Study protocol for a revised randomized trial: Remotely delivered Tai Chi and wellness for Gulf War illness.

BACKGROUND: Many of the 700,000 American military personnel deployed to the Persian Gulf region in 1990 and 1991 have since reported health symptoms of unknown etiology. This cluster of symptoms has been labeled Gulf War Illness and include chronic musculoskeletal pain, fatigue, headaches, memory and attention difficulties, gastrointestinal complaints, skin abnormalities, breathing problems, and mood and sleep problems [1,2]. There have been few high-quality intervention trials and no strong evidence to support available treatments [3]. Tai Chi is an ancient Chinese martial art with benefits that include enhancing physical and mental health and improving quality of life for those with chronic conditions. PROPOSED METHODS: In this randomized controlled trial, GW Veterans are randomly assigned to either Tai Chi or a Wellness control condition, with both remotely delivered intervention groups meeting twice a week for 12 weeks. The primary aim is to examine if Tai Chi is associated with greater improvements in GWI symptoms in Veterans with GWI compared to a Wellness intervention. Participants will receive assessments at baseline, 12 weeks (post-intervention), and follow-up assessments 3- and 9-months post-intervention. The primary outcome measure is the Brief Pain Inventory that examines pain intensity and pain interference. CONCLUSION: This trial will produce valuable results that can have a meaningful impact on healthcare practices for GWI. If proven as a helpful treatment for individuals with GWI, it would support the implementation of remotely delivered Tai Chi classes that Veterans can access from their own homes.

Preliminary Results of an Interdisciplinary Behavioral Program to Improve Access to Preventative Dental Care for Adults With Intellectual and Developmental Disabilities.

Adults with intellectual and developmental disabilities (AIDD) experience significant oral health disparities, partially due to perceived behavioral issues. This article describes the preliminary outcomes of a developing interdisciplinary (dental, medical, behavioral) program involving a behavioral intervention for AIDD previously receiving preventative dental care with sedation, general anesthesia, or protective stabilization (SAS). After a baseline assessment, a board-certified behavior analyst implemented increasingly complex behavioral interventions during simulated dental visits. Prior to COVID-19 pandemic-related restrictions, there were 32 active participants; 15 (46.9%) successfully completed a focused, real dental exam with simple behavioral interventions and 17 (53.1%) remain in treatment. These preliminary results suggest that many AIDD previously receiving SAS may participate in a preventative dental exam with minimal behavioral supports, if given the opportunity.

Faecal calprotectin is a surrogate marker of biliary inflammation in primary sclerosing cholangitis associated inflammatory bowel disease.

Objective: Faecal calprotectin (fCAL) is an established marker of intestinal inflammation in inflammatory bowel disease (IBD). Disproportionally high fCAL levels, for the severity of intestinal inflammation, have been previously observed in primary sclerosing cholangitis associated IBD (PSC-IBD). The aim of this study was to test the hypothesis that fCAL is a marker of biliary injury in PSC-IBD. Methods: We used two cohorts: (1) post hoc analysis of a colonoscopic surveillance study allowing correlation of fCAL to endoscopic severity as measured by the ulcerative colitis endoscopic index of severity (UCEIS) in PSC-IBD (n=20) and ulcerative colitis (UC, n=20) and (2) prospective recruitment of patients attending for endoscopic retrograde cholangiopancreatography allowed the correlation of fCAL to biliary calprotectin (n=8). Results: A strong correlation was seen between fCAL and UCEIS in UC (r=0.821, 95% CI (0.585 to 0.929), p<0.0001). In PSC-IBD, the correlation was weaker (r=0.596, 95% CI (0.195 to 0.8260), p=0.006). PSC-IBD patients with endoscopically quiescent colitis (UCEIS: 0-1) had higher fCAL than patients with UC (279 µg/g, IQR (68-601) vs 30 µg/g, IQR (14-107), p=0.015). This was associated with higher risk of biliary complications like need for antibiotics or instrumentation (HR 16.39, 95% CI (2.98 to 90.25)) rather than colitis flares (follow-up: 12 months). Calprotectin measured in faeces correlated positively with biliary calprotectin (r=0.898, p=0.0024). Conclusion: fCAL is a surrogate marker for biliary inflammation in PSC-IBD. Trial registration number: NCT02543021.

Assessment of oral and overall health parameters using the SillHa Oral Wellness System.

OBJECTIVE: The study evaluated use of a multipoint saliva analyzer to assess patient wellness in a contemporary dental practice setting. STUDY DESIGN: Unstimulated saliva from a diverse 104 patient cohort was analyzed using the SillHa Oral Wellness System. The device measures the following 7 analytes present in the patient's oral rinse: cariogenic bacteria, acidity, buffer capacity, blood, leukocytes, protein, and ammonia. Data obtained were compared with validated clinical assessment data independently provided by credentialed dental professionals. RESULTS: Measured leukocyte and protein levels were higher in patients with periodontal disease and/or deep gingival pockets. Patients with a history of cancer and/or diabetes presented with higher ammonia and lower leukocyte levels. Acidity levels were higher in patients using multiple xerogenic medications and lower in patients with a history of sleep apnea. Sex differences showed female patients exhibiting higher acidity, lower buffer capacity, and lower ammonia than male patients. Increasing age is associated with elevated buffer capacity. CONCLUSIONS: Multipoint saliva analyzers such as the one used in this study, along with clinical practice examination and medical history, can provide rapid salivary component analysis that augments treatment planning. A follow-up multisite study would provide the opportunity to test this analyzer in clinical sites with different practice workflows.

Azathioprine with Allopurinol Is a Promising First-Line Therapy for Inflammatory Bowel Diseases.

BACKGROUND: Beneficial response to first-line immunosuppressive azathioprine in patients with inflammatory bowel disease (IBD) is low due to high rates of adverse events. Co-administrating allopurinol has been shown to improve tolerability. However, data on this co-therapy as first-line treatment are scarce. AIM: Retrospective comparison of long-term effectiveness and safety of first-line low-dose azathioprine-allopurinol co-therapy (LDAA) with first-line azathioprine monotherapy (AZAm) in patients with IBD without metabolite monitoring. METHODS: Clinical benefit was defined as ongoing therapy without initiation of steroids, biologics or surgery. Secondary outcomes included CRP, HBI/SCCAI, steroid withdrawal and adverse events. RESULTS: In total, 166 LDAA and 118 AZAm patients (median follow-up 25 and 27 months) were evaluated. Clinical benefit was more frequently observed in LDAA patients at 6 months (74% vs. 53%, p = 0.0003), 12 months (54% vs. 37%, p = 0.01) and in the long-term (median 36 months; 37% vs. 24%, p = 0.04). Throughout follow-up, AZAm patients were 60% more likely to fail therapy, due to a higher intolerance rate (45% vs. 26%, p = 0.001). Only 73% of the effective AZA dose was tolerated in AZAm patients, while LDAA could be initiated and maintained at its target dose. Incidence of myelotoxicity and elevated liver enzymes was similar in both cohorts, and both conditions led to LDAA withdrawal in only 2%. Increasing allopurinol from 100 to 200-300 mg/day significantly lowered liver enzymes in 5/6 LDAA patients with hepatotoxicity. CONCLUSIONS: Our poor AZAm outcomes emphasize that optimization of azathioprine is needed. We demonstrated a long-term safe and more effective profile of first-line LDAA. This co-therapy may therefore be considered standard first-line immunosuppressive.

A unique type of fully covered metal stent for the management of post liver transplant biliary anastomotic strictures.

BACKGROUND: We report our experience of treating anastomotic strictures using a novel type of fully covered metal stent (FCSEMS). This stent, known as the Kaffes Stent, is short-length with an antimigration waist and is easily removable due to long retrieval wires deployed within the duodenum. METHODS: Sixty-two patients underwent ERCP and Kaffes stent insertion for post-transplant anastomotic strictures following confirmation of a stricture on MRCP. These patients were retrospectively analysed for immediate and long-term stricture resolution, improvement in symptoms and liver function tests (LFTs), stricture recurrence and complication rates. RESULTS: Of the 56 patients who had their stent removed at the time of analysis, 54 (96%) had immediate stricture resolution and 42 continued to have long-term resolution (mean follow-up period was 548 days). Of the 16 patients with symptoms of biliary obstruction, 13 had resolution of their symptoms. Overall, there was a significant improvement in LFTs after stent removal compared to before stent insertion. Complication rates were 15% with only one patient requiring biliary reconstruction. CONCLUSIONS: The Kaffes stent is effective and safe at resolving post liver transplant biliary anastomotic strictures.

Efficacy, safety and drug survival of thioguanine as maintenance treatment for inflammatory bowel disease: a retrospective multi-centre study in the United Kingdom.

BACKGROUND: Thioguanine (TG) is a thiopurine which has been used for patients with inflammatory bowel disease (IBD), who have failed azathioprine (AZA) or mercaptopurine (MP) due to adverse events or suboptimal response. Its widespread use has been hampered due to concerns about nodular regenerative hyperplasia (NRH) of the liver. The aim of this study was to investigate the long-term efficacy and safety of low-dose TG therapy in IBD patients failing AZA and MP. METHODS: A retrospective multicentre study was performed in IBD patients who failed prior treatment with conventional thiopurines with or without following immunomodulation (thiopurine-allopurinol, biologicals, methotrexate, tacrolimus) and were subsequently treated with TG as rescue monotherapy between 2003 and 2019 at three hospitals in the United Kingdom. Clinical response, adverse events, laboratory results, imaging and liver biopsies were retrospectively collected. RESULTS: A total of 193 patients (57% female and 64% Crohn's disease) were included, with a median daily TG dose of 20 mg (range: 20-40 mg), a median treatment duration of 23 months (IQR 10-47) and a median follow-up of 36 months (IQR 22-53). The clinical response rate at 12 months was 65 and 54% remained on TG until the end of follow-up. Adverse events consisted primarily of elevated liver tests (6%), myelotoxicity (7%) and rash (5%). NRH was histologically diagnosed in two patients and two other patients (1%) developed non-cirrhotic portal hypertension. The median 6-TGN and TPMT levels were 953 pmol/8 × 105 RBC (IQR 145-1761) and 47 mu/L (IQR 34.5-96). CONCLUSIONS: Long-term follow-up suggests that TG can be an effective and well-tolerated therapy in more than half of difficult-to-treat and multi-therapy failing IBD patients. Findings of this study indicate that TG can be used safely and the occurrence of hepatotoxicity was low. The incidence rate of NRH was within the background incidence.

An unusual cause of intestinal failure.

A 62-year-old man presented to the emergency department with 5 weeks of worsening lower abdominal pain associated with watery diarrhoea, vomiting and 10% loss of body weight. He had recently experienced night blindness. There was no history of foreign travel. His past medical history included hypertension, sickle cell trait and type 2 diabetes well controlled on metformin. He had not been prescribed any recent steroids and denied significant alcohol intake. On examination, he had a tachycardia at 110 bpm and was afebrile and normotensive. He was malnourished with pedal pitting oedema extending to both knees. His abdomen was soft but distended and diffusely tender. Blood tests showed a serum albumin of 12 g/L. Stool samples were negative. HIV testing was negative, and immunoglobulin levels were normal. CT of the abdomen showed thickened, hyperenhancing jejunal loops with diffuse mesenteric inflammatory fat stranding and enlarged mesenteric lymph nodes. Colonoscopy was unremarkable. Enteroscopy showed granular oedematous mucosa and extensive, deep ulcerations. Jejunal biopsies were obtained. Microscopy samples were negative for tuberculosis (TB) culture. Histology revealed inflamed and ulcerated small bowel mucosa with plump endothelial cells with the appearance below. There were no granulomata (figures 1 and 2). Figure 1Endoscopic examination of the jejunum. Figure 2Plump endothelial cells seen on microscopy. QUESTION: What is the differential diagnosis?

A practical guide to thiopurine prescribing and monitoring in IBD.

Thiopurines are often the mainstay of treatment for many patients with inflammatory bowel disease. As such, a general understanding of the evidence behind their use and of their metabolism is extremely useful in clinical practice. This review gives a practical overview of thiopurine metabolism, the importance of thiopurine S-methyltransferase testing prior to the start of therapy and the monitoring of thioguanine nucleotide levels while on treatment, guiding a personalised approach to optimising thiopurine therapy.

Guided Molecular Assembly on a Locally Reactive 2D Material.

Atomically precise engineering of the position of molecular adsorbates on surfaces of 2D materials is key to their development in applications ranging from catalysis to single-molecule spintronics. Here, stable room-temperature templating of individual molecules with localized electronic states on the surface of a locally reactive 2D material, silicene grown on ZrB2 , is demonstrated. Using a combination of scanning tunneling microscopy and density functional theory, it is shown that the binding of iron phthalocyanine (FePc) molecules is mediated via the strong chemisorption of the central Fe atom to the sp3 -like dangling bond of Si atoms in the linear silicene domain boundaries. Since the planar Pc ligand couples to the Fe atom mostly through the in-plane d orbitals, localized electronic states resembling those of the free molecule can be resolved. Furthermore, rotation of the molecule is restrained because of charge rearrangement induced by the bonding. These results highlight how nanoscale changes can induce reactivity in 2D materials, which can provide unique surface interactions for enabling novel forms of guided molecular assembly.

Vedolizumab: early experience and medium-term outcomes from two UK tertiary IBD centres.

OBJECTIVE: To gain an understanding of the efficacy of vedolizumab in a 'real-world' setting. DESIGN: Retrospective cohort study using prospectively maintained clinical records. SETTING: Two UK tertiary inflammatory bowel disease (IBD) centres. PATIENTS: Patients with IBD commenced on vedolizumab at Guy's & St Thomas' and King's College Hospitals during November 2014-November 2015. INTERVENTION: Vedolizumab, a monoclonal antibody to α-4 ß-7 integrins that selectively inhibit leucocyte migration into the gut. MAIN OUTCOME MEASURES: Clinical disease activity was assessed at baseline, weeks 14 and 30 using Harvey-Bradshaw Index (HBI) for Crohn's disease (CD) and Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis (UC). Response was defined as HBI or SCCAI reduction ≥3. Remission was defined as HBI <5 or SCCAI <3. Continuous data are summarised as medians, followed by range. RESULTS: Fifty patients were included: 27 CD, 20 UC and 3 IBD-U (included in the UC group for analysis). At baseline visit, the median HBI was 8 (1-16) and SCCAI was 6 (0-15). At week 14, these values had fallen to 5 (0-15) (p=0.117) and 4 (0-10) (p=0.005), respectively. Additionally, week 30 data were available for 19 patients (9 CD, 10 UC). The clinical disease activity scores at that point were HBI 2 (0-7) (p=0.039) and SCCAI 2 (0-10) (p=0.023). At baseline, 37 (74%) of the 50 patients had clinically active disease. Of the patients with active disease, 22 (59%) responded and 14 (38%) achieved remission at week 14. CONCLUSIONS: Our early experience with vedolizumab demonstrates a clear benefit in terms of disease control as well as a steroid-sparing effect in a cohort, which included patients with complex and previously refractory disease.

Thioguanine in inflammatory bowel disease: Long-term efficacy and safety.

BACKGROUND: Thioguanine (TG) is efficacious in inflammatory bowel disease (IBD), but its toxicity, particularly nodular regenerative hyperplasia (NRH) of the liver, has limited its use. We assessed the long-term clinical outcomes and safety of TG in patients whom were intolerant or refractory to conventional immunomodulators. METHODS: This is a retrospective, single-centre study of IBD patients treated with TG from 2001-2013. Response was defined as clinical remission (Harvey-Bradshaw Index < 5 for Crohn's disease (CD), Simple Clinical Colitis Activity Index < 4 for ulcerative colitis (UC)) without corticosteroids or, if receiving anti-tumour-necrosis-factor (anti-TNF) therapy, absence of dose escalation. We recorded TG failure, withdrawal and adverse events. Patients were monitored with biochemistry, liver biopsy and/or magnetic resonance imaging (MRI). RESULTS: 54 patients (47 CD and 7 UC) whom received TG (mean dose: 27 mg/d (range: 20-40 mg/d)) as monotherapy (n = 36) or concomitantly with anti-TNF (n = 18) for a median inter-quartile range of 16 (5-37) months (126 patient-years of follow-up). 32 (59%) patients responded to TG at 6 months and 23 (43%) at 12 months. Pancreatitis did not recur amongst the 19 patients with prior thiopurine-induced pancreatitis. 16 (30%) patients ceased TG due to intolerance or toxicity (four serious); NRH was not observed. 6-thioguanine nucleotide concentrations did not correlate with efficacy nor with toxicity. CONCLUSIONS: TG was efficacious and well tolerated in one out of two patients who had previously failed conventional immunomodulators. NRH did not occur.

Controlling electronic access to the spin excitations of a single molecule in a tunnel junction.

Spintronic phenomena underpin new device paradigms for data storage and sensing. Scaling these down to the single molecule level requires controlling the properties of current-carrying molecular orbitals to enable access to spin states through phenomena such as inelastic electron tunnelling. Here we show that the spintronic properties of a tunnel junction containing a single molecule can be controlled using the local environment as a pseudo-gate. For tunnelling through iron phthalocyanine (FePc) on an insulating copper nitride (Cu2N) monolayer above Cu(001), we find that spin transitions may be strongly excited depending on the binding site of the central Fe atom. Different interactions between the Fe and the underlying Cu or N atoms shift the Fe d orbitals with respect to the Fermi energy and control the relative strength of the spin excitations; this effect is captured in a simple co-tunnelling model. This work demonstrates the importance of the atomic-scale environment for the development of single molecule spintronic devices.

Cholecystocolonic Fistulas from Diverticulosis: A Potentially Missable Cause of Liver Abscesses.

Cholecystocolonic fistulas (CCF) due to colonic diverticulosis are a rare cause of liver abscesses. It is even rarer to simultaneously have choledocholithiasis, another cause for liver abscesses. In this case report, we found both pathologies and emphasise the need to study cholangiograms carefully so as not to miss alternative diagnoses.

Sub-molecular modulation of a 4f driven Kondo resonance by surface-induced asymmetry.

Coupling between a magnetic impurity and an external bath can give rise to many-body quantum phenomena, including Kondo and Hund's impurity states in metals, and Yu-Shiba-Rusinov states in superconductors. While advances have been made in probing the magnetic properties of d-shell impurities on surfaces, the confinement of f orbitals makes them difficult to access directly. Here we show that a 4f driven Kondo resonance can be modulated spatially by asymmetric coupling between a metallic surface and a molecule containing a 4f-like moment. Strong hybridization of dysprosium double-decker phthalocyanine with Cu(001) induces Kondo screening of the central magnetic moment. Misalignment between the symmetry axes of the molecule and the surface induces asymmetry in the molecule's electronic structure, spatially mediating electronic access to the magnetic moment through the Kondo resonance. This work demonstrates the important role that molecular ligands have in mediating electronic and magnetic coupling and in accessing many-body quantum states.

Combination esthetic treatment of anterior teeth affected by idiopathic enamel hypoplasia: a case report.

The esthetic management of enamel dysplasia presents an opportunity for the practitioner to integrate expertise in diagnosis, biomaterials, and technique. In addition to considerations of appearance, careful attention must be paid to occlusal function and restorative material properties. This case report highlights a combined approach of conservative lithium disilicate indirect restorations and composite resin direct veneers to electively restore the anterior teeth of a patient diagnosed with idiopathic enamel hypoplasia.

The impact of brush cytology from endoscopic retrograde cholangiopancreatography (ERCP) on patient management at a UK teaching hospital.

INTRODUCTION: Patients with suspected pancreaticobiliary cancers frequently undergo endoscopic retrograde cholangiopancreatography (ERCP) to obtain brush cytology for confirmatory diagnosis. The outcome of this often leads to the management of the patient and can avoid more invasive investigations. There is a wide range of sensitivities and specificities reported in the literature. AIMS: To determine the accuracy of the brush cytology obtained at ERCP by performing a retrospective audit of all patients admitted to Guy's and St. Thomas' Hospital for ERCP during 2008-2013. Also, to evaluate the impact of cytology results on patient care following ERCP. METHOD: Data were collected from 4 January 2008 to 27 December 2013. This involved analysing EndoSoft (the in-house software for endoscopic data entry), Pathnet (the pathology database) and Electronic Patient Records. RESULTS: 162 patients underwent brush cytology during ERCP. 58 patients had positive cytology. With intention-to-treat analysis, sensitivity was 54.7%, specificity was 100.0% and negative predictive value was 53.9% with a positive predictive value of 100%. Patients with a positive brush cytology result required fewer investigations compared with patients with a negative cytology result. CONCLUSIONS: Our results compare favourably with previous studies in the field. Brush cytology has been ignored in recent times due to perceived poor results and efficacy. Our audit shows that it can reduce the number of investigations required to reach a diagnosis of malignancy and so is a valuable tool in the diagnosis of pancreaticobiliary malignancies. However, better guidance on preparation of samples for cytology is needed to reduce the number of insufficient samples.