Anal duplication: is surgery indicated? A report of three cases and review of the literature.

AIM OF THE STUDY: Anal canal duplications (ACDs) are extremely rare with only approximately 90 cases described in the literature. We report on three additional patients. METHODS: Cases were analyzed to evaluate presenting symptoms, physical exam and MRI findings. A comprehensive literature review was performed to compare our patients to previously described cases. IRB approval was obtained for this study (19-0394). MAIN RESULTS: The first female patient presented with an asymptomatic ACD at 2 years old. The second patient was a 13-year-old female with perianal drainage that was initially mistaken for a fistula-in-ano and ultimately found to have an ACD associated with a dermoid cyst. Both posterior midline duplications shared a common wall with the rectum, but did not communicate with it. The ACDs and dermoid cyst were successfully excised through a posterior sagittal approach with no postoperative complications. Histology demonstrated the presence of both squamous epithelium and transitional anal epithelium in each case. The third patient was 8 months old and had a tethered cord, hemisacrum, presacral mass, and anal duplication that was initially undiagnosed. These results corroborate patterns identified in other reports of ACDs with over 90% being female and in the posterior midline. The majority are asymptomatic, but may present with symptoms of local or even systemic infection. CONCLUSION: An opening in the midline posterior to the anus should raise clinical suspicion for anal canal duplication. An associated presacral mass must be ruled out. Complete excision through a posterior sagittal approach is recommended upon diagnosis to avoid symptomatic presentations. The key part of the operation is the separation of the ACD from the posterior rectal wall.

Cognitive, physical, and mental health outcomes between long-term cannabis and tobacco users.

INTRODUCTION: Cannabis intoxication adversely affects health, yet persistent effects following short-term abstinence in long-term cannabis users are unclear. This matched-subjects, cross-sectional study compared health outcomes of long-term cannabis and long-term tobacco-only users, relative to population norms. METHODS: Nineteen long-term (mean 32.3years of use, mean age 55.7years), abstinent (mean 15h) cannabis users and 16 long-term tobacco users (mean 37.1years of use, mean age 52.9years), matched for age, educational attainment, and lifetime tobacco consumption, were compared on measures of learning and memory, response inhibition, information-processing, sustained attention, executive control, and mental and physical health. RESULTS: Cannabis users exhibited poorer overall learning and delayed recall and greater interference and forgetting than tobacco users, and exhibited poorer recall than norms. Inhibition and executive control were similar between groups, but cannabis users had slower reaction times during information processing and sustained attention tasks. Cannabis users had superior health satisfaction and psychological, somatic, and general health than tobacco users and had similar mental and physical health to norms whilst tobacco users had greater stress, role limitations from emotional problems, and poorer health satisfaction. CONCLUSIONS: Long-term cannabis users may exhibit deficits in some cognitive domains despite short-term abstinence and may therefore benefit from interventions to improve cognitive performance. Tobacco alone may contribute to adverse mental and physical health outcomes, which requires appropriate control in future studies.

Hepatic Hilar Lymph Node Reactivity at Kasai Portoenterostomy for Biliary Atresia: Correlations With Age, Outcome, and Histology of Proximal Biliary Remnant.

We hypothesized that if infection is the proximate cause of congenital biliary atresia, an appropriate response to antigen would occur in lymph nodes contiguous with the biliary remnant. We compared the number of follicular germinal centers (GC) in 79 surgically excised hilar lymph nodes (LN) and 27 incidentally discovered cystic duct LNs in 84 subjects at the time of hepatic portoenterostomy (HPE) for biliary atresia (BA) to autopsy controls from the pancreaticobiliary region of non-septic infants >3 months old at death. All 27 control LN lacked GC, a sign in infants of a primary response to antigenic stimulation. GC were found in 53% of 106 LN in 56 of 84 subjects. Visible surgically excised LN contiguous with the most proximal biliary remnants had 1 or more well-formed reactive GC in only 26/51 subjects. Presence of GC and number of GC/LN was unrelated to age at onset of jaundice or to active fibroplasia in the biliary remnant but was related to older age at HPE. Absent GC in visible and incidentally removed cystic duct LNs predicted survival with the native liver at 2 and 3 years after HPE, P = .03, but significance was lost at longer intervals. The uncommon inflammatory lesions occasionally found in remnants could be secondary either to bile-induced injury or secondary infection established as obstruction evolves. The absence of consistent evidence of antigenic stimulation in LN contiguous with the biliary remnant supports existence of at least 1 major alternative to infection in the etiology of biliary atresia.

Clinical trials of medicinal cannabis for appetite-related symptoms from advanced cancer: a survey of preferences, attitudes and beliefs among patients willing to consider participation.

BACKGROUND: Australian clinical trials are planned to evaluate medicinal cannabis in a range of clinical contexts. AIMS: To explore the preferences, attitudes and beliefs of patients eligible and willing to consider participation in a clinical trial of medicinal cannabis for poor appetite and appetite-related symptoms from advanced cancer. METHODS: A cross-sectional anonymous survey was administered from July to December 2015 online and in eight adult outpatient palliative care and/or cancer services. Respondents were eligible if they were ≥18 years, had advanced cancer and poor appetite/taste problems/weight loss and might consider participating in a medicinal cannabis trial. Survey items focused on medicinal rather than recreational cannabis use and did not specify botanical or pharmaceutical products. Items asked about previous medicinal cannabis use and preferences for delivery route and invited comments and concerns. RESULTS: There were 204 survey respondents, of whom 26 (13%) reported prior medicinal cannabis use. Tablets/capsules were the preferred delivery mode (n = 144, 71%), followed by mouth spray (n = 84, 42%) and vaporiser (n = 83, 41%). Explanations for preferences (n = 134) most commonly cited convenience (n = 66; 49%). A total of 82% (n = 168) of respondents indicated that they had no trial-related concerns, but a small number volunteered concerns about adverse effects (n = 14) or wanted more information/advice (n = 8). Six respondents volunteered a belief that cannabis might cure cancer, while two wanted assurance of efficacy before participating in a trial. CONCLUSION: Justification of modes other than tablets/capsules and variable understanding about cannabis and trials will need addressing in trial-related information to optimise recruitment and ensure that consent is properly informed.

Factors that affect fractured neck of femur outcome: Clinical commissioning groups influence length of stay and discharge destination.

BACKGROUND: The average length of stay (LOS) following a hip fracture in hospitals around the UK has been approximately 20 days in recent years. This can vary between hospitals and there are numerous factors that can affect LOS. We had the impression that LOS varied by Clinical Commissioning Group (CCG) from which the patient originates. The aim of our study was to discover whether the concern was valid, and if so, what the reasons may be. METHODS: We analysed hip fracture data collected at our Trust between September 2008 and December 2014. LOS was compared for each of three CCGs in our Trust's catchment areas, and those patients admitted from outlying CCGs. Sub-analysis was performed by patient age, ASA grade, abbreviated mental test score, procedure type and discharge destination to determine which factors influence LOS. RESULTS: 1847 patients were identified. After excluding deaths, missing data and extreme outliers, 1603 patients were included in the analysis. The median LOS varied from 14.9 to 23.4 days across CCGs. The major reason for this variation was discharge destination. CCGs associated with longer LOS had a significantly higher rate of discharge to the patient's own home, rather than institutional care. This was independent of patient age, mental status, ASA grade and promptness of surgery. CONCLUSION: We have shown that CCGs vary in their performance to aid discharge. This directly influences a Trust's performance on the National Hip Fracture Database. Compared with other hospitals, our results show a poor outcome in terms of length of stay, but much better performance regarding home discharge. We recommend that more emphasis in future be placed on discharge destination than LOS.

Does a 'direct' transfer protocol reduce time to coronary angiography for patients with non-ST-elevation acute coronary syndromes? A prospective observational study.

OBJECTIVE: National guidelines recommend 'early' coronary angiography within 96 h of presentation for patients with non-ST elevation acute coronary syndromes (NSTE-ACS). Most patients with NSTE-ACS present to their district general hospital (DGH), and await transfer to the regional cardiac centre for angiography. This care model has inherent time delays, and delivery of timely angiography is problematic. The objective of this study was to assess a novel clinical care pathway for the management of NSTE-ACS, known locally as the Heart Attack Centre-Extension or HAC-X, designed to rapidly identify patients with NSTE-ACS while in DGH emergency departments (ED) and facilitate transfer to the regional interventional centre for 'early' coronary angiography. METHODS: This was an observational study of 702 patients divided into two groups; 391 patients treated before the instigation of the HAC-X pathway (Pre-HAC-X), and 311 patients treated via the novel pathway (Post-HAC-X). Our primary study end point was time from ED admission to coronary angiography. We also assessed the length of hospital stay. RESULTS: Median time from ED admission to coronary angiography was 7.2 (IQR 5.1-10.2) days pre-HAC-X compared to 1.0 (IQR 0.7-2.0) day post-HAC-X (p<0.001). Median length of hospital stay was 3.0 (IQR 2.0-6.0) days post-HAC-X v 9.0 (IQR 6.0-14.0) days pre-HAC-X (p<0.0005). This equates to a reduction of six hospital bed days per NSTE-ACS admission. CONCLUSIONS: The introduction of this novel care pathway was associated with significant reductions in time to angiography and in total hospital bed occupancy for patients with NSTE-ACS.

Non-Fickian diffusion and the accumulation of methane bubbles in deep-water sediments.

In the absence of fractures, methane bubbles in deep-water sediments can be immovably trapped within a porous matrix by surface tension. The dominant mechanism of transfer of gas mass therefore becomes the diffusion of gas molecules through porewater. The accurate description of this process requires non-Fickian diffusion to be accounted for, including both thermal diffusion and gravitational action. We evaluate the diffusive flux of aqueous methane considering non-Fickian diffusion and predict the existence of extensive bubble mass accumulation zones within deep-water sediments. The limitation on the hydrate deposit capacity is revealed; too weak deposits cannot reach the base of the hydrate stability zone and form any bubbly horizon.

A case-control study examining inconsistencies in pain management following fractured neck of femur: an inferior analgesia for the cognitively impaired.

Previous research suggests individuals who suffer from cognitive impairment are less able to vocalise pain than the rest of the cognitively-intact population. This feature of cognitive impairment may be leading to a chronic underdetection of pain as current assessment tools strongly rely on the participation of the patient. To explore inconsistencies in pain management within the acute setting, we conducted a retrospective assessment of 224 patients presenting with fractured neck of femur at a large teaching hospital's accident and emergency (A&E) department between 2 June 2011 and 2 June 2012. These patients were split into either a cognitively-impaired or cognitively-intact cohort based on their Abbreviated Mental Test Scores. Patients with cognitive impairment, on average, received a weaker level of analgesia than individuals without impairment both in the ambulance and in A&E. In the ambulance, 45% of cognitively-impaired patients were prescribed no pain relief compared with just 8% of those individuals who remain cognitively intact. After arrival at A&E, these inconsistencies continued with 69% of the cognitively-intact cohort receiving the strongest opioid analgesia compared with just 37% of the cognitively-impaired cohort. The cognitively-impaired cohort would also wait on average an hour longer before receiving this initial pain relief. We believe that these differences stem from cognitively-impaired patients being unable to vocalise their pain through traditional assessment methods. This work discusses the potential development or adoption of a tool which can be applied in the acute setting and relies less on vocalisation but more on the objective features of pain, so making it applicable to cognitively-impaired individuals.

Optimal patient education for cancer pain: a systematic review and theory-based meta-analysis.

PURPOSE: Previous systematic reviews have found patient education to be moderately efficacious in decreasing the intensity of cancer pain, but variation in results warrants analysis aimed at identifying which strategies are optimal. METHODS: A systematic review and meta-analysis was undertaken using a theory-based approach to classifying and comparing educational interventions for cancer pain. The reference lists of previous reviews and MEDLINE, PsycINFO, and CENTRAL were searched in May 2012. Studies had to be published in a peer-reviewed English language journal and compare the effect on cancer pain intensity of education with usual care. Meta-analyses used standardized effect sizes (ES) and a random effects model. Subgroup analyses compared intervention components categorized using the Michie et al. (Implement Sci 6:42, 2011) capability, opportunity, and motivation behavior (COM-B) model. RESULTS: Fifteen randomized controlled trials met the criteria. As expected, meta-analysis identified a small-moderate ES favoring education versus usual care (ES, 0.27 [-0.47, -0.07]; P = 0.007) with substantial heterogeneity (I² = 71 %). Subgroup analyses based on the taxonomy found that interventions using "enablement" were efficacious (ES, 0.35 [-0.63, -0.08]; P = 0.01), whereas those lacking this component were not (ES, 0.18 [-0.46, 0.10]; P = 0.20). However, the subgroup effect was nonsignificant (P = 0.39), and heterogeneity was not reduced. Factoring in the variable of individualized versus non-individualized influenced neither efficacy nor heterogeneity. CONCLUSIONS: The current meta-analysis follows a trend in using theory to understand the mechanisms of complex interventions. We suggest that future efforts focus on interventions that target patient self-efficacy. Authors are encouraged to report comprehensive details of interventions and methods to inform synthesis, replication, and refinement.

Epigenetic changes in the progression of Alzheimer's disease.

The formation of 5-hydroxymethylcytosine (5hmC), a key intermediate of DNA demethylation, is driven by the ten eleven translocation (TET) family of proteins that oxidize 5-methylcytosine (5mC) to 5hmC. To determine whether methylation/demethylation status is altered during the progression of Alzheimer's disease (AD), levels of TET1, 5mC and subsequent intermediates, including 5hmC, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) were quantified in nuclear DNA from the hippocampus/parahippocampal gyrus (HPG) and the cerebellum of 5 age-matched normal controls, 5 subjects with preclinical AD (PCAD) and 7 late-stage AD (LAD) subjects by immunochemistry. The results showed significantly (p < 0.05) increased levels of TET1, 5mC, and 5hmC in the HPG of PCAD and LAD subjects. In contrast, levels of 5fC and 5caC were significantly (p < 0.05) decreased in the HPG of PCAD and LAD subjects. Overall, the data suggest altered methylation/demethylation patterns in vulnerable brain regions prior to the onset of clinical symptoms in AD suggesting a role in the pathogenesis of the disease.

Demographics of 3929 ankle injuries, seasonal variation in diagnosis and more fractures are diagnosed in winter.

INTRODUCTION: An audit took place to look at the diagnostic or pick-up rate of ankle fractures. A seasonal variation was discovered. Although it is expected that more fractures may be seen in wet or icy periods, an excess of X-rays taken in the summer months has not been previously registered. METHOD: An automated X-ray system was looked at to see the number of X-rays taken and the diagnostic yield. RESULTS: We reviewed ankle X-rays of 3929 patients over a 24-month period between 1 July 2009 and 31 June 2011; of which, 612 patients were found to have fractured their ankle giving a pick-up rate of 0.16. This is less than what might be expected with strict application of Ottawa rules. The pick-up rate fluctuated each month from an admirable 0.35 fractures per X-ray ordered in December 2009 to a lowly 0.06 fractures per X-ray in May 2010. The same pattern was noted for the other year. For both Decembers, the fewest number of X-rays were taken at 80 and 140, the most at 200 and 240 in May for both years. Less X-rays were taken in for all winter months. For younger age groups, males dominated with the crossover to females dominating in the fifth decade. CONCLUSION: We postulate that summertime sports and recreational injuries may cause less fractures than at winter periods but result in more X-rays taken. We have reviewed our practice to try to improve our diagnostic rates; the basic tenets of Ottawa rules including the presence of bony tenderness and weight-bearing status have been reinforced in our teaching sessions. It is highly likely that strict application of these methods will decrease the number of X-rays taken and improve our pick-up rates.

Adaptation to the chicken intestine in Salmonella Enteritidis PT4 studied by transcriptional analysis.

The transcriptional changes that occurred in Salmonella enterica serovar Enteritidis during colonization of the alimentary tract of newly hatched chickens were studied. A whole genome oligonucleotide microarray was used to compare the expression pattern with that from bacteria cultured in nutrient broth in vitro. Amongst other changes Salmonella Pathogenicity Island (SPI)-1, SPI-2 and SPI-5 genes were up-regulated in vivo suggesting a close association with the mucosa during colonization. Particular attention was paid to genes associated with metabolism of dicarboxylic acids and to responses to high osmolarity. Association between the colonization phenotype and gene mutations indicated that the latter was more important as a contribution to the colonization phenotype.

Salmonella enterica serovar typhimurium colonizing the lumen of the chicken intestine grows slowly and upregulates a unique set of virulence and metabolism genes.

The pattern of global gene expression in Salmonella enterica serovar Typhimurium bacteria harvested from the chicken intestinal lumen (cecum) was compared with that of a late-log-phase LB broth culture using a whole-genome microarray. Levels of transcription, translation, and cell division in vivo were lower than those in vitro. S. Typhimurium appeared to be using carbon sources, such as propionate, 1,2-propanediol, and ethanolamine, in addition to melibiose and ascorbate, the latter possibly transformed to d-xylulose. Amino acid starvation appeared to be a factor during colonization. Bacteria in the lumen were non- or weakly motile and nonchemotactic but showed upregulation of a number of fimbrial and Salmonella pathogenicity island 3 (SPI-3) and 5 genes, suggesting a close physical association with the host during colonization. S. Typhimurium bacteria harvested from the cecal mucosa showed an expression profile similar to that of bacteria from the intestinal lumen, except that levels of transcription, translation, and cell division were higher and glucose may also have been used as a carbon source.

Increased levels of 4-hydroxynonenal and acrolein in the brain in preclinical Alzheimer disease.

Previous studies demonstrate increased levels of 4-hydroxynonenal (HNE) and acrolein in vulnerable brain regions of subjects with mild cognitive impairment and late-stage Alzheimer disease (LAD). Recently preclinical AD (PCAD) subjects, who demonstrate normal antemortem neuropsychological test scores but abundant AD pathology at autopsy, have become the focus of increased study. Levels of extractable HNE and acrolein were quantified by gas chromatography-mass spectrometry with negative chemical ionization, and protein-bound HNE and acrolein were quantified by dot-blot immunohistochemistry in the hippocampus/parahippocampal gyrus (HPG), superior and middle temporal gyri (SMTG), and cerebellum (CER) of 10 PCAD and 10 age-matched normal control (NC) subjects. Results of the analyses show a significant (P<0.05) increase in levels of extractable acrolein in the HPG of PCAD subjects compared to age-matched NC subjects and a significant decrease in extractable acrolein in PCAD CER. Significant increases in protein-bound HNE in HPG and a significant decrease in CER of PCAD subjects compared to NC subjects were observed. No significant alterations were observed in either extractable or protein-bound HNE or acrolein in the SMTG of PCAD subjects. Additionally, no significant differences in levels of protein carbonyls were observed in the HPG, SMTG, or CER of PCAD subjects compared to NC subjects.

Femoral cement pressurisation for hip arthroplasty in previously fixated hips: an experimental study.

INTRODUCTION: It is common to use a cemented total hip replacement following failed hip screw fixation of a fractured femoral neck; this solution, however, is complicated by the presence of the holes that are left in the femur when the screws are removed. These holes can allow cement to leak out while being pressurised. The aim of this study was to look at the cement femoral pressures proximally and distally in a sawbone model with pre-drilled holes to assess if the commonest surgical technique of occluding the holes with fingers could maintain the cement pressure high enough. MATERIALS AND METHODS: We used eight synthetic proximal femurs, four with dynamic hip screw holes drilled in them on the lateral surface ("drilled femurs") and four with no holes ("undrilled femurs"). We used pressure sensors positioned in holes drilled in the proximal and distal parts of the medial surface to measure the pressure in the cement as it was being delivered and pressurised into the femur canal. The tests were conducted while the femur was clamped at its distal end and, in the case of the drilled femurs, while the screw holes were occluded manually. RESULTS: We found that on the proximal side, the peak cement pressure in undrilled femurs was significantly greater than in drilled femurs (p=0.006). On the distal side, the difference in peak cement pressure between the two study groups was not significant (p=0.22). At both the proximal and distal positions, the time over which the cement pressure exceeded both 5 and 100 kPa was significantly longer in undrilled femurs than in drilled femurs (p<0.05). CONCLUSION: Our results show that it is difficult to fully occlude the drill holes completely with finger tips, especially when using pressurised cement. There are significant differences in the peak cement pressures between drilled and undrilled femurs with possible consequences for patients undergoing total hip replacement.

The contribution of genes required for anaerobic respiration to the virulence of Salmonella enterica serovar Gallinarum for chickens

Salmonella enterica serovar Gallinarum (SG) is an intracellular pathogen of chickens. To survive, to invade and to multiply in the intestinal tract and intracellularly it depends on its ability to produce energy in anaerobic conditions. The fumarate reductase (frdABCD), dimethyl sulfoxide (DMSO)-trimethylamine N-oxide (TMAO) reductase (dmsABC), and nitrate reductase (narGHIJ) operons in Salmonella Typhimurium (STM) encode enzymes involved in anaerobic respiration to the electron acceptors fumarate, DMSO, TMAO, and nitrate, respectively. They are regulated in response to nitrate and oxygen availability and changes in cell growth rate. In this study mortality rates of chickens challenged with mutants of Salmonella Gallinarum, which were defective in utilising anaerobic electron acceptors, were assessed in comparison to group of bird challenged with wild strain. The greatest degree of attenuation was observed with mutations affecting nitrate reductase (napA, narG) with additional attenuations induced by a mutation affecting fumarate reductase (frdA) and a double mutant (dmsA torC) affecting DMSO and TMAO reductase.

Does the number of trauma lists provided affect care and outcome of patients with fractured neck of femur?

INTRODUCTION: Delay in surgery for fractured neck of femur is associated with increased mortality; it is recommended that patients with fractured neck of femur are operated within 48 h. North West hospitals provide dedicated trauma lists, as recommended by the British Orthopaedic Association, to allow rapid access to surgery. We investigated trauma list provision by each trust and its effects on the time taken to get neck of femur patients to surgery and patient survival. PATIENTS AND METHODS: The number of trauma lists provided by 13 acute trusts was determined by telephone interview with the theatre manager. Data on operating delays, reasons for delay and 30-day mortality were obtained from the Greater Manchester and Wirral fractured neck of femur audit. RESULTS: A total of 883 patients were included in the audit (35-126 per hospital). Overall, 5-15 trauma lists were provided each week, and 80% of lists were consultant-led. Of patients, 31.8% were operated on within 24 h and 36.9% were delayed more than 48 h; 37.7% of delays were for non-medical reasons. The 30-day mortality rates varied between 5-19% (mean, 11.8%). There were no significant relationships between the number of trauma lists and these variables. When divided into hospitals with > 10 lists per week (n = 6) and those with < 10 lists per week (n = 7) there were no significant differences in 48-h delay, non-medical delay or mortality. However, 24-h delay showed a trend to be lower in those with > 10 lists (34.6% of patients versus 28.9%; P = 0.09). CONCLUSIONS: Most trusts provided at least one dedicated daily list. This study shows that extra lists may enable trusts to cope better with fractured neck of femur but do not change mortality.

The contribution of genes required for anaerobic respiration to the virulence of Salmonella enterica serovar Gallinarum for chickens.

Salmonella enterica serovar Gallinarum (SG) is an intracellular pathogen of chickens. To survive, to invade and to multiply in the intestinal tract and intracellularly it depends on its ability to produce energy in anaerobic conditions. The fumarate reductase (frdABCD), dimethyl sulfoxide (DMSO)-trimethylamine N-oxide (TMAO) reductase (dmsABC), and nitrate reductase (narGHIJ) operons in Salmonella Typhimurium (STM) encode enzymes involved in anaerobic respiration to the electron acceptors fumarate, DMSO, TMAO, and nitrate, respectively. They are regulated in response to nitrate and oxygen availability and changes in cell growth rate. In this study mortality rates of chickens challenged with mutants of Salmonella Gallinarum, which were defective in utilising anaerobic electron acceptors, were assessed in comparison to group of bird challenged with wild strain. The greatest degree of attenuation was observed with mutations affecting nitrate reductase (napA, narG) with additional attenuations induced by a mutation affecting fumarate reductase (frdA) and a double mutant (dmsA torC) affecting DMSO and TMAO reductase.