bluuebunny/crossref_metadata_2025 huggingface dataset:
Single photon emission computed tomography imaging of cerebral blood flow, blood–brain barrier disruption, and apoptosis time course after focal cerebral ischemia in rats
Authors: Garrigue Philippe , Giacomino Laura , Bucci Chiara , Muzio Valeria , Filannino Maria A , Sabatier Florence , Dignat-George Françoise , Pisano Pascale , Guillet Benjamin
Published: January 2016

Background

Cerebral ischemia is a leading cause of disability worldwide and no other effective therapy has been validated to date than intravenous thrombolysis. In this context, many preclinical models have been developed and recent advances in preclinical imaging represent promising tools. Thus, we proposed here to characterize in vivo time profiles of cerebral blood flow, blood–brain barrier disruption and apoptosis following a transient middle cerebral artery occlusion in rats using SPECT/CT imaging.

Methods

Rats underwent a 1-h middle cerebral artery occlusion followed by reperfusion. Cerebral blood flow, blood–brain barrier disruption and apoptosis were evaluated by SPECT/CT imaging using respectively 99mTc-HMPAO, 99mTc-DTPA and the experimental 99mTc-Annexin V-128, up to 14 days after middle cerebral artery occlusion. Histological evaluation of apoptosis has been performed using TUNEL method to validate the 99mTc-Annexin V-128 uptake.

Results

99mTc-HMPAO cerebral blood flow evaluation showed hypoperfusion during occlusion, partially restored on days 4 and 7 and sustained up to 14 days after middle cerebral artery occlusion. 99mTc-DTPA SPECT/CT showed a blood–brain barrier disruption starting on day 1 post-middle cerebral artery occlusion, peaking on day 2, with barrier integrity totally restored on day 7. 99mTc-Annexin V-128 SPECT/CT imaging showed significant positive correlation with TUNEL immunohistochemistry and allowed ischemic-induced apoptosis to be detected from day 2 to day 7, peaking on day 3 after middle cerebral artery occlusion.

Conclusions

Using SPECT/CT imaging, we showed that after transient middle cerebral artery occlusion in rat there was a sustained decrease in cerebral blood flow followed by blood–brain barrier disruption preceding meanwhile apoptosis. Rodent SPECT/CT imaging of cerebral blood flow, blood–brain barrier disruption and apoptosis appears to be an efficient tool for evaluating neuroprotective drugs and regenerative therapies against cerebral ischemia and time-windows for therapeutic intervention.
Leukoaraiosis and lacunes are associated with poor clinical outcomes in ischemic stroke patients treated with intravenous thrombolysis
Authors: Arba Francesco , Palumbo Vanessa , Boulanger Jean-Martin , Pracucci Giovanni , Inzitari Domenico , Buchan Alastair M , Hill Michael D ,   on behalf of CASES Investigators
Published: January 2016

Background

The effect of preexisting small vessel disease on outcomes of patients with ischemic stroke treated with i.v. thrombolysis is not fully understood.

Aim

We aim to investigate the effect of combined leukoaraiosis and lacunes as detected on unenhanced brain computer tomography at baseline on clinical outcomes after i.v. thrombolysis.

Methods

We analyzed data from the Canadian Alteplase for Stroke Effectiveness Study. Small vessel disease was assessed on baseline computer tomography rating for leukoaraiosis and lacunes. We dichotomized the burden of small vessel disease to “absent or moderate” and “severe.” Clinical outcomes at 90 days included excellent outcome (mRS = 0–1), good outcome (mRS = 0–2), and the occurrence of symptomatic intracerebral hemorrhage. Sensitivity analysis was performed on two age groups (≤80 versus >80). We ran logistic regression adjusting for confounders to evaluate independent effect of small vessel disease on outcomes.

Results

There were 820 patients with available brain computer tomography with mean age (±SD) of 71.3 (±13.2), 455 (55.5%) were male. Of these, 123 (15%) patients had severe small vessel disease at baseline. Age group analysis revealed significant associations of small vessel disease only in patients aged ≤80. After adjustment for confounders, presence of severe small vessel disease reduced the chances of both excellent (OR = 0.42, 95% CI = 0.24–0.74) and good outcome (OR = 0.35, 95% CI = 0.21–0.58) and with an increased risk of symptomatic intracerebral hemorrhage (OR = 5.91; 95% CI = 2.40–14.57).

Conclusion

When considered together as radiological expressions of small vessel disease, presence and severity of severe leukoaraiosis and lacunes on baseline computer tomography scan are associated with poor clinical outcomes in patients treated with i.v. thrombolysis.
The predictors and clinical impact of intraventricular hemorrhage in patients with aneurysmal subarachnoid hemorrhage
Authors: Jabbarli Ramazan , Reinhard Matthias , Roelz Roland , Shah Mukesch , Niesen Wolf-Dirk , Kaier Klaus , Taschner Christian , Weyerbrock Astrid , Velthoven Vera Van
Published: January 2016

Background

Intraventricular hemorrhage is known to complicate the course and outcome of aneurysmal subarachnoid hemorrhage.

Aims

To identify independent risk factors for intraventricular hemorrhage development and its severity during aneurysm rupture.

Methods

Six hundred and twenty-five subarachnoid hemorrhage patients treated at our institution between January 2005 and December 2012 were included. The severity of intraventricular hemorrhage was assessed according to the original Graeb score. Clinical and radiographic features of patients present at the bleeding event were tested as potential risk factors for intraventricular hemorrhage. The characteristics of intraventricular hemorrhage were correlated with the clinical course and outcome.

Results

Intraventricular hemorrhage was present in 206 patients (33%) and was independently predicted by patient’s age (p = 0.001, odds ratio (OR) = 1.02/year of age increase), aneurysm size (p = 0.031, OR = 1.05/mm increase), and location (p < 0.0001, OR = 3.2 for aneurysms of posterior circulation). The severity of intraventricular hemorrhage was predicted by aneurysm size (p = 0.023) and location (higher severity for aneurysms of anterior circulation, p = 0.01). The presence of intraventricular hemorrhage (p < 0.0001, OR = 4.1) and intraventricular hemorrhage severity of >3 points on the Graeb score (p = 0.029, OR = 3.4) was independently associated with poor outcome. Shunt dependency was associated only with the occurrence of intraventricular hemorrhage (p < 0.0001, OR = 2.8) while the severity of intraventricular hemorrhage influenced the timing of shunt placement (p = 0.0156).

Conclusions

Increasing age, aneurysm size, and location in the posterior circulation are the main risk factors for occurrence of aneurysmal intraventricular hemorrhage, which is independently associated with poor outcome. The severity of intraventricular hemorrhage, however, is higher if the aneurysm is located in the anterior circulation and has impact on functional outcome, but not on shunt dependency.
Trends in risk of recurrence after the first ischemic stroke in adults younger than 55 years of age in Sweden
Authors: Giang Kok Wai , Björck Lena , Ståhl Christina H , Nielsen Susanne , Sandström Tatiana Z , Jern Christina , Torén Kjell , Rosengren Annika
Published: January 2016

Background

Previous studies on stroke recurrence in younger adults often contain small sample size which makes it difficult to study trends in stroke recurrence over a long period of time.

Aims

The aim of the present study was to investigate temporal trends in the risk of recurrence in younger patients with a first ischemic stroke.

Methods

All men and women aged 18–54 years who had survived at least 28 days after a first ischemic stroke from 1987 to 2006 were identified in the Swedish Inpatient Register. The patients were stratified into four 5-year periods according to their admission period and were followed up for a total of four years after the index event with regard to recurrent ischemic stroke. A Cox regression model was used to analyze the risk of recurrent ischemic stroke.

Results

Of the 17,149 ischemic stroke patients who were identified, 2432 (14.2%) had a recurrent ischemic stroke event within four years. From the first to the last periods (1987–1991 versus 2002–2006), the four-year risk of recurrent ischemic stroke decreased by 55% (hazard ratio 0.45, 95% confidence interval 0.39–0.53) in men and 59% (hazard ratio 0.41, 95% confidence interval, 0.33–0.50) in women. The cumulative four-year risk was 11.8% (95% CI 10.55–13.25) in men and 9.8% (95% CI 8.40–11.46) in women during the last five-year period (2002–2006).

Conclusions

The risk of recurrence among younger ischemic stroke patients has decreased over the past 20 years. Despite these improvements, younger patients are still at a high risk for recurrent ischemic stroke.
Missing voices: Profile and extent of acquired communication disorders in Aboriginal and non-Aboriginal adult stroke survivors in Western Australia using linked administrative records
Authors: Katzenellenbogen JM , Atkins ER , Thompson SC , Hersh D , Coffin J , Flicker L , Hayward C , Ciccone N , Woods D , McAllister M , Armstrong EM
Published: January 2016

Background

Limited data exist on the extent of specific functional sequelae, including acquired communication disorder, among Aboriginal stroke survivors, making planning of multidisciplinary services difficult.

Aims

To obtain estimates of the extent and profile of acquired communication disorder in Aboriginal and non-Aboriginal adult stroke survivors in Western Australia and investigate potential disparities in receiving in-hospital speech pathology services among survivors with acquired communication disorder.

Methods

Stroke cases surviving their first stroke episode during 2002–2011 were identified using Western Australia-wide person-based linked hospital and mortality data, and their five-year comorbidity profiles determined. The mid-year prevalence of stroke cases with acquired communication disorder was estimated for 2011. Regression methods were used to investigate determinants of receiving speech pathology services among acquired communication disorder cases.

Results

Of 14,757 stroke survivors aged 15–79 years admitted in 2002–2011, 33% had acquired communication disorder (22% aphasia/dysphasia) and 777 (5.3%) were Aboriginal. Aboriginal patients were more likely to be younger, live remotely, and have comorbidities. A diagnosis of aphasia was more common in Aboriginal than non-Aboriginal patients 15–44 years (p = 0.003). A minimum of 107 Aboriginal and 2324 non-Aboriginal stroke patients with acquired communication disorder lived in Western Australia in 2011. Aboriginal status was not associated with receiving in-hospital speech services among acquired communication disorder patients in unadjusted or adjusted models.

Conclusions

The relative youth, geographical distribution, high comorbidity prevalence, and cultural needs of Aboriginal stroke patients with acquired communication disorder should inform appropriate service design for speech pathology and rehabilitation. Innovative models are required to address workforce issues, given low patient volumes.
Do cognitive, language, or physical impairments affect participation in a trial of self-management programs for stroke?
Authors: Cadilhac Dominique A , Kilkenny Monique F , Srikanth Velandai , Lindley Richard I , Lalor Erin , Osborne Richard H , Batterbsy Malcolm
Published: January 2016

Background

Research studies may have limited generalizability when survivors of stroke with physical, language, or cognitive impairments are excluded.

Aims

To assess whether presence of cognitive, language, or global impairments affects participation in self-management programs.

Methods

Stroke survivors were recruited in South Australia from seven hospitals or via advertisements into a randomized controlled trial (1:1:1 ratio) of a Stroke Self-Management Program, the Stanford chronic condition self-management program, or standard care. Impairment status was measured using: Cognistat (cognition), Frenchay Aphasia assessment (language), modified Rankin Score (mRS; where score 3–5 = global disability). Primary outcomes: participation (i.e. booked, accessed, and completed a program (defined as attending ≥ 50% of sessions)) and safety (i.e. adverse events). Outcomes were compared by impairment status.

Results

Among 315 people screened 143/149 eligible were randomized (median age 71 years; 41% male; with impairments: 62% cognitive, 34% language, 64% global disability). Participation did not differ by cognitive or language impairment status (cognitive 75%, no cognitive 68%, p = 0.54; language 78%, no language 69%, p = 0.42). However, participation did vary by global impairment status (global disability 61%, no disability 96%, p < 0.001). Participants with cognitive impairment experienced more adverse events (severe n = 9 versus no cognitive impairment n = 1).

Conclusion

Survivors of stroke with cognitive, language, or global impairments are able to participate in self-management programs and should be included in these types of research studies or programs. Reduced participation by those with global disability and the possibility of more adverse events in people with cognitive impairments needs to be considered.
National stroke registries for monitoring and improving the quality of hospital care: A systematic review
Authors: Cadilhac Dominique A , Kim Joosup , Lannin Natasha A , Kapral Moira K , Schwamm Lee H , Dennis Martin S , Norrving Bo , Meretoja Atte
Published: January 2016

Background

Routine monitoring of the quality of stroke care is becoming increasingly important since patient outcomes could be improved with better access to proven treatments. It remains unclear how many countries have established a national registry for monitoring stroke care.

Aims

To describe the current status of national, hospital-based stroke registries that have a focus on monitoring access to evidence-based care and patient outcomes and to summarize the main features of these registries.

Summary of review

We undertook a systematic search of the published literature to identify the registries that are considered in their country to represent a national standardized dataset for acute stroke care and outcomes. Our initial keyword search yielded 5002 potential papers, of which we included 316 publications representing 28 national stroke registries from 26 countries. Where reported, data were most commonly collected with a waiver of patient consent (70%). Most registries used web-based systems for data collection (57%) and 25% used data linkage. Few variables were measured consistently among the registries reflecting their different local priorities. Funding, resource requirements, and coverage also varied.

Conclusions

This review provides an overview of the current use of national stroke registries, a description of their common features relevant to monitoring stroke care in hospitals. Formal registration and description of registries would facilitate better awareness of efforts in this field.
Risk of early recurrent stroke in symptomatic carotid stenosis after best medical therapy and before endarterectomy
Authors: Shahidi S , Owen-Falkenberg A , Gottschalksen B , Ellemann K
Published: January 2016

Background

The early recurrence of neurological symptoms (NR) after urgent aggressive best medical therapy (BMT) in symptomatic carotid stenosis is not well documented.

Aims

To investigate the risk of ipsilateral NR after urgent aggressive BMT in patients with symptomatic (50–99%) carotid stenosis up to carotid endarterectomy (CEA), with emphasis on the first 14 days after index-event.

Methods

Prospective population based study, covering a period of 4½ years. NR rate was determined after initiation of urgent aggressive BMT and until CEA and compared to NR up to 90 days prior to index-event. Urgent BMT consisted of loading dose aspirin and clopidogrel thereafter therapy with aspirin and clopidogrel together with a statin.

Results

Of 8200 symptomatic patients (ischemic stroke, transient ischemic attack and ocular events), 250 (3%) patients underwent CEA, 47% within 14 days of the index-event and 99% within 14 days of surgical referral. The overall NR from index-event to CEA in symptomatic patients was significantly lower 1.6% (95% CI 0.5–4%) after BMT when compared with NR in the 90 days prior to referral to a stroke clinic 25% (95% CI 20–30%, p < 0.00001). Peri-operative bleeding 5% (95% CI 3–8%) was comparable with other studies.

Conclusion

Urgent aggressive BMT after index-event is associated with a significant reduction in the risk of early NR in CEA candidates. The early risk of recurrent stroke in patients with symptomatic significant carotid stenosis is dramatically reduced after urgent aggressive BMT in specialised stroke clinics.
Mechanical thrombectomy in acute ischemic stroke: Consensus statement by ESO-Karolinska Stroke Update 2014/2015, supported by ESO, ESMINT, ESNR and EAN
Authors: Wahlgren Nils , Moreira Tiago , Michel Patrik , Steiner Thorsten , Jansen Olav , Cognard Christophe , Mattle Heinrich P , van Zwam Wim , Holmin Staffan , Tatlisumak Turgut , Petersson Jesper , Caso Valeria , Hacke Werner , Mazighi Mikael , Arnold Marcel , Fischer Urs , Szikora Istvan , Pierot Laurent , Fiehler Jens , Gralla Jan , Fazekas Franz , Lees Kennedy R ,   for ESO-KSU, ESO, ESMINT, ESNR and EAN
Published: January 2016

The original version of this consensus statement on mechanical thrombectomy was approved at the European Stroke Organisation (ESO)-Karolinska Stroke Update conference in Stockholm, 16–18 November 2014. The statement has later, during 2015, been updated with new clinical trials data in accordance with a decision made at the conference. Revisions have been made at a face-to-face meeting during the ESO Winter School in Berne in February, through email exchanges and the final version has then been approved by each society. The recommendations are identical to the original version with evidence level upgraded by 20 February 2015 and confirmed by 15 May 2015. The purpose of the ESO-Karolinska Stroke Update meetings is to provide updates on recent stroke therapy research and to discuss how the results may be implemented into clinical routine. Selected topics are discussed at consensus sessions, for which a consensus statement is prepared and discussed by the participants at the meeting. The statements are advisory to the ESO guidelines committee. This consensus statement includes recommendations on mechanical thrombectomy after acute stroke. The statement is supported by ESO, European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), and European Academy of Neurology (EAN).
Recent advances in carotid angioplasty and stenting
Authors: Calvet David , Mas Jean-Louis
Published: January 2016

Atherosclerotic carotid stenosis accounts for about 15% of ischemic strokes. Carotid endarterectomy reduces the risk of stroke in patients with severe carotid stenosis. Carotid artery stenting has emerged as a potentially less invasive alternative to carotid endarterectomy. However, randomized clinical trials in patients with symptomatic stenosis have shown that carotid artery stenting is associated with a higher risk of peri-procedural stroke compared with carotid endarterectomy. Carotid artery stenting is associated with a lower risk of peri-procedural myocardial infarction and local complications (cranial nerve palsies, access site hematoma) and appears to be as durable as carotid endarterectomy in terms of long-term protection against ipsilateral stroke and risk of restenosis. The main risk factors for peri-procedural stroke in patients treated with carotid artery stenting are age >70 years and high burden of white-matter lesions on brain imaging. Patients with asymptomatic carotid stenosis receiving modern medical treatment have a low risk (<1%/year) of ipsilateral stroke and it is uncertain whether the benefit of revascularization still justifies the procedural risk of stroke or death. In particular, the small excess of procedural risk of stroke associated with carotid artery stenting (compared with carotid endarterectomy) may offset the small benefit (if any) of carotid endarterectomy versus medical therapy in unselected patients. Randomized clinical trials are ongoing to solve this issue.
Diverticulosis today: unfashionable and still under-researched
Authors: Tursi Antonio
Published: January 2016

Diverticulosis of the colon is a widespread disease, and its prevalence is increasing especially in the developing world. The underlying pathological mechanisms that cause the formation of colonic diverticula remain unclear but are likely to be the result of complex interactions among age, diet, genetic factors, colonic motility, and changes in colonic structure. The large majority of patients remain asymptomatic throughout their life, one fifth of them become symptomatic (developing the so-called ‘diverticular disease’) while only a minority of these will develop acute diverticulitis. The factors predicting the development of symptoms remain to be identified. Again, it is generally recognized that diverticular disease occurrence is probably related to complex interactions among colonic motility, diet, lifestyle, and genetic features. Changes in intestinal microflora due to low-fiber diet and consequent low-grade inflammation are thought to be one of the mechanisms responsible for symptoms occurrence of both diverticular disease and acute diverticulitis. Current therapeutic approaches with rifaximin and mesalazine to treat the symptoms seem to be promising. Antibiotic treatment is currently advised only in acute complicated diverticulitis, and no treatment has currently proven effective in preventing the recurrence of acute diverticulitis. Further studies are required in order to clarify the reasons why diverticulosis occurs and the factors triggering occurrence of symptoms. Moreover, the reasons why rifaximin and mesalazine work in symptomatic diverticular disease but not in acute diverticulitis are yet to be elucidated.
Refining small intestinal bacterial overgrowth diagnosis by means of carbohydrate specificity: a proof-of-concept study
Authors: Enko Dietmar , Halwachs-Baumann Gabriele , Stolba Robert , Mangge Harald , Kriegshäuser Gernot
Published: January 2016

Background:

Diagnosis of small intestinal bacterial overgrowth (SIBO) remains challenging. This study aimed at proving the diagnostic concept of carbohydrate-specific SIBO (cs-SIBO) using glucose, fructose and sorbitol hydrogen (H2)/methane (CH4) breath testing (HMBT).

Methods:

In this study 125 patients referred to our outpatient clinic for SIBO testing were included. All individuals underwent glucose (50 g), fructose (25 g) and sorbitol (12.5 g) HMBT at 3 consecutive days. Patients with cs-SIBO (i.e. early H2/CH4 peak) were given rifaximin (600 mg/day) in a 10-day treatment. HMBT results were reassessed in a subset of patients 3–6 months after antibiotic therapy. In view of cs-SIBO diagnosis, agreements between HMBT results obtained for different sugars were calculated using Cohen’s kappa (κ) with 95% confidence intervals (CIs).

Results:

A total of 59 (47.2%) patients presented an early H2/CH4 peak with one or more sugars. Among these, 21 (16.8%), 10 (8.0%) and 7 (5.6%) individuals had a positive HMBT result with either glucose, fructose or sorbitol, respectively. Another 21 (16.8%) patients with a positive glucose HMBT result were also found positive with an early H2/CH4 peak obtained after ingestion of fructose and/or sorbitol. Fair agreement was observed between glucose and fructose (κ = 0.26, p = 0.0018) and between glucose and sorbitol (κ = 0.18, p = 0.0178) HMBT results. Slight agreement was observed between fructose and sorbitol (κ = 0.03, p = 0.6955) HMBT results only. Successful antibiotic therapy with rifaximin could be demonstrated in 26/30 (86.7%) of patients as indicated by normal HMBT results and symptom remission.

Conclusions:

Combined glucose, fructose and sorbitol HMBT has the potential to optimize cs-SIBO diagnosis. Furthermore, the majority of patients with cs-SIBO seem to benefit from rifaximin therapy regardless of its carbohydrate specificity.
Cardiovascular risk assessment in the treatment of nonalcoholic steatohepatitis: a secondary analysis of the MOZART trial
Authors: Lin Steven C. , Ang Brandon , Hernandez Carolyn , Bettencourt Ricki , Jain Rashmi , Salotti Joanie , Richards Lisa , Kono Yuko , Bhatt Archana , Aryafar Hamed , Lin Grace Y. , Valasek Mark A. , Sirlin Claude B. , Brouha Sharon , Loomba Rohit
Published: January 2016

Background:

Nonalcoholic steatohepatitis (NASH) is associated with increased cardiovascular risk and mortality. No US Food and Drug Administration (FDA) approved therapies for NASH are available; clinical trials to date have not yet systematically assessed for changes in cardiovascular risk. This study examines the prospective utility of cardiovascular risk assessments, the Framingham risk score (FRS) and coronary artery calcium (CAC) score, as endpoints in a NASH randomized clinical trial, and assesses whether histologic improvements lead to lower cardiovascular risk.

Methods:

Secondary analysis of a 24-week randomized, double-blind, placebo-controlled trial (MOZART) in which 50 biopsy-proven NASH patients received oral ezetimibe 10 mg daily ( n = 25) versus placebo ( n = 25). Biochemical profiling, FRS, CAC scores, liver biopsies were obtained at baseline and endpoint.

Results:

Ezetimibe improved FRS whereas placebo did not (4.4 ± 6.2 to 2.9 ± 4.8, p = 0.038; 3.0 ± 4.4 to 2.9 ± 4.2, p = 0.794). CAC scores did not change with ezetimibe or placebo (180.4 ± 577.2 to 194.1 ± 623.9, p = 0.293; 151.4 ± 448.9 to 183.3 ± 555.7, p = 0.256). Ezetimibe improved FRS and CAC scores in more patients than placebo (48% versus 23%, p = 0.079, and 21% versus 0%, p = 0.090, respectively), though not significantly. No differences were noted in cardiovascular risk scores among histologic responders versus nonresponders.

Conclusions:

Ezetimibe improved FRS whereas placebo did not. FRS and CAC scores improved in a greater proportion of patients with ezetimibe; this trend did not reach significance. These findings indicate the utility and feasibility of monitoring cardiovascular risk in a NASH trial. The utility of CAC scores may be higher in trials of longer duration (⩾52 weeks) and with older patients (age ⩾45). ClinicalTrials.gov registration: NCT01766713.
Fecal microbiota transplant for Clostridium difficile infection in older adults
Authors: Tauxe William M. , Haydek John P. , Rebolledo Paulina A. , Neish Emma , Newman Kira L. , Ward Angela , Dhere Tanvi , Kraft Colleen S.
Published: January 2016

Background:

The objective of this study was to describe the safety of fecal microbiota transplant (FMT) for Clostridium difficile infection (CDI) among older adults.

Methods:

We performed a case review of all FMT recipients aged 65 or older treated at Emory University Hospital, a tertiary care and referral center for Georgia and surrounding states.

Results:

CDI resolved in 27 (87%) of 31 respondents, including three individuals who received multiple FMTs. Among four whose CDI was not resolved at follow up, three respondents did well initially before CDI recurred, and one individual never eradicated his CDI despite repeating FMT. During the study, five deaths and eight serious adverse events requiring hospitalization were reported within the study group during the follow-up period. Fecal transplant was not a causative factor in these events. The most common adverse event reported in 4 (13%) of 31 respondents was subjective worsening of arthritis.

Conclusion:

FMT is a generally safe and effective treatment option for older adults with CDI.
A novel schedule of erlotinib/capecitabine (7/7) as salvage therapy in previously treated advanced pancreatic adenocarcinoma: a case series
Authors: Chen Jiezhong , Kaley Kristin , Garcon Marie Carmel , Rodriguez Teresa , Saif Muhammad Wasif
Published: January 2016

Background:

The objective of this study was to report a case series on the efficacy and safety of capecitabine 7/7 schedule combined with erlotinib (CAP-ERL) in patients with advanced pancreatic cancer (APC) who have failed prior therapies.

Methods:

We retrospectively evaluated 13 patients with locally advanced or metastatic pancreatic cancer previously treated with gemcitabine or oxaliplatin–irinotecan-based first-line regimens. Treatment consisted of capecitabine (Xeloda) at a flat dose of 1000 mg orally twice daily on days 1–7 out of 14 days (7/7 schedule) and erlotinib (Tarceva) 100 mg orally once daily until unacceptable toxicity or disease progression. Tumor assessments were repeated every two cycles (8 weeks) and serum tumor markers were measured every 4 weeks.

Results:

All patients (median age: 63 years; 7 female/3 male) had various previous lines of treatments of chemotherapies. Median number of cycles with CAP-ERL was 4 (range 2–12). The overall response rate was 20%. CA19-9 was reduced more than 25% in 40% patients. The median overall survival and progression-free survival from the start of CAP-ERL were 4.5 months (range 3–7.5) and 2 months (range 1.5–4), respectively. The most common grade 3 toxicities included hand–foot syndrome, nausea, vomiting, diarrhea, rash, and fatigue.

Conclusions:

Our result suggests that the combination of a fixed low dose of CAP-ERL 7/7 schedule was tolerated with manageable toxicity and showed encouraging activity as salvage treatment in patients with refractory APC with ECOG performance status 0–2. Further prospective studies are warranted to evaluate this combination.
Development of a Microsphere-Based System to Facilitate Real-Time Insulin Monitoring
Authors: Kahanovitz Lindy , Seker Erkin , Marks Robert S. , Yarmush Martin L. , Konry Tania , Russell Steven J.
Published: January 2016

Background:

The speed of insulin absorption after subcutaneous delivery is highly variable. Incorrect assumptions about insulin pharmacokinetics compromise effective glycemic regulation. Our ultimate goal is to develop a system to monitor insulin levels in vivo continuously, allowing pharmacokinetic parameters to be calculated in real time. We hypothesize that a bead-based detection system can be run on a flow-through microfluidic platform to measure insulin in subcutaneous fluid sampled via microdialysis. As a first step in development, we focused on microsphere-based measurement of insulin.

Methods:

Polystyrene microspheres coated with an anti-insulin monoclonal antibody were exposed to insulin-containing solutions, and after addition of a fluorescently labeled anti-insulin monoclonal antibody with a distinct epitope, bead-associated fluorescence was detected by fluorescence microscopy in 96-well plates or in a flow-through, microfluidic platform.

Results:

The bead detection system in plates had a linear range in buffer for regular human insulin (RHI), insulin lispro, and insulin aspart of 15-1115 µIU/ml, 14-976 µIU/ml, and 25-836 µIU/ml, respectively. Measurement on plasma samples demonstrated proportionality between basal and peak insulin levels similar to the laboratory reference method. Preliminary results in a polydimethylsiloxane-based, flow-through, microfluidic platform showed a strong signal at peak insulin levels.

Conclusions:

We have developed a microsphere-based system to rapidly measure levels of insulin and insulin analogs. We have further demonstrated proof of concept that this bead detection system can be implemented in a lab-on-a-chip format, which will be further developed and combined with microdialysis for real-time monitoring of insulin in vivo.
Understanding Perceptions of E-cigarette Use in Shared Consumption Spaces
Authors: Line Nathaniel D. , Hanks Lydia , Miao Li , Daniell Robert B.
Published: January 2016

In the absence of state or federal laws governing the public use of electronic cigarettes (e-cigarettes), hospitality organizations are often forced to decide, on an individual basis, whether or not to allow the use of these products in the consumption environment. Unfortunately, because the behavioral effects of e-cigarette use on nonusers are poorly understood, such decisions are often based on the personal views of management and/or anecdotal evidence from customers rather than on theoretically based empirical evidence. The purpose of this research is to explore the e-cigarette phenomenon from the perspective of schema congruity in an effort to better understand how consumers react to the use of e-cigarettes in shared consumption spaces. To these ends, data were collected from 228 consumers in the United States. Results of both qualitative and quantitative analyses suggest that evaluations of e-cigarettes vary significantly based on the social distance from the referent user as well as on salient contextual norms. In addition, schema congruity was found to affect both attitudinal perceptions of e-cigarette use and perceptions of restaurant policy concerning e-cigarettes. The results suggest that, when it comes to e-cigarette policy, consideration must be given to both property-level characteristics (i.e., norm salience) and product-level perceptions (i.e., schema congruity).
Analyses of Landing Mechanics in Division I Athletes Using the Landing Error Scoring System
Authors: James Joan , Ambegaonkar Jatin P. , Caswell Shane V. , Onate James , Cortes Nelson
Published: January 2016

Background:

Injury to the anterior cruciate ligament (ACL) can be detrimental to any athlete, having both short- and long-term health consequences. Examining preseason screening landing mechanics can indicate the likelihood of injury during the season. Furthermore, previous injury is also commonly referred as a predisposing factor for reinjury.

Hypothesis:

Players with a history of lower extremity injury would have higher Landing Error Scoring System (LESS) scores than those with no previous injury, and healthy soccer athletes who sustained an injury during the 2014 season would have higher LESS scores than those who remained uninjured.

Study Design:

Prospective cohort study.

Level of Evidence:

Level 3.

Methods:

Thirty-four Division I male and female soccer athletes (19 men, 15 women; mean age, 19.6 ± 1.2 years; mean height, 172.4 ± 8.7 cm; mean weight, 70.8 ± 9.1 kg). An a priori sample size estimation for a power of 0.80 (80%) and an alpha error of 0.05 with an estimated effect size of 0.6 for a sample of 30 participants was attained. Participants performed a drop-landing task and were scored on their landing mechanics using the LESS. Lower extremity injuries were tracked during the season. LESS scores between those with and without a history of injury and those who were injured and uninjured during the season were compared using 2 separate 1-way analyses of variance.

Results:

No statistically significant differences ( F1,33 = 0.47, P = 0.50) existed between LESS scores in athletes who had a previous injury history compared with those with no injury history. No statistically significant differences ( F1,20 = 0.05, P = 0.83) existed between LESS scores in healthy athletes who were injured during the 2014 season compared with those healthy athletes who were uninjured.

Conclusion:

No differences were present between athletes with and without a history of lower extremity injury. The majority of healthy participants who were injured during the season had similar LESS scores to those who remained uninjured, suggesting that the LESS may not be able to identify atypical landing mechanics in this group of athletes.
The Effect of Tibial Rotation on the Contribution of Medial and Lateral Hamstrings During Isometric Knee Flexion
Authors: Jónasson Gunnlaugur , Helgason Andri , Ingvarsson Þorsteinn , Kristjánsson Arnar Már , Briem Kristín
Published: January 2016

Background:

Selective atrophy of hamstring components may result from muscle strain or graft harvesting for anterior cruciate ligament reconstruction. Assessment and rehabilitation that specifically targets medial (MH) or lateral (LH) hamstring components may improve patient outcomes. The purpose of this study was to evaluate effects of volitional tibial rotation medially (MR) versus laterally (LR) on activation levels of MH versus LH and strength measures during isometric testing of knee flexors.

Hypothesis:

Muscle activation of MH and LH during knee flexor strength testing will be augmented when coupled with MR and LR of the tibia, respectively, without affecting knee flexor strength measures.

Study Design:

Cross-sectional laboratory study.

Level of Evidence:

Level 3.

Methods:

Surface electrodes were used to record neuromuscular activity from MH and LH of the right lower limb in 40 healthy young men and women during isometric knee flexor strength testing at 40° of knee flexion, where participants maintained concurrent volitional MR or LR of the tibia. Statistical analyses of variance included general linear models for repeated measures.

Results:

A significant interaction was found for tibial rotation and hamstring component variables ( P < 0.01). When isometric knee flexion was coupled with LR, normalized activation levels were similar for MH and LH. When performed with MR, a significant drop in LH activation led to dissimilar activation levels of the 2 components. Significantly greater strength measures were found when isometric knee flexion was performed with concurrent LR of the tibia ( P < 0.01). Both sexes demonstrated the same rotation-dependent differences.

Conclusion:

Coupling tibial rotation with knee flexor activities primarily affects the LH component.

Clinical Relevance:

Strategies involving volitional tibial rotation may be considered for specific assessment/rehabilitation of the MH or LH component.
Testicular atrophy: A complication of non-mumps orchitis after scrotal exploration for presumed testicular torsion
Authors: Lian Bertrand SY , Cheong Yee Ling , Low Yee , Nah Shireen Anne
Published: January 2016

An acute illness related to the scrotum is a common paediatric surgical emergency. Difficulty in ruling out testicular torsion means that scrotal exploration is often performed for other scrotal pathologies, including orchitis. The clinical course of orchitis is usually benign and long-term sequelae are rare. We describe two adolescent boys, previously vaccinated for mumps, whom had scrotal exploration for presumed testicular torsion. Both were found intraoperatively to have orchitis, and both subsequently developed testicular atrophy, within 2 months post-surgery. These cases demonstrate the rare, but potentially devastating, complication of testicular atrophy that may arise in non-mumps orchitis. The causative pathophysiology may involve some degree of testicular compartment syndrome and subsequent ischaemia. Patients must be made aware of the potential for this outcome and be advised on testicular self-examination after surgery.
Hepatitis C virus-associated B-cell non-Hodgkin’s lymphomas: what do we know?
Authors: Vannata Barbara , Arcaini Luca , Zucca Emanuele
Published: January 2016

Epidemiological studies have shown an increased risk of developing B-cell lymphomas in patients with chronic hepatitis C virus (HCV) infection. There is, however, a great geographic variability and it remains unclear whether additional environmental and genetic factors are involved or whether the international discrepancies represent simply a consequence of the variable prevalence of HCV infection in different countries. Other confounding factors may affect the comparability of the different studies, including the method of HCV assessment, the selection of normal controls, the lymphoma classification used and the year of publication. The most convincing evidence for a causal relationship comes from the observation, mainly limited to some indolent subtypes, of B-cell lymphoma regressions after successful HCV eradication with antiviral treatment. Yet, the molecular mechanism of HCV-induced lymphomagenesis are mainly hypothetical. According to most plausible models, lymphoma growth is a consequence of continuous antigenic stimulation induced by the chronic viral infection. This review will summarize the current knowledge on HCV-associated lymphomas and their management.
Can Radiocarpal-Spanning Fixation Be Made More Functional by Placing the Wrist in Extension? A Biomechanical Study Under Physiologic Loads
Authors: Mann Tobias , Lee Daniel J. , Dahl Jason , Elfar John C.
Published: January 2016

We investigate whether applying an internal radiocarpal-spanning plate with the wrist in slight extension affects the biomechanical stability of the construct. An unstable distal radius fracture was simulated in 10 cadaveric specimens and immobilized with a radiocarpal-spanning plate holding the wrist in a neutral position. This construct was then physiologically loaded through the wrist flexor and extensor tendons. The resulting motion at the fracture was captured with a displacement sensor. The plate was then extended using an in situ bending technique, placing the wrist in extension, and the experiment was repeated. No statistically significant difference in the biomechanical stability afforded by the radiocarpal-spanning plate was detected with the wrist in extension compared to that in the traditional neutral position. The radiocarpal-spanning plate fixation was more stable when loaded through the extensor tendons. We conclude that immobilizing a distal radius fracture with an internal radiocarpal-spanning plate that holds the wrist in extension does not compromise biomechanical stability.
Antileishmanial and Immunomodulatory Activity of Allium sativum (Garlic)
Authors: Foroutan-Rad Masoud , Tappeh Khosrow Hazrati , Khademvatan Shahram
Published: January 2016

Leishmaniasis is caused by an obligate intracellular protozoa belonging to Leishmania genus. The current drugs for treatment of leishmaniasis possess many disadvantages; therefore, researchers are continuously looking for the more effective and safer drugs. The aim of this study is to review the effectiveness, toxicities, and possible mechanisms of pharmaceutical actions of different garlic extracts and organosulfur compounds isolated from garlic against Leishmania spp. in a variety of in vitro, in vivo and clinical trials reports. All relevant databases were searched using the terms “ Allium sativum,” “Garlic,” “Allicin,” “Ajoene,” “ Leishmania,” “in vitro,” “in vivo,” and “clinical trial,” alone or in combination from 5 English databases (Web of Science, PubMed, Science Direct, Scopus, Google Scholar) and 3 Persian databases (Scientific Information Database, Iran Medex, and Magiran) from 1990 to 2014. In summary, garlic with immunomodulatory effects and apoptosis induction contributes to the treatment of leishmaniasis.
Management of Usr-i-Tamth (Menstrual Pain) in Unani (Greco-Islamic) Medicine
Authors: Sultana Arshiya , Lamatunoor Syed , Begum Mazherunnisa , Qhuddsia Q. N.
Published: January 2016

Usr-i-tamth in Unani (Greco-Arabic) medicine is pain associated with menstruation, and classical manuscripts are enriched with traditional knowledge for the management of usr-i-tamth (menstrual pain/dysmenorrhoea). Hence, a comprehensive search was undertaken to find classical manuscripts for the management of menstrual pain was. We searched the Cochrane database, PubMed/Google Scholar, and other websites for articles on complementary and alternative medicine treatment and management of menstrual pain. The principal management as per Unani manuscripts is to produce analgesia and to treat the cause of usr-i-tamth such as abnormal temperament, menstrual irregularities/uterine diseases, and psychological and environmental factors. Furthermore, Unani medicines with emmenagogue, antispasmodic, anti-inflammatory, and analgesic properties are beneficial for amelioration of usr-i-tamth. Herbs such as Apium graveolens, Cuminum cyminium, Foeniculum vulgare, Matricaria chamomilla and Nigella sativa possess the aforementioned properties and are proven scientifically for their efficacy in usr-i-tamth. Thus, validation and conservation of the traditional knowledge is essential for prospective research and valuable for use in the contemporary era.
Ayurpharmacoepidemiology en Route to Safeguarding Safety and Efficacy of Ayurvedic Drugs in Global Outlook
Authors: Debnath Parikshit , Banerjee Subhadip , Adhikari Anjan , Debnath Pratip K.
Published: January 2016

Ayurpharmacoepidemiology is a new field developed by synergy of the fields of clinical pharmacology, epidemiology, and ayurveda. It will use the effects of ayurvedic medicinal products on large populations to describe and analyze the practices, evaluate the safety and efficacy, and carry out medicoeconomic evaluations. Good pharmacoepidemiology practices in ayurveda is projected to assist with issues of ayurpharmacoepidemiologic research. The embraced good pharmacoepidemiology practices guideline in this viewpoint will be able to provide valuable evidence about the health effects of ayurvedic herbs/drugs and consider different fields like pharmacovigilance, pharmacoeconomics, and drug discovery with ayurvedic reverse pharmacology approach, also pass out significant data for further basic sciences study in ayurveda biology, ayurgenomics, ayurnutrigenomics, and systems biology. Several unanswered questions about ayurvedic drug use and informed interventions or policies that can be addressed by informatics database, which will eventually demonstrate the credibility and rationality of ayurceuticals in the future.
Spatial Release From Masking in Simulated Cochlear Implant Users With and Without Access to Low-Frequency Acoustic Hearing
Authors: Williges Ben , Dietz Mathias , Hohmann Volker , Jürgens Tim
Published: January 2016

For normal-hearing listeners, speech intelligibility improves if speech and noise are spatially separated. While this spatial release from masking has already been quantified in normal-hearing listeners in many studies, it is less clear how spatial release from masking changes in cochlear implant listeners with and without access to low-frequency acoustic hearing. Spatial release from masking depends on differences in access to speech cues due to hearing status and hearing device. To investigate the influence of these factors on speech intelligibility, the present study measured speech reception thresholds in spatially separated speech and noise for 10 different listener types. A vocoder was used to simulate cochlear implant processing and low-frequency filtering was used to simulate residual low-frequency hearing. These forms of processing were combined to simulate cochlear implant listening, listening based on low-frequency residual hearing, and combinations thereof. Simulated cochlear implant users with additional low-frequency acoustic hearing showed better speech intelligibility in noise than simulated cochlear implant users without acoustic hearing and had access to more spatial speech cues (e.g., higher binaural squelch). Cochlear implant listener types showed higher spatial release from masking with bilateral access to low-frequency acoustic hearing than without. A binaural speech intelligibility model with normal binaural processing showed overall good agreement with measured speech reception thresholds, spatial release from masking, and spatial speech cues. This indicates that differences in speech cues available to listener types are sufficient to explain the changes of spatial release from masking across these simulated listener types.