Patients' perceptions of faecal calprotectin testing in inflammatory bowel disease: results from a prospective multicentre patient-based survey.

INTRODUCTION: Despite its success, there appears to be practical issues with Faecal Calprotectin (FC) testing in Inflammatory Bowel Diseases (IBD), including sample collection, delivery and processing delays. Patients' perception and barriers to FC testing are yet to be explored in clinical practice. METHOD: A prospective patient survey was undertaken at IBD units in UK, Europe and Australia. A 9-point patient-based questionnaire was completed in clinic and included demographics, previous FC testing and FC sample difficulty rating score. Predictors of testing difficulty were derived using multivariable logistic regression analysis. RESULTS: A total of 585 patients with IBD completed the survey; 306 males with a median age of 43 years (IQR: 31-54). There were 446 patients (76%) who had prior FC testing experience. Of these, 37% (n = 165) rated FC testing difficult; 'sample collection' (n = 106; 67%) being the most common reason reported. Multivariable regression analysis identified age <49 years (odds ratio (OR): 2.5, CI:1.6-4.0), disease duration <35 months (OR 1.4, CI:0.9-2.1) and testing location (UK centre: OR 1.9, CI:1.2-3.1) as predictors of a difficult FC rating score. CONCLUSIONS: A total of 37% of patients find FC testing challenging, in particular those aged <49 years, disease duration <35 months. Further studies understanding and addressing these practical issues may aid higher FC uptake in clinic.

A real-world, long-term experience on effectiveness and safety of vedolizumab in adult patients with inflammatory bowel disease: The Cross Pennine study.

BACKGROUND: Real-life data on vedolizumab effectiveness in inflammatory bowel disease (IBD) are still emerging. Data on the comparative safety of the gut selective profile are of particular interest. AIMS: To assess clinical outcome and safety in IBD patients treated with vedolizumab. METHODS: We retrospectively collected data of patients treated with vedolizumab at eight UK hospitals (August 2014-January 2018). Clinical response and remission at 14 and 52 weeks evaluated through Physician Global Assessment (PGA) and adverse events were recorded. Possible predictors of clinical response were examined. RESULTS: Two hundred and three IBD patients (mean treatment 16 ±â€¯8 months) were included. Of these, 135 patients (mean age 40.6 ±â€¯16.0 years; F:M 1.9:1) had CD and 68 (mean age 44.5 ±â€¯18.1 years; F:M 1:1.2) had UC. According to PGA, 106/135 (78.5%) CD and 62/68 (91.2%) UC patients (p = 0.02) had a clinical response/remission at 14 weeks, whereas 76/119 (63.9%) CD and 52/63 (82.5%) UC patients (p < 0.01) showed a sustained response or remission at 52 weeks, with a high adherence rate (97%). No predictors of clinical response were found. The cumulative incidence of infectious diseases was 11.9 per 100 person-years. CONCLUSION: Vedolizumab is an effective therapy for inducing and maintaining remission of IBD, with better results for UC, and with a good safety profile.

A pictorial review of reconstructive foot and ankle surgery: hallux abductovalgus.

This pictorial review focuses on basic procedures performed within the field of podiatric surgery, specifically for the hallux abductovalgus or "bunion" deformity. Our goal is to define objective radiographic parameters that surgeons utilize to initially define deformity, lead to procedure selection and judge post-operative outcomes. We hope that radiologists will employ this information to improve their assessment of post-operative radiographs following reconstructive foot surgeries. First, relevant radiographic measurements are defined and their role in procedure selection explained. Second, the specific surgical procedures of the distal metatarsal, metatarsal shaft, metatarsal base, and phalangeal osteotomies are described in detail. Additional explanations of arthrodesis of the first metatarsal-phalangeal and metatarsal-cuneiform joints are also provided. Finally, specific plain film radiographic findings that judge post-operative outcomes for each procedure are detailed.

Tandem clerking: maximising workplace learning.

BACKGROUND: Medical assessment units (MAUs) are a valuable source of educational opportunities, but these are often not realised because of service pressures. We trialled a method of collaborative working, where junior and senior trainees work in 'tandem' to see new admissions. The roles are alternated throughout the shift with the aim of encouraging shared decisions, learning and feedback. METHODS: A 4-month trial of tandem clerking was implemented. An anonymous questionnaire of junior doctors collected quantitative and qualitative data to assess educational aspects of tandem clerking in the MAU of a busy district general hospital. RESULTS: Junior doctors (n = 14) report seeing a larger number and wider variety of patients using tandem clerking, with more useful feedback and a greater chance of meeting learning objectives and completing assessments. Some respondents expressed concern over a lack of autonomy. Respondents stated they were less likely to spend time completing mundane and non-educational tasks. Eight respondents preferred the new system, four favoured the traditional system and two had no preference. DISCUSSION: Tandem clerking is an innovative method to increase the educational aspects of the assessment unit, both in terms of feedback opportunities and exposure to a wider variety of patients. The technique is partly dependent on the enthusiasm and interest of both parties.

Clear cell sarcoma: a case report with radiological and pathological features of an atypical case.

Clear cell sarcoma of soft tissue is a rare, aggressive soft tissue tumor, which is morphologically similar to malignant melanoma but has no precursor skin lesion and, instead, has a characteristic chromosomal translocation. It is critical, yet challenging, to recognize clear cell sarcoma of soft tissue because the outcome is very different to that of metastatic melanoma. We report a case of clear cell sarcoma of soft tissue arising in the left foot of a 35-year-old African-American woman.

Republished: Daily consultant gastroenterologist ward rounds: reduced length of stay and improved inpatient mortality.

BACKGROUND: For gastroenterology, The Royal College of Physicians reiterates the common practice of two to three consultant ward rounds per week. The Royal Bolton Hospital NHS Foundation Trust operated a 26-bed gastroenterology ward, covered by two consultants at any one time. A traditional system of two ward rounds per consultant per week operated, but as is commonplace, discharges peaked on ward round days. OBJECTIVE: To determine whether daily consultant ward rounds would improve patient care, shorten length of stay and reduce inpatient mortality. METHODS: A new way of working was implemented in December 2009 with a single consultant taking responsibility for all ward inpatients. Freed from all other direct clinical care commitments for their 2 weeks of ward cover, they conducted ward rounds each morning. A multidisciplinary team (MDT) meeting followed immediately. The afternoon was allocated to gastroenterology referrals and reviewing patients on the medical admissions unit. RESULTS: The changes had an immediate and dramatic effect on average length of stay, which was reduced from 11.5 to 8.9 days. The number of patients treated over 12 months increased by 37% from 739 to 1010. Moreover, the number of deaths decreased from 88 to 62, a reduction in percentage mortality from 11.2% to 6%. However, these major quality outcomes involved a reduction in consultant-delivered outpatient and endoscopy activity. CONCLUSION: This new method of working has both advantages and disadvantages. However, it has had a major impact on inpatient care and provides a compelling case for consultant gastroenterology expansion in the UK.

Treatment failure in coeliac disease: a practical guide to investigation and treatment of non-responsive and refractory coeliac disease.

Coeliac disease is a common condition affecting up to 1% of the European adult population. Whilst the majority of patients will respond to a gluten free diet with resolution of symptoms and an improvement in histology, a significant minority have persistent problems. Refractory coeliac disease is a relatively uncommon cause of non-response to gluten free diet with potentially serious consequences of severe malabsorption and a high rate of progression to lymphoma. This review provides a practical guide to the investigation of patients who do not respond to a gluten free diet. We will highlight the differences between the more common non-responsive coeliac disease and the rare entity of refractory coeliac disease and discuss current management and treatment options for both non-responsive coeliac disease and refractory coeliac disease.

Targeting unlesioned pharyngeal motor cortex improves swallowing in healthy individuals and after dysphagic stroke.

BACKGROUND & AIMS: Patients with stroke experience swallowing problems (dysphagia); increased risk of aspiration pneumonia, malnutrition, and dehydration; and have increased mortality. We investigated the behavioral and neurophysiological effects of a new neurostimulation technique (paired associative stimulation [PAS]), applied to the pharyngeal motor cortex, on swallowing function in healthy individuals and patients with dysphagia from stroke. METHODS: We examined the optimal parameters of PAS to promote plasticity by combining peripheral pharyngeal (electrical) with cortical stimulation. A virtual lesion was used as an experimental model of stroke, created with 1-Hz repetitive transcranial magnetic stimulation over the pharyngeal cortex in 12 healthy individuals. We tested whether hemispheric targeting of PAS altered swallowing performance before applying the technique to 6 patients with severe, chronic dysphagia from stroke (mean of 38.8 ± 24.4 weeks poststroke). RESULTS: Ten minutes of PAS to the unlesioned pharyngeal cortex reversed (bilaterally) the cortical suppression induced by virtual lesion (lesioned: F(1,9) = 21.347, P = .001; contralesional: F(1,9) = 9.648, P = .013; repeated-measures analysis of variance) compared with sham PAS. It promoted changes in behavior responses measured with a swallowing reaction time task (F(1,7) = 21.02, P = .003; repeated-measures analysis of variance). In patients with chronic dysphagia, real PAS induced short-term bilateral changes in the brain; the unaffected pharyngeal cortex had increased excitability (P = .001; 95% confidence interval, 0.21-0.05; post hoc paired t test) with reduced penetration-aspiration scores and changes in swallowing biomechanics determined by videofluoroscopy. CONCLUSIONS: The beneficial neurophysiological and behavioral properties of PAS, when applied to unlesioned brain, provide the foundation for further investigation into the use of neurostimulation as a rehabilitative approach for patients with dysphagia from stroke.

Daily consultant gastroenterologist ward rounds: reduced length of stay and improved inpatient mortality.

BACKGROUND: For gastroenterology, The Royal College of Physicians reiterates the common practice of two to three consultant ward rounds per week. The Royal Bolton Hospital NHS Foundation Trust operated a 26-bed gastroenterology ward, covered by two consultants at any one time. A traditional system of two ward rounds per consultant per week operated, but as is commonplace, discharges peaked on ward round days. OBJECTIVE: To determine whether daily consultant ward rounds would improve patient care, shorten length of stay and reduce inpatient mortality. METHODS: A new way of working was implemented in December 2009 with a single consultant taking responsibility for all ward inpatients. Freed from all other direct clinical care commitments for their 2 weeks of ward cover, they conducted ward rounds each morning. A multidisciplinary team (MDT) meeting followed immediately. The afternoon was allocated to gastroenterology referrals and reviewing patients on the medical admissions unit. RESULTS: The changes had an immediate and dramatic effect on average length of stay, which was reduced from 11.5 to 8.9 days. The number of patients treated over 12 months increased by 37% from 739 to 1010. Moreover, the number of deaths decreased from 88 to 62, a reduction in percentage mortality from 11.2% to 6%. However, these major quality outcomes involved a reduction in consultant-delivered outpatient and endoscopy activity. CONCLUSION: This new method of working has both advantages and disadvantages. However, it has had a major impact on inpatient care and provides a compelling case for consultant gastroenterology expansion in the UK.

Statistical reliability of bone biopsy for the diagnosis of diabetic foot osteomyelitis.

Bone biopsy is often referred to as the reference standard for the diagnosis of diabetic foot osteomyelitis (OM), and it also serves as an important interventional tool with respect to diabetic foot infections and limb salvage. However, the phrase bone biopsy lacks a standardized definition, and the statistical reliability of the pathologic diagnosis has not been previously examined. The objective of the present study was to quantify the reliability of the histopathologic analysis of bone with respect to the diagnosis of diabetic foot OM. Four pathologists, kept unaware of the previous pathology reports and specific patient clinical characteristics, retrospectively reviewed 39 consecutive tissue specimens and were informed only that it was "a specimen of bone taken from a diabetic foot to evaluate for OM." As a primary outcome measure, the pathologists were asked to make 1 of 3 possible diagnoses: (1) no evidence of OM, (2) no definitive findings of OM, but cannot rule it out, or (3) findings consistent with OM. There was complete agreement among all 4 pathologists with respect to the primary diagnosis in 13 (33.33%) of the 39 specimens, with a corresponding kappa coefficient of 0.31. A situation of clinically significant disagreement, or in which at least 1 pathologist diagnosed "no evidence of OM," but at least 1 other pathologist diagnosed "findings consistent with OM," occurred in 16 (41.03%) of the specimens. These results indicate agreement below the level of a "reference standard" and emphasize the need for a more comprehensive diagnostic protocol for diabetic foot OM.

Endoscopic mucosal resection of colorectal polyps in typical UK hospitals.

AIM: To evaluate the outcomes of endoscopic mucosal resection (EMR) for colorectal polyps, with particular regard to procedural complications and recurrence rate, in typical United Kingdom (UK) hospitals that perform an average of about 25 colonic EMRs per year. METHODS: A total of 239 colorectal polyps (≥ 10 mm) resected from 199 patients referred to Rochdale Infirmary, Salford Royal Hospital and Royal Oldham Hospital for EMR between January 2003 and January 2009 were studied. RESULTS: The mean size of polyps resected was 19.6 ± 12.4 mm (range 10-80 mm). The overall major complication rate was 2.1%. Complications were less frequent with non-adenomas compared with the other groups (Pearson's χ(2) test, P < 0.0001). Resections of larger-sized polyps were more likely to result in complications (unpaired t-test, P = 0.021). Recurrence was associated with histology, with carcinoma-in-situ more likely to recur compared with low-grade dysplasia [hazard ratio (HR) 186.7, 95% confidence interval (95% CI): 8.81-3953.02, P = 0.001]. Distal lesions were also more likely to recur compared with right-sided and transverse colon lesions (HR 5.93, 95% CI: 1.35-26.18, P = 0.019). CONCLUSION: EMR for colorectal polyps can be performed safely and effectively in typical UK hospitals. Stricter follow-up is required for histologically advanced lesions due to increased recurrence risk.

Adjunctive functional pharyngeal electrical stimulation reverses swallowing disability after brain lesions.

BACKGROUND & AIMS: Oropharyngeal dysphagia is an important disability that occurs after stroke; it contributes to aspiration pneumonia and death, and current modalities for rehabilitation of dysphagia have uncertain efficacy. We therefore examined the role of pharyngeal electrical stimulation (PES) in expediting human swallowing recovery after experimental (virtual) and actual (stroke) brain lesions. METHODS: First, healthy subjects (n = 13) were given 1-Hz repetitive transcranial magnetic stimulation to induce a unilateral virtual lesion in pharyngeal motor cortex followed by active or sham (control) PES. Motor-evoked potentials and swallow accuracy were recorded before and after the lesion to assess PES response. Thereafter, 50 acute dysphagic stroke patients underwent either a dose-response study, to determine optimal parameters for PES (n = 22), or were assigned randomly to groups given either active or sham (control) PES (n = 28). The primary end point was the reduction of airway aspiration at 2 weeks postintervention. RESULTS: In contrast to sham PES, active PES reversed the cortical suppression induced by the virtual lesion (F(7,70) = 2.7; P = .015) and was associated with improvement in swallowing behavior (F(3,42) = 5; P = .02). After stroke, 1 PES treatment each day (U = 8.0; P = .043) for 3 days (U = 10.0) produced improved airway protection compared with controls (P = .038). Active PES also reduced aspiration (U = 54.0; P = .049), improved feeding status (U = 58.0; P = .040), and resulted in a shorter time to hospital discharge (Mantel-Cox log-rank test, P = 0.038). CONCLUSIONS: This pilot study of PES confirms that it is a safe neurostimulation intervention that reverses swallowing disability after virtual lesion or stroke.

Characterizing the application of transcranial direct current stimulation in human pharyngeal motor cortex.

Transcranial direct current stimulation (tDCS) is a novel intervention that can modulate brain excitability in health and disease; however, little is known about its effects on bilaterally innervated systems such as pharyngeal motor cortex. Here, we assess the effects of differing doses of tDCS on the physiology of healthy human pharyngeal motor cortex as a prelude to designing a therapeutic intervention in dysphagic patients. Healthy subjects (n = 17) underwent seven regimens of tDCS (anodal 10 min 1 mA, cathodal 10 min 1 mA, anodal 10 min 1.5 mA, cathodal 10 min 1.5 mA, anodal 20 min 1 mA, cathodal 20 min 1 mA, Sham) on separate days, in a double blind randomized order. Bihemispheric motor evoked potential (MEP) responses to single-pulse transcranial magnetic stimulation (TMS) as well as intracortical facilitation (ICF) and inhibition (ICI) were recorded using a swallowed pharyngeal catheter before and up to 60 min following the tDCS. Compared with sham, both 10 min 1.5 mA and 20 min 1 mA anodal stimulation induced increases in cortical excitability in the stimulated hemisphere (+44 +/- 17% and +59 +/- 16%, respectively; P < 0.005) whereas only 10 min 1.5 mA cathodal stimulation induced inhibition (-26 +/- 4%, P = 0.02). There were neither contralateral hemisphere changes nor any evidence for ICI or ICF in driving the ipsilateral effects. In conclusion, anodal tDCS can alter pharyngeal motor cortex excitability in an intensity-dependent manner, with little evidence for transcallosal spread. Anodal stimulation may therefore provide a useful means of stimulating pharyngeal cortex and promoting recovery in dysphagic patients.

Unprecedented bridged annulation approach to the construction of 5,6-dihydro-4H-benzo[kl]acridines.

A general and novel "bridged annulation" methodology for the synthesis of 5,6-dihydro-4H-benzo[kl]acridines has been developed via Michael addition of a conjugate base of 9-methyl-3,4-dihydroacridin-1(2H)-one to various cyclic or acyclic alpha,beta-unsaturated carbonyl/nitrile compounds under mild conditions at room temperature in a short time. To the best of our knowledge, such a general bridged annulation for the synthesis of fused N-heterocycles has not been reported in the literature.

Reversal of a virtual lesion in human pharyngeal motor cortex by high frequency contralesional brain stimulation.

BACKGROUND & AIMS: Excitatory brain stimulation with repetitive transcranial magnetic stimulation (rTMS) has been proposed as a treatment for dysphagia after stroke. Moreover, 1-Hz rTMS can induce a "virtual lesion" in the human pharyngeal motor cortex that suppresses brain activity and temporarily disrupts swallowing. We thus examined if rTMS could reverse the disrupted brain and swallowing functions following a unilateral virtual lesion in the pharyngeal motor cortex, such that rTMS might be developed as a therapy. METHODS: Healthy subjects (n = 23) were given varying conditions of 5-Hz rTMS over the pharyngeal motor cortex to determine the most effective excitatory parameters. Thereafter, a unilateral virtual lesion was made in the pharyngeal motor cortex using 1-Hz rTMS, followed by contralateral active or sham 5-Hz rTMS. Motor evoked potentials and serial swallowing reaction times were recorded before and for 60 minutes postlesion to assess reversibility of the disruption to the brain and swallowing. RESULTS: The greatest increase in pharyngeal motor cortex excitability was seen following 250 pulses of 5-Hz rTMS (F(1,11) = 10.3, P = .008), an effect that lasted over 2 hours. In contrast to sham rTMS, active contralateral 5-Hz rTMS completely abolished the cortical suppression induced by the virtual lesion, with effects occurring for up to 50 minutes in both unlesioned (F(1,11) = 6, P = .03) and lesioned (F(1,11) = 67, P < .001) hemispheres. Active rTMS also reversed the changes in swallowing behavior (F(1,8) = 9, P = .018), restoring function to prelesional levels. CONCLUSIONS: Contralesional-targeted neurostimulation modulates brain activity and swallowing motor behavior after experimental disruption and might be usefully applied in stroke-affected patients as a therapy for dysphagia.

5,6-Diarylanthranilo-1,3-dinitriles as a new class of antihyperglycemic agents.

Various functionalized mono- and diarylanthranilo-1,3-dinitriles were synthesized and evaluated for their in vitro antihyperglycemic activity against the PTP-1B, glucose-6-phosphatase, glycogen phosphorylase and alpha-glucosidase enzymes. Among various screened compounds, 5,6-diaryl substituted anthranilo-1,3-dinitriles 3a, 3b, and 3d showed good inhibitory activity against PTP-1B with IC(50) values of 58-72 microM. Three of the test compounds showed significant (25-37%) lowering of plasma glucose level at 24h in sucrose-challenged streptozotocin-induced diabetic Sprague-Dawley rat model.

A magnetic resonance spectroscopy study of brain glutamate in a model of plasticity in human pharyngeal motor cortex.

BACKGROUND & AIMS: Coordinated delivery of peripheral and cortical stimuli (paired associative stimulation [PAS]) has been shown to induce plasticity in limb motor cortex, however, its application in pharyngeal motor cortex and the molecular mechanisms involved in human neuroplasticity remain uncertain. Because neuroplasticity appears to form the basis for functional recovery of digestive functions such as swallowing after brain injury, the aim of this study was to characterize the induction of cortical plasticity in human pharyngeal motor cortex through PAS applied to pharyngeal musculature and investigate the potential role of glutamate in this process. METHODS: Fifteen healthy volunteers completed a series of experiments in which cortical excitability was assessed through pharyngeal motor evoked potential amplitudes in response to transcranial magnetic stimulation. The optimal parameters and interhemispheric interactions of PAS in the bilaterally represented pharyngeal system initially were investigated. Cortical glutamate after PAS then was assessed with magnetic resonance spectroscopy. RESULTS: The greatest increase in cortical pharyngeal excitability was seen if paired stimuli were separated by 100 ms (F[15,210] = 2.28; P < or = .05). Cortical excitability increased over 2 hours with analogous albeit lesser changes in the contralateral hemisphere. A focal and transient reduction in glutamate was found in the stimulated pharyngeal motor cortex (F[1,12] = 21.9; P = .001), without changes in any other measured brain metabolites. CONCLUSIONS: This study shows that PAS-induced plasticity in the human pharyngeal motor system is both timing- and hemisphere-dependent and provides novel evidence for the potential role of glutamate in modulating this effect.

Lactic acidosis expediting a diagnosis of acute lymphoblastic leukaemia.

We report the finding of a low venous bicarbonate and lactic acidosis in a patient with mild pancytopenia which raised the suspicion of haematological malignancy and expedited the diagnosis of acute lymphoblastic leukaemia. This report highlights the value of testing for lactic acidosis when haematological malignancies are considered and reviews the metabolism of lactic acidosis.