Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047).

BACKGROUND: The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. PATIENTS AND METHODS: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ('Adjuvant-RT') or an observation policy with salvage RT for PSA failure ('Salvage-RT') defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. RESULTS: Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). CONCLUSION: Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy. TRIAL IDENTIFICATION: RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047.

Consensus clinical scoring for suspected perioperative immediate hypersensitivity reactions.

BACKGROUND: Grading schemes for severity of suspected allergic reactions have been applied to the perioperative setting, but there is no scoring system that estimates the likelihood that the reaction is an immediate hypersensitivity reaction. Such a score would be useful in evaluating current and proposed tests for the diagnosis of suspected perioperative immediate hypersensitivity reactions and culprit agents. METHODS: We conducted a Delphi consensus process involving a panel of 25 international multidisciplinary experts in suspected perioperative allergy. Items were ranked according to appropriateness (on a scale of 1-9) and consensus, which informed development of a clinical scoring system. The scoring system was assessed by comparing scores generated for a series of clinical scenarios against ratings of panel members. Supplementary scores for mast cell tryptase were generated. RESULTS: Two rounds of the Delphi process achieved stopping criteria for all statements. From an initial 60 statements, 43 were rated appropriate (median score 7 or more) and met agreement criteria (disagreement index <0.5); these were used in the clinical scoring system. The rating of clinical scenarios supported the validity of the scoring system. Although there was variability in the interpretation of changes in mast cell tryptase by the panel, we were able to include supplementary scores for mast cell tryptase. CONCLUSION: We used a robust consensus development process to devise a clinical scoring system for suspected perioperative immediate hypersensitivity reactions. This will enable objectivity and uniformity in the assessment of the sensitivity of diagnostic tests.

Management of a surgical patient with a label of penicillin allergy: narrative review and consensus recommendations.

Unsubstantiated penicillin-allergy labels are common in surgical patients, and can lead to significant harm through avoidance of best first-line prophylaxis of surgical site infections and increased infection with resistant bacterial strains. Up to 98% of penicillin-allergy labels are incorrect when tested. Because of the scarcity of trained allergists in all healthcare systems, only a minority of surgical patients have the opportunity to undergo testing and de-labelling before surgery. Testing pathways can be modified and shortened in selected patients. A variety of healthcare professionals can, with appropriate training and in collaboration with allergists, provide testing for selected patients. We review how patients might be assessed, the appropriate testing strategies that can be used, and the minimum standards of safe testing.

Transdifferentiation of adult rat stem Leydig cells into prostatic and uterine epithelium, but not epidermis.

Stem Leydig cells (SLCs), precursors of testicular Leydig cells that secrete testosterone required for male sexual differentiation, spermatogenesis, and fertility, were recently identified in rat testes. Various types of stem cells have shown the ability to differentiate into other tissues, but there is no information on the plasticity of adult rat SLCs (rSLCs). This study investigated the ability of rSLCs to transdifferentiate into cell types from all three germ layers-prostatic epithelium (endoderm), uterine epithelium (mesoderm), and epidermis (ectoderm)-under the influence of inductive mesenchyme from fetal and neonatal tissues. To differentiate rSLCs into cells of other lineages, mesenchyme from green fluorescent protein (GFP)-expressing mice was used. Tissue recombinants of urogenital sinus mesenchyme (a potent prostate inducer) and rSLCs grafted into adult male hosts formed ductal structures resembling prostate after 5 weeks. Prostate epithelium was of rSLC origin as determined by absence of GFP expression, and expressed characteristic markers of prostatic epithelium. Similarly, uterine mesenchyme + rSLCs tissue recombinants contained a simple columnar epithelium that was histologically similar to normal uterine epithelium and expressed typical uterine epithelial markers, but was of rSLC origin. In contrast, epidermal tissue was absent in fetal dermis + rSLCs recombinants, suggesting rSLCs did not form skin epithelium. Thus, rSLCs can transdifferentiate into uterine and prostatic epithelium, mesodermal, and endodermal derivatives, respectively, but they may have a limited transdifferentiation potential, as shown by their inability to form epidermis, an ectodermal derivative.

Outcome of first-trimester fetal abdominal cysts: cohort study and review of the literature.

OBJECTIVES: The aims of this study were to ascertain the outcome of fetuses with an abdominal cyst detected at 11-14 weeks' gestation in our unit and to undertake a review of cases reported in the literature. METHODS: This was a retrospective study that included all fetuses found to have an abdominal cyst on ultrasound examination at 11-14 weeks, identified over a 14-year period. Pregnancy management and outcome were ascertained from maternal and neonatal records. We also performed a review of the literature using a systematic search strategy, to identify the outcome of similar cases and propose a management algorithm. RESULTS: Fourteen cases were identified during the study period, of which four had associated abnormalities. Of the 10 isolated cases, the cyst had resolved at follow-up scan in eight (80.0%), one fetus died in utero at 15 weeks' gestation and the other case underwent surgery for a choledochal cyst 9 weeks after birth. An additional 19 cases were reported in the literature. In eight fetuses there were associated structural abnormalities, of which four had a diagnosis of anorectal malformation after birth. In two of these four, the cyst resolved in the second trimester. Of those cases with an isolated cyst (n = 11), the cyst resolved in seven (63.6%). The remainder were variably diagnosed as hepatic cyst, ileal duplication or choledochal cyst. CONCLUSION: Fetal abdominal cysts at 11-14 weeks' gestation are rare. They constitute an isolated finding in the majority of cases and are usually associated with a good perinatal outcome. In view of the reported association with anorectal and other gastrointestinal malformations, perinatal assessment is recommended, even if the cyst resolves during pregnancy.

The Manchester-Oxford Foot Questionnaire (MOXFQ): Development and validation of a summary index score.

OBJECTIVES: The Manchester-Oxford Foot Questionnaire (MOXFQ) is a validated 16-item, patient-reported outcome measure for evaluating outcomes of foot or ankle surgery. The original development of the instrument identified three domains. This present study examined whether the three domains could legitimately be summed to provide a single summary index score. METHODS: The MOXFQ and Short-Form (SF)-36 were administered to 671 patients before surgery of the foot or ankle. Data from the three domains of the MOXFQ (pain, walking/standing and social interaction) were subjected to higher order factor analysis. Reliability and validity of the summary index score was assessed. RESULTS: The mean age of the participants was 52.8 years (sd 15.68; 18 to 89). Higher order principle components factor analysis produced one factor, accounting for 74.7% of the variance. The newly derived single index score was found to be internally reliable (α = 0.93) and valid, achieving at least moderate correlations (r ≥ 0.5, p < 0.001) with related (pain/function) domains of the SF-36. CONCLUSIONS: Analyses indicated that data from the MOXFQ can be presented in summary form. The MOXFQ summary index score (MOXFQ-Index) provides an overall indication of the outcomes of foot and ankle surgery. Furthermore, the single index reduces the number of statistical comparisons, and hence the role of chance, when exploring MOXFQ data.

Uterine gland development begins postnatally and is accompanied by estrogen and progesterone receptor expression in the dog.

During neonatal and juvenile life, mammalian uteri undergo extensive structural and functional changes, including uterine gland differentiation and development. In sheep and mice, inhibition of neonatal uterine gland development induced by progestin treatment led to a permanent aglandular uterine phenotype and adult infertility, suggesting that this strategy might be useful for sterilizing dogs and other companion animals. The goal of this study was to define temporal patterns of adenogenesis (gland development), cell proliferation, and progesterone and estrogen receptor expression in uteri of neonatal and juvenile dogs as a first step toward determining whether neonatal progestin treatments might be a feasible contraceptive approach in this species. Uteri obtained from puppies at postnatal wk 1, 2, 4, 6, or 8 were evaluated histologically and immunostained for MKI67, a marker of cell proliferation, estrogen receptor-1, and progesterone receptor. Adenogenesis was under way at 1 wk of age, as indicated by the presence of nascent glands beginning to bud from the luminal epithelium, and rapid proliferation of both luminal epithelial and stromal cells. By Week 2, glands were clearly identifiable and proliferation of luminal, glandular, and stromal cells was pronounced. At Week 4, increased numbers of endometrial glands were evident penetrating uterine stroma, even as proliferative activity decreased in all cell compartments as compared with Week 2. Whereas gland development was most advanced at Weeks 6 to 8, luminal, glandular, and stromal proliferation was minimal, indicating that the uterus was nearly mitotically quiescent at this age. Both estrogen receptor-1 and progesterone receptor were expressed consistently in uterine stromal and epithelial cells at all ages examined. In summary, canine uterine adenogenesis was underway by 1 wk of age and prepubertal glandular proliferation was essentially complete by Week 6. These results provided information necessary to facilitate development of canine sterilization strategies based on neonatal progestin treatments designed to permanently inhibit uterine gland development and adult fertility.

The use of surgeon-performed ultrasound assessment in a foot and ankle clinic.

BACKGROUND: We describe the first reported use of ultrasound examination performed by an orthopaedic surgeon in the setting of a foot and ankle clinic. METHODS: The senior author attended a course in musculoskeletal ultrasound and performed 100 examinations each checked against the results from a consultant radiologist. Records were kept of all examinations performed in the clinic over a 6-month period with results. RESULTS: Of the 622 patients seen, 91 had an ultrasound scan and 36 had guided injections. All patients had one hospital attendance spared, for most two. Time saved on the treatment pathway per patient was on average 6 weeks. CONCLUSION: Ultrasound assessment performed by a clinician during an outpatient clinic appointment reduces delay in treatment and cuts costs by reducing patient episodes.

Responsiveness of the Manchester-Oxford Foot Questionnaire (MOXFQ) compared with AOFAS, SF-36 and EQ-5D assessments following foot or ankle surgery.

The responsiveness of the Manchester-Oxford Foot Questionnaire (MOXFQ) was compared with foot/ankle-specific and generic outcome measures used to assess all surgery of the foot and ankle. We recruited 671 consecutive adult patients awaiting foot or ankle surgery, of whom 427 (63.6%) were female, with a mean age of 52.8 years (18 to 89). They independently completed the MOXFQ, Short-Form 36 (SF-36) and EuroQol (EQ-5D) questionnaires pre-operatively and at a mean of nine months (3.8 to 14.4) post-operatively. Foot/ankle surgeons assessed American Orthopaedic Foot and Ankle Society (AOFAS) scores corresponding to four foot/ankle regions. A transition item measured perceived changes in foot/ankle problems post-surgery. Of 628 eligible patients proceeding to surgery, 491 (78%) completed questionnaires and 262 (42%) received clinical assessments both pre- and post-operatively. The regions receiving surgery were: multiple/whole foot in eight (1.3%), ankle/hindfoot in 292 (46.5%), mid-foot in 21 (3.3%), hallux in 196 (31.2%), and lesser toes in 111 (17.7%). Foot/ankle-specific MOXFQ, AOFAS and EQ-5D domains produced larger effect sizes (> 0.8) than any SF-36 domains, suggesting superior responsiveness. In analyses that anchored change in scores and effect sizes to patients' responses to a transition item about their foot/ankle problems, the MOXFQ performed well. The SF-36 and EQ-5D performed poorly. Similar analyses, conducted within foot-region based sub-groups of patients, found that the responsiveness of the MOXFQ was good compared with the AOFAS. This evidence supports the MOXFQ's suitability for assessing all foot and ankle surgery.

The MOXFQ patient-reported questionnaire: assessment of data quality, reliability and validity in relation to foot and ankle surgery.

Previously validated for hallux valgus surgery, the Manchester-Oxford Foot Questionnaire (MOXFQ) is here evaluated for use with different regions of the foot and ankle. The study recruited 671 consecutive patients (87.8% of those eligible), mean age 52.8 years, 64% female, who completed the MOXFQ and SF-36 general health survey before foot or ankle surgery. Surgeons completed the American Orthopaedic Foot & Ankle Society (AOFAS) scales and indicated that the patients' main regions for surgery were: Hallux 210 (31.3%), Lesser toes 119 (17.7%), Mid foot 22 (3.3%), Ankle/hind foot 311 (46.3%), Multiple/whole foot 9 (1.3%). Individual MOXFQ items were assessed in terms of response rate and floor/ceiling effects, with the validity of the three MOXFQ scales (Walking/standing, Pain, and Social interaction) being assessed in terms of item-total correlations, internal and test-retest reliability, and construct validity. MOXFQ item response rates were high (all >98%). Cronbach's alphas of >0.7 confirmed internal consistency of all three scales. Test-retest ICCs were all ≥0.89. Correlations of >0.4 obtained with related SF-36 and AOFAS scales supported a priori hypotheses. Good measurement properties are confirmed for the MOXFQ in the context of baseline assessment of patients receiving surgery for a variety of foot or ankle problems.

Colonization of cashew plants by Lasiodiplodia theobromae: microscopical features.

Lasiodiplodia theobromae is a phytopathogenic fungus causing gummosis, a threatening disease for cashew plants in Brazil. In an attempt to investigate the ultrastructural features of the pathogen colonization and its response to immunofluorescence labeling, light, confocal and electron microscope studies were conducted on different severity scale patterns of diseased plants. Lasiodiplodia-antisera was checked for cross reactivity against common cashew plants fungi. Optical microscopy analysis revealed a longitudinally sectioned hyphae located within the xylem vessels, showing an extensive hyphal development in the secondary xylem tissue. SEM images demonstrated that the fungus was found in some asymptomatic samples, particularly within the xylem vessels as confirmed by the optical images. Symptomatic sample images showed an extensive distribution of the fungus along the secondary xylem, within the vessels, infecting xylem parenchyma. A closer look in the secondary xylem parenchyma reveals a heavy and profuse invasion of the cells with a distinguishable cell wall disintegration and fully hyphae dispersal. There was no reactivity of Lasiodiplodia-antisera against mycelial extracts of Colletotrichum gloeosporioides, Phomopsis anardii and Pestalotiopsis guepinii. Following incubation of sections with the polyclonal antisera, the hyphae were intensely and regularly labeled. Rays, vessels and parenchyma cells were the preferred pathway for L. theobromae colonization. Artificial infection provides the information that the vascular cylinder is undoubtedly employed and used by the fungus for hyphae distribution. Immunofluorescence assay employed in situ was applied and the polyclonal antisera produced was able to recognize the fungus and proved to be a sensitive technique to detect it.

Non-laxative CT colonography with barium-based faecal tagging: is additional phosphate enema beneficial and well tolerated?

OBJECTIVE: The purpose of this study was to investigate the efficacy and tolerance of an additional phosphate enema prior to non-laxative CT colonography (CTC). METHODS: 71 patients (mean age 80 years, 28 male, 43 female) underwent non-laxative CTC following 4 oral doses of diluted 2% w/w barium sulphate. Patients were invited to self-administer a phosphate enema 2 h before CTC. An experienced observer graded the volume of retained stool (1 (nil) to 4 (>75% bowel circumference coated)), retained fluid ((1 (nil) to 4 (>50% circumference obscured)), retained stool tagging quality (1 (untagged) to 5 (≥75% to 100%) tagged) and confidence a polyp ≥6 mm could be excluded (yes/no) for each of six colonic segments. Tolerance of the enema was assessed via questionnaire. Data were analysed between those using and not using the enema by Mann-Whitney and Fisher's exact test. 18/71 patients declined the enema. RESULTS: There was no reduction in residual stool volume with enema use compared with non-use either overall (mean score 2.6 vs 2.7, p = 0.76) or in the left colon (mean 2.3 vs 2.4, p = 0.47). Overall tagging quality was no different (mean score 4.4 vs 4.3, p = 0.43). There was significantly more retained left colonic fluid post enema (mean score 1.9 vs 1.1, p<0.0001), and diagnostic confidence in excluding polyps was significantly reduced (exclusion not possible in 35% segments vs 21% without enema, p = 0.006). Of 53 patients, 30 (56%) found the enema straightforward to use, but 4 (8%) found it unpleasant. CONCLUSION: Phosphate enema use prior to non-laxative CTC leads to greater retained fluid, reducing diagnostic confidence, and is not recommended.

Localization, growth, and inactivation of Salmonella Saintpaul on jalapeño peppers.

Consumption of Salmonella-contaminated jalapeño peppers has been implicated in one of the largest foodborne illness outbreaks in the summer of 2008. The objective of this study was to investigate representative groups of native microflora and the distribution, growth, and inactivation of experimentally-inoculated Salmonella Saintpaul on jalapeño peppers. Two genetically modified strains of Salm. Saintpaul producing either green- or red-fluorescent protein were constructed and used in the study. Microbiological analyses showed that jalapeño peppers contained an average of 5.6 log units of total aerobic count and 3.5, 1.8, and 1.9 log units, respectively, of enterobacteriaceae, lactic acid bacteria, and yeast/mold per gram of tissue. Strains typical of Pseudomonas accounted for 8.3% of total aerobic count, and 0.2% of which exhibited pectolytic activity. On inoculated peppers, a vast majority (>90%) of Salm. Saintpaul was recovered from stem/calyx and only a small proportion recovered from fleshy pods. Growth of Salm. Saintpaul on peppers was indicated by an increase in the population of 3 log units after incubation of samples at 20 degrees C for 48 h. Fluorescent Salm. Saintpaul aggregates could be readily detected on stem/calyx using stereofluorescence imaging microscopy and scanning electron microscopy. Data presented showed that Salm. Saintpaul could survive for at least 8 wk on peppers stored at 4 degrees C. Immersion of inoculated peppers in 200 ppm of sodium hypochlorite, acidified sodium chlorite, or peroxy acetic acid for 10 min could reduce the number of Salm. Saintpaul on stem/calyx by 1.5 to 1.7 and that on flesh by 2.1 to 2.4 log units. Practical Application: Consumption of Salmonella-contaminated jalapeño peppers has been implicated in foodborne illness outbreaks. The vast majority of Salmonella Saintpaul recovered from inoculated jalapeño peppers (>90%) was from stem/calyx. Salmonella increased by 3 log units during storage at 68 degrees F (20 degrees C) for 48 h. Salmonella could survive for at least 8 wk on peppers stored at 4 degrees C. Immersion of inoculated peppers in 200 ppm of sodium hypochlorite, acidified sodium chlorite, or peroxyacetic acid for 10 min reduced Salmonella on stem/calyx by 1.5 to 1.7 log units, compared with reductions of 2.1 to 2.4 log units on flesh. These results highlight the need to consider the stem/calyx as the most likely area for contamination of jalapeño peppers, and to process this commodity accordingly to minimize exposure and cross-contaminations.

The advantages gained by the use of modern materials in the post operative casting procedure for foot and ankle surgery.

BACKGROUND: In June 2006, the post operative plaster immobilisation protocol for patients undergoing hindfoot and ankle surgery, at our institution, changed from multiple plaster changes to the immediate application of a definitive removable and reusable split synthetic cast. This study aims to assess the savings to the hospital and patient, following this change in practice. METHODS: A retrospective analysis of plaster room records from June 2005 to June 2007 was performed. The difference in cost to the hospital of the two different post operative journeys was then calculated. RESULTS: Two-hundred and twenty-two patients from 2005 to 2006 were managed at a total cost of 97,125 euro. From 2006 to 2007, 203 patients were managed with the new technique at a total cost of 37,860 euro. The net saving to the hospital of this change in practice was 251 euro per patient and 50,953 euro in total, while 203 patient visits and costs associated therewith were also saved. CONCLUSIONS: This study demonstrates how small changes in local practice can result in significant financial and temporal savings for hospitals and patients.

Cultivation of 'Candidatus Liberibacter asiaticus', 'Ca. L. africanus', and 'Ca. L. americanus' associated with huanglongbing.

A new medium designated Liber A has been designed and used to successfully cultivate all three 'Candidatus Liberibacter spp.,' the suspect causative agents of huanglongbing (HLB) in citrus. The medium containing citrus vein extract and a growth factor sustained growth of 'Ca. Liberibacter spp.' for four or five single-colony transfers before viability declined. Colonies, positive for 'Ca. L. asiaticus' by a 16s-based rDNA real-time polymerase chain reaction (RT-PCR) assay and sequencing, were irregular-shaped, convex, and 0.1 to 0.3 mm after 3 to 4 days. Suspect 'Ca. L. asiaticus' and 'Ca. L. americanus' cells were observed in infected tissue and on agar culture by scanning electron microscopy. The cells were ovoid to rod shaped, 0.3 to 0.4 by 0.5 to 2.0 microm, often with fimbriae-like appendages. Two strains of 'Ca. L. asiaticus' and one of 'Ca. L. americanus' grown on Liber A medium were pathogenic on citrus and could be isolated from noninoculated tissues of inoculated trees and seedlings 9 and 2 months later, respectively. The identity was confirmed by RT-PCR and 16s rDNA sequencing. This is the first report of the cultivation and pathogenicity of 'Ca. L. asiaticus' and 'Ca. L. americanus' associated with symptoms of HLB.

Ultraviolet light (254 nm) inactivation of Listeria monocytogenes on frankfurters that contain potassium lactate and sodium diacetate.

Listeria monocytogenes, a psychrotrophic foodborne pathogen, is an occasional postprocess contaminant on ready-to-eat meat (RTE) products including frankfurters. Ultraviolet C light (UVC) is an FDA-approved technology for the decontamination of food surfaces. In this study, the ability of UVC to inactivate L. monocytogenes on frankfurters that contained potassium lactate (PL) and sodium diacetate (SDA), either before or after packaging, was investigated. UVC irradiation of frankfurters that were surface-inoculated with L. monocytogenes resulted in a 1.31, 1.49, and 1.93 log reduction at doses of 1, 2, and 4 J/cm(2), respectively. UVC treatment had no effect on frankfurter color or texture at UVC doses up to 4 J/cm(2). Frankfurter meat treated with UVC doses up to 16 J/cm(2) did not increase mutagenesis in bacterial or human cells, either with or without exogenous metabolic activation. UVC treatment of single-layer frankfurter packs at a dose of 2 J/cm(2) resulted in a 0.97 (+/- 0.14) log reduction of L. monocytogenes. Following 8 wk of refrigerated storage L. monocytogenes levels decreased by only 0.65 log in non-UVC-treated frankfurter packs compared with 2.5 log in the UVC-treated packs. Because the numbers of L. monocytogenes associated with contaminations of ready-to-eat meats are typically very low, the use of UVC in combination with potassium lactate and sodium diacetate has the potential to reduce the number of frankfurter recalls and foodborne illness outbreaks.