Prolonged interval to surgery following neoadjuvant chemoradiotherapy in locally advanced rectal cancer: A meta-analysis of randomized controlled trials.

BACKGROUND: Long-course neoadjuvant chemoradiotherapy (NCRT), followed by surgery after an interval of 6-8 weeks, represents standard of care for patients with locally advanced rectal cancer (LARC). Increasing this interval may improve rates of complete pathological response (pCR) and tumour downstaging. We performed a meta-analysis comparing standard (SI, within 8 weeks) versus longer (LI, after 8 weeks) interval from NCRT to surgery. METHODS: PubMed, Embase, and Cochrane databases were searched up to 31 August 2022. Randomized controlled trials (RCTs) comparing SI with LI after NCRT for LARC were included. The primary endpoint was pCR rate. Secondary endpoints included rates of R0 resection, circumferential resection margin positivity (+CRM), TME completeness, lymph node yield (LNY), operative duration, tumour downstaging (TD), sphincter preservation, mortality, postoperative complications, surgical site infection (SSI) and anastomotic leak (AL). Random effects models were used to calculate pooled effect size estimates. RESULTS: Four RCTs encompassing 867 patients were included. There were 539 males (62.1%). LI was associated with a higher pCR rate (OR 0.61, 95%CI â€‹= â€‹0.39-0.95, p â€‹= â€‹0.03), and more TD (OR 0.60, 95%CI â€‹= â€‹0.37-0.97, p â€‹= â€‹0.04) compared to SI. However, there was no difference in rates of R0 resection (p â€‹= â€‹0.87), +CRM (p â€‹= â€‹0.66), sphincter preservation (p â€‹= â€‹0.26), incomplete TME (p â€‹= â€‹0.49), LNY (p â€‹= â€‹0.55), SSI (p â€‹= â€‹0.33), AL (p â€‹= â€‹0.20), operative duration (p â€‹= â€‹0.07), mortality (p â€‹= â€‹0.89) or any surgical complication (p â€‹= â€‹0.91). CONCLUSIONS: A LI to surgery after NCRT for LARC increases pCR and TD rates. Local recurrence or survival were not assessed due to unavailable data. We recommend deferring TME until after an interval of 8 weeks following completion of NCRT.

Excisional haemorrhoidectomy: is it safe in patients with an ileal pouch-anal anastomosis?

AIM: Excisional haemorrhoidectomy in patients with ulcerative colitis (UC), especially those undergoing an ileal pouch-anal anastomosis (IPAA), remains controversial. The aim of our study was to determine the safety of excisional haemorrhoidectomy in UC patients with and without an IPAA. METHOD: A retrospective review of all adult UC patients undergoing excisional haemorrhoidectomy between 1 January 1995 and 1 January 2019 at a tertiary inflammatory bowel disease referral centre was performed. Data collected included patient demographics, clinical characteristics of UC, prior surgical intervention for UC (colectomy, IPAA) and complications after haemorrhoidectomy. RESULTS: Forty-one adult patients [50% male; median age 52 (range 25-79) years] with UC underwent excisional haemorrhoidectomy between 1 January 1995 and 1 January 2019. The majority (n = 23) had not previously undergone surgery for UC. However, eight had already undergone construction of an IPAA at the time of haemorrhoidectomy, seven had IPAA at the time of haemorrhoidectomy and three had an IPAA constructed subsequent to haemorrhoidectomy. Two (4.9%) patients need to go back to theatre for postoperative bleeding. There were no further 30-day complications or long-term nonhealing of the surgical site. There were no pouch complications in those who had haemorrhoidectomy at the time of IPAA construction or in the presence of an IPAA. CONCLUSION: Our data suggest that excisional haemorrhoidectomy may be performed safely in carefully selected UC patients with symptomatic haemorrhoids with or without IPAA and even at the time of IPAA construction.

A qualitative analysis of radiography students' reflective essays regarding their experience of clinical placement during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic significantly impacted healthcare services and clinical placement for healthcare students. There is a paucity of qualitative research into radiography students' experiences of clinical placement during the pandemic. METHOD: Students in stages three and four of a 4-year BSc Radiography degree in Ireland wrote reflective essays regarding their experience of clinical placement during the COVID-19 healthcare crisis. Permission was granted by 108 radiography students and recent graduates for their reflections to be analysed as part of this study. A thematic approach to data analysis was used, allowing themes to emerge from the reflective essays. Two researchers independently coded each reflective essay using the Braun and Clarke model. RESULTS: Four themes were highlighted; 1) Challenges associated with undertaking clinical placement during the pandemic, such as reduced patient throughput and PPE-related communication barriers; 2) Benefits of clinical placement during the pandemic, in terms of personal and professional development and completing degree requirements to graduate without delay; 3) Emotional impact and 4) Supporting students in clinical practice. Students recognised their resilience and felt proud of their contribution during this healthcare crisis but feared transmitting COVID-19 to family. Educational and emotional support provided by tutors, clinical staff and the university was deemed essential by students during this placement. CONCLUSIONS: Despite the pressure hospitals were under during the pandemic, students had positive clinical placement experiences and perceived these experiences to have contributed to their professional and personal growth. IMPLICATIONS FOR PRACTICE: This study supports the argument for clinical placements to continue throughout healthcare crisis periods, albeit with additional learning and emotional support in place. Clinical placement experiences during the pandemic prompted a deep sense of pride amongst radiography students in their profession and contributed to the development of professional identity.

Supporting radiography clinical placements in Ireland during the COVID-19 pandemic: The practice educators perspective.

INTRODUCTION: The COVID-19 pandemic has significantly impacted healthcare services and the clinical learning environment. Several studies have investigated radiography students' experiences of clinical placement during the pandemic; however, few have investigated the Clinical Practice Educator's (CPEs) perspective. CPEs play a pivotal role in supporting clinical education. METHOD: A qualitative study was conducted using a purposeful sample of twenty-two CPEs, each working in a different Irish hospital. Four semi-structured focus groups were used to gather data. To maintain reasonable homogeneity, CPEs who were new to the role (n = 8) were assigned a separate focus group from experienced CPEs (n = 14). Inductive thematic analysis was applied. RESULTS: CPEs experienced role expansion, particularly in managerial and administrative aspects of the role. They described arranging COVID-19 vaccinations locally for radiography students and the complexities of student rostering during the pandemic. CPEs perceived the pandemic to have impacted students' emotional wellbeing with 'high anxiety levels' and 'loneliness' being reported. They also perceived issues with clinical readiness and the student transition to clinical practice. Many challenges were faced by CPEs including arranging clinical recovery time for numerous students when sites were already at full capacity, fewer learning opportunities due to decreased patient throughput and range of imaging examinations, social distancing constraints, resistance from staff to student placements, and a shortage of staff for student supervision. Flexibility, communication, and multi-level support helped CPEs to fulfil their role. CONCLUSION: The results provide insight into how CPEs supported radiography clinical placements during the pandemic and into the challenges faced by CPEs in their role. CPEs supported student placement through multi-level communication, teamwork, flexibility, and student advocacy. IMPLICATIONS FOR PRACTICE: This will aid understanding of the support mechanisms needed by CPEs to provide quality clinical placements.

Student perceptions of the use of three-dimensional (3-D) virtual reality (VR) simulation in the delivery of radiation protection training for radiography and medical students.

BACKGROUND: VR simulation-based learning is increasingly used in healthcare education to prepare students for clinical practice. This study investigates healthcare students' experience of learning radiation safety in a simulated interventional radiology (IR) suite. METHOD: Radiography students (n = 35) and medical students (n = 100) were introduced to 3D VR radiation dosimetry software designed to improve the learners' understanding of radiation safety in IR. Radiography students underwent formal VR training and assessment, which was complemented with clinical placement. Medical students practiced similar 3D VR activities informally without assessment. An online questionnaire containing Likert questions and open-ended questions was used to gather student feedback on the perceived value of VR-based radiation safety education. Descriptive statistics and Mann-Whitney U tests were used to analyse Likert-questions. Open-ended question responses were thematically analysed. RESULTS: A survey response rate of 49% (n = 49) and 77% (n = 27) was obtained from radiography and medical students respectively. Most respondents (80%) enjoyed their 3D VR learning experience, favouring the in-person VR experience to online VR. 73% felt that VR learning enhanced their confidence across all relevant learning outcomes. Whilst confidence was enhanced across both cohorts, VR learning had a greater impact on confidence levels amongst medical students with respect to their understanding of radiation safety matters (U = 375.5, p < 0.01). 3D VR was deemed a valuable assessment tool. CONCLUSION: Radiation dosimetry simulation-based learning in the 3D VR IR suite is perceived to be a valuable pedagogical tool by radiography and medical students and enhances curricula content.

Mycobacterium abscessus in cystic fibrosis lung transplant recipients: report of 2 cases and risk for recurrence.

Mycobacterium abscessus is increasingly recognized as an important pathogen in some individuals with advancing lung disease related to cystic fibrosis (CF). Because of its resistance to antimicrobial agents and virulence, its presence in the lungs of potential lung transplant recipients can be problematic. We present 2 cases of individuals with CF in whom M. abscessus was present in the preoperative sputum cultures. The organism manifested different degrees of invasiveness in the 2 cases after transplantation with different outcomes, suggesting an approach to future candidates for lung transplantation that may be of clinical significance to their physicians and surgeons.

Influence of delays on perforation risk in adults with acute appendicitis.

PURPOSE: This study analyzed whether prehospital or in-hospital delay was the more significant influence on perforation rates for acute appendicitis and whether any clinical feature designated patients requiring higher surgical priority. METHODS: A retrospective analysis was conducted over one year at a tertiary referral hospital without a dedicated emergency surgical theater. Admission notes, theater logbook, and the Hospital Inpatient Enquiry system were reviewed to identify the characteristics and clinical course of patients aged greater than 16 years who were operated upon for histologically confirmed acute appendicitis. RESULTS: One hundred and fifteen patients were studied. The overall perforation rate was 17 percent. The mean duration of symptoms prior to hospital presentation was 38.1 hours with the mean in-hospital waiting time prior to operation being 23.4 hours. Although body temperature on presentation was significantly greater in patients found to have perforated appendicitis (P < 0.05), only patient heart rate at presentation and overall duration of symptoms, but not in-hospital waiting time, independently predicted perforation by stepwise linear regression modeling. CONCLUSION: In-hospital delay was not an independent predictor of perforation in adults with acute appendicitis although delays may contribute if patients are left to wait unduly. Tachycardia at presentation may be a quantifiable feature of those more likely to have perforation and who should be given higher surgical priority.

Weekend surgical handover enhances early management of acute clinical changes using a red flag system.

INTRODUCTION: Recent implementation of the European Working Time Directive in Ireland has resulted in a change from thetraditional model of patient care to a system characterised by shift work among clinicians. Effective handover ofpatient information is essential for transfer of responsibility between clinicians and maintaining continuity of care. The weekend has been identified as a particularly vulnerable transition of patient care. AIMS AND METHODS: Our study aims to determine if implementing a formal face-to-face handover accompanied by an electronictemplate in our surgical department can improve the number of adverse events reported back to the primary teamafter a weekend on call. Data was collected over 12 weekends between February and May 2016. A list of adverseevents was established, and during an initial observation period of 6 weeks, we documented the number of adverseevents that were informally handed over. A 6-week intervention was then performed, involving a formal face-to-facehandover on Monday morning supported by an electronic patient census using a red-flag system to highlightpatients who experienced an adverse event over the weekend. RESULTS: Our results showed the mean number of adverse events recorded pre-intervention was 3.17 ± 0.6 over the 6-week period. Following the introduction of weekend face-to-face handover, there was 147% increase in the number of adverse events recorded with a mean of 7.83 ± 1.2. CONCLUSION: The introduction of a formal face-to-face weekend handover with a red-flag system resulted in increased reporting of patient adverse events, allowing earlier recognition and management.

Activation of direct and indirect pathways of glycogen synthesis by hepatic overexpression of protein targeting to glycogen.

Glycogen-targeting subunits of protein phosphatase-1, such as protein targeting to glycogen (PTG), direct the phosphatase to the glycogen particle, where it stimulates glycogenesis. We have investigated the metabolic impact of overexpressing PTG in liver of normal rats. After administration of PTG cDNA in a recombinant adenovirus, animals were fasted or allowed to continue feeding for 24 hours. Liver glycogen was nearly completely depleted in fasted control animals, whereas glycogen levels in fasted or fed PTG-overexpressing animals were 70% higher than in fed controls. Nevertheless, transgenic animals regulated plasma glucose, triglycerides, FFAs, ketones, and insulin normally in the fasted and fed states. Fasted PTG-overexpressing animals receiving an oral bolus of [U-(13)C]glucose exhibited a large increase in hepatic glycogen content and a 70% increase in incorporation of [(13)C]glucose into glycogen. However, incorporation of labeled glucose accounted for only a small portion of the glycogen synthesized in PTG-overexpressing animals, consistent with our earlier finding that PTG promotes glycogen synthesis from gluconeogenic precursors. We conclude that hepatic PTG overexpression activates both direct and indirect pathways of glycogen synthesis. Because of its ability to enhance glucose storage without affecting other metabolic indicators, the glycogen-targeting subunit may prove valuable in controlling blood glucose levels in diabetes.

Functional and clinical characterization of a mutation in KCNJ2 associated with Andersen-Tawil syndrome.

BACKGROUND: Andersen-Tawil syndrome (ATS) is a rare inherited disorder, characterised by periodic paralysis, cardiac dysarrhythmias, and dysmorphic features, and is caused by mutations in the gene KCNJ2, which encodes the inward rectifier potassium channel, Kir2.1. This study sought to analyse KCNJ2 in patients with familial ATS and to determine the functional characteristics of the mutated gene. METHODS AND RESULTS: We screened a family with inherited ATS for the mutation in KCNJ2, using direct DNA sequencing. A missense mutation (T75R) of Kir2.1, located in the highly conserved cytoplasmic N-terminal domain, was identified in three affected members of this family. Using the Xenopus oocyte expression system and whole cell voltage clamp analyses, we found that the T75R mutant was non-functional and possessed a strong dominant negative effect when co-expressed with the same amount of wild type Kir2.1. Transgenic (Tg) mice expressing the mutated form of Kir2.1 in the heart had prolonged QTc intervals compared with mice expressing the wild type protein. Ventricular tachyarrhythmias were observed in 5 of 14 T75R-Tg mice compared with 1 of 7 Wt-Tg and none of 6 non-transgenic littermates. In three of five T75R-Tg mice with ventricular tachycardia, their ECG disclosed bidirectional tachycardia as in our proband. CONCLUSIONS: The in vitro studies revealed that the T75R mutant of Kir2.1 had a strong dominant negative effect in the Xenopus oocyte expression system. It still preserved the ability to co-assemble and traffic to the cell membrane in mammalian cells. For in vivo studies, the T75R-Tg mice had bidirectional ventricular tachycardia after induction and longer QT intervals.

Cyclooxygenase-1 and -2-dependent prostacyclin formation in patients with atherosclerosis.

BACKGROUND: The formation of prostacyclin (PGI(2)), thromboxane (TX) A(2), and isoprostanes is markedly enhanced in atherosclerosis. We examined the relative contribution of cyclooxygenase (COX)-1 and -2 to the generation of these eicosanoids in patients with atherosclerosis. METHODS AND RESULTS: The study population consisted of 42 patients with atherosclerosis who were undergoing surgical revascularization. COX-2 mRNA was detected in areas of atherosclerosis but not in normal blood vessel walls, and there was evidence of COX-1 induction. The use of immunohistochemical studies localized the COX-2 to proliferating vascular smooth muscle cells and macrophages. Twenty-four patients who did not previously receive aspirin were randomized to receive either no treatment or nimesulide at 24 hours before surgery and then for 3 days. Eighteen patients who were receiving aspirin were continued on a protocol of either aspirin alone or a combination of aspirin and nimesulide. Urinary levels of 11-dehydro-TXB(2) and 2,3-dinor-6-keto-PGF(1alpha), metabolites of TXA(2) and PGI(2), respectively, were elevated in patients with atherosclerosis compared with normal subjects (3211+/-533 versus 679+/-63 pg/mg creatinine, P<0.001; 594+/-156 versus 130+/-22 pg/mg creatinine, P<0.05, respectively), as was the level of the isoprostane 8-iso-PGF(2alpha). Nimesulide reduced 2, 3-dinor-6-keto-PGF(1alpha) excretion by 46+/-5% (378.3+/-103 to 167+/-37 pg/mg creatinine, P<0.01) preoperatively and blunted the increase after surgery. Nimesulide had no significant effect on 11-dehydro-TXB(2) before (2678+/-694 to 2110+/-282 pg/mg creatinine) or after surgery. The levels of both products were lower in patients who were taking aspirin, and no further reduction was seen with the addition of nimesulide. None of the treatments influenced urinary 8-iso-PGF(2alpha) excretion. CONCLUSIONS: Both COX-1 and -2 are expressed and contribute to the increase in PGI(2) in patients with atherosclerosis, whereas TXA(2) is generated by COX-1.

Sudden death and cardiovascular collapse in children with restrictive cardiomyopathy.

BACKGROUND: Restrictive cardiomyopathy (RCM) is rare in children, and the prognosis is poor. In the present study, we evaluated all pediatric patients with RCM who were at our institution during a 31-year period to determine the clinical outcome and cause of death. Those who sustained sudden, unanticipated cardiac arrests were evaluated for risk factors that are predictive of sudden death. METHODS AND RESULTS: Eighteen consecutive patients were reviewed. Presentation, clinical course, laboratory data, and histopathological evidence of ischemia were compared between patients with and without sudden death events. The results demonstrated that patients who were at risk for sudden death were girls with chest pain, syncope, or both at presentation and without congestive heart failure. Although not statistically significant for sudden death, Holter monitor evidence of ischemia predicted death within months. Histopathological evidence of acute or chronic ischemia was found in the majority of patients, with acute ischemia more common among those who sustained sudden death events. CONCLUSIONS: All children with RCM are at risk for ischemia-related complications and death, and some are at risk of sudden death. In the present study, patients at risk of sudden death appeared well and had no evidence of ongoing heart failure but often had signs or symptoms of ischemia characterized by chest pain, syncope, or both. ECGs and Holter monitors may be useful screening tools. The use of beta-blockade, the placement of an implantable cardioverter-defibrillator, and preferential status 1A or B listing for cardiac transplantation are proposed for pediatric patients with RCM and evidence of ongoing ischemia.

Persistence of ventricular arrhythmia after resolution of occult myocarditis in children and young adults.

OBJECTIVES: We sought to examine whether resolution of occult myocarditis in children with associated ventricular arrhythmia correlated with the presence of arrhythmia at late follow-up. BACKGROUND: Complex ventricular arrhythmias have been documented in children with myocarditis. Therapy is aimed at controlling the arrhythmia and any associated ventricular dysfunction. However, no reported studies have documented whether resolution of myocarditis in children is associated with resolution of the associated arrhythmias. METHODS: We performed a retrospective analysis of 12 patients (mean age 12 years) with myocarditis. Ambulatory electrocardiographic (Holter) monitors were reviewed for ventricular arrhythmias at presentation and follow-up. Patients were assigned to Group I if they received corticosteroids in addition to any antiarrhythmic agents and to Group II if they did not receive steroids. Follow-up endomyocardial biopsy was performed in some patients, and results were analyzed in relation to the presence of arrhythmias at follow-up. RESULTS: Eleven patients had ventricular tachycardia, and one had multiform couplets. Corticosteroids were given to seven patients (Group I). Follow-up biopsy was performed in seven patients (six received steroids), with resolution of inflammation in all; four of the seven still had ventricular arrhythmias but with improved control. Of the five patients without follow-up biopsy, three had persistent arrhythmia. Absence of inflammation at follow-up biopsy did not correlate with loss of ventricular arrhythmias, and there was no difference between Group I and II patients with respect to resolution of arrhythmia (Fisher exact test, p = 0.70, power 11%). CONCLUSIONS: Complex ventricular arrhythmias persist after apparent resolution of occult myocarditis in children. Although these arrhythmias are easier to control after such resolution, the patients may require long-term antiarrhythmic therapy.

Incessant ventricular tachycardia in infants: myocardial hamartomas and surgical cure.

Infants with incessant ventricular tachycardia (occurring greater than 10% of the day) have generally been described in pathologic studies. This report describes 21 patients with incessant ventricular tachycardia present greater than 90% of the day and night; the age at diagnosis ranged from birth to 30 months (mean 10.5 months). The most common clinical presentation was cardiac arrest (11 patients, in 5 after digitalis for presumed supraventricular tachycardia); another 6 patients had congestive heart failure and 4 were asymptomatic. Three patients had coexisting Wolff-Parkinson-White syndrome. The rate of incessant ventricular tachycardia ranged from 167 to 440 (mean 260 beats/min) and the QRS duration from 0.06 to 0.11 second. The most common electrocardiographic (ECG) pattern (10 of 21) was right bundle branch block with left axis deviation, but other right and left bundle branch block patterns were observed. Conventional and investigational antiarrhythmic agents (nine patients received amiodarone) failed to eliminate incessant ventricular tachycardia in all. Electrophysiologic studies localized incessant ventricular tachycardia to the left ventricle in 17 (to the apex in 2, the free wall in 9 and the septum in 6) and to the right ventricular septum in 4. No structural abnormalities were found on the echocardiogram or angiocardiogram. All 21 patients had surgery at an age of 3.5 to 31 months (mean 16). In 15 a tumor was found: 13 myocardial hamartomas (9 discrete, 4 diffuse throughout both ventricles) and 2 rhabdomyomas (1 multiple). Myocarditis was found in one patient (the oldest). In four, only myocardial fibrosis was found; results of one biopsy were normal.(ABSTRACT TRUNCATED AT 250 WORDS)

The detection of viral genomes by polymerase chain reaction in the myocardium of pediatric patients with advanced HIV disease.

OBJECTIVES: The aim of this study was to investigate the frequency of viral nucleic acid detection in the myocardium of human immunodeficiency virus (HIV)-infected children to determine whether an association exists with the development of heart disease. BACKGROUND: As improved medical interventions increase the life expectancy of HIV-infected patients, increased incidences of myocarditis and dilated cardiomyopathy (DCM) are becoming more apparent, even in patients without clinical symptoms. METHODS: Myocardial samples were obtained from the postmortem hearts of 32 HIV-infected children and from 32 age-matched controls consisting of patients with structural congenital heart disease and no myocardial inflammation and no cardiac or systemic viral infection. The hearts were examined histologically and analyzed for the presence of viral sequences by polymerase chain reaction (PCR) or reverse transcription-PCR. RESULTS: Myocarditis was detected histologically in 11 of the 32 HIV-infected patients, and borderline myocarditis was diagnosed in another 13 cases. Infiltrates were confined to the epicardium in two additional hearts. Virus sequences were detected by PCR in 11 of these 26 cases (42.3%); adenovirus in 6, CMV in 3 and both adenovirus and CMV in 2. Two cases without infiltrates were also positive for adenovirus: one had congestive heart failure (CHF) and the other adenoviral pneumonia. No other viruses were detected by PCR, including HIV proviral DNA. All control samples were negative for all viruses tested. CONCLUSIONS: These data suggest that the presence of viral nucleic acid in the myocardium is common in HIV-infected children, and may relate to the development of myocarditis, DCM or CHF and may contribute to the rapid progression of HIV disease.

Is Helicobacter pylori seropositivity related to body mass index in the United States?

BACKGROUND: Helicobacter pylori infection may decrease serum ghrelin and increase gastric leptin levels, which may, in turn, decrease body mass index. AIM: To determine whether H. pylori seropositivity is associated with body mass index. METHODS: Serum H. pylori and cytotoxin-associated gene product A (CagA) antibody levels were measured on 6724 adult participants of the third National Health and Nutrition Examination Survey (1988-91). We evaluated the association between H. pylori/CagA antibody status [both negative (-/-), H. pylori-positive/CagA-negative (+/-), or both positive (+/+)] and body mass index, adjusting for sociodemographic factors. We also investigated whether H. pylori/cytotoxin-associated gene product A antibody status was associated with fasting serum leptin levels. RESULTS: H. pylori/CagA antibody status was not associated with obesity (body mass index > or = 30 kg/m(2)) [adjusted odds ratio (OR) 1.2, 95% CI: 0.9-1.6 comparing (+/+) to (-/-) and adjusted OR 1.1, 95% CI: 0.8-1.5 comparing (+/-) to (-/-)], overweight (body mass index 25 to <30 kg/m(2)) [adjusted OR 1.0, 95% CI: 0.7-1.2 comparing (+/+) to (-/-) and adjusted OR 1.0, 95% CI: 0.8-1.3 comparing (+/-) to (-/-)], or fasting serum leptin level in the USA population. CONCLUSIONS: H. pylori seropositivity and CagA antibody status are not associated with body mass index or fasting serum leptin level.

Molecular basis of Celmer's rules: role of the ketosynthase domain in epimerisation and demonstration that ketoreductase domains can have altered product specificity with unnatural substrates.

BACKGROUND: Polyketides are structurally diverse natural products with a range of medically useful activities. Non-aromatic bacterial polyketides are synthesised on modular polyketide synthase multienzymes (PKSs) in which each cycle of chain extension requires a different 'module' of enzymatic activities. Attempts to design and construct modular PKSs that synthesise specified novel polyketides provide a particularly stringent test of our understanding of PKS structure and function. RESULTS: We show that the ketoreductase (KR) domains of modules 5 and 6 of the erythromycin PKS, housed in the multienzyme subunit DEBS3, exert an unexpectedly low level of stereochemical control in reducing the keto group of a synthetic analogue of the diketide intermediate. This led us to construct a hybrid triketide synthase based on DEBS3 with ketosynthase domain ketosynthase (KS)5 replaced by the loading module and KS1. The construct in vivo produced two major triketide stereoisomers, one expected and one surprising. The latter was of opposite configuration at three out of the four chiral centres: the branching alkyl centre was that produced by KS1 and, surprisingly, both hydroxyl centres produced by the reduction steps carried out by KR5 and KR6 respectively. CONCLUSIONS: These results demonstrate that the epimerising activity associated with module 1 of the erythromycin PKS can be conferred on module 5 merely by transfer of the KS1 domain. Moreover, the normally precise stereochemical control observed in modular PKSs is lost when KR5 and KR6 are challenged by an unfamiliar substrate, which is much smaller than their natural substrates. This observation demonstrates that the stereochemistry of ketoreduction is not necessarily invariant for a given KR domain and underlines the need for mechanistic understanding in designing genetically engineered PKSs to produce novel products.

Combined laparoscopic-assisted nephrectomy and complete mesocolic excision for synchronous renal and colon cancers.

Cancers of the colon and kidney are common malignancies, however, the occurrence of primary synchronous neoplasms of these two organs is uncommon. To the best of our knowledge, this is the first case report of a laparoscopic radical left nephrectomy and extended right complete mesocolic excision (CME) for a patient with synchronous renal and colon cancers. While a radical nephrectomy has long been the standard of care for a renal malignancy, CME has only recently been used. Combined surgeries provide the patient with various benefits such as decreased hospital stay, less postoperative pain and morbidity, early return to work and better cosmoses.

An evaluation of the relationship between Enterobius vermicularis infestation and acute appendicitis in a paediatric population--A retrospective cohort study.

BACKGROUND: Enterobius vermicularis is an often unexpected finding in appendectomy specimen, most commonly seen in paediatric cases. Predicting the presence of E. vermicularis in the setting of appendectomy is important to avoid unnecessary appendectomy and associated morbidity. We sought to identify the incidence of E. vermicularis in a paediatric population undergoing appendectomy for clinically suspected acute appendicitis and identify predictive factors for E. vermicularis. METHODS: This study was performed in an 800-bed University Teaching Hospital, in the Republic of Ireland. We identified all paediatric appendectomies performed at our institute from January to December 2012 using prospectively maintained operating theatre logbooks. In-hospital Histopathology database, medical notes and operative findings were reviewed for each patient and relevant data recorded. Statistical analysis was performed using IBM SPSS, version 21. RESULTS: In total 182 paediatric appendectomies were performed during the year 2012 for clinically suspected acute appendicitis. Demographics included: Mean age 11.14 years (3-16), gender 1M: 1F. 58.8% of procedures were completed laparoscopically, 39% open and 2.2% were converted. The negative appendectomy rate was 22.5%. The annual incidence of E. vermicularis in acute appendicitis specimen from a paediatric cohort at our institute was 7% (1 in 14). In specimen containing E. vermicularis, 69% had no evidence of appendicitis and of those that had, no gangrene or perforation was seen. The presence of E. vermicularis in paediatric patients with RIF pain may be predicted by Eosinophilia (p = 0.016), normal WCC (p = 0.034) and normal Neutrophil count (p = 0.014). CONCLUSIONS: E. vermicularis is responsible for 7% of acute appendicitis. It is responsible for a significantly higher negative appendectomy rate which if predicted may avoid unnecessary appendectomy and associated morbidity.