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Multiple sclerosis; Clinical efficacy; Ozanimod Esclerosis múltiple; Eficacia clínica; Ozanimod Esclerosi múltiple; Eficàcia clínica; Ozanimod Background: Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for treatment of relapsing forms of MS. Objective: To characterize long-term safety and efficacy of ozanimod. Methods: Patients with relapsing MS who completed a phase 1‒3 ozanimod trial were eligible for an open-label extension study (DAYBREAK) of ozanimod 0.92 mg/d. DAYBREAK began 16 October 2015; cutoff for this interim analysis was 2 February 2021. Results: This analysis included 2494 participants with mean 46.8 (SD 11.9; range 0.033‒62.7) months of ozanimod exposure in DAYBREAK. During DAYBREAK, 2143 patients (85.9%) had treatment-emergent adverse events (TEAEs; similar in nature to those in the parent trials), 298 (11.9%) had a serious TEAE, and 75 (3.0%) discontinued treatment due to TEAEs. Serious infections (2.8%), herpes zoster infections (1.7%), confirmed macular edema cases (0.2%), and cardiac TEAEs (2.8%) were infrequent. Adjusted annualized relapse rate was 0.103 (95% confidence interval, 0.086‒0.123). Over 48 months, 71% of patients remained relapse free. Adjusted mean numbers of new/enlarging T2 lesions/scan and gadolinium-enhancing lesions were low and similar across parent trial treatment subgroups. Conclusions: This long-term extension of ozanimod trials confirmed a favorable safety/tolerability profile and sustained benefit on clinical and magnetic resonance imaging measures of disease activity. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The ozanimod RMS trials were supported by Celgene International II. The sponsor was involved in data analysis and interpretation, and manuscript preparation, review, and approval. All authors vouch for data accuracy, reviewed all drafts, and approved the final manuscript.

Objective: To review the pharmacology, dosing and administration, safety, clinical efficacy, and role of eptacog beta in the treatment of congenital hemophilia with inhibitors. Data Sources: A literature search of PubMed (1966 to August 2021) was conducted using the keywords eptacog beta, recombinant FVII, and hemophilia. Study Selection and Data Extraction: All relevant published articles and prescribing information on eptacog beta for the treatment of congenital hemophilia with inhibitors were reviewed. Data Synthesis: Eptacog beta is a novel recombinant activated factor VII (rVIIa) product that demonstrated efficacy in controlling bleeding and associated pain in patients with hemophilia A or B with inhibitors. Eptacog beta has limited Food and Drug Administration–approved and off-label indications compared with other bypassing agents (BPAs; activated prothrombin complex concentrates [aPCC; eptacog alfa]). Eptacog beta costs less than eptacog alfa, but still more than aPCCs. Relevance to Patient Care and Clinical Practice: This review provides insight into the role of eptacog beta for treatment of congenital hemophilia with inhibitors and reviews important health system formulary considerations for available BPAs. Conclusions: Eptacog beta is more cost-effective than eptacog alfa and, as such, may become the preferred rVIIa formulary product. However, eptacog alfa availability remains necessary for the treatment of disorders where eptacog beta has limited data. aPCC should remain the first-line BPA for the treatment of bleeding in patients with inhibitors with no contraindications to use because of its equivocal efficacy and safety and in light of the magnitude of cost savings associated with this strategy.

Objective: To evaluate the clinical efficacy and safety of cefetamet pivoxil for the treatment of acute bacterial rhinosinusitis in Korean patients compared to treatment with cefdinir. Methods: A prospective, multicenter, randomized double-blind, comparative study was conducted by the Departments of Otorhinolaryngology–Head and Neck Surgery at 17 hospitals or universities in the Republic of Korea from March 2017 to April 2019. A total of 309 patients were screened and 249 patients participated in the study. Results: Treatment with cefetamet pivoxil for 2 weeks showed 82.4% clinical cure and improvement rates in patients with acute bacterial rhinosinusitis compared to 84.68% in those taking cefdinir for 2 weeks, showing that cefetamet pivoxil administered twice a day for 2 weeks was as effective as cefdinir 3 times a day for 2 weeks for the treatment of acute bacterial rhinosinusitis. The overall adverse reaction rates of both drugs were 10.56% in the cefetamet pivoxil group and 15.49% in the cefdinir group, without serious adverse events or drug reactions. Conclusions: Cefetamet pivoxil twice a day was as efficacious and safe as cefdinir 3 times a day for the treatment of acute bacterial rhinosinusitis, which suggested that cefetamet pivoxil may be a suitable alternative to cefdinir.

Background The clinical efficacy of mechanical thrombectomy has been unequivocally demonstrated in multiple randomized clinical trials. However, these studies were performed in carefully selected centers and utilized strict inclusion criteria. Aim We aimed to assess the clinical effectiveness of mechanical thrombectomy in a prospective registry. Methods A total of 2008 patients from 76 sites across 12 countries were enrolled in a prospective open-label mechanical thrombectomy registry. Patients were categorized into the corresponding cohorts of the SWIFT-Prime, DAWN, and DEFUSE 3 trials according to the basic demographic and clinical criteria without considering specific parenchymal imaging findings. Baseline and outcome variables were compared across the corresponding groups. Results As compared to the treated patients in the actual trials, registry-derived patients tended to be younger and had lower baseline ASPECTS. In addition, time to treatment was earlier and the use of intravenous tissue plasminogen activator (IV-tPA) and general anesthesia were higher in DAWN- and DEFUSE-3 registry derived patients versus their corresponding trials. Reperfusion rates were higher in the registry patients. The rates of 90-day good outcome (mRS0-2) in registry-derived patients were comparable to those of the patients treated in the corresponding randomized clinical trials (SWIFT-Prime, 64.5% vs. 60.2%; DAWN, 50.4% vs. 48.6%; Beyond-DAWN: 52.4% vs. 48.6%; DEFUSE 3, 52% vs. 44.6%, respectively; all P > 0.05). Registry-derived patients had significant less disability than the corresponding randomized clinical trial controls (ordinal modified Rankin Scale (mRS) shift odds ratio (OR), P Conclusion Our study provides favorable generalizability data for the safety and efficacy of thrombectomy in the “real-world” setting and supports that patients may be safely treated outside the constraints of randomized clinical trials.

Distally based sural fasciocutaneous (DBSF) flaps are widely used for reconstructing soft tissue defects of the foot. The purpose of this paper was to compare the clinical efficacy of the use of flaps to repair defects in areas proximal and distal to the level of the tarsometatarsal joints in a relatively large number of patients and to analyze the effects of factors on the risk of developing partial necrosis of the flaps. Between April 2001 and December 2019, a total of 355 DBSF flaps were utilized to cover soft tissue defects in the foot. According to the furthest location of the defects reconstructed with the flaps, the flaps were divided into the proximal foot group (n = 260) and the distal foot group (n = 95). The partial necrosis rates, their influencing factors, and the clinical outcomes of the procedure were compared between the two groups. In the proximal foot group, the partial necrosis rate (6.2%, 16 of 260) was significantly lower than that in the distal foot group (14.7%, 14 of 95) ( P .05). The ratio of unfavorable conditions in the distal foot group was higher than that in the proximal foot group ( P

Background The clinical efficacy of migraine therapeutic agents directed towards the calcitonin-gene related peptide (CGRP) pathway has confirmed the key role of this axis in migraine pathogenesis. Three antibodies against CGRP – fremanezumab, galcanezumab and eptinezumab – and one antibody against the CGRP receptor, erenumab, are clinically approved therapeutics for the prevention of migraine. In addition, two small molecule CGRP receptor antagonists, ubrogepant and rimegepant, are approved for acute migraine treatment. Targeting either the CGRP ligand or receptor is efficacious for migraine treatment; however, a comparison of the mechanism of action of these therapeutic agents is lacking in the literature. Methods To gain insights into the potential differences between these CGRP pathway therapeutics, we compared the effect of a CGRP ligand antibody (fremanezumab), a CGRP receptor antibody (erenumab) and a CGRP receptor small molecule antagonist (telcagepant) using a combination of binding, functional and imaging assays. Results Erenumab and telcagepant antagonized CGRP, adrenomedullin and intermedin cAMP signaling at the canonical human CGRP receptor. In contrast, fremanezumab only antagonized CGRP-induced cAMP signaling at the human CGRP receptor. In addition, erenumab, but not fremanezumab, bound and internalized at the canonical human CGRP receptor. Interestingly, erenumab also bound and internalized at the human AMY1 receptor, a CGRP receptor family member. Both erenumab and telcagepant antagonized amylin-induced cAMP signaling at the AMY1 receptor while fremanezumab did not affect amylin responses. Conclusion The therapeutic effect of agents targeting the CGRP ligand versus receptor for migraine prevention (antibodies) or acute treatment (gepants) may involve distinct mechanisms of action. These findings suggest that differing mechanisms could affect efficacy, safety, and/or tolerability in migraine patients.

Background: A number of works provide information on the effectiveness of dienogest in uterine adenomyosis. However, information on the use of the drug at various degrees of the adenomatous nodes, is not presented in the available literature. Aim: The aim of the study was to evaluate the clinical efficacy of dienogest in the treatment of patients with adenomyosis 2nd and 3rd stage and chronic pelvic pain. Materials and methods: A comprehensive clinical survey and treatment of 46 patients with signs of adenomyosis were carried out. Patients were divided into two groups: 28 patients with stage 2 adenomyosis, 18 patients with type 3 adenomyosis were included in the 2nd group. On the first phase of the menstrual cycle all patients underwent hysteroscopy for endoscopic verification of the diagnosis using the traditional Karl Storz hysteroscopic stand with separate treatment and diagnostic curettage of the uterine cavity and cervical canal, followed by histological examination. After surgical treatment all patients received dienogest at a dose 2 mg/day for 6 months. The treatment was performed during 6 months. After 3, 6, and 12 months of the study, the patients included in the survey underwent a comprehensive examination with a clinical assessment of the manifestations of the disease. The level of pain manifestations was evaluated on a visual analog scale (VAS) with a range of 0–10 points. During pain assessment, its manifestations were differentiated—pain due to dyspareunia, dysmenorrhea, dyschezia, and chronic pelvic pain were evaluated. Results: In the group of patients with 2nd adenomyosis stage, the intake of dienogest for 6 months led to the absence of manifestations of uterine bleeding and dyschezia, a decrease in the frequency of dyspareunia—by 7.7 times. In patients with the 3rd stage of the disease, the decrease in the symptoms of adenomyosis was less pronounced, however, after taking the drug, a decrease in the frequency of uterine bleeding was found to be 6 times, dyspareunia 4 times, and dyschezia 5 times. Twelve months after the start of observation (6 months after the end of treatment), none of the patients with 2nd stage of disease showed severe pelvic pain, in the group with 3rd stage of adenomyosis there were only two of these patients (11.1%). At the same time, the vast majority of patients included in the study did not have manifestations of chronic pelvic pain—78.6% of patients with 2nd stage of adenomyosis and 55.6% of patients with 3rd stage of disease, the remaining 21.4% and 33.3% of patients of the first and second groups reported a significant decrease in the severity of pain. Conclusions: The inclusion of dienogest in the combined treatment of adenomyosis is clinically effective, contributing to the rapid and reliable relief of the main manifestations of the disease in patients with adenomyosis with grade 2 and 3 nodes. Treatment of adenomyosis with the use of dienogest is clinically effective, contributing to the rapid and reliable relief of the main manifestation of the disease.

Background: Although platelet-rich plasma (PRP) has potential as a regenerative treatment for knee osteoarthritis, its efficacy varies. Compositional differences among types of PRP could affect clinical outcomes, but the biological characterization of PRP is lacking. Purpose: To assess the efficacy of intra-articular PRP injection in knee osteoarthritis as compared with hyaluronic acid (HA) injection and to determine whether the clinical efficacy of PRP is associated with its biological characteristics. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 110 patients with symptomatic knee osteoarthritis received a single injection of leukocyte-rich PRP (1 commercial kit) or HA. Clinical data were assessed at baseline and at 6 weeks and 3 and 6 months after injection. The primary endpoint was an improvement in the International Knee Documentation Committee (IKDC) subjective score at 6 months, and the secondary endpoints were improvements in scores based on the Patient Global Assessment, the visual analog scale (VAS) for pain, the Western Ontario and McMaster Universities Osteoarthritis Index, and the Samsung Medical Center patellofemoral score. Cell counts and concentrations of growth factors and cytokines in the injected PRP were assessed to determine their association with clinical outcomes. Results: PRP showed significantly improvement in IKDC subjective scores at 6 months (11.5 in the PRP group vs 6.3 in the HA group; P = .029). There were no significant differences between groups in other clinical outcomes. The Patient Global Assessment score at 6 months was better in the PRP group ( P = .035). The proportion of patients who scored above the minimal clinically important difference (MCID) for VAS at 6 months was significantly higher in the PRP group ( P = .044). Within the PRP group, the concentrations of platelet-derived growth factors were high in patients with a score above the MCID for VAS at 6 months. The incidence of adverse events did not differ between the groups ( P > .05). Conclusion: PRP had better clinical efficacy than HA. High concentrations of growth factors were observed in patients who scored above the MCID for clinical outcomes in the PRP group. These findings indicate that concentration of growth factors needs to be taken into consideration for future investigations of PRP in knee osteoarthritis. Registration: NCT02211521 (ClinicalTrials.gov identifier).

Background: Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist compound recently introduced to treat schizophrenia and bipolar disorder. Although cariprazine is clinically classified as a low-somnolence drug, to date no detailed polysomnographic study is available on its effect on sleep. Aims: This study examined the acute systemic effects of cariprazine on the rat sleep architecture and electroencephalography spectral power. Methods: Sprague Dawley rats were recorded during their normal sleep period for four hours, and their sleep stages were classified. Results: Cariprazine (0.3 mg/kg i.p.) reduced the time spent in rapid eye movement (REM) sleep and increased REM latency. This dose of cariprazine decreased the gamma (40–80 Hz) band frequency oscillations and increased the theta (4–9 Hz) and alpha (9–15 Hz) frequencies during the wake periods but not during slow-wave sleep. The 0.03 mg/kg dose of cariprazine only increased the alpha power during the wake periods, while the 0.003 mg/kg dose was without any effect. Conclusion: Taken together, the present results suggest that the REM-suppressing effect of cariprazine may be related to its effectiveness in improving depressive symptoms, as various drugs with similar REM-reducing properties effectively treat the depressive state, whereas the gamma power-reducing effect of cariprazine may be indicative of its efficacy in schizophrenia or mania, as similar effects have been observed with other D2 and 5-HT2 receptor antagonist drugs. These data contribute to our understanding of the complex mechanism of action that may stand behind the clinical efficacy of cariprazine.

Introduction. Complex anal fistula (CAF) is a challenging anorectal condition. Although numerous treatments for its management have been proposed, none is ideal. Herein, we investigated the clinical efficacy of video-assisted modified ligation of the intersphincteric fistula tract (LIFT) in comparison with the incision-thread-drawing procedure for Parks type II anal fistulas. Methods. Male and female adult patients with Parks type II anal fistula who were randomized to receive one of two procedures in the Anorectal Surgery Unit of the Affiliated People’s Hospital of Ningbo University: video-assisted modified LIFT (test group, 30 cases) or incision thread drawing (control group, 30 cases). Healing and recurrence, postoperative pain, and postoperative autonomous anal control ability were compared. Results. In the test group, the pain scores were significantly lower ( P = .001) and wound healing was faster ( P = .001). However, there were no marked differences between groups in operative efficacy or postoperative infection rate (all P > .05). We followed all the patients for more than 18 months, with the test group having lower Jorge–Wexner incontinence ( P = .005) and fecal incontinence (FI) severity index ( P = .000) scores. No significant difference in recurrence ( χ2 = .351, P = .554) or healing ( χ2 = 1.071, P = .301) rate was found between the 2 groups. Conclusions. We established that video-assisted modified LIFT is superior in repairing Parks type II anal fistulas, with less trauma, quicker recovery, and better anal function.

No guidelines exist for the conduct and reporting of manuscripts with systematic searches of app stores for, and then appraisal of, mobile health apps (‘health app-focused reviews’). We undertook a scoping review including a systematic literature search for health app-focused reviews describing systematic app store searches and app appraisal, for apps designed for patients or clinicians. We created a data extraction template which adapted data elements from the PRISMA guidelines for systematic literature reviews to data elements operationalised for health app-focused reviews. We extracted the data from included health app-focused reviews to describe: (1) which elements of the adapted ‘usual’ methods of systematic review are used; (2) methods of app appraisal; and (3) reporting of clinical efficacy and recommendations for app use. From 2798 records, the 26 included health app-focused reviews showed incomplete or unclear reporting of review protocol registration; use of reporting guidelines; processes of screening apps; data extraction; and appraisal tools. Reporting of clinical efficacy of apps or recommendations for app use were infrequent. The reporting of methods in health app-focused reviews is variable and could be improved by developing a consensus reporting standard for health app-focused reviews.

Study Design: Retrospective cohort study. Objective: To evaluate the clinical efficacy of minimally invasive endoscopic surgery in patients with spinal extradural and intradural-extramedullary tumors. Methods: This was a study of 15 consecutive patients with spinal extradural or intradural-extramedullary tumors up to 2 levels treated by minimal invasive surgery using a full endoscopic visualization and Caspar’s retraction system (for cervical, thoracic, and lumbar tumors) over a 4-year period between January 2015 to April 2019 at a tertiary center. Results: A gross total remove was achieved in all patients (100%), determined by postoperative contrast computed tomography scans and magnetic resonance imaging. There was no postoperative spinal instability. All patients had equal or better neurologic functions after surgery at follow-up. The average preoperative Nurick’s grade mean was 1.9 and the postoperative was 1.1. The average preoperative McCormick’s grade mean was 2.9 versus 1.3 in the postoperative period. Conclusions: Selective extradural or intradural-extramedullary tumors well localized and up to 2 levels can be safely and effectively treated by minimally invasive surgery using a full endoscopic visualization and the Caspar’s retractor. However, there is insufficient evidence to recommend this approach over the classical or other microsurgical approach described.

Background While the percutaneous approach is increasingly preferred, suture-mediated closure devices have been put into clinical practice to close the femoral artery during procedures requiring a large-sized introducer. However, scar in the groin is considered a contraindication or an exclusion criterion for percutaneous procedures. The aim of our study was to investigate the outcomes and safety of Pro-Glide device as suture-mediated closure device in patients who underwent thoracic endovascular aortic repair with percutaneous femoral access ≥22 F who had previous groin intervention. Methods A total of 73 patients who underwent endovascular repair with percutaneous femoral access were retrospectively included in the study. Previous groin intervention was defined as history of open surgical access or large sheath insertion (>18 F) to femoral artery because of endovascular or valvular intervention. Patients were divided into two groups as who had previous groin intervention PGI (+) and had not PGI (−). Results A total of 73 patients [60 male (82.2%)] were included in the study. Seventeen patients had PGI, and 56 did not. When groups were compared in terms of sheath sizes, a significantly higher sheath sizes were used in PGI (+) patients (24.5 ± 1.1 F vs. 23.8 ± 0.9 F, p = 0.005). The overall success rate in the femoral approach with pre-close technique was statistically insignificant between two groups (94.1% vs. 96.4%, p = 0.55). One patient in PGI (+) group and two patients in PGI (−) had technical failure for percutaneous femoral approach. One patient (5.9%) in PGI (+) group and one patient (1.8%) in PGI (−) group had femoral complications after the procedures; however, there was no significant difference between the groups in terms of complications (5.9% vs. 1.8%, p = 0.13). Conclusion Pro-Glide device may be a safe and less invasive method for femoral access in patients with PGI and might not be considered as a contraindication for patients with history of PGI.

The purpose of this study was to investigate the clinical efficacy of compound polymyxin B ointment for treating chronic refractory wounds. A retrospective analysis was performed on 111 patients who underwent chronic refractory wound treatment. Patients were divided into 2 groups, with 45 patients included in the experimental group (compound polymyxin B group) and 66 patients included in the control group (silver sulfadiazine group). After thorough debridement in both groups, either compound polymyxin B ointment or silver sulfadiazine cream was evenly applied to the patient’s wound and covered with sterile gauze. In both groups, dressing changes were dependent on the wound’s condition and secretions. Using the Bates-Jensen Wound Assessment Tool (BWAT), patients in both groups were scored, after which wound healing, infection, and healing time were compared. There was no significant difference in BWAT scores between the 2 groups on the 7th or 14th day; however, on the 21st day, the BWAT score in the experimental group was significantly lower than that of the control group. The difference was statistically significant ( P < .05). There was no significant difference in the BWAT-I scores between the 2 groups on the seventh day. The healing time in the experimental group was significantly shorter than that of the control group, and the difference was statistically significant ( P < .05). For the treatment of chronic refractory wounds, thorough debridement followed by compound polymyxin B ointment topical application can reduce and control wound infection effectively and accelerate the process of wound repair.

Background There are only a few studies in which the clinical efficacy of SLIT has been compared between children and adults. In addition, there is a lack of research on other factors, associated with the treatment, including immunological parameters and quality of life (QOL). Objective To compare the effects of sublingual immunotherapy (SLIT) in adults and children on various factors: clinical efficacy, quality of life (QOL), satisfaction, immunological parameters, and adverse events. Methods Subjects who were sensitized to house dust mites and treated with SLIT for at least 2 years were enrolled. Seventy patients who completed questionnaires measuring nasal symptoms and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores and underwent serologic tests for immunological parameters at initial, 1-year, and 2-year follow-up were selected and divided into two groups based on age: a child group (age 4–12 years, n = 44) and an adult group (age 19–59 years, n = 26). Results The Total Nasal Symptom Score (TNSS) was significantly decreased after 2 years of SLIT in both the child and adult groups ( p Conclusion Although more adult patients were satisfied with SLIT, the clinical effects of SLIT on nasal symptoms were comparable between child and adult groups. Despite different immunological values at baseline between the two groups, changing patterns of immunological parameters did not differ.

Background Two new drugs, abiraterone and enzalutamide, had recently shown beneficial effects on survival in patients with metastatic castration-resistant prostate cancer. We systematically reviewed the efficacy and safety of abiraterone and enzalutamide in metastatic castration-resistant prostate cancer in real-world practice. Methods A search from PubMed, Web of Science, Cochrane, Embase was conducted up to 6 March 2019. Available articles from conferences were searched. The endpoint was prostate-specific antigen response, overall survival, progression-free survival, number of patients with any adverse event. Results Fourteen cohort studies involving 3469 participants were included. Pooled result showed that prostate-specific antigen response was higher for patients receiving enzalutamide than abiraterone (790 patients, odds ratio (OR) 0.47, 95% confidence interval (CI) 0.29–0.77, P = 0.003, I2=59%). Enzalutamide was significantly associated with increased adverse events rate in comparison with abiraterone (730 patients, OR 0.35, 95%CI 0.13–0.92, P = 0.03, I2=65%). There was no statistical difference between abiraterone and enzalutamide with respect to perceived cognitive impairments (1856 patients, OR 0.90, 95%CI 0.29–2.76, P = 0.85, I2=5%). Enzalutamide was significantly associated with increased fatigue risk in comparison with abiraterone (2477 patients, OR 0.46, 95%CI 0.34–0.63, P＜0.00001, I2=0%). Conclusions Our results demonstrated that enzalutamide was more efficacious than abiraterone for patients with metastatic castration-resistant prostate cancer, but was associated with a significantly elevated risk of side effects, particularly fatigue.

Objective: To objectively evaluate the effectiveness of Baduanjin exercise on cardiopulmonary function and quality of life in chronic obstructive pulmonary disease patients. Data sources: Articles published in PubMed, EMBASE, China National Knowledge Infrastructure Database, the Cochrane Library, Wanfang Database, and China Biological Medicine Database from inception to March 2020. Review Method: Articles on randomized controlled trials about Baduanjin exercise for the treatment of chronic obstructive pulmonary disease were identified. Cochrane handbook was applied to assess the quality of included trials. Stata (version 14.0) and Review Manager (version 5.3) were employed for data analysis. Mean difference with 95% confidence intervals were calculated for pulmonary function, 6-minute walking distance, and the quality of life. Results: Thirty-one randomized controlled trials including 3045 patients were included. The result of meta-analysis indicated that comparing with any other type of treatment alone, Baduanjin exercise combined other type of treatment revealed well efficacy in improving exercise capability on 6-minute walking distance (mean difference = 43.83, 95% confidence interval (29.47, 58.20), P Conclusions: Baduanjin exercise could improve exercise capacity, pulmonary function, and quality of life for patients with chronic obstructive pulmonary disease.

Dental composites are routinely placed as part of tooth restoration procedures. The integrity of the restoration is constantly challenged by the metabolic activities of the oral microbiome. This activity directly contributes to a less-than-desirable half-life for the dental composite formulations currently in use. Therefore, many new antimicrobial dental composites are being developed to counteract the microbial challenge. To ensure that these materials will resist microbiome-derived degradation, the model systems used for testing antimicrobial activities should be relevant to the in vivo environment. Here, we summarize the key steps in oral microbial colonization that should be considered in clinically relevant model systems. Oral microbial colonization is a clearly defined developmental process that starts with the formation of the acquired salivary pellicle on the tooth surface, a conditioned film that provides the critical attachment sites for the initial colonizers. Further development includes the integration of additional species and the formation of a diverse, polymicrobial mature biofilm. Biofilm development is discussed in the context of dental composites, and recent research is highlighted regarding the effect of antimicrobial composites on the composition of the oral microbiome. Future challenges are addressed, including the potential of antimicrobial resistance development and how this could be counteracted by detailed studies of microbiome composition and gene expression on dental composites. Ultimately, progress in this area will require interdisciplinary approaches to effectively mitigate the inevitable challenges that arise as new experimental bioactive composites are evaluated for potential clinical efficacy. Success in this area could have the added benefit of inspiring other fields in medically relevant materials research, since microbial colonization of medical implants and devices is a ubiquitous problem in the field.

Objective: This study aims to evaluate the clinical efficacy and visual function prognosis of macular hole retinal detachment treatment for high myopia by inverting the internal limiting membrane to overlay the macular hole with the assistance of perfluorocarbon liquids. Methods: A total of 55 high myopia patients, who received macular hole retinal detachment treatment from 2013 to 2016, were included in this study. Among these patients, 38 patients were assigned to the first group and 17 patients (perfluorocarbon liquids) were assigned to the second group. The second group was further divided into two subgroups, according to the overlaying layer number of the internal limiting membrane valve: A group (multiple layers) and B group (single layer). Results: The success rate of the internal limiting membrane inversion and overlaying on the macular hole was 23.68% and 100% in the first and second group, respectively. The differences in macular hole closing rate and postoperative best-corrected visual acuity between these two groups were statistically significant ( p Conclusion: Perfluorocarbon liquids play a positive role in the operation process of the internal limiting membrane.

Background Non-thermal non-tumescent methods for varicose vein treatment have rapidly gained popularity in recent years due to clinical efficacy comparable to other endovenous methods, but with a superior safety and tolerability profile. Cyanoacrylate is an adhesive that rapidly polymerises during endovenous treatment to cause rapid occlusion of veins and initiate vein fibrosis. Method Cyanoacrylate glue treatment is known to cause complications such as phlebitis, cellulitis and deep vein thrombosis in rare instances. We present the first reported case of cyanoacrylate extravasation with chronic foreign body reaction in a patient nine months after initial treatment. Results We discuss the aetiology of this complication, its treatment, patient outcome and its significance to both clinicians and patients. Conclusion Cyanoacrylate glue embolisation can, in rare instances, lead to extravasation and chronic foreign body reaction, necessitating surgical intervention. The relative novelty of cyanoacrylate glue embolisation in the treatment of varicose veins requires clinicians to monitor for rare complications during its use in clinical practice. Patients should be aware of the rare risk of glue extravasation and foreign body reaction for fully informed consent prior to treatment.

Background: The application of fiberoptic endoscopic evaluation of swallowing (FEES) in the pediatric dysphagia protocol requires specialized knowledge of pediatric conditions that result in dysphagia, recognition of normal and abnormal laryngopharyngeal anatomy and function across ages, and the ability to identify maturational changes in anatomy and function of the aerodigestive tract that pertain to airway protection and swallowing function. Methods: Over the past 25 years, we have performed over 7,000 collaborative Otolaryngology and Speech-Language Pathology FEES examinations in patients ranging from 2 days of age to young adults. During this time period, we have monitored the safety of the procedure, explored the feasibility and utility of FEES across conditions, compared and contrasted FEES to the videofluoroscopic evaluation of swallowing (VFSS), and developed specific pediatric FEES protocols with operational definitions for identification and interpretation of swallowing parameters. Results: FEES has proved to be a safe procedure in patients across ages. There have been no significant adverse events. FEES is comparable to the VFSS in the assessment of events before and after the swallow. It provides unique information regarding laryngopharyngeal anatomy and function, airway protection integrity, sensory threshold, and secretion management ability, as well as pharyngeal swallowing dynamics and the efficacy of compensatory swallowing strategies. Conclusions: There are specific indications and contraindications for pediatric FEES, and unique components that characterize the pediatric FEES protocols across ages and conditions. FEES procedures performed jointly by an Otolaryngologist and Speech-Language pathologist offer a team approach to interpretation and management recommendations.

Aims and Objectives: The high esthetic demands led to the promotion of various esthetic appliances like lingual orthodontics. This study aimed to review clinical outcome and potential complications of lingual orthodontics to achieve an evidence-based decision for orthodontic therapies. Materials and Methods: A comprehensive electronic search was conducted from January 1975 to March 2019 which was limited to English language and administrations of lingual orthodontics treatment which evaluated its efficacy and potential complications. Data extraction was performed according to the PRISMA statement. Results: 49 studies were selected and analyzed in this systematic review. The pain of lingual appliances starts a little earlier and lasts longer, and patients with lingual appliances experience more tongue discomfort and less cheek and lip pain and greater eating difficulties especially after placement and take a longer time to adapt to appliances. Lingual appliances generally cause more plaque accumulation and gingivitis especially in lingual anterior teeth; however, labial appliances are associated with high frequency in posterior maxillary teeth. Conclusion: This systematic review shows that despite the drawbacks of these appliances such as pain and eating difficulties, they can accomplish treatment goals with the same outcomes in comparison with conventional approaches, within the same duration and even lesser anchorage loss.

Object To investigate the clinical efficacy and safety of dexmedetomidine in flexible bronchoscopy under general anesthesia. Methods A total of 114 patients were randomly divided into intervention group A and control group B. Group A received dexmedetomidine, fentanyl, and propofol as anesthesia, while Group B received fentanyl and propofol only. Changes in heart rate, mean arterial pressure, pulse oxygen saturation, stress indices (blood cortisol, adrenaline, and norepinephrine levels), incidence of adverse events, anesthesia dose, duration of procedure, and recovery time were compared between the groups at specific time points T0, T1, and T2 during bronchoscopy. Results There was no statistical difference between the groups at T0. At T1 and T2, pulse oxygen saturation, mean arterial pressure, heart rate, and stress indices in group A were significantly more favorable than those in group B. The incidence of adverse events (5.26%) in group A was significantly lower than that in group B (17.54%), and patients in group A required less propofol and had a faster recovery time than patients in group B. Conclusion Dexmedetomidine use in flexible bronchoscopy under general anesthesia is safe and effective and decreases the stress response in synergy with propofol to provide hemodynamic stability.

Background: The repair of porcine articular cartilage defects by using particulated juvenile allograft cartilage (PJAC) has demonstrated good short-term clinical efficacy, but the repair process and mechanism have not been fully elucidated. Purpose: To study the efficacy of PJAC in repairing full-thickness cartilage defects and to provide an experimental basis for its clinical application. Study Design: Controlled laboratory study. Methods: Thirty Guizhou minipigs were randomly divided into an experimental group and control group. An 8-mm cylindrical full-thickness cartilage defect was created in the femoral trochlea of either knee in all minipigs. The experimental group received the PJAC transplantation (PJAC group; n = 15) and the control group received autologous cartilage chips (ACC group; n = 15). Five minipigs were euthanized at 1, 3, and 6 months in each group to obtain samples, which were evaluated by general view of the knee joint and histomorphometry of the chondral defect area (hematoxylin and eosin, safranin O). International Cartilage Repair Society (ICRS) II semiquantitative evaluation and collagen type II staining immunohistochemistry were also performed. Results: All 30 Guizhou minipigs were followed; there was no infection or incision healing disorder after the operation. At 1 month postoperatively, more hyaline cartilage was found in the ACC group (29.4%) compared with the PJAC group (20.1%) ( P < .05); there was no statistical difference between the 2 groups at 3 and 6 months after operation. The fibrocartilage content in the ACC group was significantly more than that in the PJAC group at 1 and 3 months postoperatively (27.4% vs 18.2% and 49.9% vs 41.1%, respectively; P < .05); significant differences disappeared at 6 months postoperatively. The PJAC group produced more fibrous tissue than the ACC group at 1 and 3 months postoperatively (60.1% vs 40.6% and 38.8% vs 24.4%, respectively; P < .05) but showed no statistical difference at 6 months postoperatively. Regarding the ICRS II scores, those of the ACC group were significantly better than the scores of the PJAC group in some subclasses at 3 and 6 months postoperatively. The positive rates of immunohistochemical staining in the ACC group were higher at 1 and 3 months postoperatively than those in the PJAC group (54.2% vs 37.8% and 46.4% vs 34.4%, respectively; P < .05). The difference was not statistically significant between the 2 groups at 6 months postoperatively. Conclusion: Both PJAC and ACC can produce a good repair effect on cartilage defects. At 1 and 3 months postoperatively, ACC resulted in better outcomes than PJAC, but there was no statistical difference in the repair effect between the 2 techniques at 6 months postoperatively. Clinical Relevance: Based on this animal experiment, further clinical studies are needed to investigate PJAC as a possible alternative first-line treatment for cartilage defects.

This study aimed to investigate the effects of CYP2C19 metabolizer status on the clinical therapeutic efficacy of cerebral infarction. Patients with cerebral infarction ( n = 180; NIHSS score ≤ 5) were recruited and divided into Group A and Group B according to CYP2C19 metabolizer status. In Group A, patients received routine clopidogrel therapy for 1 year; in Group B, the patients with extensive metabolizer (EM) were treated with clopidogrel, and patients with intermediate metabolizer (IM) and poor metabolizer (PM) were treated with aspirin for 1 year. On admission, National Institutes of Health Stroke Scale score was determined, and the therapeutic efficacy was evaluated with Modified Rankin Scale score after 1 year of treatment. The outcomes and adverse effects were recorded during the treatment. After routine clopidogrel treatment, the efficacy in EM patients was significantly better than in PM and IM patients. After adjustment of therapeutic protocol, the therapeutic efficacy in PM and IM patients was markedly improved, which was accompanied by significant reduction in recurrence rate of cerebral infarction. Although the adverse effects increased in patients receiving aspirin treatment, they resolved after symptomatic therapy. CYP2C19 metabolizer status is closely related to the clinical efficacy of clopidogrel. Thus, it is necessary to adjust the anti-platelet treatment according to the CYP2C19 metabolizer status to maximize therapeutic efficacy without increasing recurrence and adverse effects.

As a pivotal part of the elbow joint structure, the coronoid process of the ulna plays a vital role in maintaining elbow joint stability. Loss of coronoid process height causes instability of the elbow joint depending on the fracture characteristics and size. The diagnosis and treatment of coronoid process fractures has gained widespread attention from orthopedic surgeons. Nevertheless, few reports have described reconstruction of coronoid process fractures and defects that affect elbow joint stability. Treatment of elbow joint instability induced by coronoid process defects is challenging because most cases are complicated by other elbow joint injuries. Moreover, the clinical efficacy remains unclear. The present narrative review was performed to examine the research progress on reconstruction of the coronoid process. The findings of this review provide evidence for clinical repair and reconstruction of coronoid process defects and contribute to the published literature on this topic.

Background Inflammatory bowel disease (IBD) represents a series of digestive system abnormalities and parenteral manifestations. Stem cell therapy has been regarded as a promising treatment for IBD. Methods We searched Web of Science Core Collection for publications of interest from 1991 to 2019. Publication performance was analyzed using several bibliometric parameters, including Statplanet to reveal the geographic distribution of the publications, VOSviewer to identify the research landscape of hot topics, and CiteSpace to show keywords with the strongest citation bursts. Results A total of 1230 publications were identified, of which 674 articles were analyzed further. The United States was the most productive country and Spanish researchers published the highest quality articles. At a journal level, Gastroenterology published the greatest number of articles, while articles from Gut had the highest citation number. Results from the research landscape analysis of hot topics and the top 20 terms with the strongest citation bursts indicated that animal experiments, immunocytes, intestinal epithelial cells, cytokine expression, and clinical efficacy were the main focuses of research. Conclusion Stem cell therapy for IBD is currently receiving increasing attention by researchers, with focuses on animal experiments, immunocytes, intestinal epithelial cells, cytokine expression, and clinical efficacy.

Objective Complications frequently occur in patients with breast cancer after surgery. Anesthesia nursing plays an important role in decreasing complications for such patients. Thus, this study investigated the effects of anesthesia with intensive care nursing (AICN) on complication rates in patients with breast cancer after surgery. Methods Eighty-two patients with breast cancer were recruited in this study. Complications were compared between the anesthesia with usual nursing care (AUCN) and AICN groups. Results The results demonstrated that AICN decreased the rates of incision infection, drug extravasation, and catheter exposure, as well as pain and inflammation scores, compared with the findings in the AUCN group. AICN improved the time to orientation and decreased the incidence of nausea, anxiety, depression, and vomiting versus AUCN. In addition, AICN shortened the time to awakening after anesthesia compared with the effects of AUCN. Furthermore, AICN shortened hospital stay and increased survival rates. Notably, AICN improved health-related quality of life as measured using the EORTC QLQ-C30 questionnaire. Conclusion AICN provided more benefits and better postoperative outcomes than AUCN, suggesting its utility for minimizing complications in patients with breast cancer after surgery.

Objective: To investigate the long-term clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with human herpes virus 8 (HHV8)-positive multicentric Castleman’s disease (MCD). Methods: A 17-year-old female patient was admitted to Henan Provincial People’s Hospital with the complaint of febrile for half a month, headache, and enlarged superficial lymph nodes on October 5, 2010. HHV8-positive mixed cellular Castleman’s disease was found by pathological diagnosis of lymph nodes biopsy. After the administration of CHOP and Hyper-CVAD-B, the patient was still febrile, we administrated the followed COAP, two courses of VAD(Vincristine, Adriamycin, Dexamethasone), the patient received CR. Six months after CR, the patient relapsed, we administrated VAD and two courses of bortezomide+dexamethasone chemotherapy, and then the patient received PR. After that, the patient underwent allo-HSCT from his human leukocyte antigen (HLA)-matched unrelated donor after conditioning with Bu/Cy+Etoposide+Smoustin.graft-vs-host disease (GVHD) prophylaxis, which consisted of ATG (7.5 mg/kg, qd, ivdrip) from d-5 to d-2, cyclosporine (3 mg/kg/d, qd, ivdrip, for 24 h) started from day-1, MMF(0.5 g, tid, po.) started from day+1 to +28, and MTX (15 mg per time, ivdrip, d+1,+4,+7,+11). She received 3.5×106/L CD34+cells and 8.1×108/LMNC. Results: Granulocyte engraftment occurred on day+12, platelet engrafted on day+14. Bone marrow biopsy showed normalization of trilineage hematopoiesis on day+33, chimerism: 97.6%. The transplantation was successful and followed up for 7 years with CR. Conclusion: Allo-HSCT might cure patients with refractory/relapsed HHV8+ MCD.

Objectives:Regulatory approval of new medicines requires a thorough assessment of the potential clinical benefits and risks. Study end-points are expected to demonstrate a clinically relevant treatment effect that will translate into direct patient benefits. This study sought to review the ophthalmic medicines with European Union–wide approval granted via the Centralised Procedure and characterise the key efficacy end-points underpinning the demonstration of clinical benefit.Methods:This study was a retrospective review of published data pertaining to the European regulatory authorisation of centrally approved ophthalmic products between 1999 and 2017, inclusive. All sources and data consulted are in the public domain. European Public Assessment Reports published by the European Medicines Agency were consulted for data concerning the pivotal clinical efficacy studies supporting the applications. Data analyses were descriptive.Results:The European Medicines Agency have authorised 30 products via the Centralised Procedure between 1999 and 2017. For these products, a total of 24 additional approvals for line extensions or additional therapeutic indications were granted. Four products have been approved for orphan indications, including one approval ‘under exceptional circumstances’ and one ‘Conditional Marketing Authorisation’. Approvals for products in retina (36%) and glaucoma (28%) indications together accounted for the majority of authorisations, with trial end-points predominantly based on visual acuity and intraocular pressure parameters, respectively. Products were also approved for indications in ocular surface disease, inflammation, optic neuropathy and surgical adjuncts, with a range of functional and anatomical end-points.Conclusion:Approvals for ophthalmic medicines have been granted for a range of clinical indications, representing a considerable portion of available major therapeutics for practitioners. Benefit–risk assessments rely on clinical trial data demonstrating a clearly relevant patient benefit.

Allogeneic hematopoietic transplantation (allo-HCT) is a curative therapy for a variety of hematologic malignancies, primarily through immune-mediated clearance of malignant cells. This graft- versus-leukemia (GvL) effect is mediated by alloreactive donor T-cells against recipient malignant cells. Unfortunately, graft versus host disease is a potentially lethal complication of this procedure, also mediated by alloreactive donor T-cells against recipient normal tissues. Graft- versus-host disease (GVHD) remains a key contributor to nonrelapse mortality and long-term morbidity in patients undergoing allo-HCT. Reducing GVHD without interfering with – or ideally while enhancing – GvL, would improve outcomes and increase patient eligibility for allo-HCT. The JAK/STAT signaling pathway acts downstream of over 50 cytokines and is central to a wide variety of inflammatory pathways. These pathways play a role in the development and maintenance of GVHD throughout the disease process and within T-cells, B-cells, macrophages, neutrophils, and natural killer cells. Agents targeting JAK/STAT signaling pathways have shown clinical efficacy and gained US Food and Drug Administration approval for numerous diseases. Here, we review the preclinical and clinical evidence for the role of JAK/STAT signaling in the development and maintenance of GVHD and the utility of blocking agents at preventing and treating GVHD.

Background: Hypothermic therapy has been shown to have clinical efficacy in a variety of cardiovascular injuries including cardiac arrest and myocardial infarction.1 It is standard of care for the treatment of neonates with hypoxic-ischemic encephalopathy (HIE) and has shown improved outcomes with traumatic brain injury (TBI)2, and sports-related injuries. Additionally, in several anecdotal studies, cold therapy has been hypothesized to be equally as effective in limiting the damaging effects of the body’s response to mild traumatic brain injury, commonly known as concussion; but the primary limitation of these studies has been sample size.3, 4 Hypothesis/Purpose: This study is being conducted to quantify the clinical safety and efficacy of head and neck cooling when applied after mild traumatic brain injury (mTBI) among adolescents participating in sporting activities. Methods: A multi-center, prospective, randomized, non-blinded, dual-arm comparator study employing an adaptive design with two-phases: the 60-patient pilot study presented here, and the pivotal phase currently underway. After randomization, subjects in the standard of care arm receive brain rest. Subjects in the treatment group receive brain rest plus 30 minutes of cooling therapy at the initial and 72 hour visits. Primary endpoint: SCAT5 symptom severity score, evaluated from initial clinic visit through 4 weeks post injury. SCAT5 measured at initial visit (pre/post treatment, both arms), 72 hour visit (pre/post treatment for intervention arm, once for standard of care arm) and once at 10 day and 4 week follow up visits for both arms. Results: To evaluate primary endpoint, a Repeated Measures Analysis of Variance was conducted as intended for pivotal phase, with unstructured covariance and utilizing last observation carried forward technique. Dependent variable modelled as absolute change from initial SCAT5. Significant main effects and interaction effects noted (p-value < 0.01, < 0.01 and 0.02 respectively). To evaluate secondary endpoint, a Wilcoxon Rank Sum Test was conducted to examine potential differences in ImPACT Cognitive Efficiency Index, there was no evidence in the sample of significant differences (p-value = 0.600). All testing evaluated at alpha level of significance = 0.05. Conclusion: Preliminary results from pilot phase indicate significant treatment effects that change differently over time, depending on group. Pivotal phase to determine efficacy is currently underway. Tables/Figures: Table 1.1. Summary Statistics for Baseline Demographics and Clinical Outcomes; Repeated Measures ANOVA Results Summary Statistics Standard of Care Arm (n = 27) Treatment Arm (n = 28) Mean (SD) Min/Max Mean (SD) Min/Max Age at Consent (yrs) 14.3 (1.4) 12.0/17.0 14.7 (1.6) 12.0/17.0 Height 167.9 (9.6) 141.0/184.9 169.1 (9.2) 151.5/188.0 Weight 66.9 (16.6) 40.1/105.0 66.1 (17.6) 36.7/116.2 SCAT5 Absolute Differences Baseline - Time 1 (Initial Visit, Post Tx Score) 0.9 (14.2) -40.0/33.0 -13.2 (13.0) -48.0/7.0 Baseline - Time 2 (72 Hr Visit, Pre Tx Score) -2.6 (9.6) -21.0/19.0 -11.8 (12.1) -40.0/7.0 Baseline - Time 3 (72 Hr Visit, Post Tx Score) -3.7 (12.7) -40.0/19.0 -19.2 (14.0) -54.0/0.0 Baseline - Time 4 (10 Day Visit) -13.9 (14.9) -45.0/15.0 -19.8 (13.6) -55.0/4.0 Baseline - Time 5 (4 Wk Visit) -22.7 (20.3) -63.0/12.0 -23.4 (17.3) -76.0/4.0 Repeated Measures ANOVA Post Hoc Pairwise Analyses: SCAT5 Mean Difference Between Groups (95% Confidence Interval) Baseline - Time 1 (Initial Visit, Post Tx Score) 14.1 (6.7, 21.4) Baseline - Time 2 (72 Hr Visit, Pre Tx Score) 9.2 (3.3, 15.1) Baseline - Time 3 (72 Hr Visit, Post Tx Score) 15.5 (8.2, 22.8) Baseline - Time 4 (10 Day Visit) 5.8 (-1.9, 13.5) Baseline - Time 5 (4 Wk Visit) 0.7 (-9.5, 10.9) Figure 1.2. References: The effect of mild induced hypothermia on outcomes of patients after cardiac arrest: a systematic review and meta-analysis of randomized controlled trials. Zhang et al. Critical Care (2015) 19:417.Therapeutic hypothermia for acute brain injuries. Andresen et al. Scandinavian Journal of trauma, Resuscitation and Emergency Medicine (2015) 23:42.The effect of selective head-neck cooling on physiological and cognitive functions in healthy volunteers. Jackson et al. Translational Neuroscience (2015) 6:131.Neurobiological effect of selective brain cooling after concussive injury. Walter et al. Brain imaging and behavior (2018) 2:891.

Objectives: To evaluate the clinical efficacy of smartphone-assisted self-rehabilitation in patients with frozen shoulder. Design: A single-center, randomized controlled trial. Setting: Orthopedic department of a university hospital. Subjects: A total of 84 patients with frozen shoulder were recruited. Intervention: Patients were randomly divided into two groups: a smartphone-assisted exercise group ( n = 42) and a conventional self-exercise group ( n = 42). The study was performed over three months, during which each group performed home-based rehabilitation. Main measures: Visual analogue scale for pain and passive shoulder range of motion were assessed at baseline and after 4, 8, and 12 weeks of treatment. Technology Acceptance Model–2 and Usefulness, Satisfaction, and Ease of Use scores were evaluated in the smartphone group. Results: Initial visual analogue scale for pain of the smartphone group was 6.0 ± 2.2 and ended up with 1.8 ± 2.5 after 12 weeks, whereas the self-exercise group showed 5.8 ± 2.3 for the baseline visual analogue scale for pain and 2.2 ± 1.7 at the end. Significant time-dependent improvements in all measured values were observed in both groups (all Ps Conclusion: There was no difference between home-based exercise using a smartphone application and a conventional self-exercise program for the treatment of frozen shoulder in terms of visual analogue scale for pain and range of motions.

Objective To compare the clinical efficacy of cyclophosphamide (CTX) and cyclosporine A (CSA) in initial treatment of children with steroid-resistant nephrotic syndrome (SRNS). Methods Prospectively maintained databases were reviewed to retrospectively compare two cohorts with SRNS that received peroral administration of 2 to 2.5 mg/kg/d CTX for 3 to 6 months or 1 to 5 mg/kg/d CSA for 2 years until the primary analysis cut-off date during 2007 to 2011. The time to first on-study relapse of SRNS was the primary endpoint. The effective rate was the second endpoint. Results A total of 127 children with SRNS were included (CTX-treated cohort: n = 62; CSA-treated cohort: n = 65), with a mean 5-year follow-up. CTX-treated children showed a significantly delayed time to first on-study relapse of SRNS compared with CSA-treated children (hazard ratio 0.66, 95% confidence interval 0.32–1.75). The relapse rate (rate/year) in CTX-treated children (1.1 ± 0.1) at the 24-month follow-up was significantly higher than that with CSA (0.4 ± 0.2). This difference persisted until the final follow-up. Conclusions CSA is associated with a significantly lower relapse rate and significantly higher effective rate compared with CTX, especially in children with minimal change disease.

BackgroundTotal shoulder arthroplasty has shown good clinical efficacy in treating primary and secondary degenerative conditions of the glenohumeral joint. Glenoid loosening, however, remains the commonest cause of failure. The purpose of this study was to investigate the rate of radiographic periprosthetic lucency associated with the use of an uncemented, pegged, metal-backed polyethylene glenoid component.Materials and methodsA retrospective, single-centre study using the Epoca (Synthes, Paoli, Pennsylvania) metal-backed glenoid component. Operations were performed by two experienced consultant upper limb surgeons. Radiographs were analysed for immediate post-operative component seating and periprosthetic radiolucent lines at predefined regular post-operative intervals. Intra- and inter-observer reliability was assessed to improve validity of results.ResultsMean age and follow-up was 72 (48–91) years and 2.5 years (2–5), respectively. Main indications for total shoulder arthroplasty were primary osteoarthritis, rheumatoid arthritis, revision for failed hemi-arthroplasty and acute fracture. Ninety-six per cent of components were completely seated post-operatively. Fifty-four (95%) of the 57 shoulders had no periprosthetic radiolucent lines at most recent follow-up. Complete post-operative glenoid seating was significantly associated with the absence of later periprosthetic radiolucency (p ConclusionThis study reports low early radiolucency rates with the pegged, uncemented, metal-backed polyethylene glenoid prosthesis used. Excellent post-operative glenoid seating is associated with a significantly lower rate of radiolucency. Longer follow-up data are required to confirm these early promising results. Level of evidence: Therapeutic, level IV.

Background/aim Mesenteric venous thrombosis is a rare lethal disease. The main aim of the present study was to evaluate clinical efficacy and safety of direct oral anticoagulants and vitamin K antagonists in mesenteric venous thrombosis patients. Methods Retrospective study of 102 mesenteric venous thrombosis patients treated between 2004 and 2017 at a center with a conservative medical first approach. Median clinical follow-up was 4 years. Results Computed tomography showed successful recanalization of thrombosis in 71% of patients on vitamin K antagonists and 69% of patients on direct oral anticoagulants ( p = 0.88). Overall major and esophageal variceal bleeding rate was 14.7% and 2.9%, respectively. No difference in major bleeding ( p = 0.54) was found between vitamin K antagonists and direct oral anticoagulants. No mesenteric venous thrombosis recurrence occurred during follow-up, and one venous thromboembolism occurred after cessation of anticoagulation. Conclusion Anticoagulation with direct oral anticoagulants and vitamin K antagonists was efficient in patients with mesenteric venous thrombosis. Bleeding complications was a concern during treatment in both groups.

Traditional metronidazole dosing regimens utilize an every 8 h dosing strategy to treat anaerobic and mixed anaerobic infections. However, pharmacokinetic data demonstrate that the half-life of metronidazole is 8–12 h and blood levels at 12 h exceed the in vitro minimum inhibitory concentration (MIC) for most anaerobic infections. The primary objective of this study was to evaluate the frequency of clinical cure among patients who received metronidazole every 12 h compared with those who received an every 8 h frequency. Secondary endpoints included duration of antibiotics, hospital length of stay, escalation of antibiotic therapy, microbiologic cure, and mortality. Methods: This retrospective, single-center, pre–post intervention study of 200 patients between June 2014 to July 2016. Results: No significant differences in clinical cure for every 12 h versus every 8 h metronidazole dosing regimens (85% for both groups, p = 1.00) were found. There were no differences in any of the secondary endpoints, with a mean duration of antibiotic therapy being 5.9 versus 5.8 days and a hospital length of stay averaging 8.1 versus 6.7 days for the 12- and 8-h dosing groups, respectively ( p > 0.05). Discussion: Findings validate pharmacokinetic data suggesting that an extended metronidazole dosing interval effectively treats anaerobic infections.

Background: Diphenylcyclopropenone (DPCP) immunotherapy for viral warts has been used for many years, but no studies have analyzed the treatment effects of DPCP alone, without the use of conventional therapy before immunotherapy. Objectives: We evaluated clinical efficacy of DPCP monotherapy compared to cryotherapy and pulsed dye laser (PDL) therapy. We also assessed the impact of initial sensitization on clinical response. Methods: We retrospectively analyzed the medical records of 250 patients with multiple viral warts between January 2008 and December 2015. Results: The DPCP-only group (n = 43) showed a lower clinical response (75.6%) than the cryotherapy-only group (n = 171, 89.8%, P < .01) and PDL-only group (n = 36, 90.3%, P < .01). The positive clinical response was 76.3% (119/156) in the successful sensitization group (n = 21) and 74.4% in the failed sensitization group ( P = .870). Conclusions: DPCP monotherapy has a lower clinical response than conventional therapy. Initial sensitization to DPCP does not predict a failed response with continued immunotherapy for viral warts.

Background. Constraint-induced movement therapy (CIMT) is a method of physical rehabilitation that has demonstrated clinical efficacy in patients with chronic stroke, cerebral palsy, and multiple sclerosis (MS). Objective. This pilot randomized controlled trial tested whether CIMT can also induce increases in white matter integrity in patients with MS. Methods. Twenty adults with chronic hemiparetic MS were randomized to receive either CIMT or complementary and alternative medicine (CAM) treatment (reported in the first article of this pair). Structural white matter change was assessed by tract-based spatial statistics (TBSS); measures included fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Results. CIMT and CAM groups did not differ in pretreatment disability or expectancy to benefit. As noted in the companion paper, the motor activity log (MAL) improved more after CIMT than CAM ( P < .001); the within-group effect size for CIMT was 3.7 (large d′ = 0.57), while for CAM it was just 0.7. Improvements in white matter integrity followed CIMT and were observed in the contralateral corpus callosum (FA, P < .05), ipsilateral superior occipital gyrus (AD, P < .05), ipsilateral superior temporal gyrus (FA, P < .05), and contralateral corticospinal tract (MD and RD, P < .05). Conclusion. CIMT produced a very large improvement in real-world limb use and induced white matter changes in patients with hemiparetic MS when compared with CAM. The findings suggest in preliminary fashion that the adverse changes in white matter integrity induced by MS might be reversed by CIMT. Clinical trial registration number: ClinicalTrials.gov (NCT01081275)

Gene-engineered T-cell therapies have the potential to revolutionize the treatment of cancer. These therapies have shown exceptional clinical efficacy specifically in the field of B-cell malignancies and the first products (Kymriah™ and Yescarta™) have recently been approved in the United States for specific indications. The power of these treatments is also linked with a distinct set of toxicities both predicted and unpredicted, including off-tumor activity, cytokine release syndromes, and neurotoxicity, occasionally with fatal consequences. As these therapies begin to reach more patients, it is critical to develop the nonclinical tools to adequately determine the mechanisms driving these toxicities, to assess the safety risks of candidate products, and to develop strategies for safety management.

Background In recent years, intersphincteric resection (ISR) has been increasingly used to replace abdominoperineal resection (APR) in the surgical treatment of ultra-low rectal cancer. Aim This study was to compare the clinical efficacy of ISR and APR. Methods Between 2012 and 2018, 74 consecutive patients with ultra-low rectal cancer underwent ISR or APR in our medical center. A retrospective comparison of these 2 procedures was performed. Results A total of 43 patients underwent ISR and 31 underwent APR were included in the study. No significant differences were found between 2 groups in gender, age, BMI, and ASA score. Intersphincteric resection group showed shorter operative time ( P = .02) and less blood loss ( P = .001). Hospital stays, time to soft diet, and postoperative 30-day complications were not significantly different between the 2 groups. R0 resection achieved 100% in both the groups. As for the long-term outcomes, the survival and recurrence rate were similar between 2 groups. Moreover, the LARS and Wexner score showed that the postoperative anal function after ISR were satisfactory. Conclusion This study suggested that ISR was feasible and safe for selected patients with ultra-low rectal cancer, with clinically superior outcomes in select patients (small tumors/further from the anal verge) and similar oncological outcomes to APR, and the anal functional outcomes after ISR were acceptable.