Pedicled chimeric superficial circumflex iliac artery perforator (SCIP) flap with external oblique fascia for vesicocutaneous bladder fistula repair: A case report and literature review on the utility of pedicled chimeric SCIP.

Following its initial description by Koshima in 2004, the superficial circumflex iliac artery perforator (SCIP) flap has become a ubiquitous and extremely useful flap in coverage of defects whereby bulkiness must be avoided. It also allows direct closure and concealment of the donor site. Its use as a free tissue transfer has been demonstrated by various surgeons globally. Nevertheless, there are few cases illustrating the utility of the pedicled SCIP flap in the reconstruction of lower abdominal defects. We present a case of a pedicled SCIP flap utilized as a chimeric flap incorporating external oblique muscle fascia on a deep branch along with the typical fasciocutaneous component based on the superficial branch to cover the suprapubic defect after vesicocutaneous fistula repair. We thereafter report on the literature of pedicled chimeric SCIP flap for locoregional reconstruction. A 26-year-old female was referred to the Plastic and Reconstructive Surgery unit after suffering a functional bladder outlet obstruction necessitating the creation of a urinary stoma. Subsequently, stoma obstruction occurred, and a suprapubic catheter was performed that was complicated by infection and resulted in the development of a vesicocutaneous fistula. Accordingly, the urological surgeons were planning surgical closure of the suprapubic vesicocutaneous defect, measuring 5 × 4 cm. A pedicled SCIP flap was designed to match the defect size; and raised as a chimeric flap with external oblique muscle fascia based on the deep branch, along with the fasciocutaneous component based on the superficial branch. The external oblique fascial component was used to secure the suture line of fistula repair, over which the fasciocutaneous component was inset, effectively double breasting the fistula repair and full thickness lower abdominal defect. The patient had an unremarkable postoperative recovery and has since been followed up in the outpatient setting without complication for the past 24 months. Robust coverage of the suprapubic defect was reliably achieved and no further fistulation has occurred. This case illustrates that a pedicled SCIP flap can be harvested as a chimeric flap and used to reliably cover defects in the infra-umbilical region.

Evidence of Electron Heating by Alpha Particles in JET Deuterium-Tritium Plasmas.

The fusion-born alpha particle heating in magnetically confined fusion machines is a high priority subject for studies. The self-heating of thermonuclear fusion plasma by alpha particles was observed in recent deuterium-tritium (D-T) experiments on the joint European torus. This observation was possible by conducting so-called "afterglow" experiments where transient high fusion yield was achieved with neutral beam injection as the only external heating source, and then termination of the heating at peak performance. This allowed the first direct evidence for electron heating of plasmas by fusion-born alphas to be obtained. Interpretive transport modeling of the relevant D-T and reference deuterium discharges is consistent with the alpha particle heating observation.

Comparative efficacy and acceptability of drug treatments for bipolar depression: a multiple-treatments meta-analysis.

OBJECTIVE: Treatment of bipolar depression is complicated by variable response and risk of switch to mania. Guidance is informed by the strength of evidence rather than by comparative data. METHOD: We performed a multiple-treatments meta-analysis of randomised, double-blind, controlled comparisons of 4-16 weeks in adults in bipolar depression. The primary efficacy outcome was effect size. The primary acceptability outcome was 'switch to mania'. Secondary outcomes were likelihood of response and withdrawals from trials. RESULTS: Twenty-nine studies were included (8331 participants). Olanzapine + fluoxetine and olanzapine performed best on primary outcome measure being ranked highest for effect size. Switch to mania was least likely with ziprasidone and then quetiapine. Olanzapine + fluoxetine was also ranked the highest for response with lurasidone second, but olanzapine + fluoxetine and olanzapine had the optimal effect on response and withdrawal from treatment when the two parameters were considered together. Several treatments [monoamine oxidase inhibitors (MAOIs), ziprasidone, aripiprazole and risperidone] have limited or no therapeutic activity in bipolar depression. CONCLUSION: Olanzapine + fluoxetine should be first-line treatment. Olanzapine, quetiapine, lurasidone, valproate and selective serotonin re-uptake inhibitors are also recommended. Tricyclic antidepressants and lithium are worthy of consideration but lamotrigine (high risk of switching, less robust efficacy) and MAOIs, ziprasidone, aripiprazole and risperidone (no evidence of efficacy) should not be used.

Reported ingested dose of paracetamol as a predictor of risk following paracetamol overdose.

PURPOSE: To evaluate reported ingested dose of paracetamol as a risk assessment tool in acute paracetamol overdose. METHODS: Data was retrospectively obtained from a clinical toxicology database linked to one Australian and two United Kingdom hospitals. Plasma paracetamol concentrations (PPCs) of adult patients presenting with acute single ingestion, non-staggered paracetamol deliberate self-poisoning between 2006 and 2012 were recorded and plotted on a treatment nomogram to determine accuracy of reported dose ingested as an indicator for antidotal treatment. PPC plotted on a treatment nomogram with a line intersecting a 4-h concentration of 100 mg/L [667 µmol/L] was considered an indication for antidotal treatment in the UK; the corresponding Australasian population utilised a line intersecting 150 mg/L [1000 µmol/L]. RESULTS: Of 1246 patients, 65.7 % were female and 88 % were from the UK. Fifty-two percent of patients reporting ingestion of ≥8 g paracetamol had a PPC above the 100 mg/L treatment line; PPV 52 % [95 % confidence interval (CI) 49 %, 55 %], sensitivity 81 % [95 %CI 78 %, 85 %]. Forty-four of patients reporting percent ingestion of ≥10 g had a PPC above the 150 mg/L treatment line; PPV 44 % [95 % CI 41 %, 49 %], sensitivity 85 % [95 % CI 78 %, 89 %], 72 % of patients reporting ingestion of ≥16 g had a PPC above the 100 mg/L treatment line; PPV 72 % [95% CI 67 %, 77 %], sensitivity 50 % [95 % CI 45 %, 54 %]. Overall, there was moderate correlation (R = 0.58) between reported paracetamol dose ingested and extrapolated 4-h PPC. CONCLUSIONS: There is a positive correlation between reported ingested dose of paracetamol and subsequent chance of a PPC being above a defined treatment line; however, ingested dose of paracetamol alone is a poor risk assessment tool in accurately determining need for treatment with an antidote.

The incidence of pelvic fractures with traumatic lower limb amputation in modern warfare due to improvised explosive devices.

AIMS: A frequently-seen injury pattern in current military experience is traumatic lower limb amputation as a result of improvised explosive devices (IEDs). This injury can coexist with fractures involving the pelvic ring. This study aims to assess the frequency of concomitant pelvic fracture in IED-related lower limb amputation. METHODS: A retrospective analysis of the trauma charts, medical notes, and digital imaging was undertaken for all patients arriving at the Emergency Department at the UK military field hospital in Camp Bastion, Afghanistan, with a traumatic lower limb amputation in the six months between September 2009 and April 2010, in order to determine the incidence of associated pelvic ring fractures. RESULTS: Of 77 consecutive patients with traumatic lower limb amputations, 17 (22%) had an associated pelvic fracture (eleven with displaced pelvic ring fractures, five undisplaced fractures and one acetabular fracture). Unilateral amputees (n = 31) had a 10% incidence of associated pelvic fracture, whilst 30 % of bilateral amputees (n = 46) had a concurrent pelvic fracture. However, in bilateral, trans-femoral amputations (n = 28) the incidence of pelvic fracture was 39%. CONCLUSIONS: The study demonstrates a high incidence of pelvic fractures in patients with traumatic lower limb amputations, supporting the routine pre-hospital application of pelvic binders in this patient group.

Augmentation of clozapine with a second antipsychotic - a meta-analysis.

OBJECTIVE: To examine using meta-analysis the effect of adding a second antipsychotic to established clozapine monotherapy. METHOD: A literature search was conducted in April 2011, and randomised placebo-controlled double-blind studies were identified. We performed a meta-analysis of efficacy (as standardised mean difference) and tolerability (withdrawals from trials) and a regression analysis of duration of study versus effect size. We also examined publication bias using funnel-plot analysis. RESULTS: Overall, 14 studies were included (734 subjects). Individual study numbers ranged from 10 to 207 (mean 52.6, median 40). Augmentation of clozapine with a second antipsychotic conferred a small benefit over placebo (effect size -0.239 (95% CI: -0.452, -0.026); P = 0.028). Meta-regression of the effect of length of treatment on effect size showed no relationship (P = 0.254). The risk of discontinuing antipsychotic augmentation was no greater than the risk of discontinuing placebo (RR = 1.20, 95% CI 0.80-1.82). There was no evidence of publication bias. CONCLUSION: Augmentation with a second antipsychotic is modestly beneficial in patients not responding fully to clozapine. Tolerability seems not to be adversely affected, at least in the short term. Longer studies do not appear to increase the probability of showing positive effects for augmentation.

Anti-glomerular basement membrane disease in Auckland.

BACKGROUND: Anti-glomerular basement membrane (GBM) antibody-mediated disease is rare and classically presents with the syndrome of glomerulonephritis and pulmonary haemorrhage. AIM: This aim of this report was to determine the incidence, clinical features, management and outcomes of anti-GBM disease in Auckland between 1998 and 2008. METHODS: Potential patients were identified by a search for positive anti-GBM antibody serology, diagnostic renal biopsy, or in-hospital admissions using International Classification of Diseases 9 and 10 codes between 1998 and 2008. A retrospective case notes review of all potential cases was performed with data censored at 31 December 2010. RESULTS: Twenty-three cases were identified. The rate of anti-GBM disease was estimated at 1.79 per million person-years. There were 12 men and 11 women. The median age was 45 years, range 12-74 years. Sixteen patients were European, three were Pacific peoples, three were NZ Maori and one was Chinese. Eleven were regular smokers and eight ex-smokers, significantly higher proportions than the population (P ≤ 0.001). Smokers were significantly more likely to have respiratory disease (P= 0.03). The mean creatinine at presentation was 474 µmol/L. All patients had a renal biopsy; 20 had crescentic glomerulonephritis. One patient recovered renal function without treatment. Twenty-two were immunosuppressed with cyclophosphamide and corticosteroids. Seventeen received plasmapheresis. Eighteen were alive, eight with end-stage renal disease, two with chronic kidney disease and eight with normal renal function. CONCLUSIONS: Anti-GBM disease is a rare condition, which is not overrepresented among indigenous people. With aggressive therapy the prognosis has improved; however, the morbidity and mortality of this condition remain significant.

Augmentation of clozapine with a second antipsychotic--a meta-analysis of randomized, placebo-controlled studies.

OBJECTIVE: Inadequate response to clozapine treatment is frequently encountered in practice and augmentation strategies have been developed in an attempt to improve response. Aims of the study were to evaluate the therapeutic effect of adding an antipsychotic drug to clozapine treatment. METHOD: Meta-analysis of randomized, placebo-controlled studies of antipsychotic augmentation of clozapine treatment. RESULTS: Ten studies (including 522 subjects) met inclusion criteria. Antipsychotic augmentation showed significant benefit over the addition of placebo on only one outcome measure examined [mean effect size for rating scale score (BPRS/PANSS) -0.180, 95% CI -0.356 to -0.004]. Antipsychotic augmentation showed no advantage on withdrawals from trials (risk ratio 1.261, 95% CI 0.679-2.345) or on CGI scores (effect size -0.661, 95% CI -1.475 to 0.151). Duration of study was not associated with outcome (P = 0.95). There was no evidence of publication bias. CONCLUSION: In studies lasting up to 16 weeks, the addition of an antipsychotic to clozapine treatment has marginal therapeutic benefit. Longer and larger trials are necessary to demonstrate the precise therapeutic utility of antipsychotic co-therapy with clozapine.

Comparison of a supra-sternal cardiac output monitor (USCOM) with the pulmonary artery catheter.

BACKGROUND: Cardiac output (CO) cannot reliably be estimated by clinical examination. We aimed to measure the agreement between CO measurements using a supra-sternal Doppler monitor (USCOM, Coffs Harbour, Australia) and the pulmonary artery catheter (PAC). METHODS: The study was conducted in the intensive care unit of a tertiary teaching hospital. All patients with PAC in situ were eligible. Simultaneous CO readings were taken when clinically indicated. Investigators and clinicians were blinded to each other's results. The CO values used were the mean of three consecutive supra-sternal Doppler readings for patients with a sinus rhythm and seven for atrial fibrillation, and the mean of three thermodilution curves with acceptable form and values within 10% of each other for the PAC. Agreement was measured using both the paired t-test to calculate bias and limits of agreement and the intraclass correlation (ICC) coefficient. RESULTS: Ninety-four subjects were enrolled. From 89 subjects, 250 paired comparisons were obtained. USCOM monitor readings were unobtainable in five patients. Mean supra-sternal Doppler CO was 5.5 litre min(-1). Bias was -0.09 litre min(-1) and levels of agreement were +/- 2.92 litre min(-1) when compared with PAC. ICC was 0.46 (95% CI 0.36-0.56), and mean percentage difference was 19 (IQR 6-31)%. CONCLUSIONS: In our subjects, there was poor agreement between CO measurements done with the supra-sternal Doppler monitor and PAC.

Biological and potential therapeutic roles of sirtuin deacetylases.

Sirtuins comprise a unique class of nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylases that target multiple protein substrates to execute diverse biological functions. These enzymes are key regulators of clinically important cellular and organismal processes, including metabolism, cell division and aging. The desire to understand the important determinants of human health and lifespan has resulted in a firestorm of work on the seven mammalian sirtuins in less than a decade. The implication of sirtuins in medically important areas such as diabetes, cancer, cardiovascular dysfunction and neurodegenerative disease has further catapulted them to a prominent status as potential targets for nutritional and therapeutic development. Here, we present a review of published results on sirtuin biology and its relevance to human disease.

Training tomorrow's military surgeons: lessons from the past and challenges for the future.

The nature of conflict is evolving, with current warfare being associated with an initial "shock and awe" phase followed by protracted periods ofcounter-insurgency and peace support missions. As conflict has changed, so have the munitions deployed and the resulting patterns of injury. Improvised Explosive Devices have become the preferred weapon of the insurgent and the resultant explosive and fragmentation injuries are the hallmark of modern military wounding. These injuries pose a significant challenge to deployed medical forces, requiring a well-defined, seamless approach from injury to rehabilitation. Traditionally, military medical services demonstrate a poor 'institutional memory' in the maintenance of combat surgical skills. Numerous publications detail the re-learning of key tenets of war surgery by generations of surgeons deploying onto the field of battle. While the maintenance of military surgical capability in trained surgeons may be addressed through combat surgical courses, concern exists as to the generic competency of those currently in training and their ability to deal with the burden of injury associated with modern conflict. The training of junior doctors in the United Kingdom and further afield is in a state of flux. New curriculum development, streamlined and run-through training programmes have combined with the legal requirements of the European Working Time Directive to produce a training landscape almost unrecognisable with that of previous years. This article investigates the development of current military wounding patterns and modern surgical training programmes. It describes processes already in place to address the unique training needs of military surgeons and proposes a framework for enabling appropriate training opportunities in the future.

The biokinetics and radiotoxicology of curium: a comparison with americium.

The human and animal data on the biokinetics of (242)Cm and (244)Cm are reviewed and shown to be very similar to those for (241)Am. Liver and skeleton are the main organs of deposition and the retention of curium in the skeleton is very prolonged in all the species examined. Retention of both curium and americium in the liver appears to be species-dependent, being relatively rapidly removed from the liver of rats, and probably humans, but being tenaciously retained in dogs and some other species. The radiotoxicity of curium is also reviewed and it is shown that, as with (241)Am, lung and bone tumour induction are the major hazards from inhaled and systemically deposited (244)Cm. The use of chelating agents for the treatment of accidental contamination of the human body with (242,244)Cm is also discussed.

Treatment and functional outcomes of complex tibial fractures in children and adolescents using the Ilizarov method.

Aims: The aim of this study was to report the clinical, functional and radiological outcomes of children and adolescents with tibial fractures treated using the Ilizarov method. Patients and Methods: Between 2013 and 2016 a total of 74 children with 75 tibial fractures underwent treatment at our major trauma centre using an Ilizarov frame. Demographic and clinical information from a prospective database was supplemented by routine functional and psychological assessment and a retrospective review of the notes and radiographs. Results: Of the 75 fractures, 26 (35%) were open injuries, of which six (8%) had segmental bone loss. There were associated physeal injuries in 18 (24%), and 12 (16%) involved conversion of treatment following failure of previous management. The remaining children had a closed unstable fracture or significant soft-tissue compromise. The median follow-up was 16 months (7 to 31). All fractures united with a median duration in a frame of 3.6 months (interquartile range 3.1 to 4.6); there was no significant difference between the types of fracture and the demographics of the patients. There were no serious complications and no secondary procedures were required to achieve union. Health-related quality of life measures were available for 60 patients (80%) at a minimum of six months after removal of the frame. These indicated a good return to function (median Paediatric quality of life score, 88.0; interquartile range 70.3 to 100). Conclusion: The Ilizarov method is a safe, effective and reliable method for the treatment of complex paediatric tibial fractures. Cite this article: Bone Joint J 2018;100-B:396-403.

Cryo scanning transmission x-ray microscope optimized for spectrotomography.

A cryo scanning transmission X-ray microscope, the cryo-STXM, has been designed and commissioned at the Canadian Light Source synchrotron. The instrument is designed to operate from 100 to 4000 eV (λ = 12.4 - 0.31 nm). Users can insert a previously frozen sample, through a load lock, and rotate it ±70° in the beam to collect tomographic data sets. The sample can be maintained for extended periods at 92 K primarily to suppress radiation damage and a pressure on the order of 10-9 Torr to suppress sample contamination. The achieved spatial resolution (30 nm) and spectral resolution (0.1 eV) are similar to other current soft X-ray STXMs, as demonstrated by measurements on known samples and test patterns. The data acquisition efficiency is significantly more favorable for both imaging and tomography. 2D images, 3D tomograms, and 4D chemical maps of automotive hydrogen fuel cell thin sections are presented to demonstrate current performance and new capabilities, namely, cryo-spectrotomography in the soft X-ray region.

Extraction algorithms for cortical control of arm prosthetics.

Now that recordings of multiple, individual action potentials are being made with chronic electrodes, it seems that previous work showing simple encoding of movement parameters in these spike trains can be used as a real-time control signal for prosthetic arms. Efficient extraction algorithms can compensate for the limited ensemble sample acquired with this emerging technology.

Studies with cyclophosphamide labeled with phosphorus-32: nucleic acid alkylation and its effect on DNA synthesis in rat tumor and normal tissues.

The gross distribution of levels of [32P]cyclophosphamide ([32P]CY) in August female rats was similar in tumor, intestinal mucosa, spleen, bone marrow, and striated muscle tissue, with slightly higher levels in liver and kidney tissue. A triphasic association with nucleic acids was found and actual alkylation of DNA and RNA reached a maximum of 48 hours post treatment. There was no evidence of 32P-label reutilization that could have accounted for prolonged alkylation. We found that 100 mg CY/kg suppressed the incorporation of [3H]thymidine, [3H]deoxyuridine, and [14C]sodium formate into the DNA of the BICR-A15 carcinoma for at least 10 days. This correlated well with the observed regression of tumor volume. Bone marrow and intestinal mucosa, two tissues which limit chemotherapuetic treatment of the tumor, were less affected by 100 mg CY/kg. Bone marrow had regained normal levels of DNA precursor incorporation by 5 days, and intestinal mucosa had regained normal levels by 3 days. Results indicated that this differential in recovery time may assist in the successful scheduling of vital tissue-sparing drug regimens.

Inactivation of transmissible spongiform encephalopathy agents during the manufacture of dicalcium phosphate from bone.

Dicalcium phosphate was prepared from industrial crushed bone artificially contaminated with transmissible spongiform encephalopathy agents in two experiments carried out in an accurately scaled-down laboratory model of the industrial manufacturing process. In one experiment, 10 g of mouse brain infected with the 301V strain of mouse-passaged bovine spongiform encephalopathy agent was added to the crushed bone; in the other experiment, 10 g of hamster brain infected with the 263K strain of hamster-passaged scrapie agent was added. Samples of the infectious brain and dried dicalcium phosphate were assayed for the amount of 301V or 263K infectivity present. The titre of infectivity of the 301V-infected brain was 10(7.7) intracerebral ID50/g; that of the 263K-infected brain was 10(8.0) intracerebral ID50/g. The titres of the dried samples of dicalcium phosphate were 10(2.5) ID50/g in the experiment spiked with 301V and 10(2.7) ID50/g in the experiment spiked with 263K. The calculated clearance factors were 10(3.9) for the experiment with 301V and 10(3.8) for the experiment with 263K.

Uptake of 67Ga in the regenerating rat liver and its relationship to lysosomal enzyme activity.

The uptake of 67Ga citrate has been studied in the regenerating rat liver over a period up to 72 hr after partial hepatectomy. The concentration of 67Ga was found to be maximal (four times that of controls) 42 hr after hepatectomy. This was shown to be related to lysosomal enzyme activity rather than to specific phases of the cell cycle, there being a highly significant correlation (p smaller than 0.001) with aryl sulfatase activity. In both regenerating and normal rat livers, it was shown that 67Ga uptake is reduced when protein synthesis is inhibited by cycloheximide but is unaffected by inhibition of DNA synthesis by cytosine arabinoside.

The concentration of 67Ga and 45Ca in the lactating mammary gland and its relevance to the tumor uptake of 67Ga citrate.

67Ga is known to concentrate in the breasts of pregnant and postpartum women, and a case is now described in which 67Ga uptake was seen in the breasts of a woman who was neither pregnant nor postpartum, but was receiving chemotherapy for Hodgkin's disease. Comparative studies of the uptake of 67Ga and 45Ca in lactating dogs have shown that both nuclides are secreted in the milk in similar amounts and in protein-bound form. The concentration of 67Ga in mammary tissue is about one-half of that found in the milk at 5 hr postinjection but, by 48 hr, the concentrations are approximately equal. There were similarities in the subcellular distributions of 67Ga and 45Ca in the lactating mammary gland at 5 and 48 hr. Although there was a correlation between 67Ga and 45Ca in individual pieces of a lactating mammary gland at 5 hr after injection, no such correlation was seen between the two nuclides in multiple samples of a transmissible venereal tumor measured at various time intervals. The rate of dispersion of 67Ga and 45Ca from the lactating mammary gland was similar but, in the tumor, 67Ga was present in very much greater amounts than 45Ca and was retained longer. It is concluded that, although there may be similarities in the metabolic pathways of gallium and calcium in the lactating mammary gland, there is no similarity in the mechanism of uptake of these two elements into tumors.

Effect of paliperidone palmitate on hospitalisation in a naturalistic cohort - a four-year mirror image study.

BACKGROUND: Clinical trial outcomes are heavily influenced by the non-naturalistic clinical trial process. Observations of outcomes in clinical practice are a valuable adjunct to clinical trial results. HYPOTHESIS: Our null hypothesis was that clinically indicated switching to paliperidone palmitate had no effect on hospital admissions or hospital bed days. METHOD: This was a part-prospective mirror image study examining outcomes 2years before starting paliperidone palmitate and 2years after. Sensitivity analyses examined the effect of different placings of the mirror in the mirror image design. RESULTS: We prospectively followed-up 225 patients prescribed paliperidone palmitate in clinical practice. At 2years, 41.8% of patients were still receiving paliperidone palmitate. In the primary analysis, the mean number of admissions fell from 1.80 in the two years before starting paliperidone palmitate to 0.81 in two years following the drug's initiation (outpatients) or two years following hospital discharge (inpatients) (P<0.001). More than half of patients were not admitted to hospital during two years follow-up. Mean total bed days was reduced from 79.6 in the two years before to 46.2 in the two years after paliperidone palmitate initiation or discharge (P<0.001). Sensitivity analyses gave broadly similar outcomes. Continuers demonstrated better outcomes than discontinuers in sensitivity analyses but not in the primary analysis. CONCLUSION: Paliperidone palmitate initiation is associated with a substantial reduction in hospital admissions and days spent in hospital. The reduction in costs associated with reduced use of health care facilities is likely to exceed the purchase and administration costs of the drug.