Diet and irritable bowel syndrome: an update from a UK consensus meeting.

There has been a renewed interest in the role of dietary therapies to manage irritable bowel syndrome (IBS), with diet high on the agenda for patients. Currently, interest has focussed on the use of traditional dietary advice (TDA), a gluten-free diet (GFD) and the low FODMAP diet (LFD). A consensus meeting was held to assess the role of these dietary therapies in IBS, in Sheffield, United Kingdom.Evidence for TDA is from case control studies and clinical experience. Randomised controlled trials (RCT) have demonstrated the benefit of soluble fibre in IBS. No studies have assessed TDA in comparison to a habitual or sham diet. There have been a number of RCTs demonstrating the efficacy of a GFD at short-term follow-up, with a lack of long-term outcomes. Whilst gluten may lead to symptom generation in IBS, other components of wheat may also play an important role, with recent interest in the role of fructans, wheat germ agglutinins, as well as alpha amylase trypsin inhibitors. There is good evidence for the use of a LFD at short-term follow-up, with emerging evidence demonstrating its efficacy at long-term follow-up. There is overlap between the LFD and GFD with IBS patients self-initiating gluten or wheat reduction as part of their LFD. Currently, there is a lack of evidence to suggest superiority of one diet over another, although TDA is more acceptable to patients.In view of this evidence, our consensus group recommends that dietary therapies for IBS should be offered by dietitians who first assess dietary triggers and then tailor the intervention according to patient choice. Given the lack of dietetic services, novel approaches such as employing group clinics and online webinars may maximise capacity and accessibility for patients. Further research is also required to assess the comparative efficacy of dietary therapies to other management strategies available to manage IBS.

Patient preference for virtual versus in-person visits in neuromuscular clinical practice.

INTRODUCTION/AIMS: It is unknown if patients with neuromuscular diseases prefer in-person or virtual telemedicine visits. We studied patient opinions and preference on virtual versus in-person visits, and the factors influencing such preferences. METHODS: Telephone surveys, consisting of 11 questions, of patients from 10 neuromuscular centers were completed. RESULTS: Five hundred and twenty surveys were completed. Twenty-six percent of respondents preferred virtual visits, while 50% preferred in-person visits. Sixty-four percent reported physical interaction as "very important." For receiving a new diagnosis, 55% preferred in-person vs 35% reporting no preference. Forty percent were concerned about a lack of physical examination vs 20% who were concerned about evaluating vital signs. Eighty four percent reported virtual visits were sufficiently private. Sixty eight percent did not consider expenses a factor in their preference. Although 92% were comfortable with virtual communication technology, 55% preferred video communications, and 19% preferred phone calls. Visit preference was not significantly associated with gender, diagnosis, disease severity, or symptom management. Patients who were concerned about a lack of physical exam or assessment of vitals had significantly higher odds of selecting in-person visits than no preference. DISCUSSION: Although neither technology, privacy, nor finance burdened patients in our study, more patients preferred in-person visits than virtual visits and 40% were concerned about a lack of physical examination. Interactions that occur with in-person encounters had high importance for patients, reflecting differences in the perception of the patient-physician relationship between virtual and in-person visits.

Assessment of seminal cystatin C levels in infertile men with varicocele: A preliminary study.

Varicocele has been raised as a contributor to male infertility supported by the improvement of sperm parameters after varicocelectomy. Cystatin C (Cys C) has been linked to several cellular changes that are common in male infertility cases associated with varicocele such as apoptosis and autophagy. This preliminary study aimed to assess the seminal levels of Cys C in infertile oligoasthenoteratozoospermic (OAT) men associated with varicocele that have been shown to have spermatic vein vasodilation and active death pathway. Overall, 60 men were investigated being divided into two equivalent groups-infertile OAT men with varicocele who underwent varicocelectomy and healthy fertile men as a control group. These men were subjected to history taking, clinical examination, semen analysis and assessment of seminal Cys C pre and 6 months post-varicocelectomy. The results showed a significant increase of seminal Cys C in infertile OAT men with varicocele than the fertile control (55.57 ± 25.6 ng/ml versus 10.78 ± 1.88 ng/ml, p = .001). Seminal Cys C was a significantly decreased post-operative than its pre-operative level (34.69 ± 14.02 versus 55.57 ± 25.6 ng/ml, p = .01). These results show a potential role of Cys C in varicocele-induced infertility.

Mechanics of dystrophin deficient skeletal muscles in very young mice and effects of age.

The MDX mouse is an animal model of Duchenne muscular dystrophy, a human disease marked by an absence of the cytoskeletal protein, dystrophin. We hypothesized that 1) dystrophin serves a complex mechanical role in skeletal muscles by contributing to passive compliance, viscoelastic properties, and contractile force production and 2) age is a modulator of passive mechanics of skeletal muscles of the MDX mouse. Using an in vitro biaxial mechanical testing apparatus, we measured passive length-tension relationships in the muscle fiber direction as well as transverse to the fibers, viscoelastic stress-relaxation curves, and isometric contractile properties. To avoid confounding secondary effects of muscle necrosis, inflammation, and fibrosis, we used very young 3-wk-old mice whose muscles reflected the prefibrotic and prenecrotic state. Compared with controls, 1) muscle extensibility and compliance were greater in both along fiber direction and transverse to fiber direction in MDX mice and 2) the relaxed elastic modulus was greater in dystrophin-deficient diaphragms. Furthermore, isometric contractile muscle stress was reduced in the presence and absence of transverse fiber passive stress. We also examined the effect of age on the diaphragm length-tension relationships and found that diaphragm muscles from 9-mo-old MDX mice were significantly less compliant and less extensible than those of muscles from very young MDX mice. Our data suggest that the age of the MDX mouse is a determinant of the passive mechanics of the diaphragm; in the prefibrotic/prenecrotic stage, muscle extensibility and compliance, as well as viscoelasticity, and muscle contractility are altered by loss of dystrophin.

Coeliac disease and noncoeliac wheat or gluten sensitivity.

Coeliac disease (CD) and noncoeliac wheat or gluten sensitivity (NCWS/NCGS) are common gluten-related disorders. Both conditions can present with gastrointestinal and extraintestinal manifestations, which can be a challenge for physicians to discern between. Whilst coeliac serology and histological assessment are required for the diagnosis of CD, there are no clear biomarkers for the diagnosis of NCGS. The management of both conditions is with a gluten-free diet (GFD), although the duration, as well as strictness of adherence to a GFD in NCGS, is unclear. Adherence to a GFD in CD can also be challenging, with recent developments of noninvasive assessments, although histological assessment via duodenal biopsies remains the gold standard. The management of refractory coeliac disease remains particularly challenging, often requiring specialist input. Whilst wheat is noted to be a trigger for symptom generation in NCGS, it is unclear which components of wheat are responsible for symptom generation in this group, with further research required to elucidate the pathophysiology.

Randomized Trial of Thymectomy in Myasthenia Gravis.

BACKGROUND: Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. METHODS: We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period. RESULTS: A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (44 mg vs. 60 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003). CONCLUSIONS: Thymectomy improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.).

The role of diet in irritable bowel syndrome: implications for dietary advice.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that affects approximately 10% of the population. Diet triggers symptoms in the vast majority of individuals with IBS. In view of this, there has been a focus on the role of diet in IBS. The diets currently being headlined for IBS include (i) traditional dietary advice, (ii) the low fermentable oligo-, di-, mono- saccharides and polyols (FODMAPs) diet and (iii) the gluten-free diet (GFD). Although traditional dietary advice is considered as the first-line dietary therapy, its evidence base is variable, with a few randomized controlled trials (RCTs) exploring the efficacy of this approach, other than for fibre. There are now a growing number of RCTs demonstrating the efficacy of the low FODMAP diet in the short-term, with some emerging data on the long-term 'adapted' low FODMAP diet. There are also several RCTs showing the benefits of a GFD in IBS; however, this concept is hampered with uncertainty as to the mechanism of action. Nevertheless, all of these dietary therapies are viable options for individuals with IBS, with the dietitian and patient engagement at the forefront of achieving success. However, future pragmatic studies are needed to clarify the comparative efficacy and convenience of implementing these various diets into routine life. Moreover, it is imperative to better delineate the concern that restrictive diets - such as the low FODMAP and GFD - may promote nutritional inadequacies, disordered eating behaviours, and lead to detrimental alterations to the gut microbiota.

Association among tenascin-C and NT-proBNP levels and arrhythmia prevalence in heart failure.

PURPOSE: Tenascin-C (TN-C) and amino-terminal fragment of the B-type natriuretic peptide (NT-proBNP) are the important predictors in prognosis of heart failure (HF). The aim of this study was to analyze the relationship of TN-C and NT-proBNP levels with the frequency and severity of ventricular arrhythmia. MATERIALS AND METHODS: Our study included 107 HF patients with EF < 45%. According to Holter analysis, the patients were divided into two groups as malignant arrhythmia group (n=29) with Lown Class 4a and 4b arrhythmia and benign arrhythmia group(n=78) with Lown Class 0-3b arrhythmia. The groups were compared with respect to levels of TN-C and NT-proBNP. The relationship of TN-C and NT-proBNP levels with frequency of ventricular premature beat (VPB) was also analyzed. FINDINGS: NT-proBNP (5042.1±1626 versus 1417.1±1711.6 pg/ml) and TN-C (1089±348.6 versus 758.5±423.9 ng/ml) levels were significantly higher in the malignant arrhythmia group than that of the benign arrhythmia group (p.

Schistosome infection aggravates HCV-related liver disease and induces changes in the regulatory T-cell phenotype.

Schistosome infections are renowned for their ability to induce regulatory networks such as regulatory T cells (Treg) that control immune responses against homologous and heterologous antigens such as allergies. However, in the case of co-infections with hepatitis C virus (HCV), schistosomes accentuate disease progression and we hypothesized that expanding schistosome-induced Treg populations change their phenotype and could thereby suppress beneficial anti-HCV responses. We therefore analysed effector T cells and n/iTreg subsets applying the markers Granzyme B (GrzB) and Helios in Egyptian cohorts of HCV mono-infected (HCV), schistosome-co-infected (Sm/HCV) and infection-free individuals. Interestingly, viral load and liver transaminases were significantly elevated in Sm/HCV individuals when compared to HCV patients. Moreover, overall Treg frequencies and Helios(pos) Treg were not elevated in Sm/HCV individuals, but frequencies of GrzB(+) Treg were significantly increased. Simultaneously, GrzB(+) CD8(+) T cells were not suppressed in co-infected individuals. This study demonstrates that in Sm/HCV co-infected cohorts, liver disease is aggravated with enhanced virus replication and Treg do not expand but rather change their phenotype with GrzB possibly being a more reliable marker than Helios for iTreg. Therefore, curing concurrent schistosome disease could be an important prerequisite for successful HCV treatment as co-infected individuals respond poorly to interferon therapy.

Quality not quantity for transglutaminase antibody 2: the performance of an endomysial and tissue transglutaminase test in screening coeliac disease remains stable over time.

National Institute of Clinical Excellence (NICE) and European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidance for the diagnosis of coeliac disease has been published. However, there is some controversy regarding the advice on the use of stratifying levels of immunoglobulin (IgA) tissue transglutaminase antibody (TG2) test positivity in the absence of test standardization and the vagueness of the indication to test equivocal samples. Using repeat service audit, we demonstrate that a combination of TG2 followed by IgA endomysial antibodies (EMA) is the best strategy for all degrees of mucosal abnormality using our test combination. Reliance upon immunoassay titre is not as effective, and cannot be applied consistently across populations in the absence of assay standardization. Guidelines advocating the use of tests should involve experts in laboratory diagnostics and external quality assurance to ensure that errors of generalization do not occur and that test performance is achievable in routine diagnostic use.

Heat Transfer Enhancement Using Al2O3-MWCNT Hybrid-Nanofluid inside a Tube/Shell Heat Exchanger with Different Tube Shapes.

The high demand for compact heat exchangers has led researchers to develop high-quality and energy-efficient heat exchangers at a lower cost than conventional ones. To address this requirement, the present study focuses on improvements to the tube/shell heat exchanger to maximize the efficiency either by altering the tube's geometrical shape and/or by adding nanoparticles in its heat transfer fluid. Water-based Al2O3-MWCNT hybrid nanofluid is utilized here as a heat transfer fluid. The fluid flows at a high temperature and constant velocity, and the tubes are maintained at a low temperature with various shapes of the tube. The involved transport equations are solved numerically by the finite-element-based computing tool. The results are presented using the streamlines, isotherms, entropy generation contours, and Nusselt number profiles for various nanoparticles volume fraction 0.01 ≤ φ ≤ 0.04 and Reynolds numbers 2400 ≤ Re ≤ 2700 for the different shaped tubes of the heat exchanger. The results indicate that the heat exchange rate is a growing function of the increasing nanoparticle concentration and velocity of the heat transfer fluid. The diamond-shaped tubes show a better geometric shape for obtaining the superior heat transfer of the heat exchanger. Heat transfer is further enhanced by using the hybrid nanofluid, and the enhancement goes up to 103.07% with a particle concentration of 2%. The corresponding entropy generation is also minimal with the diamond-shaped tubes. The outcome of the study is very significant in the industrial field and can solve many heat transfer problems.

Safety and efficacy of arimoclomol for inclusion body myositis: a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Inclusion body myositis is the most common progressive muscle wasting disease in people older than 50 years, with no effective drug treatment. Arimoclomol is an oral co-inducer of the cellular heat shock response that was safe and well-tolerated in a pilot study of inclusion body myositis, reduced key pathological markers of inclusion body myositis in two in-vitro models representing degenerative and inflammatory components of this disease, and improved disease pathology and muscle function in mutant valosin-containing protein mice. In the current study, we aimed to assess the safety, tolerability, and efficacy of arimoclomol in people with inclusion body myositis. METHODS: This multicentre, randomised, double-blind, placebo-controlled study enrolled adults in specialist neuromuscular centres in the USA (11 centres) and UK (one centre). Eligible participants had a diagnosis of inclusion body myositis fulfilling the European Neuromuscular Centre research diagnostic criteria 2011. Participants were randomised (1:1) to receive either oral arimoclomol 400 mg or matching placebo three times daily (1200 mg/day) for 20 months. The randomisation sequence was computer generated centrally using a permuted block algorithm with randomisation numbers masked to participants and trial staff, including those assessing outcomes. The primary endpoint was the change from baseline to month 20 in the Inclusion Body Myositis Functional Rating Scale (IBMFRS) total score, assessed in all randomly assigned participants, except for those who were randomised in error and did not receive any study medication, and those who did not meet inclusion criteria. Safety analyses included all randomly assigned participants who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT02753530, and is completed. FINDINGS: Between Aug 16, 2017 and May 22, 2019, 152 participants with inclusion body myositis were randomly assigned to arimoclomol (n=74) or placebo (n=78). One participant was randomised in error (to arimoclomol) but not treated, and another (assigned to placebo) did not meet inclusion criteria. 150 participants (114 [76%] male and 36 [24%] female) were included in the efficacy analyses, 73 in the arimoclomol group and 77 in the placebo group. 126 completed the trial on treatment (56 [77%] and 70 [90%], respectively) and the most common reason for treatment discontinuation was adverse events. At month 20, mean IBMFRS change from baseline was not statistically significantly different between arimoclomol and placebo (-3·26, 95% CI -4·15 to -2·36 in the arimoclomol group vs -2·26, -3·11 to -1·41 in the placebo group; mean difference -0·99 [95% CI -2·23 to 0·24]; p=0·12). Adverse events leading to discontinuation occurred in 13 (18%) of 73 participants in the arimoclomol group and four (5%) of 78 participants in the placebo group. Serious adverse events occurred in 11 (15%) participants in the arimoclomol group and 18 (23%) in the placebo group. Elevated transaminases three times or more of the upper limit of normal occurred in five (7%) participants in the arimoclomol group and one (1%) in the placebo group. Tubulointerstitial nephritis was observed in one (1%) participant in the arimoclomol group and none in the placebo group. INTERPRETATION: Arimoclomol did not improve efficacy outcomes, relative to placebo, but had an acceptable safety profile in individuals with inclusion body myositis. This is one of the largest trials done in people with inclusion body myositis, providing data on disease progression that might be used for subsequent clinical trial design. FUNDING: US Food and Drug Administration Office of Orphan Products Development and Orphazyme.

Efficacy and safety of dextromethorphan/quinidine at two dosage levels for diabetic neuropathic pain: a double-blind, placebo-controlled, multicenter study.

OBJECTIVE: To evaluate dextromethorphan coadministered with quinidine as treatment of diabetic peripheral neuropathic pain. DESIGN: In a 13-week, phase 3, randomized controlled trial, 379 adults with daily symmetric diabetic peripheral neuropathy (DPN) leg pain for ≥3 months received double-blind placebo, dextromethorphan/quinidine (DMQ) 45/30 mg, or DMQ 30/30 mg, administered once daily for 7 days and twice daily thereafter. Efficacy measures included four pain rating scales applied daily using patient diaries, and another two applied at five clinic visits. RESULTS: On all six scales, DMQ 45/30 mg was significantly superior to placebo, including the primary efficacy analysis, which utilized mixed-effects modeling to test all scores on an 11-point numerical Pain Rating Scale (P < 0.0001). Sensitivity analyses gave consistent results. Efficacy vs placebo was also seen for diary ratings of present pain intensity, and pain interference with sleep and with activities (all P < 0.0001). Among clinic visit assessments, DMQ 45/30 mg demonstrated greater leg pain relief (P = 0.0002) and greater reduction of leg pain intensity (P = 0.0286) vs placebo. The efficacy of DMQ 30/30 mg was numerically less than for 45/30 mg but for most outcomes remained significantly greater vs placebo. Adverse events were mostly mild or moderate and of expected types. Discontinuation for adverse events in the DMQ groups was at least twice as common as placebo. CONCLUSIONS: Throughout a 13-week trial, DMQ was effective, with an acceptable safety profile, for treatment of DPN pain. Other fixed-dose combinations of DMQ should be studied to improve overall tolerability while maintaining significant efficacy.

ONCOLYTIC ACTIVITY OF HUMAN ORTHOPNEUMOVIRUS IN CANCER CELL LINES.

Oncolytic virotherapy is an emerging biotherapeutic platform for selectively infecting cancer cells and triggering apoptosis in a number of malignant cells due to robust viral replication. Studies related to the oncolytic activity of human orthopneumovirus (hOPV) are conflicting. AIM: This study was designed to elucidate the possible role of hOPV in the modulation of cell growth and apoptosis in cancer cell lines including human epidermoid carcinoma (HEp-2), lung epithelial cell line (A549), and breast cancer cell line (MCF-7). MATERIALS AND METHODS: The oncolytic activity of hOPV on cancer cells was studied in vitro. The virus titers were determined by tissue culture infectious dose (TCID50/mL) in A549 cell. The cytotoxic effect of the virus on HEp-2, A549, and MCF-7 was determined using MTT and trypan blue dye exclusion test assays. hOPV in the infected cells was detected using real-time reverse transcription polymerase chain reaction (rRT-PCR) and indirect immunofluorescence (IIF) assays. The relative expression of apoptosis-related genes (CASP-3, -8, -9, Bax, Bcl-2, Bcl-XL, TP53, P21) during virus infection was estimated using rRT-PCR assay in comparison with the house-keeping gene (GAPDH). RESULTS: hOPV infection inhibited the growth of HEp-2, A549, and MCF-7 cells in a dose-and time-dependent manner. At a multiplicity of infection (MOI) of 5, hOPV reduced the viability of A549 cells to about 16%, HEp-2 to 22%, and MCF-7 to 28% (p = 0.001), while no significant inhibitory effect was observed when cells were infected at MOI of 1 and 2. hOPV mRNA and antigens were detected in infected HEp-2, A549, and MCF-7 cells by RT-PCR and IIF. Upon hOPV infection, expression of CASP-3, -8, -9, as well as Bax, TP53, and p21 mRNA increased while expression of Bcl-2, Bcl-xL anti-apoptotic genes decreased. In hOPV-infected A549 cells, the fold increase of CASP-8 and CASP-9, Bax, TP53, and P21 expression exceeded significantly compared to that in HEp-2 or MCF-7 cells. CONCLUSIONS: Our results provide evidence that hOPV could be a potential candidate for oncolytic virotherapy.

MHD Flow of a Hybrid Nano-Fluid in a Triangular Enclosure with Zigzags and an Elliptic Obstacle.

The current study uses the multi-physics COMSOL software and the Darcy-Brinkman-Forchheimer model with a porosity of ε = 0.4 to conduct a numerical study on heat transfer by Cu-TiO2/EG hybrid nano-fluid inside a porous annulus between a zigzagged triangle and different cylinders and under the influence of an inclined magnetic field. The effect of numerous factors is detailed, including Rayleigh number (103 ≤ Ra ≤ 106), Hartmann number (0 ≤ Ha ≤ 100), volume percent of the nano-fluid (0.02 ≤ ϕ ≤ 0.08), and the rotating speed of the cylinder (-4000 ≤ w ≤ 4000). Except for the Hartmann number, which decelerates the flow rate, each of these parameters has a positive impact on the thermal transmission rate.

Metalcones: hybrid organic-inorganic films fabricated using atomic and molecular layer deposition techniques.

Hybrid organic-inorganic films can be deposited using atomic layer deposition (ALD) and molecular layer deposition (MLD) techniques. A special set of hybrid organic-inorganic films based on metal precursors and various organic alcohols yields metal alkoxide films that can be described as "metalcones." Many metalcone films are possible such as the "alucones" and "zincones" based on the reaction of trimethylaluminum and diethylzinc, respectively, with various organic alcohols such as ethylene glycol (EG). This paper reviews the previous work on metalcone MLD and discusses a variety of new metalcone systems. "Titanicones" are grown using TiCl4 and glycerol or EG and "zircones" are grown using zirconium tetra-tert-butoxide and EG. In addition, the organic alcohol can also be varied to change the properties within one metalcone family. For example, the glycerol triol precursor allows for more cross-linking and higher toughness in alucones than the EG diol precursor. Alloys can also be formed by combining metalcone MLD and metal oxide ALD. By varying the relative number of cycles of MLD and ALD, the composition and properties of the hybrid organic-inorganic films can be tuned from pure metalcone MLD to pure metal oxide ALD.

Are Dropped Bone Grafts Safe to be Re-used? - An Experimental Study Comparing Efficacy of Chlorhexidine, Povidone-Iodine and Alcohol.

INTRODUCTION: A dilemma arises when a bone graft or fracture fragment is accidentally dropped on the operation theatre floor and becomes contaminated. This study aimed to determine the efficacy of simple and readily available antiseptic solutions in disinfecting contaminated bones. MATERIAL AND METHODS: This experimental study involved 225 bone specimens prepared from discarded bone fragments during a series of 45 knee and hip arthroplasty surgeries. The bone fragments were cut into five identical cubes and were randomly assigned to either control (positive or negative), or experimental groups (0.5% chlorhexidine, 10% povidone-iodine or 70% alcohol). The control negative was to determine pre-contamination culture. All bone specimens, except the control negative group were uniformly contaminated by dropping on the operation theatre floor. Subsequently, the dropped bone specimens except for the control positive group, were disinfected by immersing in a respective antiseptic solution for 10 minutes, before transported to the microbiology laboratory for incubation. RESULTS: The incidence of a positive culture from a dropped bone fragment was 86.5%. From the 37 specimens sent for each group, the incidence of positive culture was 5.4% (2 specimens) after being disinfected using chlorhexidine, 67.6% (25 specimens) using povidone-iodine and 81.1% (30 specimens) using alcohol. Simple logistic regression analysis demonstrated that chlorhexidine was significantly effective in disinfecting contaminated bones (p-value <0.001, odd ratio 0.009). Povidone-iodine and alcohol were not statistically significant (p-value 0.059 and 0.53, respectively). Organisms identified were Bacillus species and coagulase negative Staphylococcus. No gram-negative bacteria were isolated. CONCLUSION: A total of 0.5% chlorhexidine is effective and superior in disinfecting contaminated bones.

Efficacy and Safety of Bimagrumab in Sporadic Inclusion Body Myositis: Long-term Extension of RESILIENT.

OBJECTIVE: To assess long-term (2 years) effects of bimagrumab in participants with sporadic inclusion body myositis (sIBM). METHODS: Participants (aged 36-85 years) who completed the core study (RESILIENT [Efficacy and Safety of Bimagrumab/BYM338 at 52 Weeks on Physical Function, Muscle Strength, Mobility in sIBM Patients]) were invited to join an extension study. Individuals continued on the same treatment as in the core study (10 mg/kg, 3 mg/kg, 1 mg/kg bimagrumab or matching placebo administered as IV infusions every 4 weeks). The co-primary outcome measures were 6-minute walk distance (6MWD) and safety. RESULTS: Between November 2015 and February 2017, 211 participants entered double-blind placebo-controlled period of the extension study. Mean change in 6MWD from baseline was highly variable across treatment groups, but indicated progressive deterioration from weeks 24-104 in all treatment groups. Overall, 91.0% (n = 142) of participants in the pooled bimagrumab group and 89.1% (n = 49) in the placebo group had ≥1 treatment-emergent adverse event (AE). Falls were slightly higher in the bimagrumab 3 mg/kg group vs 10 mg/kg, 1 mg/kg, and placebo groups (69.2% [n = 36 of 52] vs 56.6% [n = 30 of 53], 58.8% [n = 30 of 51], and 61.8% [n = 34 of 55], respectively). The most frequently reported AEs in the pooled bimagrumab group were diarrhea 14.7% (n = 23), involuntary muscle contractions 9.6% (n = 15), and rash 5.1% (n = 8). Incidence of serious AEs was comparable between the pooled bimagrumab and the placebo group (18.6% [n = 29] vs 14.5% [n = 8], respectively). CONCLUSION: Extended treatment with bimagrumab up to 2 years produced a good safety profile and was well-tolerated, but did not provide clinical benefits in terms of improvement in mobility. The extension study was terminated early due to core study not meeting its primary endpoint. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02573467. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with sIBM, long-term treatment with bimagrumab was safe, well-tolerated, and did not provide meaningful functional benefit. The study is rated Class IV because of the open-label design of extension treatment period 2.