All of these mycobacteria contain versions of the M. ulcerans pMUM plasmid, produce mycolactones, and show a high degree of genetic relatedness to both M. ulcerans and Mycobacterium marinum. Here, we show by multiple genetic methods, including multilocus sequence analysis and DNA-DNA hybridization, that all MPM have evolved from a common M. marinum progenitor to form a genetically cohesive group among a more diverse assemblage of M. marinum strains. Like M. ulcerans, the fish and frog MPM show multiple copies of the insertion sequence IS2404. Comparisons of pMUM and chromosomal gene sequences demonstrate that plasmid acquisition and the subsequent ability to produce mycolactone were probably the key drivers of speciation. Ongoing evolution among MPM has since produced at least two genetically distinct ecotypes that can be broadly divided into those typically causing disease in ectotherms (but also having a high zoonotic potential) and those causing disease in endotherms, such as humans.