bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab
Authors: Arnold Jack , Dass Shouvik , Twigg Sarah , Jones Colin H , Rhodes Ben , Hewins Peter , Chakravorty Mithun , Courtney Phil , Ehrenstein Michael , Md Yusof Md Yuzaiful , Vital Edward M 
Published: March 2022

Abstract

Objectives
Secondary inefficacy with infusion reactions and anti-drug antibodies (secondary non-depletion nonresponse, 2NDNR) occurs in 14% of SLE patients receiving repeated rituximab courses. We evaluated baseline clinical characteristics, efficacy and safety of obinutuzumab, a next-generation humanized type-2 anti-CD20 antibody licensed for haematological malignancies in SLE patients with 2NDNR to rituximab.

Methods
We collated data from SLE patients receiving obinutuzumab for secondary non-response to rituximab in BILAG centres. Disease activity was assessed using BILAG-2004, SLEDAI-2K and serology before, and 6 months after, obinutuzumab 2× 1000 mg infusions alongside methylprednisolone 100 mg.

Results
All nine patients included in the study received obinutuzumab with concomitant oral immunosuppression. At 6 months post-obinutuzumab, there were significant reductions in median SLEDAI-2K from 12 to 6 (P = 0.014) and total BILAG-2004 score from 21 to 2 (P = 0.009). Complement C3 and dsDNA titres improved significantly (both P = 0.04). Numerical, but not statistically significant improvements were seen in C4 levels. Of 8/9 patients receiving concomitant oral prednisolone at baseline (all &gt;10 mg/day), 5/8 had their dose reduced at 6 months. Four of nine patients were on 5 mg/day and were in Lupus Low Disease Activity State following obinutuzumab. After obinutuzumab, 6/9 patients with peripheral B cell data achieved complete depletion, including 4/4 assessed with highly sensitive assays. Of the nine patients, one obinutuzumab non-responder required CYC therapy. One unvaccinated patient died from COVID-19.

Conclusions
Obinutuzumab appears to be effective and steroid-sparing in renal and non-renal SLE patients with secondary non-response to rituximab. These patients have severe disease with few treatment options but given responsiveness to B cell depletion, switching to humanized type-2 anti-CD20 therapy is a logical approach.
Developmental responses and survival ofAnopheles stephensilarval stages at different salinity levels
Authors: Jude Justin , Gunathilaka Nayana , Udayanaga Lahiru , Fernando Deepika , Premarathne Prasad , Wickremasinghe Rajitha , Abeyewickreme Wimaladharma 
Published: March 2022

AbstractBackgroundAnopheles stephensi is a newly invaded vector in Sri Lanka. It has been identified in coastal areas in the northern and eastern parts of the country and evidences the ability to breed in brackish water environments.MethodsLaboratory investigations were conducted with batches of 100 first and third instar larvae exposed to a salinity gradient (0–40 ppt). Survival rates at 1 h, 24 h and until pupation were recorded for first and third instar larvae at different salinity levels. The experiment was repeated four times for both instars. Data were analysed using the general linear model and probit analysis.ResultsSignificant variations in adult emergence were observed from both larval stages at different salinity levels (p&lt;0.05). The highest pupation rates were observed at 2.5 ppt salinity. The survival rate of first instar larvae after 24 h of salinity exposure was &gt;80% up to 12.5 ppt, while 100% mortality was observed for from the ≥25 ppt level of salinity. More than 90% of the third instar larvae pupated from salinity levels &lt;15 ppt. The lowest survival rate was reported as 15.8±2.47% at 25 ppt.ConclusionsThis indicates a high potential of increasing density of A. stephensi in coastal ecosystems in lagoons and other saline water bodies. Hence it is high time to redesign vector control interventions for vector breeding in coastal ecosystems.
Surgical management of a calzone-like posttraumatic infolding of a 10-year-old LASIK flap
Authors: Elahi Sina , Mazharian Adrien , Gatinel Damien 
Published: March 2022

Introduction:
The popularity of femtosecond laser–assisted in situ keratomileusis (LASIK) has increased, but flap-related complications such as trauma and possibility of displacement, even years after surgery with complications such as striae, diffuse lamellar keratitis, and epithelial ingrowth, may still be challenging.

Patient and Clinical Findings:
A 45-year-old woman was referred a week after trauma and flap displacement on a 10-year-long myopic LASIK correction. Corrected distance visual acuity was 20/30 (0, −2.25 at 35 degrees) due to epithelial ingrowth involving the visual axis. The external third of the flap was rolled inward (calzone-like), exposing the underlying edematous stroma associated with dense fibrosis at the level of the roll.

Diagnosis, Intervention and Outcomes:
Emergency flap surgical revision was performed using a technique of mechanical debridement and a 20% alcohol-dipped sponge application to help with epithelial cells lysis, and fibrin glue was applied on the flap. Uncorrected distance visual acuity was restored and examination revealed a stable, well-apposed flap, without epithelial cell ingrowth, and an otherwise unremarkable examination.

Conclusions:
This study showed the 10-month-efficacy of a combined approach of mechanical debridement, ethanol-based cell lysis, and fibrin glue in traumatic 10-year-old-flap management with infolding or invagination and extensive epithelial ingrowth.
Macular phototoxicity after corneal crosslinking
Authors: Alfayyadh Mohammed A. , AlAbdulhadi Halla A. , Ahad Muhammad A. 
Published: March 2022

Introduction:
Keratoconus is a progressive degenerative corneal disease of variable severity. Its management includes medical and surgical treatment. Corneal crosslinking (CXL) is being increasingly used to stabilize the condition. Macular phototoxicity is a well-known side effect of light exposure; however, its incidence after treatment with riboflavin and UV light is unknown. This study reported the clinical features of a patient with macular phototoxicity after UV-A exposure and described the structural and angiographic retinal changes observed in the patient.

Patient, Clinical Findings, and Diagnosis:
A 37-year-old man with keratoconus underwent corneal refractive surgery (topography-guided custom ablation with accelerated and high-fluence CXL). Postoperatively, he had decreased vision in the operated eye. Ophthalmoscopy, spectral-domain optical coherence tomography, and fluorescein angiography revealed retinal pigment epithelial changes, ellipsoid zone disruption, and window defects, respectively. The patient was diagnosed with macular phototoxicity. The corrected distance visual acuity stabilized at 20/100 after 6 months.

Conclusions:
Macular phototoxicity may occur after UV-A exposure during CXL. The use of accelerated and high-fluence protocols might have contributed to its occurrence in this patient.
Hydration Interventions Among Agricultural Workers
Authors: Chicas Roxana , Suarez Jonathan , Elon Lisa , Xiuhtecutli Nezahualcoyotl , House Madelyn C. , Berra Liris , Sands Jeff M. , Hertzberg Vicki , McCauley Linda 
Published: March 2022

Objective:
To estimate the impact of hydration interventions on postworkday hydration status and incidence of acute kidney injury (AKI).

Methods:
Thirty agricultural workers were first monitored on a workday without any interventions. On the intervention workday, the same workers were randomized to one of two groups: 169 ounces (oz) (5 L) of plain water (n = 16) or 169 oz (5L) of water with electrolytes (n = 14).

Results:
No participants in the electrolyte group had an estimate glomerular filtration rate (eGFR) at the end of the workday of less than 90 mL/min/1.73 m2 or met the criteria for AKI in comparison to the water group (eGFR < 90: 15%; AKI: 23%) or the control group (eGFR < 90: 28%; AKI: 18%).

Conclusion:
The study showed that drinking water with electrolytes may lower the risk for development of AKI among agricultural workers.
Impact of Residual Limb Volume Loss on Socket Internal Pressures: A Preliminary Study
Authors: Sirrs Díaz Nora Emilia , Galván-Duque Carlos , Zavaleta José Luis , Letechipia Moreno Jorge 
Published: March 2022

ABSTRACT

Introduction
Daily volume loss of residual limb is a condition that most prosthetic users face, negatively affecting their life. One of the consequences is the loss of contact between the residual limb and the socket, which modifies internal pressures.

Objective
The aim of this study was to study how the loss of volume of the residual limb affects socket adjustment through measuring pressures inside the socket.

Study design
The study design is prospective longitudinal.

Materials and Methods
Four subjects with unilateral transtibial amputation, with at least 1 year of prosthetic use, and walking with a comfortable prosthesis participated in this study. The pressure between the socket and the subject's residual limb was measured with an FSocket System (Tekscan). Residual limb volume was measured before and after each test with two different methods: optical scanning (Structure Sensor, Occipital) and conical frustum model. Sanders' protocol for volume loss was followed (Sanders et al. J Rehabil Res Dev. 2012;49:1467–1478). Volume changes in the residual limb and socket internal pressures were analyzed.

Results/Discussion
The pressure graph obtained is consistent with Sanders' volume graphs. The pressure distribution inside the socket is lost after 5 hours of use of the prosthetic device; this can be related to volume loss and alignment. The only area where the pressure increases is in the distal zone, given that once the prosthetic fit is lost, weight bearing is transferred to the socket's distal section (mean volume loss, intrasession −3%; mean pressure loss, intrasession −39%).

Conclusions
The study suggests that a small change in the volume can cause a change in the distribution of pressures inside the socket, indicating that the prosthetic fit may be compromised. For patient follow-up, measuring pressure inside the socket could be a useful indicator of socket misfit.

Clinical Relevance
Daily volume changes in the prosthesis can produce pressures that lead to pain, injuries, an inefficient gait, and prosthesis abandonment. Consequently, it is important to understand the behavior of the pressures inside the socket and the influence of the daily changes of volume on the socket adjustment to design better strategies and techniques of daily volume changes management.
Enlarged Vestibular Aqueduct: Disease Characterization and Exploration of Potential Prognostic Factors for Cochlear Implantation
Authors: Saeed Haroon S. , Rajai Azita , Nash Robert , Saeed Shakeel R. , Stivaros Stavros M. , Black Graeme , Bruce Iain A. 
Published: March 2022

Objectives:
There is an unmet need to match the anticipated natural history of hearing loss (HL) in enlarged vestibular aqueduct (EVA) with clinical management strategies. The objectives of this study are therefore to provide a detailed case characterization of an EVA cohort and explore the relationship between candidate prognostic factors and timing of cochlear implant (CI) surgery.

Study Design:
A multicenter retrospective review of patients diagnosed with EVA.

Setting:
Patient data recruitment across three CI centers in the UK.

Patients:
One hundred fifty patients with a radiological diagnosis of EVA from January 1995 to January 2021.

Main Outcome Measures:
Age at audiological candidacy for CI and age at first implant surgery.

Results:
EVA was predominately a bilateral condition (144/ 150) with increased prevalence in women (M:F, 64:86). 51.7% of patients failed new-born hearing screening, with 65.7% having HL diagnosed by 1 year. Initial moderate to severe and severe to profound HL were reported most frequently. In 123 patients, median age that audiological candidacy for CI was met for at least one ear was 2.75 years. Median age at first CI was 5 years (140/150).
Pendred syndrome (confirmed in 73 patients) and ethnicity, were not significantly associated with earlier CI surgery. Multivariate linear regression demonstrated that male patients have first CI surgery significantly earlier than females (coefficient −0.43, 95% CI [−0.82, −0.05), p-value = 0.028).

Conclusions:
This large UK EVA cohort provides evidence that patients should be closely monitored for CI candidacy within the first 3 years of life. Significantly, male gender is emerging as an independent prognostic factor for earlier assessment and first CI surgery.
Accuracy of 2D BLADE Turbo Gradient- and Spin-Echo Diffusion Weighted Imaging for the Diagnosis of Primary Middle Ear Cholesteatoma
Authors: Lin Mengyan , Sha Yan , Sheng Yaru , Chen Wei 
Published: March 2022

Objective
To evaluate the diagnostic accuracy of 2D BLADE turbo gradient- and spin-echo diffusion weighted imaging (TGSE BLADE DWI) for primary middle ear cholesteatoma diagnosis, using qualitative and quantitative methods.

Study Design
Retrospective case series.

Setting
University hospital.

Patients
Participants included those with suspected primary middle ear cholesteatoma after assessment by clinical otorhinolaryngologists combined with magnetic resonance imaging (MRI) examination. Finally, of the 85 ears from 65 patients enrolled in the study, 73 had cholesteatoma, and 12 had otitis media.

Intervention
Two radiologists independently assessed images and measured apparent diffusion coefficient (ADC) values. Sensitivity, specificity and accuracy were evaluated. Kappa (k) statistics, the intraclass correlation coefficient (ICC), the Kolmogorov–Smirnov normality test, the independent t test, and receiver operating characteristic (ROC) analysis were used for statistical analysis. Pair-wise comparison of the area under the ROC curve (AUC) was also performed using the Delong test.

Main Outcome Measures
Imaging and histopathologic findings.

Results
The mean ADC value of cholesteatoma group (mean, 0.923 ± 0.246 × 10–3 mm2/s) was significantly lower than that of noncholesteatoma group (mean, 1.744 ± 0.205 × 10–3 mm2/s; p < 0.001). In ≤3 mm cholesteatoma group, the AUC of qualitative DWI was 0.846; the sensitivity, specificity, and accuracy for diagnosing cholesteatoma were 69.23%, 100%, and 84%, respectively; while the AUC of quantitative diagnosis was significantly increased to 1.0 (p = 0.0209); and based on the optimal threshold of ADC, ≤1.352 × 10–3 mm2/s, the sensitivity, specificity and accuracy improved to 100%. For >3 mm cholesteatoma group, there were no significant differences in diagnostic performance. Excellent interobserver agreement and ICC for the qualitative and quantitative evaluations (k = 0.90 and ICC = 0.80, respectively) was noted between reviewers.

Conclusion
TGSE BLADE DWI is useful for the detection of primary middle ear cholesteatomas, especially ≤3 mm lesions.
A Healthcare Physician Can Be Trained to Perform Intestinal Ultrasound in Children With Inflammatory Bowel Disease
Authors: van Wassenaer Elsa A. , van Rijn Rick R. , de Voogd Floris A.E. , Noels Floor L. , Deurloo Eline E. , van Schuppen Joost , Verbeke Jonathan I.M.L. , Gecse Krisztina B. , D'Haens Geert R. , Benninga Marc A. , Koot Bart G.P. ,   RAINBOW‐group
Published: March 2022

ABSTRACTObjectives:Training healthcare physicians to perform intestinal ultrasound (IUS) during outpatient visits with equal accuracy as radiologists could improve clinical management of IBD patients. We aimed to assess whether a healthcare‐physician can be trained to perform IUS, with equal accuracy compared with experienced radiologists in children with iBD, and to assess inter‐observer agreement.Methods:Consecutive children, 6 to 18 years with IBD or suspicion of IBD, who underwent ileo‐colonoscopy were enrolled. iUS was performed independently by a trained healthcare‐physician and a radiologist in 1 visit. Training existed of an international training curriculum for IUS. Operators were blinded for each other's IUS, and for the ileocolonoscopy. Difference in accuracy of IUS by the healthcare‐physician and radiologist was assessed using areas under the ROC curve (AUROC). Inter‐observer variability was assessed in terminal ileum (TI), transverse colon (TC) and descending‐colon (DC), for disease activity (ie, bowel wall thickness [BWT] >2 mm with hyperaemia or fat‐proliferation, or BWT >3 mm).Results:We included 73 patients (median age 15, interquartile range [IQR]:13–17, 37 [51%] female, 43 [58%] with Crohn disease). AUROC ranged between 0.71 and 0.81 for the healthcare‐physician and between 0.67 and 0.79 for radiologist (P > 0.05). Inter‐observer agreement for disease activity per segment was moderate (K: 0.58 [SE: 0.09], 0.49 [SE: 0.12], 0.52 [SE: 0.11] respectively for TI, TC, and DC).Conclusions:A healthcare‐ physician can be trained to perform IUS in children with IBD with comparable diagnostic accuracy as experienced radiologists. The interobserver agreement is moderate. Our findings support the usage of IUS in clinical management of children with IBD.
Ibalizumab shows in-vitro activity against group A and group B HIV-2 clinical isolates
Authors: Le Hingrat Quentin , Collin Gilles , Bachelard Antoine , Ghosn Jade , Chalal Solayah , Pacanowski Jérôme , Peytavin Gilles , Weinheimer Steven , Marsolais Christian , Damond Florence , Matheron Sophie , Charpentier Charlotte , Descamps Diane ,   and the ANRS CO5 HIV-2 cohort
Published: March 2022

Objective:
Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. The aim of this study was to determine the susceptibility of HIV-2 primary isolates to ibalizumab, a long-acting monoclonal antibody that binds to CD4 that is approved for the treatment of MDR HIV-1.

Methods:
In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. Susceptibility to ibalizumab was assessed through 50% inhibitory concentrations and maximum percentage inhibitions (MPI), and gp105 was sequenced to look for determinants of reduced susceptibility.

Results:
Ibalizumab inhibited viral replication of all 16 isolates, with a median IC50 value of 0.027 μg/ml (range = 0.001–0.506 μg/ml), and a median MPI of 93%. Although two isolates presented higher IC50 (above 0.1 μg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. However, both presented shorter V1 and V2 loops than the HIV-2 reference strain.

Conclusion:
Ibalizumab inhibits HIV-2 replication, with IC50 and MPI in the range of those reported for HIV-1. These in vitro data support the use of ibalizumab in patients with MDR HIV-2, in combination with an optimized background regimen.
A Two-Stage Training Program for Auricular Framework Fabrication Practicing Using Three-Dimensional Printing Silicone Ribs and Porcine Costal Cartilage
Authors: Tao Ran , Dong Weiwei , Sun Pengfei , Xue Chunyu , Pan Bo 
Published: March 2022

Background:
The manufacture of cartilage framework is a key element in the success of total ear reconstruction. Appropriate training can improve cartilage curving and fabricating skills, which is especially helpful for the novice clinicians. Based on threedimensional printing silicone model and porcine rib cartilage, the authors have designed a 2-stage training program to improve skills and cosmetic cognition for ear reconstruction.

Methods:
The training program includes 2 successive stages. In the first stage, trainees completed observation of framework fabrication, design and sculpturing practice on silicone rib models. Porcine costal cartilages are used for fabrication in the second stage. After that, the framework was put in a latex glove connected with a suction to simulate the skin cover procedure in operation.

Results:
At the end of the training program, all trainees could fabricate an ear-shaped cartilage framework successfully. Their cosmetic cognitions of the ear have also improved.

Conclusions:
Based on three-dimensional printing silicone model and porcine rib cartilage, the authors have designed a 2-stage training program to improve trainee’s carving techniques and cosmetic cognition for ear reconstruction. The authors believe that this training program is helpful in training, practicing and teaching activities of framework fabrication in total ear reconstruction.
The Efficiency of Different Arthroscopic Discopexy Techniques Based on Clinical and Radiographic Findings: A Systematic Review
Authors: Pliavga Vykintas , Šakalys Dovydas , Leketas Marijus 
Published: March 2022

The aim of this systematic review was to evaluate the effectiveness of different temporomandibular joint arthroscopic discopexy techniques.
The systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement and an electronic search was performed using MEDLINE (PubMed), The Cochrane Library, ScienceDirect databases using a combination of the terms ‘‘discopexy,’’ ‘‘disc recapture,’’ ‘‘disc fixation,’’ and ‘‘temporomandibular joint’’ to identify clinical trials published from 2010.
In total, 493 records were screened, of which only 9 fulfilled the inclusion criteria and were included in qualitative data synthesis.
The results of clinical findings evaluation showed that arthroscopic discopexy statistically significantly improved levels of pain (VAS) and maximum interincisal opening whereas magnetic resonance imaging evaluation showed disc position improvement of up to 90% to 100%.
In conclusion, this review provides the evidence of the potential benefits of arthroscopic disc fixation in the treatment of patients with internal derangements : reduced pain, increased maximum interincisal opening, and improved disc position evaluated by magnetic resonance imaging, whereas disc fixation using suturing techniques seems to be the most appropriate method.