Tocilizumab for the Management of Corticosteroid-Resistant Mild to Severe Graves’ Ophthalmopathy,a Report of Three Cases

ABSTRACT

Purpose: To discuss the use of tocilizumab in mild to severe Graves’ ophthalmopathy as corticosteroid-adjunctive therapy.

Methods: Retrospective case reports.

Results: Three patients with corticosteroid-resistant or advanced diplopia-associated Graves’ ophthalmopathy were subsequently treated with monthly intravenous tocilizumab at a dose of 8 mg/kg. None reported a past or present history of dysthyroidism. The adjunction of interleukin-6-receptor monoclonal antibody treatment was associated with a significant improvement in ocular symptoms, notably diplopia and proptosis, and functional prognosis in all patients, with one relapse approximately two months after the end of the treatment.

Conclusion: These clinical reports confirm the relative efficacy and tolerability profile of intravenous tocilizumab in severe or corticosteroid-resistant Graves’ ophthalmopathy.     

Prolonged mechanical ventilation after cardiac surgery: substudy of the Transfusion Requirements in Cardiac Surgery III trial

Purpose

Prolonged mechanical ventilation (MV) is a major complication following cardiac surgery. We conducted a secondary analysis of the Transfusion Requirements in Cardiac Surgery (TRICTS) III trial to describe MV duration, identify factors associated with prolonged MV, and examine associations of prolonged MV with mortality and complications.

Methods

Four thousand, eight hundred and nine participants undergoing cardiac surgery at 71 hospitals worldwide were included. Prolonged MV was defined based on the Society of Thoracic Surgeons definition as MV lasting 24 hr or longer. Adjusted associations of patient and surgical factors with prolonged MV were examined using multivariable logistic regression. Associations of prolonged MV with complications were assessed using odds ratios, and adjusted associations between prolonged MV and mortality were evaluated using multinomial regression. Associations of shorter durations of MV with survival and complications were explored.

Results

Prolonged MV occurred in 15% (725/4,809) of participants. Prolonged MV was associated with surgical factors indicative of complexity, such as previous cardiac surgery, cardiopulmonary bypass duration, and separation attempts; and patient factors such as critical preoperative state, left ventricular impairment, renal failure, and pulmonary hypertension. Prolonged MV was associated with perioperative but not long-term complications. After risk adjustment, prolonged MV was associated with perioperative mortality; its association with long-term mortality among survivors was weaker. Shorter durations of MV were not associated with increased risk of mortality or complications.

Conclusion

In this substudy of the TRICS III trial, prolonged MV was common after cardiac surgery and was associated with patient and surgical risk factors. Although prolonged MV showed strong associations with perioperative complications and mortality, it was not associated with long-term complications and had weaker association with long-term mortality among survivors.

Study registration

www.ClinicalTrials.gov (NCT02042898); registered 23 January 2014. This is a substudy of the Transfusion Requirements in Cardiac Surgery (TRICS) III trial.

     

Effect of reverse manual wheelchair propulsion on shoulder kinematics,kinetics and muscular activity in persons with paraplegia

Objective: Shoulder pain after spinal cord injury (SCI) is attributed to increased mobility demands on the arms and negatively impacts independence and quality of life. Repetitive superior and posterior shoulder joint forces produced during traditional wheelchair (WC) locomotion can result in subacromial impingement if unopposed, as with muscular fatigue or weakness. ROWHEELS^® (RW), geared rear wheels that produce forward WC movement with backward rim pulling, could alter these forces.

Design: Cross sectional.

Setting: Research laboratory at a rehabilitation hospital.

Participants: Ten manual WC users with paraplegia.

Outcome measures: Propulsion characteristics and right upper extremity/trunk kinematics and shoulder muscle activity were collected during ergometer propulsion: (1) self-selected free speed reverse propulsion with RW, (2) matched-speed reverse (rSW), and (3) forward propulsion (fSW) with instrumented Smartwheels (SW). Inverse dynamics using right-side SW rim kinetics and kinematics compared shoulder kinetics during rSW and fSW.

Results: Free propulsion velocity, cycle distance and cadence were similar during RW, rSW and fSW. Overall shoulder motion was similar except that peak shoulder extension was significantly reduced in both RW and rSW versus fSW. Anteriorly and inferiorly directed SW rim forces were decreased during rSW versus fSW propulsion, but posteriorly and superiorly directed rim forces were significantly greater. Superior and posterior shoulder joint forces and flexor, adductor, and external rotation moments were significantly less during rSW, without a significant difference in net shoulder forces and moments. Traditional propulsive-phase muscle activity was significantly reduced and recovery-phase muscle activity was increased during reverse propulsion.

Conclusion: These results suggest that reverse propulsion may redirect shoulder demands and prevent subacromial impingement, thereby preventing injury and preserving independent mobility for individuals with paraplegia.     

Positive association between cerebral grey matter metabolism and dopamine D2/D3 receptor availability in healthy and schizophrenia subjects: An 18F-fluorodeoxyglucose and 18F-fallypride positron emission tomography study

Abstract

Objectives: Overlapping decreases in extrastriatal dopamine D₂/D₃-receptor availability and glucose metabolism have been reported in subjects with schizophrenia. It remains unknown whether these findings are physiologically related or coincidental.

Methods: To ascertain this, we used two consecutive ¹⁸F-fluorodeoxyglucose and ¹⁸F-fallypride positron emission tomography scans in 19 healthy and 25 unmedicated schizophrenia subjects. Matrices of correlations between ¹⁸F-fluorodeoxyglucose uptake and ¹⁸F-fallypride binding in voxels at the same xyz location and AFNI-generated regions of interest were evaluated in both diagnostic groups.

Results: ¹⁸F-fluorodeoxyglucose uptake and ¹⁸F-fallypride binding potential were predominantly positively correlated across the striatal and extrastriatal grey matter in both healthy and schizophrenia subjects. In comparison to healthy subjects, significantly weaker correlations in subjects with schizophrenia were confirmed in the right cingulate gyrus and thalamus, including the mediodorsal, lateral dorsal, anterior, and midline nuclei. Schizophrenia subjects showed decreased D₂/D₃-receptor availability in the hypothalamus, mamillary bodies, thalamus and several thalamic nuclei, and increased glucose uptake in three lobules of the cerebellar vermis.

Conclusions: Dopaminergic system may be involved in modulation of grey matter metabolism and neurometabolic coupling in both healthy human brain and psychopathology. Hyperdopaminergic state in untreated schizophrenia may at least partly account for the corresponding decreases in grey matter metabolism.     

Empowering future physicians to advocate for health equity: A blueprint for a longitudinal thread in undergraduate medical education

Abstract

In light of a growing body of evidence demonstrating pervasive health disparities, medical schools are increasingly incorporating educational programs on social medicine in undergraduate and graduate medical curricula. In 2015, we significantly restructured the cultural competency instruction for medical students at our institution, focusing on achieving greater health equity through caring for vulnerable populations and acknowledging and addressing bias and stereotyping. In order to facilitate educational sustainability while students were immersed in clinical care, a key element of our approach included extending teaching into the clerkship year. The resulting longitudinal thread, Health Equity and Social Justice, empowers future physicians with the knowledge and skills to work towards greater health equity. This article discusses the lessons learned in the implementation of this novel educational program. Our approach can serve as a model for other institutions considering similar instructional reform.     

Does ablation of atrial fibrillation at the time of septal myectomy improve survival of patients with obstructive hypertrophic cardiomyopathy?

ObjectiveTo evaluate the outcomes after septal myectomy in patients with obstructive hypertrophic cardiomyopathy according to atrial fibrillation and surgical ablation of atrial fibrillation.MethodsWe reviewed patients with obstructive hypertrophic cardiomyopathy who underwent septal myectomy at the Mayo Clinic from 2001 to 2016. History of atrial fibrillation was obtained from patient histories and electrocardiograms. All-cause mortality was the primary end point.ResultsA total of 2023 patients underwent septal myectomy, of whom 394 (19.5%) had at least 1 episode of atrial fibrillation preoperatively. Among patients with atrial fibrillation, 76 (19.3%) had only 1 known episode, 278 (70.6%) had recurrent paroxysmal atrial fibrillation, and 40 (10.2%) had persistent atrial fibrillation. Surgical ablation was performed in 190 patients at the time of septal myectomy, including 148 with pulmonary vein isolation and 42 with the classic maze procedure. Among all patients, operative mortality was 0.4%, and there were no early deaths in patients undergoing surgical ablation. Over a median follow-up of 5.6 years, patients with preoperative atrial fibrillation had increased mortality (hazard ratio, 1.36; 95% confidence interval, 0.97-1.91; P = .070) after multivariable adjustment for comorbidities. When considering the impact of atrial fibrillation with or without surgical treatment, the adjusted hazard ratio for mortality in patients undergoing ablation compared with no ablation was 0.93 (95% confidence interval, 0.52-1.69; P = .824).ConclusionsAtrial fibrillation is present preoperatively in one-fifth of patients with obstructive hypertrophic cardiomyopathy undergoing myectomy and showed a trend toward higher all-cause mortality. Survival of patients undergoing septal myectomy with preoperative atrial fibrillation was similar between those who did and did not receive concomitant surgical ablation.     

Comparison of Patch Materials for Pulmonary Artery Reconstruction

Graphical abstract summarizing the overall results of our study comparing reintervention for a main or central branch pulmonary artery reconstruction site and various patch materials. Autologous pericardium was associate with the lowest reintervention and was free. Multivariable analysis demonstrated lack of superiority of homograft branch patch, which clearly has a much higher cost.

1. Download : Download high-res image (131KB)
2. Download : Download full-size image

     

Chlorthalidone with potassium citrate decreases calcium oxalate stones and increases bone quality in genetic hypercalciuric stone-forming rats

1. Download : Download high-res image (331KB)
2. Download : Download full-size image

     

Ospemifene plus fractional CO2 laser: a powerful strategy to treat postmenopausal vulvar pain

Abstract

This study is a single-center, retrospective analysis of postmenopausal women presenting with dyspareunia and vulvar pain, aiming to evaluate relative effectiveness of vestibular CO₂ laser therapy as a treatment. Three monthly sessions of laser were performed to each patient and thereafter a three-months follow-up was stablished. A total number of 72 patients undergoing vestibular laser treatment were recruited from patient files in the period between 2016 and 2018. Among these, 39 women also received a concomitant treatment with ospemifene (60?mg/day) during the study period. There was a statistically significant reduction of all the symptoms in both groups up to the three month follow-up. Regarding dryness and dyspareunia, the relief tent to be more prominent in the ospemifene?+?laser group at all follow-ups and remained statistically significant at three-month follow-up. Specifically, vestibular dryness was significantly lower in the ospemifene?+?laser group compared with the laser treatment group (?87% vs???34%, respectively), and the vestibular health score started declining faster in the ospemifene?+?laser group. Although, additional research is needed to understand the mechanism of action, our data shows that a combination regimen of laser and ospemifene may improve clinical effectiveness for long-term treatment of symptoms associated with the under-recognized genitourinary syndrome of menopause.