bluuebunny/crossref_metadata_2025_split huggingface dataset:
Double-blind trials in hyperbaric medicine: A narrative review on past experiences and considerations in designing sham hyperbaric treatment
Authors: Lansdorp Nina CA , van Hulst Rob A 
Published: June 2018

Background Hyperbaric oxygen therapy, which consists of breathing 100% oxygen under a higher atmospheric pressure than normal, is utilized worldwide in the treatment of several diseases. With the growing demand for evidence-based research, hyperbaric oxygen therapy has been criticized for delivering too little high-quality research, mainly in the form of randomized controlled trials. While not always indispensable, the addition of a sham-controlled group to such a trial can contribute to the quality of the research. However, the design of a sham (hyperbaric) treatment is associated with several considerations regarding adequate blinding and the use of pressure and oxygen. This narrative review discusses information on the sham profile and the blinding and safety of double-blind trials in hyperbaric medicine, irrespective of the indication for treatment. Methods MEDLINE, Embase and CENTRAL were searched for sham-controlled trials on hyperbaric oxygen therapy. The control treatment was considered sham if patients were blinded to their allocation and treatment took place in a hyperbaric chamber, with no restrictions regarding pressurization, oxygen levels or indication. Studies involving children or only one session of hyperbaric oxygen were excluded. Information on (the choice of) treatment profile, blinding measures, patient’s perception regarding allocation and safety issues was extracted from eligible studies. Results A total of 42 eligible trials were included. The main strategies for sham treatment were (1) use of a lower pressure than that of the hyperbaric oxygen group, while breathing 21% oxygen; (2) use of the same pressure as the hyperbaric oxygen group, while breathing an adjusted percentage of oxygen; and (3) use of the same pressure as the hyperbaric oxygen group, while breathing 21% oxygen. The advantages and disadvantages of each strategy are discussed using the information provided by the trials. Conclusion Based on this review, using a lower pressure than the hyperbaric oxygen group while breathing 21% oxygen best matches the inertness of the placebo. Although studies show that use of a lower pressure does allow adequate blinding, this is associated with more practical issues than with the other strategies. The choice of which sham profile to use requires careful consideration; moreover, to ensure proper performance, a clear and detailed protocol is also required.
Different clinical outcomes in Crohn’s disease patients with esophagogastroduodenal, jejunal, and proximal ileal disease involvement: is L4 truly a single phenotype?
Authors: Mao Ren , Tang Rui-Han , Qiu Yun , Chen Bai-Li , Guo Jing , Zhang Sheng-Hong , Li Xue-Hua , Feng Rui , He Yao , Li Zi-Ping , Zeng Zhi-Rong , Eliakim Rami , Ben-Horin Shomron , Chen Min-Hu 
Published: June 2018

Background: The Montreal classification defines L4 Crohn’s disease (CD) as any disease location proximal to the terminal ileum, which anatomically includes L4-esophagogastroduodenal (EGD), L4-jejunal, and L4-proximal ileal involvement. L4-jejunal disease was established to be associated with poor prognosis. However, the outcome of patients with L4-proximal ileal disease or L4-EGD remains to be clarified. Our study aimed to investigate whether the outcome differs among CD patients with L4-EGD, L4-jejunal, and L4-proximal ileal disease. Methods: In our retrospective cohort study, 483 patients with confirmed CD were included. The primary outcome was intestinal surgery. Demographic features and outcomes were compared among L4-EGD, L4-jejunal, and L4-proximal ileal disease. Results: Thirty-nine (8.1%) patients had isolated L4 disease, whereas 146 patients had L4 as well as concomitant L1, L2, or L3 disease. During a median follow up of 5.8 years, L4 patients were more likely to have intestinal surgeries compared to non-L4 patients (31% versus 16%, p < 0.001). The percentage of L4-jejunal patients who underwent surgery was higher than that of L4-proximal ileal (66% versus 28%, p < 0.001), and both of these subtypes of L4 were at higher risk for intestinal resection compared to L4-EGD patients (66% and 28% versus 9%, respectively, p < 0.001 and p < 0.05). On multi-variable analysis, L4-jejunal (HR 3.08; 95% CI 1.30–7.31) and L4-proximal ileal disease (HR 1.83; 95% CI 1.07–3.15) were independent predictors for intestinal resection. Conclusions: L4 disease had worse prognosis compared to non-L4 disease. Within L4 disease, phenotype of L4-jejunal and L4-proximal ileal disease indicated higher risk for intestinal surgery. It might be justified to further characterize the L4 phenotype of the Montreal classification into three specific subgroups including L4-EGD, L4-jejunal, and L4-proximal ileal disease, similar to the Paris classification of pediatric patients.
Precision diagnostics of Ewing’s sarcoma by liquid biopsy: circulating EWS-FLI1 fusion transcripts
Authors: Allegretti Matteo , Casini Beatrice , Mandoj Chiara , Benini Stefania , Alberti Laurent , Novello Mariangela , Melucci Elisa , Conti Laura , Covello Renato , Pescarmona Edoardo , Milano Giuseppe Maria , Annovazzi Alessio , Anelli Vincenzo , Ferraresi Virginia , Biagini Roberto , Giacomini Patrizio 
Published: June 2018

Background: Limited information is available on the applicative value of liquid biopsy (LB) in rare tumors, including Ewing’s sarcoma (ES). The accepted precision diagnostics standards would greatly benefit from a non-invasive LB test monitoring pathognomonic gene rearrangements in the bloodstream. Methods: Tissue and blood samples were collected from six and four ES patients, respectively. Plasma was cleared by two successive rounds of centrifugation and stored frozen until RNA extraction by the QIAmp CNA kit. RNA was retro-transcribed and subjected to real-time quantitative polymerase chain reaction (RT-qPCR) and digital polymerase chain reaction (dPCR). Reactions were set up using two custom primer sets identifying types 1 and 2 EWS-FLI1 fusion transcripts. Results: The two prevalent types of EWS-FLI1 rearrangements could be identified using only two sets of polymerase chain reaction primers, regardless of patient-specific EWS-FLI1 DNA breakpoints. RT-qPCR and dPCR discriminated the two variants in five tumor tissue RNAs and in four circulating tumor RNAs (ctRNAs). Of note, EWS-FLI1 molecular diagnosis was possible using blood samples even when tumor tissue was not available. ctRNA levels correlated ( p < 0.05) with volume-based positron emission tomography (PET) parameters (metabolic tumor volume and total lesion glycolysis), and allowed the fine tracking of disease course after surgery, during adjuvant as well as neoadjuvant chemotherapy, and at follow up in one patient. Conclusions: To our knowledge, this is one of the few single-marker LB assays in solid tumors specifically designed to detect rearranged RNAs in blood, and the first study describing EWS circulating tumor RNAs in ES patients. Altogether, our results support the idea that LB may have a considerable impact on ES patient monitoring and management.
The Infinity Total Ankle System: Early Clinical Results With 2- to 4-Year Follow-up
Authors: Penner Murray , Davis W. Hodges , Wing Kevin , Bemenderfer Thomas , Waly Feras , Anderson Robert B. 
Published: June 2018

Aims. This study presents the first report of clinical and radiographic outcomes of the Infinity Total Ankle System (Wright Medical, Memphis, TN) with minimum 2-year follow-up. Patients and Methods. The first 67 consecutive patients who underwent primary total ankle arthroplasty (TAA) with the Infinity system at 2 North American sites between August 2013 and May 2015 were reviewed in a prospective, observational study. Demographic, radiographic, and functional outcome data were collected preoperatively, at 6 to 12 months postoperatively, and annually thereafter. Results. The overall implant survival rate was 97% (65 of 67 implants) at a mean follow-up of 35.4 months (27 to 47 months). Two cases underwent talar component revision for aseptic loosening. Six of the 67 cases (9%) required a nonrevision reoperation. Mean Foot Function Index and Ankle Osteoarthritis Scale scores at latest follow-up improved from preoperative by 21.6 ( P < .0001) and 34.0 ( P < .0001), respectively. No radiographic loosening of any talar or tibial components was identified in the 65 nonrevised cases. Conclusion. Early clinical and radiographic outcomes with the Infinity TAA are promising and compare favorably to those reported for both fixed- and mobile-bearing third-generation TAA designs, even when used in cases with deformity and increased case complexity. Levels of Evidence: Level IV
Technical notes on the endoscopic endonasal approach to the craniovertebral junction for odontoidectomy
Authors: Tang Dennis , Roxbury Christopher , D'Anza Brian , Kshettry Varun , Woodard Troy , Recinos Pablo , Sindwani Raj 
Published: June 2018

Introduction: Odontoidectomy can help decompress ventral compression of the brainstem and upper cervical spinal cord in the presence of bony abnormalities of the craniovertebral junction (CVJ), e.g., an odontoid pannus. Endonasal approaches have been shown to be associated with lower morbidity compared with traditional transoral approaches. We demonstrated an entirely endonasal approach to the CVJ. Materials and Methods: We presented our technique for performing an endoscopic endonasal odontoidectomy. Results: The patient underwent an open posterior cervical spinal fusion to stabilize the CVJ due to destabilization that occurs with odontoidectomy either as part of a single procedure or in a staged manner, depending on the surgeon's preference. By using a two-surgeon, multihanded technique in collaboration with neurosurgery, the anterior CVJ was safely approached endoscopically through the nasopharynx. A midline incision was created and the soft tissue was lateralized widely. The first cervical vertebra (C1) arch was removed with a drill exposing the odontoid process and any associated pannus, which were then resected. Because this approach was entirely extradural, no reconstruction was necessary. Closure was accomplished by placing absorbable packing material in the defect and medializing the nasopharyngeal tissues. Conclusion: Endoscopic endonasal odontoidectomy offers excellent exposure and less morbidity than traditional transoral approaches. This technique should be considered in appropriately selected patients.
Novel Radiographic Assessment of the Cribriform Plate
Authors: Ganjaei Kimia G. , Soler Zachary M. , Mappus Elliott D. , Taylor Robert J. , Worley Mitchell L. , Mulligan Jennifer K. , Mattos Jose L. , Rowan Nicholas R. , Garcia Guilherme J. M. , Dubno Judy R. , Eckert Mark A. , Matthews Lois J. , Schlosser Rodney J. 
Published: June 2018

Background The cribriform plate (CP) is a common site of spontaneous cerebrospinal fluid (SCSF) leaks. Radiographic assessment of the anterior and lateral skull base has shown thinner bone in patients with SCSFs; however, prior assessment of the CP has required postmortem cadaver dissection. Objective To develop novel radiographic techniques to assess the anatomy of the CP. Methods Computed tomography (CT) scans were performed on cadaveric specimens. Bone density and anatomy of a predefined volume of interest of the posterior CP were assessed by two independent reviewers. CT assessment of olfactory foramina was also performed and validated using anatomic dissection of cadaver specimens. Results Interclass correlation coefficients (ICCs) for measuring the same volume of each CP was 0.96, confirming reproducible anatomic localization. Cadaver CPs had a mean Hounsfield units of 263, indicating a mix of bone and soft tissue, and ICC was 0.98, confirming reproducible radiographic measurements. Optimal CT estimates of bone composition of CPs averaged 85% (range 76% to 96%) compared to actual anatomic dissection which averaged 84% bone (range 74% to 91%, r = .690, P = .026). Conclusion Our novel, noninvasive CT method for assessing CP anatomy is reproducible and correlates with anatomic dissection assessing bone composition. The clinical implications of anatomic changes in the CP are an area for further study.
Long-term Clinical Outcomes of Aspirin Desensitization With Continuous Daily Aspirin Therapy in Aspirin-exacerbated Respiratory Disease
Authors: Walters Kristen M. , Waldram Jeremy D. , Woessner Katharine M. , White Andrew A. 
Published: June 2018

Background Aspirin-exacerbated respiratory disease (AERD), also known as Samter’s triad or aspirin (ASA)-intolerant asthma, affects 7% of asthmatics and has a higher prevalence in those with chronic rhinosinusitis and concomitant nasal polyposis. ASA desensitization with daily ASA therapy is a uniquely beneficial treatment for this disease entity and has been shown to have a significant impact on symptom scores, polyp disease, and need for systemic corticosteroids. However, no long-term studies have demonstrated whether or not ASA therapy remains safe and beneficial for these patients beyond 5–10 years. Objective This study was designed to determine the clinical course of AERD patients desensitized between 1995 and 2010. Methods A 20-question survey was distributed to patients who successfully completed ASA desensitization between January 1995 and April 2010. The questions were designed to assess ASA safety and longitudinal effects of ASA therapy in AERD. Results Of the 285 patients contacted, 92 (32%) completed the questionnaire. Average length of follow-up was 15 years. Of survey responders, 35 patients had discontinued ASA therapy. Although adverse reactions occurred, many also discontinued due to lack of efficacy or need for surgery. For those remaining on ASA (62%), significant improvement in sense of smell, asthma, sinus, and allergic rhinitis scores were noted ( P ≤ .001). The majority of ASA patients (68%) had a positive response to treatment and did not require further sinus surgery. However, ASA therapy did not delay the time to next sinus/polyp surgery ( P = .27) or reduce total number of sinus surgeries ( P = .56) compared to those who stopped treatment. Nearly 85% of AERD patients on ASA therapy found it to be helpful in improving airway disease and quality of life. Conclusion Aspirin desensitization followed by daily maintenance ASA therapy appears to be safe and effective even after 10+ years of continuous use.
Thalamus volume change and cognitive impairment in early relapsing–remitting multiple sclerosis patients
Authors: Rojas Juan I , Murphy Georgina , Sanchez Francisco , Patrucco Liliana , Fernandez Maria C , Miguez Jimena , Funes Jorge , Golimstok Angel , Cristiano Edgardo 
Published: June 2018

Aims The objective of the study was to assess whether changes in the volume of the thalamus during the onset of multiple sclerosis predict cognitive impairment after accounting for the effects of brain volume loss. Methods A prospective study included patients with relapsing–remitting multiple sclerosis less than 3 years after disease onset (defined as the first demyelinating symptom), Expanded Disability Status Scale of 3 or less, no history of cognitive impairment and at least 2 years of follow-up. Patients were clinically followed up with annual brain magnetic resonance imaging and neuropsychological evaluations for 2 years. Measures of memory, information processing speed and executive function were evaluated at baseline and follow-up with a comprehensive neuropsychological test battery. After 2 years, the patients were classified into two groups, one with and the other without cognitive impairment. Brain dual-echo, high-resolution three-dimensional T1-weighted magnetic resonance imaging scans were acquired at baseline and every 12 months for 2 years. Between-group differences in thalamus volume, total and neocortical grey matter and white matter volumes were assessed using FIRST, SIENA, SIENAXr, FIRST software (logistic regression analysis P < 0.05 significant). Results Sixty-one patients, mean age 38.4 years, 35 (57%) women were included. At 2 years of follow-up, 17 (28%) had cognitive impairment. Cognitive impairment patients exhibited significantly slower information processing speed and attentional deficits compared with patients without cognitive impairment ( P < 0.001 and P = 0.02, respectively). In the cognitive impairment group a significant reduction in the percentage of thalamus volume ( P < 0.001) was observed compared with the group without cognitive impairment. Conclusion We observed a significant decrease in thalamus volume in multiple sclerosis-related cognitive impairment.
HSP110 sustains chronic NF-κB signaling in activated B-cell diffuse large B-cell lymphoma through MyD88 stabilization
Authors: Boudesco Christophe , Verhoeyen Els , Martin Laurent , Chassagne-Clement Catherine , Salmi Leila , Mhaidly Rana , Pangault Céline , Fest Thierry , Ramla Selim , Jardin Fabrice , Wolz Olaf-Oliver , Weber Alexander N. R. , Garrido Carmen , Jego Gaetan 
Published: June 2018

Key Points
HSP110 sustains chronic NF-κB signaling in ABC-DLBCL through MyD88 stability. HSP110 is highly expressed in cells of patients with ABC-DLBCL and correlates with MyD88 expression.
Carbapenem non-susceptibility of Klebsiella pneumoniae isolates in hospitals from 2011 to 2016, data from the German Antimicrobial Resistance Surveillance (ARS)
Authors: Koppe Uwe , von Laer Anja , Kroll Lars E. , Noll Ines , Feig Marcel , Schneider Marc , Claus Hermann , Eckmanns Tim , Abu Sin Muna 
Published: June 2018

Abstract
Background
Carbapenem resistance in Klebsiella pneumoniae is of significant public health concern and recently spread across several countries. We investigated the extent of carbapenem non-susceptibility in K. pneumoniae isolates in Germany.

Methods
We analysed 2011–2016 data from the German Antimicrobial Resistance Surveillance (ARS) System, which contains routine data of antimicrobial susceptibility testing from voluntarily participating German laboratories. Klebsiella pneumoniae isolates tested resistant or intermediate against an antibiotic were classified as non-susceptible.

Results
We included 154,734 isolates from 655 hospitals in the analysis. Carbapenem non-susceptibility in K. pneumoniae isolates was low in Germany 0.63% (95% CI 0.51–0.76%). However, in continuously participating hospitals the number of K. pneumoniae isolates almost doubled and we found evidence for a slowly increasing trend for non-susceptibility (OR = 1.20 per year, 95% CI 1.09–1.33, p < 0.001). Carbapenem non-susceptibility was highest among isolates from patients aged 20–39 in men but not in women. Moreover, carbapenem non-susceptibility was more frequently reported for isolates from tertiary care, specialist care, and prevention and rehabilitation care hospitals as well as from intensive care units. Co-resistance of carbapenem non-susceptible isolates against antibiotics such as tigecycline, gentamicin, and co-trimoxazole was common. Co-resistance against colistin was 13.3% (95% CI 9.8–17.9%) in carbapenem non-susceptible isolates.

Conclusion
Carbapenem non-susceptibility in K. pneumoniae isolates in Germany is still low. However, it is slowly increasing and in the light of the strong increase of K. pneumoniae isolates over the last year this poses a significant challenge to public health. Continued surveillance to closely monitor trends as well as infection control and antibiotic stewardship activities are necessary to preserve treatment options.
NS1‐binding protein radiosensitizes esophageal squamous cell carcinoma by transcriptionally suppressing c‐Myc
Authors: Wang Yuwen , Cheng Jingjing , Xie Dan , Ding Xiaofeng , Hou Hailing , Chen Xi , Er Puchun , Zhang Furong , Zhao Lujun , Yuan Zhiyong , Pang Qingsong , Wang Ping , Qian Dong 
Published: June 2018

AbstractBackgroundCisplatin‐based chemotherapy with concurrent radiotherapy is a standard treatment for advanced esophageal squamous cell carcinoma (ESCC). NS1‐binding protein (NS1‐BP), a member of the BTB‐kelch protein family, has been shown to inhibit the proliferation of Hela cells by suppressing c‐Myc. In the present study, we examined the potential function role of NS1‐BP expression in ESCC, and particularly, the sensitivity of ESCC to radiotherapy.MethodsNS1‐BP expression was examined using immunohistochemistry in two cohorts (n = 98 for the training cohort; n = 46 for independent validation cohort) of ESCC patients receiving cisplatin‐based chemotherapy and concurrent radiotherapy. Normal esophageal mucosal tissue blocks were used as a control. We also conducted a series of in vitro and in vivo experiments to examine the potential effects of over‐expressing NS1‐BP on ESCC cells, and particularly their sensitivity to ionizing irradiation.ResultsIn the training cohort, NS1‐BP downregulation was observed in 59% (85/144) of the ESCC specimens. NS1‐BP downregulation was associated with chemoradiotherapeutic resistance and shorter disease‐specific survival (DSS) in both the training and validation cohorts. Over‐expressing NS1‐BP in cultured ESCC cells substantially increased the cellular response to irradiation both in vitro and in vivo. NS1‐BP also significantly enhanced IR‐induced apoptosis, and abrogated IR‐induced G2/M cell‐cycle arrest and ATM/Chk1 phosphorylation. Immunoprecipitation assays indicated that NS1‐BP could interact with c‐Myc promoter regions to inhibit its transcription. In ESCC tissues, c‐Myc expression was inversely correlated with NS1‐BP levels, and was associated with a shorter DSS.ConclusionsOur findings highlight the role and importance of NS1‐BP in radiosensitivity of ESCC. Targeting the NS1‐BP/c‐Myc pathway may provide a novel therapeutic strategy for ESCC.
A tale of traded specimens, or what to know when selecting types from Ernst Ule’s collections
Authors: Borges Leonardo M. , Schultz Matthias , Poppendieck Hans-Helmut , Kalhinki Jacquelyn A. , Trovó Marcelo 
Published: June 2018

AbstractMany Brazilian plant names are based on specimens gathered by European naturalists working in the 19th and early 20th centuries. Among these explorers is Ernst Ule, a German naturalist who collected profusely in Brazil. Ule’s specimens were largely used to publish names before the need to indicate types for valid publication and, hence, many of those names need to be typified. Because typification is not always a straightforward process, we use examples from Mimosa and Paepalanthus to show how an understanding of the historical background of these collections is necessary to support nomenclatural work with names based on specimens he gathered. We present a set of guidelines for typification of names based on his collections and, as examples, we provide lectotypifications for 35 species of Mimosoid legumes.