Recombinant human bone morphogenetic protein-2: adverse events reported to the Manufacturer and User Facility Device Experience database

Background context

Adverse effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) in spinal surgery have previously been observed. However, because of its size, scope, and nature, the US Food and Drug Administration’s database of postmarketing reports is useful for detecting new and unexpected safety concerns.

Purpose

To characterize adverse events reported to the FDA; to characterize off-label use of rhBMP-2.

Study design

Review of adverse events reported to the FDA after the use of rhBMP-2 (INFUSE Bone Graft) in spinal surgery.

Methods

The Manufacturer and User Facility Device Experience database was searched for the brand name “infuse bone graft,” for reports received from July 2, 2002, through August 31, 2011. Adverse events were reviewed, summarized, and classified by an MD. For each report, the most important clinical entity was identified as the principal adverse event. Off-label uses were summarized.

Results

Of 834 reports, four (0.5%) described procedures in which rhBMP-2 was used in accordance with the approved indication. Nearly half of all the reports, 370 (44.4%), stated that the patient required revision surgery or other invasive interventions to address the reported adverse event. Swelling, fluid collections, osteolysis, pain/radiculopathy, heterotopic bone, pseudarthrosis, surgical site infections and other wound complications, thromboembolic events, respiratory distress, cancer, and other events were reported.

Conclusions

Because of their duration, scope, and expense, prospective studies designed to estimate the risk of rare adverse events may be impractical. Despite its imperfections, postmarketing surveillance helps to narrow the focus by revealing patterns and prioritizing topics for further research. One should not extrapolate from these results to the rhBMP-2 experience as a whole; the findings reported here might not be representative. This analysis indicates that serious adverse events can occur after the use of rhBMP-2 in spinal surgery and raises many points that surgeons may wish to consider when deciding when and how to use this product in their patients.     

Extralobar Pulmonary Sequestration Mimicking an Adrenal Tumor

Pulmonary sequestration is a rare cystic malformation composed of bronchopulmonary tissue that is discontinuous from the tracheobronchial tree and has an anomalous systemic blood supply. We present a case of a 40-y-old male who presented with an extralobar pulmonary sequestration and underwent a laparoscopic retroperitoneal mass excision. Preoperative imaging revealed a large 11.3-cm retroperitoneal tumor consisting of a multiloculated cystic lesion. The patient was discharged home, and at 3-mo follow-up no complaints were reported.     

Stent Compression in Iliac Vein Compression Syndrome Associated with Acute Ilio-Femoral Deep Vein Thrombosis

ObjectiveThis study was conducted to evaluate stent compression in iliac vein compression syndrome (IVCS) and to identify its association with stent patency.ResultsAll of the stents used were laser-cut nitinol stents. The proportion of limbs showing significant stent compression was 33%. Fifty-six percent of limbs in the significant stent compression group developed stent occlusion. On the other hand, only 9% of limbs in the insignificant stent compression group developed stent occlusion. Significant stent compression was inversely correlated with stent patency (p < 0.001). The median patency period evaluated with Kaplan-Meier analysis was 20.0 months for patients with significant stent compression. Other factors including gender, age, and type of stent were not correlated with stent patency. Significant stent compression occurred most frequently (87.5%) at the upper end of the stent (ilio-caval junction).ConclusionSignificant compression of nitinol stents placed in IVCS highly affects stent patency. Therefore, in order to prevent stent compression in IVCS, nitinol stents with higher radial resistive force may be required.     

Fluoroscopy-Guided Lumbar Drainage of Cerebrospinal Fluid for Patients in Whom a Blind Beside Approach Is Difficult

ObjectiveTo evaluate the rates of technical success, clinical success, and complications of fluoroscopy-guided lumbar cerebrospinal fluid drainage.ResultsThe technical and clinical success rates were 99.0% (95/96) and 89.6% (86/96), respectively. The mean hospital stay for an external lumbar drain was 4.84 days. Nine cases of minor complications and eight major complications were observed, including seven cases of meningitis, and one retained catheter requiring surgical removal.ConclusionFluoroscopy-guided external lumbar drainage is a technically reliable procedure in difficult patients with failed attempts at a bedside procedure, history of lumbar surgery, difficulties in cooperation, or obesity.     

Relations Between Pathological Markers and Radioiodine Scan and 18F-FDG PET/CT Findings in Papillary Thyroid Cancer Patients With Recurrent Cervical Nodal Metastases

Purpose

The aim of this study was to investigate relationships between the immunohistochemical results and radioiodine scan and ¹⁸F-FDG PET findings in papillary thyroid cancer (PTC) patients with recurrent cervical nodal metastases.

Methods

A total of 46 PTC patients who had undergone a radioiodine scan and/or ¹⁸F-FDG PET/CT and a subsequent operation on recurrent cervical lymph nodes were enrolled. Twenty-seven patients underwent ¹⁸F-FDG PET/CT, 8 underwent radioiodine scans, and 11 underwent both scans. In all surgical specimens, the immunoexpressions of thyroglobulin (Tg), sodium-iodide symporter (NIS), glucose transporter 1 (Glut-1), and somatostatin receptor 1 and 2A (SSTR1 and SSTR2A) were assessed, and associations between these expressions and radioiodine scan and ¹⁸F-FDG PET findings were evaluated.

Results

Of the 38 patients who underwent ¹⁸F-FDG PET/CT, all patients with weak Tg expression had positive ¹⁸F-FDG uptake, while only 45 % of the patients with moderate or strong Tg expression showed positive uptake (p = 0.01). The proportion of patients with positive ¹⁸F-FDG uptake increased as the degree of Glut-1 expression with luminal accentuation increased. Of the 19 patients who underwent a radioiodine scan, the proportion with positive radioiodine uptake was greater among patients with strong NIS and SSTR2A expression than among patients expressing these markers at weak levels (p = 0.04 for all). All three patients with weak Tg expression were negative for radioiodine uptake.

Conclusion

The ¹⁸F-FDG uptakes of recurrent cervical nodes are related to strong Glut-1 expression with luminal accentuation and weak Tg expression, whereas radioiodine uptake is related to the strong expressions of NIS and SSTR2A.     

A Novel Surgical Technique for Neglected Volar Dislocation of the Lunate: Cases Report and Literature Review

Background

Treatments for chronic perilunate or lunate dislocations are very difficult and associated with poor prognoses. There is no established treatment method and are still many controversies.

Case Presentation

We reported three cases of chronic neglected lunate volar dislocation treated with a novel surgical technique. All three cases were males with wrist pain and tingling sensation. Radiographs confirmed chronic volar dislocation of the lunate. Open reduction was performed by combined volar and dorsal approaches. After anatomical reduction, scapholunate and lunotriquetral interosseous ligament reconstructions were performed with the palmaris longus tendon and synthetic tape. The patients had an uneventful postoperative period with satisfactory functional outcomes at the last follow-up.

Conclusions

We believe that open reduction and interosseous ligament reconstruction using the autogenous tendon and synthetic tape may be a valuable option for treating chronic volar dislocation of the lunate.     

Analysis and management of pathogens isolated from patients with complicated facial lacerations and abrasions

Plastic surgeons commonly encounter patients with facial lacerations and/or abrasions in the emergency room. If they are properly treated, facial wounds generally heal well without complications. However, infection can sometimes cause delayed wound healing. We performed wound culture for the early detection of infection and to promote the healing of infected facial wounds. We included 5033 patients with facial wounds who visited the emergency room of Kangnam Sacred Heart Hospital between January 2018 and February 2021. Among them, 104 patients underwent wound culture. We analysed the pathogens isolated and the patients' age, sex, wound site, mechanism of injury, wound healing time, time from injury to culture, time to culture results, and dressing methods used. Pathogens were isolated in slightly less than half of the patients (38.46%); among them, Staphylococcus epidermidis was the most common (47.5%). Methicillin-resistant coagulase-negative staphylococci were isolated in six (15%) patients. Patients with complicated wounds had a longer mean wound healing time (10.83 ± 5.91 days) than those with non-complicated wounds (6.06 ± 1.68 days). Wound culture of complicated facial wounds resulted in the isolation of various types of pathogens, including antibiotic-resistant bacteria and fungi. We recommend the use of wound culture for early detection of infection to prevent delayed wound healing.     

Tumour volume doubling time of molecular breast cancer subtypes assessed by serial breast ultrasound

Objectives

The aim of our study was to evaluate the tumour volume doubling time (TVDT) of molecular breast cancer subtypes by serial ultrasound (US).

Methods

Sixty-six patients (mean age, 50 years; range, 29–78 years) with invasive breast cancer underwent initial and follow-up breast US examinations (at least three months apart) with no intervention. TVDT was determined using the tumours’ greatest dimensions in two orthogonal planes. The results were compared with clinical, imaging, and tumour variables and molecular subtypes (oestrogen receptor [ER]-positive, human epidermal growth factor receptor 2 [HER2]-positive, and triple negative) using a multiple linear regression analysis.

Results

TVDT exhibited a wide range (46–825 days; median, 141 days) with an overall mean of 193?±?141 days and mean values of 241?±?166 days for ER-positive tumours (n?=?37), 162?±?60 days for HER2-positive tumours (n?=?12), and 103?±?43 days for triple-negative tumours (n?=?17) (P?P?Conclusions TVDT differed significantly among the three molecular breast cancer subtypes, with the triple-negative tumours showing the fastest growth.

Key Points

? Knowledge of tumour volume doubling time provides clues for improving screening. ? TVDT assessed by serial US differed significantly between breast cancer subtypes. ? Triple-negative tumours had 2.4-fold shorter TVDT compared to ER-positive tumours. ? Tumours classified as BI-RADS 3 had shorter TVDT than BI-RADS 4.     

Comparison of anatomic ACL reconstruction between selective bundle reconstruction and double-bundle reconstruction

Purpose

The objective of this study was to compare the clinical and radiologic results of preserved ligament remnants in the selective bundle anterior cruciate ligament (ACL) reconstruction and totally sacrificed ligament remnant in the double-bundle ACL reconstruction in order to confirm the evidence of selective bundle reconstruction.

Methods

This retrospective comparative study was conducted for comparison between preserved ligament remnants in the selective bundle ACL reconstruction and totally sacrificed ligament remnant in the double-bundle ACL reconstruction. From 2008 to 2010, 16 patients (group I) underwent selective bundle ACL reconstruction and 30 patients (group II) underwent double-bundle ACL reconstruction. Clinical, stability and radiologic results (tunnel locations of femoral tunnels using 3-D computed tomography and graft signal intensity using magnetic resonance imaging) were compared.

Results

In comparison with functional results, no statistical differences in the Lysholm, Tegner and International Knee Documentation Committee scores were observed between the two groups (n.s.). In comparison with stability results between the two groups, no statistical differences were observed in the Lachman, pivot shift and anterior drawer stress tests using a Telos^® device at 30° and 90° flexed positions (n.s.). In evaluation of the femoral tunnel location, no statistical significant differences in the tunnel position were observed between the groups (n.s.). No statistically significant differences in signal intensity were observed between the two groups (n.s.).

Conclusions

Compared to the double-bundle ACL reconstruction, selective bundle ACL reconstruction produced comparable clinical and radiologic results. Selective bundle ACL reconstruction could be performed instead of double-bundle ACL reconstruction if some intact bundle exists.

Level of evidence

Comparative study, Level III.     

Clinical Significance of Diffuse Intrathoracic Uptake on Post-Therapy I-131 Scans in Thyroid Cancer Patients

Purpose

The purpose of this study was to identify the frequency and possible cause of diffuse intrathoracic uptake on post-therapy I-131 scans in thyroid cancer patients.

Methods

We retrospectively reviewed 781 post-therapy scans of 755 thyroid cancer patients who underwent total thyroidectomy and radioactive iodine therapy between January and December 2010. Diffuse intrathoracic uptake on post-therapy scans was examined, and clinical patient characteristics including sex, age, regimen for thyroid-stimulating hormone (TSH) stimulation (thyroid hormone withdrawal or recombinant human TSH injection), TSH, thyroglobulin (Tg) and anti-thyroglobulin antibody (anti-Tg Ab) levels, therapeutic dose of radioactive iodine therapy and prior history of radioactive iodine therapy were recorded.Scan findings were correlated with chest CT, chest radiographs, laboratory tests and/or clinical status. Diffuse intrathoracic uptake without evidence of pathologic condition was categorized as indeterminate. The association between clinical characteristics and intrathoracic uptake were analyzed for negative intrathoracic uptake and indeterminate uptake groups.

Results

Diffuse intrathoracic uptake on post-therapy scans was demonstrated in 39 out of 755 (5.2 %) patients, among which 3 were confirmed as lung metastasis. The 14 patients that showed high Tg or anti-Tg Ab levels were considered to be at risk of having undetected micrometastasis on other imaging modalities. The remaining 22 were indeterminate (2.9 %).Upon comparison of negative intrathoracic uptake and indeterminate uptake groups, TSH stimulation by thyroid hormone withdrawal was shown to be significantly correlated with diffuse intrathoracic uptake (p < 0.05).

Conclusion

The frequency of diffuse intrathoracic uptake on post-therapy scans was 5.2 % and could be seen in thyroid cancer patients with underlying lung metastasis as well as those without definite pathologic condition. In the latter, there was a higher frequency for diffusely increased intrathoracic uptake in those who underwent thyroid hormone withdrawal rather than recombinant human TSH injection.