A fatal case of bortezomib‐induced lung toxicity in a young adult heart transplant recipient

Bortezomib is approved for the treatment of multiple myeloma but increasingly used in heart transplant (HTx) recipients with antibody‐mediated rejection (AMR). Severe pulmonary toxicity is a rare complication in multiple myeloma patients treated with bortezomib, but has not been described in a solid organ transplant recipient. A 20‐year‐old man 7 years post‐HTx presented with acute rejection with hemodynamic compromise. Endomyocardial biopsy showed mixed rejection (ISHLT grade 2R‐3R acute cellular rejection (ACR) and pAMR 1 (I+) with diffuse C4d staining). Two new high MFI circulating MHC class‐II donor‐specific antibodies (DSA) were detected. Treatment included corticosteroids, antithymocyte globulin, plasmapheresis, IVIG, rituximab, and bortezomib (1.3 mg/m²). Due to rebound in DSA, a second course of bortezomib was started. Thrombocytopenia and peripheral neuropathy prompted a 50% dose reduction during the 2nd course. Shortly after the 3rd reduced dose, the patient developed hypoxemic respiratory failure. Bronchoscopy revealed pulmonary hemorrhage with negative infectious studies. Chest CT showed bilateral parenchymal disease with bronchiectasis and alveolar bleeding. Despite treatment with high‐dose steroids, severe ARDS ensued with multisystem organ failure. The patient expired 23 days after the final dose of bortezomib. Post‐mortem lung histology revealed diffuse alveolar damage, pulmonary fibrosis, and hemorrhage. Cardiac histology showed resolving/residual ACR 1R and pAMR 1 (I+). While rare, bortezomib‐induced lung toxicity (BILT) can occur in HTx recipients and can carry a high risk of mortality. Drug reaction and immediate drug withdrawal should be considered in patients who develop respiratory symptoms, though optimal management of BILT is unclear.     

Debugging Adaptive Deep Brain Stimulation for Parkinson's Disease

Deep brain stimulation (DBS) is a successful treatment for patients with Parkinson's disease. In adaptive DBS, stimulation is titrated according to feedback about clinical state and underlying pathophysiology. This contrasts with conventional stimulation, which is fixed and continuous. In acute trials, adaptive stimulation matches the efficacy of conventional stimulation while delivering about half the electrical energy. The latter means potentially fewer side-effects. The next step is to determine the long-term efficacy, efficiency, and side-effect profile of adaptive stimulation, and chronic trials are currently being considered by the medical devices industry. However, there are several different approaches to adaptive DBS, and several possible limitations have been highlighted. Here we review the findings to date to ascertain how and who to stimulate in chronic trials designed to establish the long-term utility of adaptive DBS. © 2020 International Parkinson and Movement Disorder Society     

Long-term outcomes of en-bloc renal transplantation from paediatric donors into adult recipients

Introduction

Transplant units are exploring strategies to increase the availability of donor kidneys. The use of en-bloc kidney transplantation (EBKT) from paediatric donors represents one potential solution. We present our long-term experience with paediatric EBKT among adult recipients.

The Axillary View Typically Does Not Contribute to Decision Making in Care for Proximal Humeral Fractures

Background

Convention dictates that an axillary view be obtained when evaluating proximal humerus fractures (PHF). However, the axillary view is frequently omitted because of pain and technical considerations. Furthermore, its diagnostic utility is unclear in this setting.

Questions/Purposes

The purpose of this study was to (1) determine the rate of obtaining an adequate axillary X-ray and complete shoulder series at a level I trauma center, (2) understand the cost of ordering and attempting an axillary radiograph, and (3) determine if axillary radiographs influence the management of PHF.

Patients and Methods

PHF treated between 2009 and 2011 that were ordered for an AP, scapular Y, and axillary view was identified. The types of radiographs actually obtained were recorded. The cost of obtaining three views and a single view of the shoulder with X-ray was determined. Lastly, three surgeons reviewed 42 PHF, both with and without an axillary view (AV), and treatment recommendations were compared.

Results

30% of PHF in this series had an adequate axillary view, and 14% received a complete trauma series. No factors could be identified that were associated with successfully obtaining an axillary view. Reviewers demonstrated substantial intraobserver reliability (κ = 0.759–0.808) regarding treatment recommendations for PHF with and without the axillary view. The addition of the AV had minimal influence on treatment recommendations.

Conclusion

Considering that the axillary view for PHF is painful, labor-intensive, costly, and does not appear to provide additional diagnostic value, orthopedic surgeons can consider foregoing the use of the axillary view when evaluating and treating PHF, particularly if other advanced imaging is utilized.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-015-9445-9) contains supplementary material, which is available to authorized users.     

Differential effect of body mass index on pediatric heart transplant outcomes based on diagnosis

The impact of nutritional status on HTx waitlist mortality in children is unknown, and there are conflicting data regarding the role of nutrition in post‐HTx survival. This study examined the influence of nutrition on waitlist and post‐HTx outcomes in children. Children 2–18 yr listed for HTx from 1997 to 2011 were identified from the OPTN database and stratified by BMI percentile. Multivariable logistic regression evaluated the influence of BMI on waitlist mortality. Cox proportional hazard regression assessed the impact of BMI on post‐HTx mortality. When all 2712 patients were analyzed, BMI did not impact waitlist, one‐, or five‐yr mortality. However, when stratified by diagnosis, BMI > 95% (AOR 1.96; 95% CI 1.24, 3.09) and BMI < 1% (AOR 2.17; 95% CI 1.28, 3.68) were independent risk factors for waitlist mortality in patients with CM. BMI did not impact waitlist mortality in CHD and did not impact post‐HTx outcomes, regardless of diagnosis. BMI > 95% and BMI < 1% are independent risk factors for waitlist mortality in patients with CM, but not CHD. This suggests differing risk factors based on disease etiology, and an individualized approach to risk assessment based on diagnosis may be warranted.