Effective treatment with rituximab for the maintenance of remission in frequently relapsing minimal change disease

AIM: Treatment of frequently relapsing or steroid-dependent minimal change disease (MCD) in children and adults remains challenging. Glucocorticoids and/or other immunosuppressive agents are the mainstay of treatment, but patients often experience toxicity from prolonged exposure and may either become treatment dependent and/or resistant. Increasing evidence suggests that rituximab (RTX) can be a useful alternative to standard immunosuppression and allow withdrawal of maintenance immunosuppressants; however, data on optimal treatment regimens, long-term efficacy and safety are still limited. METHODS: We undertook a prospective study of RTX to allow immunosuppression minimization in 15 young adults with frequently relapsing or steroid-dependent, biopsy-proven MCD. All patients were in remission at the start of treatment and on a calcineurin inhibitor. Two doses of RTX (1 gr) were given 6 months apart. A subset of patients also received an additional dose 12 months later, in order to examine the benefit of re-treatment. Biochemical and clinical parameters were monitored over an extended follow-up period of up to 43 months. RESULTS: Median steroid-free survival after RTX was 25 months (range 4-34). Mean relapse frequency decreased from 2.60 ± 0.28 to 0.4 ± 0.19 (P < 0.001) after RTX. Seven relapses occurred, five of which (71%) when CD19 counts were greater than 100 µ. Immunoglobulin levels remained unchanged, and no major side effects were observed throughout the follow-up period. CONCLUSIONS: Rituximab therapy is effective at maintaining prolonged steroid-free remission and reducing relapse frequency in this group of patients. Our study lends further support for the role of RTX in the treatment of patients with frequently relapsing or steroid-dependent MCD

Lack of regional pathways impact on surgical delay: Analysis of the Orthopaedic Trauma Hospital Outcomes-Patient Operative Delays (ORTHOPOD) study.

INTRODUCTION: Current practice following injury within the United Kingdom is to receive surgery, at the institution of first contact regardless of ability to provide timely intervention and inconsiderate of neighbouring hospital resource and capacity. This can lead to a mismatch of demand and capacity, delayed surgery and stress within hospital systems, particularly with regards to elective services. We demonstrate through a multicentre, multinational study, the impact of this at scale. METHODOLOGY: ORTHOPOD data collection period was between 22/08/2022 and 16/10/2022 and consisted of two arms. Arm 1 captured orthopaedic trauma caseload and capacity in terms of sessions available per centre and patients awaiting surgery per centre per given week. Arm 2 recorded patient and injury demographics, time of decision making, outpatient and inpatient timeframes as well as time to surgery. Hand and spine cases were excluded. For this regional comparison, regional trauma networks with a minimum of four centres enroled onto the ORTHOPOD study were exclusively analysed. RESULTS: Following analysis of 11,202 patient episodes across 30 hospitals we found no movement of any patient between hospitals to enable prompt surgery. There is no current system to move patients, between regional centres despite clear discrepancies in workload per capacity across the United Kingdom. Many patients wait for days for surgery when simple transfer to a neighbouring hospital (within 10 miles in many instances) would result in prompt care within national guidelines. CONCLUSION: Most trauma patients in the United Kingdom are managed exclusively at the place of first presentation, with no consideration of alternative pathways to local hospitals that may, at that time, offer increased operative capacity and a shorter waiting time. There is no oversight of trauma workload per capacity at neighbouring hospitals within a regional trauma network. This leads to a marked disparity in waiting time to surgery, and subsequently it can be inferred but not proven, poorer patient experience and outcomes. This inevitably leads to a strain on the overall trauma system and across several centres can impact on elective surgery recovery. We propose the consideration of inter-regional network collaboration, aligned with the Major Trauma System

The Effect of Prone and Supine Limb Positioning on the Radiographic Evaluation of Posterolateral Plate Fixation of the Posterior Malleolus.

AIM: To facilitate the posterolateral approach to the posterior malleolus patients are often positioned prone initially, then turned supine to complete fixation at the medial malleolus. We sought to define observed differences in the radiographic appearance of implants relative to the joint line, in prone and supine positions. METHODS: A 3.5 mm tubular plate and a 3.5 mm posterior distal tibial periarticular plate were applied sequentially to 3 individual cadaveric legs, via a posterolateral approach. The tubular plate was positioned to simulate buttress fixation and the posterolateral plate placed more distally. Each limb was secured on a custom jig and radiographs were taken on a mobile c-arm fluoroscopy machine with a calibration ball. A series of prone AP, supine PA and mortise radiographs were taken. Prone radiographs were also taken in different degrees of caudal tilt to simulate knee flexion which occurs in practice, during intraoperative positioning. Plate tip-joint line distances were measured and Mann-Whitney U tests performed. RESULTS: There was no statistically significant difference in plate tip-joint line distance when comparing equivalent prone and supine views (PA/AP or mortise). However, significant differences in apparent implant position were noted with alterations in caudal tilt. When taking a prone image, when the knee is flexed to 20 degrees, the plate tip will appear 6.5-8.5 mm more proximal than in the equivalent supine image where the knee is extended and the fluoroscopy beam is orthogonal to the anatomic axis of the tibia. CONCLUSION: Observed differences in radiographic appearance of metalwork in the prone and supine position are most likely due to knee flexion and the resulting variation in the angle of the fluoroscopy beam, rather than projectional differences between supine and prone views. Surgeons should be alert to this when analysing intraoperative images

Exploring associations between positive and negative valanced parental comments about adolescents' bodies and eating and eating problems : a community study

Background: Adolescence is a time of rapid emotional and physical development when foundational self-concepts (including beliefs about one’s weight and shape) are established. Parents are key influencers of adolescent beliefs and behaviours. This study aimed to investigate associations between perceived positive and negative parental comments on weight/shape and eating, with sons’ and daughters’ psychological distress and eating disorder cognitions (EDCs). Methods: A representative mixed-sex sample of 2204 Australian adolescents (12–19 years) from the EveryBODY Study completed an online survey exploring eating behaviours, psychological wellbeing and experiences of parental comments regarding weight, shape and eating behaviours. Results: Correlation analyses revealed that adolescents’ reports of perceived positive parental comments on shape/ weight were significantly associated with lower psychological distress and EDCs only for daughters. All perceived negative parental comments on shape/weight or eating were associated with greater psychological distress and EDCs for both sons and daughters. In the final model of the regression analysis, only perceived parental negative shape/weight and maternal negative eating comments, adolescent stage and biological sex were significantly associated with EDCs. When known contributors such as BMI percentile and psychological distress were included in the regression model, adolescent stage and perceived negative paternal comments were no longer significantly associated with EDCs. Conclusions: Overall, results show perceived negative comments were associated with poorer adolescent mental health, both their specific EDCs and general distress. Findings highlight the importance of raising awareness of potential negative impacts within family systems of comments around weight/shape and eating in these key formative years

Schrodinger cat states prepared by Bloch oscillation in a spin-dependent optical lattice

We propose to use Bloch oscillation of ultra-cold atoms in a spin-dependent optical lattice to prepare schrodinger cat states. Depending on its internal state, an atom feels different periodic potentials and thus has different energy band structures for its center-of-mass motion. Consequently, under the same gravity force, the wave packets associated with different internal states perform Bloch oscillation of different amplitudes in space and in particular they can be macroscopically displaced with respect to each other. In this way, a cat state can be prepared.Comment: 4 pages, 3 figures; slightly modifie

Solitons in one-dimensional nonlinear Schr\"{o}dinger lattices with a local inhomogeneity

In this paper we analyze the existence, stability, dynamical formation and mobility properties of localized solutions in a one-dimensional system described by the discrete nonlinear Schr\"{o}dinger equation with a linear point defect. We consider both attractive and repulsive defects in a focusing lattice. Among our main findings are: a) the destabilization of the on--site mode centered at the defect in the repulsive case; b) the disappearance of localized modes in the vicinity of the defect due to saddle-node bifurcations for sufficiently strong defects of either type; c) the decrease of the amplitude formation threshold for attractive and its increase for repulsive defects; and d) the detailed elucidation as a function of initial speed and defect strength of the different regimes (trapping, trapping and reflection, pure reflection and pure transmission) of interaction of a moving localized mode with the defect.Comment: 12 pages, 10 figure

Impact of Excess Auditor Remuneration on the Cost of Equity Capital around the World

This study examines the relation between excess auditor remuneration and the implied required rate of return (IRR hereafter) on equity capital in global markets. We conjecture that when auditor remuneration is excessively large, investors may perceive the auditor to be economically bonded to the client, leading to a lack of independence. This perceived lack of independence increases the information risk associated with the credibility of financial statements, thereby increasing IRR. Consistent with this notion, we find that IRR is increasing in excess auditor remuneration, but only in countries with stronger investor protection. Finding evidence of a relation only in stronger investor protection countries is consistent with the more prominent role of audited financial statements for investors' decisions in these countries. In settings in which investors are less likely to rely on audited financial statements and instead rely on alternative sources of information (i.e., in countries with weaker investor protection), the impact of client-auditor bonding should have less of an effect on investors' decisions.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

The Open-Fracture Patient Evaluation Nationwide (OPEN) study : epidemiology of open fracture care in the UK.

AIMS: Understanding of open fracture management is skewed due to reliance on small-number lower limb, specialist unit reports and large, unfocused registry data collections. To address this, we carried out the Open Fracture Patient Evaluation Nationwide (OPEN) study, and report the demographic details and the initial steps of care for patients admitted with open fractures in the UK. METHODS: Any patient admitted to hospital with an open fracture between 1 June 2021 and 30 September 2021 was included, excluding phalanges and isolated hand injuries. Institutional information governance approval was obtained at the lead site and all data entered using Research Electronic Data Capture. Demographic details, injury, fracture classification, and patient dispersal were detailed. RESULTS: In total, 1,175 patients (median age 47 years (interquartile range (IQR) 29 to 65), 61.0% male (n = 717)) were admitted across 51 sites. A total of 546 patients (47.1%) were employed, 5.4% (n = 63) were diabetic, and 28.8% (n = 335) were smokers. In total, 29.0% of patients (n = 341) had more than one injury and 4.8% (n = 56) had two or more open fractures, while 51.3% of fractures (n = 637) occurred in the lower leg. Fractures sustained in vehicle incidents and collisions are common (38.8%; n = 455) and typically seen in younger patients. A simple fall (35.0%; n = 410) is common in older people. Overall, 69.8% (n = 786) of patients were admitted directly to an orthoplastic centre, 23.0% (n = 259) were transferred to an orthoplastic centre after initial management elsewhere, and 7.2% were managed outwith specialist units (n = 81). CONCLUSION: This study describes the epidemiology of open fractures in the UK. For a decade, orthopaedic surgeons have been practicing in a guideline-driven, network system without understanding the patient features, injury characteristics, or dispersal processes of the wider population. This work will inform care pathways as the UK looks to the future of trauma networks and guidelines, and how to optimize care for patients with open fractures.Cite this article: Bone Jt Open 2022;3(10):746-752

Experience with tacrolimus in children with steroid-resistant nephrotic syndrome

Children with steroid-resistant nephrotic syndrome (SRNS) are at risk of developing renal failure. We report here the results of a single-center retrospective observational study of the remission rate in pediatric patients with SNRS receiving tacrolimus. Serial renal biopsies from children on tacrolimus therapy were evaluated for tubulointerstitial fibrosis and transforming growth factor-β immunostaining. Of the 16 children with SRNS, 15 went into complete remission after a median of 120 days of therapy. Nine children were able to stop steroids, while the others were on tapering doses. Forty-seven percent had relapses, most of which were steroid-responsive. Serial renal biopsies were obtained from seven children after a median treatment duration of 24 months; two of these children had increased tubulointerstitial fibrosis and four showed increased transforming growth factor-β tissue staining. Children with worsening histological findings were younger. There was no significant association between tacrolimus exposure and biopsy changes, although the average trough level was higher in those children with worsening histological findings. In conclusion, tacrolimus may be a safe and effective alternative agent for inducing remission in children with SRNS. However, caution needs to be taken when prescribing this agent due to its narrow therapeutic index. Serial renal biopsies are necessary to check for subclinical nephrotoxicity, especially in younger children and those with higher trough levels